The emergence of M. tuberculosis strains resistant to Isoniazid (INH) and Rifampicin (RIF), the two most potent drugs of first-line anti-TB therapy is termed multidrug drug-resistant TB (MDR-TB). Multidrug-resistant tuberculosis has been a serious medical and epidemic problem all over the world. We present here a series of clinical cases consist of two patients diagnosed with isoniazid resistant tuberculosis. Histopathological examination supports the diagnosis of tuberculous granulomas. And the pathology molecular examination revealed the presence of Isoniazid-resistant Mycobacterium tuberculosis1,2 via the following mutation c.947G>A; p.Gly316Asp. Isoniazid-resistance is associated with mutations in the furA-katG and fabG1-inhA operons, as well as mutations in the ahpC gene. 64% of the isoniazid-resistance phenotypes were associated with the katG315 mutation worldwide. The second most common mutation is inhA-15, and it has been reported in 19% of the Isoniazid-resistant isolates. The significant association between the two mutations, inhA c-15 and katG 315 respectively, and the high-level resistance is of interest in the interpretation of current and future molecular diagnostic testing, as an early prediction of the level of Isoniazid-resistance is essential to decide the benefit of high-dose Isoniazid use.

Multidrug-resistant tuberculosis emerged as a serious challenge to tuberculosis management and control. In the Eastern Cape, the Beijing variants are prevalent and a driving force of multidrug-resistant tuberculosis; hence, we investigated the distribution of gene mutations in Beijing strains compared to non-Beijing strains. Multidrug-resistant tuberculosis and heteroresistant isolates were identified in 412 sputum cultures by drug susceptibility testing. The isolates were analyzed for mutations in three genes associated with resistance to antituberculosis first-line drugs: katG and inhA promoters for isoniazid and rpoB for rifampicin. All isolates were genotyped by spoligotyping. There were more males than females and a more economically active age group in the study. The most prevalent mutations in rpoB resistance were in S531L, katG in S315Tb, and inhA in c-15tb. Heteroresistance was found in 18 isolates. Beijing variants were predominant. Most of the heteroresistant isolates were INH, with heteroresistance occurring more in the inhA gene mutation region c-15tb. Beijing and LAM variants were found more frequently in INH heteroresistant isolates. Mutations in katG S315Tb and rpoB S531L were higher in Beijing variants. The Beijing family is a major contributor to the epidemiological picture and accounts for most of the multidrug-resistant tuberculosis in the study area.

Multidrug-resistant-tuberculosis (MDR-TB) patients are treated with a standardised, short, WHO-regimen, which includes clofazimine (CFZ) and bedaquiline (BDQ) antibiotics. These two antibiotics lead to development of QT prolongation in patients, inhibiting potassium (K+) uptake by targeting the Kv11.1 (hERG) channel of the cardiomyocytes (CMs). However, the involvement of these antibiotics on other K+ transporters of the CMs, as potential mechanisms of QT prolongation, has not been explored. This study determined the effects of CFZ and BDQ on the sodium, potassium-adenosine triphosphatase (Na+,K+-ATPase) activity of CMs, using the rat cardiomyocytes (RCMs). These cells were treated with varying concentrations of CFZ and BDQ individually and in combination (1.25 - 5 mg/L). Thereafter Na+,K+-ATPase activity was determined, followed by intracellular adenosine triphosphate (ATP) quantification and cellular viability determination. Both antibiotics demonstrated dose-response inhibition of the Na+,K+-ATPase activity of the RCMs. The greatest inhibition was demonstrated by combinations of CFZ and BDQ, followed by BDQ alone and lastly CFZ. Neither antibiotic, individually or in combination, demonstrated cytotoxicity under the experimental conditions used. The inhibitory effects of CFZ and BDQ individually and in combination, on the activity of the Na+,K+-ATPase pump of the RCMs highlight the existence of additional mechanisms of QT prolongation by these antibiotics.

The global spread of multidrug-resistant (MDR) microbial infections is currently one of the most severe risks to global public health, with 10 million fatalities expected by 2050 unless action is taken. Nanotechnology has revolutionized science and medicine. The reliance on nanotechnology is growing. Nanoparticles have distinct properties that improve biological, chemical, and physical properties studied for various uses. A significant area of attention in the synthesis of nanoscale modulators is the utilization of crude formulations, retro-synthesized, and pure chemicals, mainly from herbal sources, with fewer adverse effects. Green chemistry has devised a tangential technique for synthesizing metals and metal oxides to produce nanoparticles. Plant extracts (leaves, stems, and shoots) and microorganisms (bacteria, fungus, and yeast) are used as reducing intermediates to make nanoparticles. Studies in microbiology have shown that nanoparticles kill bacteria, fungi, viruses, and protozoa. These green nanoparticles contain antibacterial, antifungal, and anti-inflammatory effects. Most nanoparticles have high antibacterial properties, indicating they may be used to combat diseases and biological contaminants. These nanoparticles have antibacterial action against pathogenic microorganisms that cause serious illnesses, including multidrug-resistant pathogens. The current research will pave the way for future applications and improved methods for producing nanoparticles, paving the way for an innovative route in nano-life sciences with widespread recognition.

Acinetobacter baumannii is a multidrug-resistant and invasive pathogen associated with the etiopathology of both an increasing number of nosocomial infections and of relevance to poultry production systems. Multidrug-resistant Acinetobacter baumannii has been reported in connection to severe challenges to clinical treatment, mostly due to an increase rate of resistance to carbapenems. Amid the possible strategies aiming to reduce the insurgence of antimicrobial resistance, phage therapy has gained particular importance for the treatment of bacterial infections. This review summarises the different phage-therapy approaches currently in use for multiple-drug resistant Acinetobacter baumannii, including single phage therapy, phage cocktails, phage -antibiotic combination therapy, phage coding Acinetobacter baumannii and the novel phage enzyme treatment. Although phage therapy represents a potential treatment solution for multidrug-resistant Acinetobacter baumannii, further research is needed to unravel some unanswered questions especially in regard to its in vivo applications, before possible routine clinical use.

Background: Although Tuberculosis (TB) is one of the oldest diseases known to mankind, many practitioners are still unaware of various aspects of management of TB including drug resistant TB. To be able to make an impact on the disease burden we need to understand the knowledge, attitude and practices (KAP) of practitioners, both in government and private sector, towards TB case management. Methodology: A random cross-sectional survey of 99 respondents to assess the KAP towards TB case management using a digital semi-structured questionnaire which was pre-tested and administered to allopathic practitioners from across States in North and Central India. Results: 77% responders were government doctors and 23% were private practitioners. Chest physicians accounted for 61% of the responders. 26% of government and 78% of private doctors relied on sources which are difficult to validate for their knowledge on drug resistant TB management. There were large variations seen in knowledge on modes of transmission, standard precautions, extent of drug resistant TB, diagnostics as well as treatment regimen for drug resistant TB. Conclusion: The knowledge of both sector doctors especially amongst private practitioners with respect to the awareness of extent, diagnosis, and treatment and infection control measures for drug resistant TB is suboptimal which translates to poor diagnostic, therapeutic and infection control choices amongst private practitioners. If India has to achieve the targets for TB Elimination by 2025, serious work needs to be done to upgrade the knowledge of the private sector doctors on drug resistant tuberculosis. The Ministry of Health and Family Welfare, GoI needs to have regular educational programs for the private practitioners coupled with awareness campaigns and frequent surveys to assess the knowledge, attitude and practices being followed in the private sector for TB management including drug resistant TB.

Carbapenems-resistant enterobacteria are considered multidrug-resistant, making the control of their nosocomial infections a major challenge in healthcare settings. It is important to know the incubation site and source of the spread of these strains, especially in neonatal intensive care units (NICU). Colonization of the colon of preterm neonates per se by multidrug-resistant bacterial strains could be the source of dissemination of these multidrug-resistant strains and their site of incubation. In this study, colonization of the colon of preterm neonates with enterobacteria and their multidrug-resistant strains was investigated. The presence of enterobacteria in the stool of preterm neonates was investigated on EMB (eosin-methylene blue) agar, followed by morphological and biochemical characterization and phylogenetic analysis of the 16S rRNA-encoding gene sequences. Antibiotic susceptibility of all isolated strains was tested using VITEK 2 technology. All cases examined at two weeks of age and older showed bacterial colonization of the colon. Klebsiella pneumoniae colonized the colon in 56.2% of the preterm neonates and Klebsiella quasipneumoniae was found in 6.3%, corresponding to 62.5% in total. The colonizing Klebsiella pneumoniae was multidrug-resistant in 2 of 9 cases. One strain of Klebsiella pneumoniae was resistant to carbapenems and another showed intermediate resistance to these antibiotics. These Klebsiella pneumoniae strains showed resistance to most of the other antibiotics tested. Some cases contained more than one genus, with Escherichia coli found in 50% of cases in preterm neonates. In contrast to Klebsiella pneumoniae, none of the E. coli strains colonizing the colon of preterm neonates in this study showed resistance to carbapenems. The results of this study suggest that Klebsiella pneumoniae and its carbapenems multidrug-resistant strains are well marked in preterm neonates colonizing their colon, which is the incubation site and source of such multidrug-resistant bacterial strains in NICU. This study highlights the importance of careful management of preterm neonates in the NICU and possible contamination with multidrug-resistant Klebsiella pneumoniae incubated in their colon. Further studies would be of interest to avoid the possibility of fecal-oral transmission and infection by these multidrug-resistant bacteria and their treatment in the colon, where their incubation site is located.

Introduction Infections caused by multidrug-resistant bacteria (MDR) occur more frequently after pancreaticoduodenectomy (PD) compared to other abdominal surgeries, and infective complications are a leading cause of postoperative morbidity following PD. Pre-operative biliary stent (PBS) placement often leads to biliary contamination, which in turn plays a significant role in postoperative infections. The aim of this study is to evaluate the impact of MDR contamination on short-term postoperative outcomes in patients undergoing PD and to examine the relationship between MDR bacteria, PBS, and bile contamination. Methods This is a retrospective study based on a prospectively maintained database comprising 825 consecutive patients who underwent pancreaticoduodenectomy (PD) between January 2010 and December 2020 at our center. All procedures were conducted with a standardized resection by a dedicated group of surgeons in a specialized pancreatic surgery unit, and the patients were managed according to the same perioperative enhanced recovery protocol. Results MDR bacteria were present in 17.5% of bile cultures, exclusively within the stented group. In our multivariate analysis, the development of a major postoperative complication (MPC) was correlated with the presence of MDR bacteria in the bile (OR 1.66, 95% CI: 1.1-2.52; p = 0.02). MDR bacteria were detected early in the surgical drainage in 144 out of 825 patients (12.1%), with 72.2% having a previous biliary stent placement and 27.8% without stents (p < 0.001). In our multivariate analysis, the development of an MPC was associated with the presence of MDR bacteria in the drainage (OR=1.81, 95% CI: 1.21-2.73, p= 0.0042). Conclusions We demonstrated that MDR contamination worsens the short-term outcomes of patients undergoing PD. Specifically, when MDR bacteria are present in both the bile and drainage, there is a statistically significant increase in the incidence of major postoperative complications (MPC). Our data suggest that the majority of MDR surgical site infections stem from biliary contamination resulting from the placement of a pre-operative biliary stent (PBS).

Xpert MTB/RIF is rapid molecular diagnostic tool capable of simultaneously detecting Mycobacterium tuberculosis and rifampicin resistance. This study aimed to access the diagnostic precision of Xpert MTB/RIF assay to detect pulmonary and extra-pulmonary tuberculosis and to evaluate the performance for the detection of rifampicin resistance. Of 37695 samples, 7156(18.98%) were tuberculosis positive, 509(7.11%) were rifampicin-resistant. The sensitivity, specificity, PPV, NPV, Diseases prevalence and accuracy of Xpert MTB/RIF assay for PTB were 99.87% (95%CI:99.75-99.94), 99.92%(95%CI:99.88-99.95), 99.71%(95%CI:99.54-99.82),99.97%(95%CI:99.93-99.98),21.38% (95%CI:20.92-21.86),and 99.91%(95%CI:99.87-99.94), respectively. For EPTB, the sensitivity, specificity, PPV, NPV, Diseases prevalence and accuracy of Xpert MTB/RIF assay accounted for 99.45% (95%CI:98.73-99.82),99.84%(95%CI:99.73-99.92),98.70%(95%CI:97.73-99.25),99.93% (95%CI:99.84-99.97),10.64%(95%CI:9.99-11.31),and 99.80%(95%CI:99.68-99.88), respectively. Despite its high sensitivity for detecting tuberculosis and rifampicin resistance, Xpert MTB/RIF had contradictory results for 20.5% of cases among patients with negative smear results and 54.9% of cases among patients with a high risk of Multidrug-resistant tuberculosis. Of 47 fluoroquinolone-resistant, 16.56% (26/157) of Multidrug-resistant tuberculosis isolates and 4.02% (20/498) isoniazid-resistant are fluoroquinolone-resistant, a characteristic distribution leading to about 17.2% of fluoroquinolone resistance events and relevant marker gyr-A mutations in MDR tuberculosis isolates. Further, our study indicated that increased fluoroquinolone resistance among Rifampicin-resistant and isoniazid-resistant tuberculosis endangers the success of newly endorsed MDR-TB regimens.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

Klebsiella pneumoniae is a multidrug-resistant opportunistic human pathogen related to various infections. As such, synthetic peptides have emerged as potential alternative molecules. Mo-CBP3-PepI has presented great activity against K. pneumoniae by presenting an MIC50 at a very low concentration (31.25 µg mL-1). Here, fluorescence microscopy and proteomic analysis revealed the alteration in cell membrane permeability, ROS overproduction, and protein profile of K. pneumoniae cells treated with Mo-CBP3-PepI. Mo-CBP3-PepI led to ROS overaccumulation and membrane pore formation in K. pneumoniae cells. Furthermore, the proteomic analysis highlighted changes in essential metabolic pathways. For example, after treatment of K. pneumoniae cells with Mo-CBP3-PepI, it was seen a reduction in the abundance of protein related to DNA and protein metabolism, cytoskeleton and cell wall organization, redox metabolism, regulation factors, ribosomal proteins, and resistance to antibiotics. These reductions lead to the inhibition of DNA repair, inhibition of cell wall turnover, protein turnover, and ROS accumulation leading to cell death. Our findings indicated that Mo-CBP3-PepI might have mechanisms of action against K. pneumoniae cells, mitigating the development of resistance and thus being a potent molecule to be employed in producing new drugs against K. pneumoniae infections.

The ESKAPE pathogens are public health concerns worldwide, defining the present major antibiotic resistance issues: E. faecium vancomycin-R, S. aureus methicillin-R, Ps. Aeruginosa and A. baumannii carbapenem-R, resistance to 3rd generation cephalosporins of Kl. pneumoniae and Enterobacter spp. Covid-19 pandemic disturbed the health care usual procedures, contributing to the spread of antibiotic-resistant bacteria. The present study retrospectively assessed the prevalence and antimicrobial resistance (AMR) profile of ESKAPE microorganisms during 2020-2022 in a multidisciplinary emergency hospital from Romania, based on microbiological reports. The AMR issues mainly interest the urology department. ESKAPE group accounts for 33.5% of the total bacterial isolated. The specific AMR of ESKAPE pathogens cumulates 30.9%, while antimicrobial multidrug resistance characterizes 21% from all ESKAPE strains. Kl. Pneumoniae, followed by S. aureus, and Ps. aeruginosa are the main hospital problems concerning the ESKAPE surveillance. The directions of the near future antibiotic stewardship program focus to revise the clinical protocols for diagnostic and treatment in each department, to intensify the bacteriological samples collection, to improve the microbiological diagnostic techniques for AMR identification, to continue the epidemiological current actions of surveillance, control, and education.

Nowadays, healthcare-associated infections (HAIs) represent a major global public health problem and the burden of these infections is high. In order to reduce the incidence of HAIs and to prevent the spread antibi-otics resistant organisms is mandatory to develop surveillance systems. We undertook a retrospective case-control study of all patients presenting HAIs admitted in Intensive Care Unit (ICU) in order to assess risk factors associated with death among patients with HAIs. Patients admitted to Intensive Care Unit who died were more likely to present an infection with a multidrug resistant bacteria, an infection with Acineto-bacter baumannii, and to suffer from acute myocardial infarction. Among the patients enrolled in the study, a higher probability of death was also observed in association with certain gram-negative pathogens: Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. The longer the patient remains admitted in ICU, the higher the risk of getting an infection that can often become fatal. Acquiring a noso-comial infection also increases the length of hospitalization which will lead to increased financial damage.

Post-COVID-19 bacterial infections are a significant threat to global health, mainly due to the overuse and misuse of antibiotics. The review highlights the importance of using antibiotics judiciously and following appropriate guidelines and recommendations. The article also examines the potential indirect contribution of steroids to antibiotic resistance through immune suppression in severe cases of COVID-19. Anti-microbial resistance (AMR) is one of the leading causes of death worldwide that continues as a silent pandemic caused by the major AMR superbug includes Carbapenem-resistant Acinetobacter baumannii (CRAB), Methicillin-resistant Staphylococcus aureus (MRSA), Carbapenem-resistant Enterobacterales (CRE), Extended-spectrum Beta Lactamase producing Enterobacterales (ESBL) which is resistant to cephalosporin and Multidrug-resistant (MDR) Pseudomonas aeruginosa. Ongoing surveillance and monitoring of antibiotic use and resistance helped to minimize the risk of antibiotic resistance and shrink it from pandemic to endemic.

Urinary tract infections (UTIs) caused by pathogens, particularly E. coli, have spontaneously become resistant to antimicrobial drugs in recent years. Therefore, regular monitoring and alternative strategies for the antimicrobial agent are crucial for combating antimicrobial resistance and bacterial biofilms. Here, we report a new cobalt iron oxide-conjugated tin oxide nanocomposite that can kill bacteria and treat multidrug-resistant E. coli posing UTIs. Following the isolation and identification of E. coli, we tested 57/134 samples against sixteen commonly used antibiotics phenotypically using the disk diffusion method to determine their sensitivity pattern. Of the 57 E. coli isolates, 66% (38/57) were multidrug-resistant. The E. coli isolates were resistant to cephradine (70.17%), ceftriaxone (59.64%), and azithromycin (59.64%), followed by cefixime (54.38%), cefuroxime sodium (52.63%), and co-trimoxazole (50.87%). X-ray diffraction results showed the crystallite sizes were about 5.68 and 8.84 nm in pure SnO2 nanoparticles and 95% SnO2-5% CoFe2O4 nanocomposite, respectively. Energy-dispersive X-ray spectroscopy and Fourier transform infrared determined the fundamental structure of the nanocomposite, encompassing Co, Fe, Sn, and O. Moreover, FTIR measurements implied that the distinct functional groups in both SnO2 and CoFe2O4 nanoparticles existed in a 95% SnO2-5% CoFe2O4 nanocomposite. Field emission scanning electron microscope analysis uncovered that the SnO2-CoFe2O4 nanocomposite had a size of roughly 24 nm and was spherical. In addition, the biosynthesized SnO2 nanoparticles and SnO2-CoFe2O4 nanocomposite were evaluated for their antibacterial activity. At a minimum 100 µg/mL concentration, SnO2 nanoparticles and SnO2-CoFe2O4 nanocomposite showed high antibacterial activity. The SnO2 nanoparticles and SnO2-CoFe2O4 nanocomposite demonstrated antibacterial activity on multidrug-resistant E. coli at 10 ± 0.7 and 16 ± 0.8 mm zone of inhibition, respectively. In conclusion, the new SnO2-CoFe2O4 nanocomposite might be a potential candidate for treating UTIs caused by drug-resistant E. coli in the foreseeable future.

Infections by methicillin-resistant Staphylococcus aureus (MRSA) are continuously expanding within the community. Chicken meat is usually contaminated by MRSA, and this contaminated chicken meat is an important source of foodborne infections in humans. In this study, a cross-sectional supershop survey was conducted to determine the prevalence and antimicrobial resistance pattern of MRSA in 113 domestic frozen chicken meat samples purchased from nine branded supershops available in five divisional megacities of Bangladesh. The study also focused on the determination of methicillin resistance gene in MRSA isolates. S. aureus was identified by standard culture-based and molecular methods, and subjected to antimicrobial susceptibility testing. MRSA was screened by cefoxitin disk diffusion test. Methicillin resistance gene was identified by PCR. Of samples, 54.9% were positive for S. aureus, and, of these, 37.1% isolates were identified as MRSA. All the isolates were multidrug resistant (MDR): 52.2% were resistant to 6−8 antimicrobial classes, and 47.8% isolates to 9−12 classes. Three (3.2%) isolates of S. aureus were possible extensively drug resistant. The highest rates of resistance were observed against cefoxitin (100%), followed by nalidixic acid, ampicillin and oxacillin (97.7%), colistin (91.3%), amoxicillin-clavulanic acid and amoxicillin (87%), penicillin-G and cloxacillin (82.6%), oxytetracycline (78.3%) and cefixime (73.9%). Screening of methicillin resistance gene revealed that 43.5% isolates of MRSA were positive for mecA gene. The high prevalence of MDR MRSA in frozen chicken meat samples in this study emphasizes the need for better sanitary education of food handlers in hygienic practices focusing on their potential role as reservoirs and spreaders of MRSA.

Acetyleugenol is a phytochemical compound with broad effect against infectious diseases and tumors. Here, we extracted, characterized and elucidated the structure of acetyeugenol, for the first time, from the leaves of Acacia nilotica (L.)―a well-known medicinal plant. The broad antibacterial potential of acetyleugenol was first confirmed against seven bacterial pathogenic isolates with best activity against Proteus sp., Salmonella typhi, Staphylococcu aureus, and Streptococcus pneumonia, which showed similar or better zone of inhibition to that of the control amoxicillin. To further investigate its effect against Mycobacterium tuberculosis, acetyleugenol and its indole and phenyl analogs were subjected to molecular docking experiments against two potential tuberculosis drug targets―MtPknE and MtPknB Ser/Thr protein kinases. The results reveal that all of the analogs have improved docking scores comparing to the acetyleugenol. The indole analogs EUG-1 and EUG-3 were more effective with better docking scores for MtPknE with –11.08 and –10.05 kcal/mol, respectively. Similar results were obtained for the MtPknB. In contrast, only the EUG-2 phenyl analog has given rise to similar docking scores for both targets. This opens the door for further comprehensive studies on these acetyleugenol analogs with in vitro and in vivo experiments to validate and get more insights into their mechanisms of action.

We report a facile route for the green synthesis of trimethylchitosan nitrate-capped silver nanoparticles (TMCN-AgNPs) with positive surface charge. In this synthesis, silver nitrate, glucose, and trimethyl chitosan nitrate (TMCN) were used as silver precursor, reducing agent, and stabilizer, respectively. The reaction was carried out in a stirred basic aqueous medium at room temperature without the use of energy-consuming or expensive equipment. We investigated the effects of the concentrations of NaOH, glucose, and TMCN on the particle size, zeta potential, and formation yield. The AgNPs were characterized by UV-visible spectroscopy, photon correlation spectroscopy, laser Doppler anemometry, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The catalytic activity of the TMCN-AgNPs was studied by the reduction of 4-nitrophenol using NaBH₄ as a reducing agent. We evaluated the antibacterial effects of the TMCN-AgNPs on Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus using the broth microdilution method. The results showed that both gram-positive and gram-negative bacteria were killed by the TMCN-AgNPs at very low concentration (< 6.13 μg/mL). Moreover, the TMCN-AgNPs also showed high antibacterial activity against clinically isolated multidrug-resistant A. baumannii strains, and the minimum inhibitory concentration (MIC) was ≤ 12.25 μg/mL.

The increasing prevalence of multidrug-resistant pathogens (MDR), persistent biofilms, oxidative stress, and cancerous cell proliferation pose significant challenges in healthcare and environmental settings, highlighting the urgent need for innovative and sustainable therapeutic solutions. The exploration of nanotechnology, particularly the use of green-synthesized nanoparticles, offers a promising avenue to address these complex biological challenges due to their multifunctional properties and biocompatibility. Utilizing a green synthesis approach, Mauritia flexuosa Mf-AgONPs were synthesized and characterized exhibiting potent antibacterial effects against both non-resistant and MDR bacterial strains, with minimum inhibitory concentrations (MICs) ranging from 11.25 to 45 µg/mL. Mf-AgONPs also demonstrated significant antifungal efficacy, particularly against Candida glabrata, with a MIC of 5.63 µg/mL. Moreover, the nanoparticles showed strong biofilm inhibition capabilities and substantial antioxidant properties, underscoring their potential to combat oxidative stress. Additionally, Mf-AgONPs exhibited pronounced anti-tumor properties against various cancer cell lines, displaying low IC50 values across various cancer cell lines while maintaining minimal hemolytic activity at therapeutic concentrations. These findings suggest that Mf-AgONPs synthesized via an eco-friendly approach offer a promising alternative for biomedical applications, including antimicrobial, antifungal, antioxidant, and anticancer therapies, warranting further in vivo studies to fully exploit their therapeutic potential.

Public restrooms are often a hub of microbial contamination, and the examination of bacterial contamination in these facilities can serve as an important indicator of the transmission of infectious diseases. This study was conducted to determine the prevalence of bacterial contamination in public restrooms based on the economic class of the building. Samples were collected from various spots in 32 restrooms found in 10 shopping malls, classifying them into two categories: upper-end restrooms and lower-end restrooms. The findings showed that the level of contamination was higher in the lower-end restrooms, with the seat being the most contaminated area. The most dominant Gram-positive bacteria were coagulase-negative staphylococci species, making up 86% of the identified Gram-positive isolates. The most dominant Gram-negative bacteria identified were Klebsiella pneumoniae and Pseudomonas aeruginosa. The antibiotic sensitivity test results revealed the presence of multi-drug resistant bacteria among the Gram-positive and negative isolates, including Staphylococcus haemolyticus, Staphylococcus kloosi, Acinetobacter baumanii, and Pseudomonas aeruginosa. In conclusion, the study underscores the significance of monitoring bacterial contamination in public restrooms and the need for measures to reduce the spread of infectious diseases. Further research is crucial to gain a complete understanding of the bacterial contamination in public restrooms and their resistance patterns, to ensure the safety and health of the public. The implementation of improved cleaning practices and hands-free designs in restrooms can help reduce the risk of cross-contamination and prevent the spread of diseases.

Carbapenem resistant Enterobacteriaceae (CRE) has been public health risk in several countries and recent reports indicate the emergence of CRE in food animals. This study was conducted to investigate the occurrence, resistance patterns, and phylogenetic diversity of CRE E.coli from chicken. Routine bacteriology, PCR detection of E.coli species, multiplex PCR to detect carbapenemase encoding genes and phylogeny of CRE E. coli were conducted. The results show that 24.36 % (19/78) were identified as CRE based on the phenotypic identifications of which 17 were positive for the tested carabanemase genes. The majority, 57.99% (11/19) of the isolates harbored multiple carbapenemase genes. Four isolates harbored all blaNDM blaOXA, blaIMP, five and two different isolates harbored blaNDM and blaOXA, and blaOXA and blaIMP respectively. The Meropenem, Imipenem and Ertapenem MIC values for the isolates ranged from 2g/mL to ≥256g/mL. Phylogenetic grouping showed that the CRE E.coli isolates belonged to five different groups; groups A, B1, C, D and unknown. The detection of carbapenem resistant E.coli in this study shows that CRE is has become an emerging problem in farm animals, particularly, in poultry farms. This also implies the potential public health risks posed by CRE from chicken to the consumers.

Tuberculosis (TB) remains the leading cause of death from a single infectious agent. Among children, TB can have a wide range of non-specific clinical and radiological manifestations becoming a challenging diagnosis, particularly in areas with a low prevalence. We present the case of a 14 month-old female with a history of fever of unknown origin (FUO) and later diagnosed with miliary tuberculosis.

Background: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation. Methods: We performed a prospective study in 5 referral centers for HIV care in Italy. PLHIV who consented to participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI that started chemoprophylaxis were followed until the ending of therapy. Results: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, 6 were lost to follow-up before discriminating between latent and active TB. Among PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6-9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment.

Multidrug resistant organisms (MDROs) outbreaks have been steadilyincreasing in Intensive care units (ICUs). Still, healthcare institutions and workers (HCW) reached no unanimity on how and when implementing infection prevention and control (IPC) strategies. We aimed to provide a pragmatic, physician practice-oriented, resume of strategies towards different MRDOs outbreaks in ICU. We performed a narrative review on IPC in ICUs, investigating patient-to-staff ratios, education, isolation, decolonization, screening and hygiene practices, outbreak reporting, cost-effectiveness, reproduction-number(R0), and future perspectives. The most effective IPC strategy remains unknown. Most studies focus on a specific pathogen or disease, making the clinician losing the big picture. IPC strategies proved their cost-effectiveness regardless typology, country, or pathogen. A standardized, universal, pragmatic protocol for HCW education should be elaborated. Likewise, a rapid outbreak recognition tool elaboration (i.e., an easy-to-use mathematical model) would improve early diagnosis and spreading prevention. Further studies are needed to express in favor or against MDROs decolonization. New promising strategies are emerging and need to be tested in the field. The lack of IPC strategies application has made, and still makes ICUs a major MDROs reservoir into the community. In a not-too-distant future genetic engineering and phage therapies could represent a plot-twist in MDROs IPC strategies.

The lung microbiota is a complex community of microorganisms that colonize the respiratory tract of individuals from or even before birth. Although the lungs were traditionally believed to be sterile, recent research has shown that there is a diversity of bacterial species in the respiratory system. Knowledge about the lung microbiota in the newborn and its relationship with bacterial infections is of vital importance to understand the pathogenesis of respiratory diseases in neona-tal patients undergoing mechanical ventilation. In this article, the current evidence on the compo-sition of the lung microbiota in the newborn will be reviewed, as well as its role in the develop-ment of bacterial infections in mechanically ventilated neonates. Although advances in many as-pects of the neonatal intensive care unit care have significantly improved the survival of preterm infants, the diagnosis and treatment of ventilator-associated pneumonia has not progressed in recent decades. Avoiding dysbiosis caused by inappropriate use of antibiotics around birth, as well as avoiding intubation of patients or promoting early removal of endotracheal tubes are among the most important preventive measures for ventilator-associated pneumonia. The use of probiotics and prebiotics to prevent infectious, allergic or metabolic complications in the short or long term constitutes a very important field of research in perinatal medicine.

Transparent materials used for facial protection equipment provide protection against microbial infections caused by viruses and bacteria, including multidrug-resistant strains. However, transparent materials used for this type of application are made of materials that do not possess antimicrobial activity. They just avoid direct contact between the person and the biological agent. Therefore, healthy people can get infected through contact of the contaminated material surfaces and this equipment constitute an increasing source of infectious biological waste. Furthermore, infected people can transmit microbial infections easily because the protective equipment do not inactivate the microbial load generated while breathing, sneezing, or coughing. In this regard, the goal of this work consisted of fabricating a transparent face shield with intrinsic antimicrobial activity that could provide extra-protection against infectious agents and reduce the generation of infectious waste. Thus, a single-use transparent antimicrobial face shield composed of polyethylene terephthalate and an antimicrobial coating of benzalkonium chloride has been developed for the next generation of facial protective equipment. The antimicrobial coating was analyzed by atomic force microscopy and field emission scanning electron microscopy with elemental analysis. This is the first facial transparent protective material capable of inactivating enveloped viruses such as SARS-CoV-2 in less than one minute of contact, and the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Bacterial infections contribute to severe pneumonia associated with the SARS-CoV-2 infection, and their resistance to antibiotics is increasing. Our extra protective broad-spectrum antimicrobial composite material could also be applied for the fabrication of other facial protective tools such as such as goggles, helmets, plastic masks and space separation screens used for counters or vehicles. This low-cost technology would be very useful to combat the current COVID-19 pandemic and protect health care workers from multidrug-resistant infections in developed and underdeveloped countries.

The increasing emergence of multidrug resistant (MDR) pathogens causes difficult-to-treat infections, with long-term hospitalizations and high incidence of death, thus representing a global public health problem. To manage MDR bacteria bugs, new antimicrobial strategies are necessary, and their introduction in practice is a daily challenge for scientists in the field. An extensively studied approach to treat MDR infections consists in inducing high levels of reactive oxygen species (ROS) by several methods. Although further clinical investigations are mandatory on the possible toxic effects of ROS to mammalian cells, clinical evaluations are extremely promising, and their topical use to treat infected wounds and ulcers, also in presence of biofilm, is already clinically approved. Biochar (BC) is a carbonaceous material obtained by pyrolysis of different vegetable and animal biomass feedstocks, at 200−1000 °C in limited presence of O2. Recently, it has been demonstrated that BC capability of removing organic and inorganic xenobiotics is mainly due to the presence of persistent free radicals (PFRs), which can activate oxygen, H2O2 or persulfate in the presence or not of transition metals by electron transfer thus generating ROS, which in turn degrade pollutants by advanced oxidation processes (AOPs). In this context, the antibacterial effects of BC containing PFRs have been demonstrated by some authors against Escherichia coli and Staphylococcus aureus, thus giving birth to our idea of the possible use of BC-derived PFRs as a novel method capable of inducing ROS generation for antimicrobial oxidative therapy. Here, the general aspects concerning ROS physiological and pathological production and regulation, and the mechanism by which they could exert antimicrobial effects have been reviewed. The methods currently adopted to induce ROS production for antimicrobial oxidative therapy have been discussed. Finally, for the first time, BC-related PFRs have been proposed as a new source of ROS for antimicrobial therapy via AOPs.

Tuberculosis (TB) is an infectious-contagious disease caused by M. tuberculosis (Koch’s bacillus). About one-quarter of the world’s population is infected with that bacillus and at risk of developing TB disease. Latent tuberculosis corresponds to people who have been infected by TB bacteria but are not (yet) ill. The most vulnerable population to TB activation includes HIV infected, drug abuse and autoimmune disease patients. Multiple Sclerosis (MS) is a chronic and autoimmune neurological disease caused by lymphocytic infiltration. Its prevalence worldwide is 22.2 million cases of MS. There is a relation between TB and MS: due to immunomodulation or immunosuppression treatment of MS (reactivation of latent infection), or due to the intense inflammatory response before the infection of the bacillus (increased susceptibility to the development of autoimmune diseases). Screening for TB includes complete patient history, physical exam, chest radiography, and Tuberculin Skin Test or IGRA (Interferon Gamma Release Assay). This investigation is suggested when MS drugs (immunomodulatory and immunosuppressant medications) are prescribed. If a patient has positive results, the treatment for MS should not be delayed for the finishing TB treatment. In this paper, considering the high prevalence of tuberculosis, we recommend that TB screening should be also done at the moment of Multiple Sclerosis diagnosis.

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulate disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified 3 MTBC lineages of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (N=149 and N=127). We found a significant interaction between a SNP in PPIAP2 and the Uganda lineage (combined p=4x10-8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host-pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human-MTBC coevolution is likely to explain patterns of disease severity.

Tuberculosis (TB) associated with diabetes (DM) is a growing problem, particularly in low and medium-resource countries. We conducted an open-label, parallel-group, randomized, and controlled trial in a tertiary care center in Mexico City to assess TB preventive treatment with isoniazid (INH) or rifampicin (RIF) in people with DM. Participants were assigned six months of INH 300mg/day plus pyridoxine 75mg or three months of RIF 600mg/day. The primary outcomes were adverse events resulting in permanent treatment cessation and considered possibly or probably related to study drugs. We included 130 subjects, 68 randomized to INH and 62 to RIF. We prematurely halted the study based on recommendations of the Adverse Event Safety Panel. There was no difference between arms in the overall frequency of adverse events. However, the INH group had significantly more permanent treatment interruptions due to grade 2 recurrent or grade 3 or 4 hepatoxicity. In comparison, the RIF arm had more treatment interruptions due to grade 3 or 4 gastrointestinal intolerance. TB preventive treatment is not safe enough to be considered a universal indication to patients with DM and LTBI. These results underline the need to search for alternative TB prevention in DM patients with better safety profiles.

(1) Background: A history of TB is a known risk factor for long-term respiratory impairment affecting lung functions in both restrictive and obstructive lung disease. (2) Methods: We analyzed data from the NHANES 1 Epidemiologic Follow-up Study (NHEFS), a longitudinal study conducted on non-institutionalized adult US population, ages 25-74 years. Approximately 93 percent (n=13,383) of the cohort was successfully traced by the end of the survey period and was available for analysis. The final adjusted model included age groups, gender, family income, lifetime smoking, BMI, and frequency of alcohol consumption as potential confounders. (3) Results: Estimated hazards ratio of developing Emphysema during follow-up in individuals that had a past diagnosis of TB was 54% lower (95% CI = 0.35, 0.61) as compared to individuals with no past TB, after controlling for potential confounders and using proportional hazards regression appropriate to the complex sample design. The association, however, was not statistically significant (HR = 0.862, p-value = 0.38) when only self-reported history of TB was considered as the exposure. (4) Conclusion: Tuberculosis (self-reported or LTBI) was strongly (but inversely) associated with Emphysema incidence. The association was not statistically significant with only self-reported history of TB as exposure.

Diabetes is a major risk factor for tuberculosis (TB). Diabetes increases the risk of progression from latent tuberculosis infection (LTBI) to active pulmonary TB and TB patients with diabetes are at greater risk of more severe disease and adverse TB treatment outcomes compared to TB patients without co-morbidities. Diabetes is a complex disease characterized not only by hyperglycemia but also various forms of dyslipidemia. However, the relative contribution of these underlying metabolic factors to increased susceptibility to TB are poorly understood. This review summarizes our current knowledge on epidemiology and clinical manifestation of TB and diabetes comorbidity. We subsequently dissect the relative contribution of body mass index, hyperglycemia, elevated cholesterol and triglycerides on TB disease severity and treatment outcomes. Lastly, we discuss the impact of selected glucose and cholesterol lowering treatments frequently used in the management of diabetes on TB treatment outcomes.

Fermented food products are widely consumed for their nutritional and health-promoting properties earning them a central place in diets around the globe. However, these foods can present a paradox, as they have the potential to harbor not only beneficial probiotics but also antibiotic-resistant (AR) microbes and genes. The impact of AR in fermented foods has far-reached implications, such as its potential effects on human health, repercussions in the food industry, and environmental consequences. An in-depth analysis of AR in fermented foods, including dairy products, fermented fruits and vegetables, meat products, and beverages, would provide insights into the extent and ramifications of the issue with these foods. Therefore, this review systematically presents the status of AR in fermented foods, with a particular focus on AR bacteria and genes within this category of food products. The review also highlights the complexities of AR in fermented foods, emphasizing the role of bacterial adaptation during the fermentation process and the dynamics of bacterial gene transfer. Various contributing factors to AR are brought into focus, including intrinsic resistance among bacteria in fermented foods and the potential risk of contamination with pathogenic bacteria. Moreover, this review presents a range of mitigation strategies, from the development of novel antimicrobials to advances in fermentation technology and regulatory control. This comprehensive perspective on the intricate interplay between AR and fermented food will potentially pave the way for more targeted research and mitigation strategies in this critical area.

This article describes the challenges, pharmacological strategies, and recommendations for managing multidrug-resistant breast cancer in Sub-Saharan Africa (SSA). By examining the current breast cancer treatment landscape, region-specific challenges, and promising pharmacological interventions, the objective is to bring to light the insufficient research on breast cancer and its multidrug resistance in this part of the world and guide healthcare professionals, policymakers, and researchers in developing evidence-based strategies for improved breast cancer care in SSA. Breast cancer is the leading cause of cancer morbidity in SSA, necessitating continuous advancements in its management. This overview explores the evolution of breast cancer treatment, including surgery, targeted therapy, immunotherapy, radiotherapy, and chemotherapy. Despite these advancements, multidrug resistance poses a significant challenge, impacting treatment efficacy and patient outcomes.The article provides insights into various breast cancer treatment modalities, emphasizing surgery, targeted therapy, immunotherapy, radiotherapy, and chemotherapy. Each approach is discussed in detail, highlighting its significance in managing breast cancer. The effectiveness of these treatments is contingent on timely diagnosis and intervention. Multidrug resistance is examined as a critical obstacle in breast cancer treatment, elucidating its impact on treatment failure and patient outcomes. Mechanisms such as the efflux system, enhanced DNA repair, apoptosis inhibition, alterations in drug targets, and the tumor microenvironment contribute to multidrug resistance, emphasizing the need for a multifaceted understanding.The unique challenges faced in SSA regarding multidrug-resistant breast cancer are delineated. These include the lack of comprehensive data, late presentation and diagnosis, poor genomic studies, limited access to specialized care, financial constraints, inadequate infrastructure, and psychosocial support issues. Addressing these challenges is crucial for devising effective strategies. In response to multidrug resistance, the article discusses contemporary treatment strategies such as P-glycoprotein inhibitors, combined chemotherapy, and immunotherapy. Notable advancements, including the use of Tariquidar and synergistic effects of combined chemotherapy, are highlighted, presenting promising avenues for overcoming resistance.The article proposes recommendations to enhance breast cancer management in SSA, encompassing strengthening primary healthcare services, creating specialized oncology facilities and long-term monitoring and data collection. Breast cancer management in SSA is multifaceted, marked by challenges and evolving solutions. Multidrug resistance remains a significant hurdle, demanding a holistic approach. Promising advancements in pharmacological interventions offer hope, while comprehensive recommendations serve as a roadmap for progress. By implementing these strategies, SSA can substantially improve multidrug-resistant breast cancer care and overall patient well-being.

Tuberculosis (TB) remains a global public health issue, particularly in developing countries. Hematopoietic stem cell transplant (HSCT) recipients are at elevated risk for TB due to immunosuppression. This retrospective study (2005-2022) assessed a preemptive latent tuberculosis infection (LTBI) screening and treatment strategy in 338 HSCT recipients and their donors. Screening included tuberculin skin test (TST) or QuantiFERON-TB Gold (QFT), and pulmonary imaging, with positive cases receiving isoniazid (INH) therapy. Statistical analyses aimed to compare TB reactivation rates, overall survival (OS), and relapse-free survival (RFS) across HSCT groups. Of 338 patients, 92 (27%) were diagnosed with LTBI. Screening involved TST in 325 cases and QFT in 13. INH therapy was completed by 81 patients, with 5 discontinuing due to hepatotoxicity. The cumulative incidence of active TB was 0.6%, and LTBI reactivation rate in patients who received INH was 1.2%. LTBI status did not affect OS or RFS. Our study exemplifies the effectiveness of LTBI protocols incorporating TST/QFT and CT-scan testing, followed by INH therapy, in reducing TB reactivation among HSCT recipients in a high-burden region.

In the present study, we aimed to investigate whether an automated molecular diagnostic method based on PCR-reverse blot hybridization assay can discriminate between human Mycobacterium tuberculosis (MTB)-positive and -negative FFPE tissues and to compare the relative mRNA expression levels of various host immune markers between MTB-infected and uninfected human tissues using quantitative reverse transcription (qRT) PCR. A total of 52 human FFPE tissue samples from various regions of the body, including the lungs, lymph nodes, tendons, colon, and appendix, were collected and used for the molecular identification of Mycobacterium species and analysis of cytokine mRNA expression. As a result, IFN-γ, TNF-α, IP-10, CXCL9, CXCL11, and GM-CSF mRNA expression levels in MTB-infected tissues were significantly higher than those in uninfected samples. Additionally, the differences in the mRNA expression levels of IFN-γ, CXCL9, and GM-CSF between MTB-infected and uninfected tissues were statistically significant were statistically significant (p < 0.05). Correlation curve analysis indicated that the mRNA expression of IFN-γ was inversely proportional to that of IP-10 and that the mRNA expression levels of IFN-γ, TNF-α, CXCL9, CXCL11, GM-CSF, and TNFR were proportional and well-correlated. Furthermore, to establish marker profiles for detecting MTB infection, the statistically significant expression levels of three markers were combined. We confirmed that the combined profile of IFN-γ, CXCL9, and GM-CSF expression levels was statistically significant (P < 0.001). Although the mRNA expression patterns of host immune markers may vary according to MTB infection status, these patterns may be highly correlated and can be simultaneously used as an additional indicator for diagnosing TB.

In the interest of developing more effective and safer anti-Tuberculosis treatment, we aimed for a better understanding of the antimycobacterial action of ciprofloxacin against Mycobacterium tuberculosis (Mtb). We used GCxGC-TOF-MS and well described metabolomics statistical approaches, to investigate and compare the metabolic profiles of Mtb in the presence and absence of the drug. The metabolites that best describe the differences between the compared groups were identified as markers characterizing the changes induced by ciprofloxacin. Malic acid was ranked as the most significantly altered metabolite marker induced by ciprofloxacin, indicative of an inhibition of the tricarboxylic acid (TCA) and glyoxylate cycle of Mtb. The altered fatty acid, myo-inositol and triacylglycerol metabolism seen in this group, supports the previous observations of ciprofloxacin action on the Mtb cell wall. Furthermore, the altered pentose phosphate intermediates, glycerol metabolism markers, glucose accumulation, and the reduction in the glucogenic amino acids specifically, indicates a flux towards DNA (as well as cell wall) repair, also supporting previous findings of DNA damage caused by ciprofloxacin. This study further provides insights useful for designing network whole-system strategies for the identification of possible modes of actions of various drugs and possibly adaptations by Mtb resulting in resistance.

Management of resistant Tuberculosis (TB) can be extremely difficult, especially in case of novel unpredicted complications. In this report, we present a case of a 48-year-old patient with pre-extensive-drug-resistant-(XDR)-TB who received a treatment regimen including Pretomanid, Bedaquiline, Linezolid, Cycloserine and Amikacin and died due to myocarditis. Acquired resistance to first- and second-line drugs developed due to previous poor adherence to medication. The clinical presentation of the patient, along with her initial ultrasonographical, electrocardiogram (ECG) and laboratory examinations, were typical for acute myocarditis, however, the patient was considered unstable and further investigation with Magnetic Resonance Imaging (MRI), pericardiocentesis and endomyocardial biopsy were not performed. To our knowledge, this is the first case of myocarditis in such a patient, the clinical features of which set a high suspicion of drug-induction that could be attributed to the treatment regimen that was administered. Clinicians who manage cases of drug-resistant TB should be aware of this, newly reported, potentially lethal, adverse event.

Tuberculosis (TB) is an infectious disease of global public health importance, caused by the Mycobacterium tuberculosis complex. Despite advances in diagnosis and treatment, this disease has worsened with the emergence of multidrug-resistant strains of tuberculosis We aim to present and review the history, progress, and future directions in the diagnosis of tuberculosis by evaluating the current methods of laboratory diagnosis of tuberculosis, with a special emphasis on microscopic examination, cultivation on solid and liquid medium, as well as an approach to molecular assays. The microscopic method, although widely used, has its limitations, and the use and evaluation of other techniques are essential for a complete and accurate diagnosis. Bacterial culture, both in solid and liquid mediums, are essential methods in the diagnosis of TB. Culture on solid medium provides specificity and accuracy, while culture on liquid medium brings rapidity and increased sensitivity. Molecular tests such as LPA and Xpert MTB/RIF have been found to offer significant benefits in the rapid and accurate diagnosis of TB, including drug-resistant forms. These tests allow the identification of resistance mutations and provide essential information for choosing the right treatment. We conclude that combined diagnostic methods, using several techniques and approaches, provide the best result in the laboratory diagnosis of TB. Improving the quality and accessibility of tests, as well as the implementation of advanced technologies, is essential to help improve the sensitivity, efficiency, and accuracy of TB diagnosis.

Interferon-gamma release assays (IGRAs) gained attention for diagnosing latent tuberculosis infection (LTBI) due to their higher specificity compared to the tuberculin skin test (TST). However, IGRA performance varied across different populations. This study evaluated the diagnostic performance of three IGRA assays (TBF-FIA, TBF-ELISA, and QFT-Plus) in Ghana, comparing them among individuals exposed and unexposed to MTB infection. Conducted in TB clinics across three regions, this prospective and cross-sectional study included healthy individuals with no known TB exposure (unexposed group) and patients with confirmed active TB (exposed group). Blood samples were tested using all three assays per manufacturers’ guidelines. The TBF-ELISA showed 3.4% higher sensitivity, but 4.6% lower specificity compared to QFT-Plus. The TBF-FIA had a sensitivity of 78.5%-87.3% and a specificity of 82.9%-90.0%. These findings indicated that while the three IGRA assays offered similar diagnostic accuracy, variations in specificity and limited data on point-of-care assays like TBF-FIA required further investigation.

Pulmonary tuberculosis (PTB) is one of the leading causes of death in developing countries. This global health burden is worsened by the emergence of multi-drug resistance, which calls for new interventions to address the pandemic and medicinal plants remain a source for the new interventions. This study aimed to investigate the in vitro immunomodulatory effects of three plants used traditionally for the treatment of PTB in the Eastern Cape Province of South Africa. Eradication of Mycobacterium. tuberculosis in the lung tissue, requires the pro-inflammatory M1 phenotype. Thus, a plant extract with a high potential for anti-tuberculosis effects is expected to produce a high concentration of nitric oxide (NO) as the indicator for the pro-inflammatory M1 phenotype. To test this effect, lipopolysaccharide-activated RAW 264.7 macrophages were cultured and treated with the ethanolic crude extracts of three plants: Anthrixia philycoides, Lippia javaniva, and Sanicula elata at concentrations of 50µg/ml, 100µg/ml, and 200 µg/ml. After 24h, 50µl Griess reagent was added to the plates and absorbance was measure at 540nm. A standard curve of sodium nitrite dissolved in culture media was used to determine the concentration of NO in each sample. The results showed Anthrixia philycoides, and Lippia javanica, as anti-inflammatory when compared with the positive control, while Sanicula elata pro-inflammatory, producing a high amount of NO, compared with the positive control. Our results revealed the polarizing activity of Sanicula elata on macrophages towards M1 phenotype, with evidence of the nitric oxide production, warranting further in-vivo investigations of medicinal plant for anti-TB activity.

Tuberculosis (TB) is the primary cause of death by a single infectious agent; responsible for around two million deaths in 2016. A major virulence factor of TB is the ability to enter a latent or Non-Replicating Persistent (NRP) state which is presumed untreatable. Approximately, 1.7 billion people are latently infected with TB and on reactivation many of these infections are drug resistant. As the current treatment is ineffective and diagnosis remains poor, millions of people have the potential to reactivate into active TB disease. The immune system seeks to control the TB infection by containing the bacteria in a granuloma, where it is exposed to stressful anaerobic and nutrient deprived conditions. It is thought to be these environmental conditions that trigger the NRP state. A number of in vitro models have been developed that mimic conditions within the granuloma to a lesser or greater extent. These different models have all been utilised for the research of different characteristics of NRP Mycobacterium tuberculosis, however their disparity in approach and physiological relevance often results in inconsistencies and a lack of consensus between studies. This review provides a summation of the different NRP models and a critical analysis of their respective advantages and disadvantages relating to their physiological relevance.

Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antide-pressants (TCAs) were studied for their potential application in different diseases es-pecially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from SSRIs class for the treatment of several neuropsychiatric disorders with a favourable safety profile. FLX exhibited different oncolytic effects via mechanisms dis-tinct from its main serotonergic activity. Taking advantage of its ability to rapidly pen-etrate the blood-brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers highlighting the multifaceted activities of FLX and its ability to interrupt cancer prolif-eration via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX on car-riers to enhance its safety and efficacy on cancer cells. This is the first review article ex-tensively summarizing all previous FLX repurposing studies for the management of cancer.

Background: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to find a genetic basis for such differences. Methods: Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (SLCA11, VDR, TLR2, TLR4, TLR8, IRGM, P2RX7, LTA4H, SP110, DCSIGN and NOS2A) and twelve cytokine (TNFA, IFNG, IL2, Il12, IL18, IL1B, IL10, IL6, IL4, IL1RA, IL8 and TNFB) genes were investigated to find genetic associations in both PTB and LNTB as compared to healthy community controls. The serum cytokine levels were correlated for association with the genotypes. Results: PTB and LNTB showed differential genetic associations. The genetic variants in the cytokine genes (IFNG, IL12, IL4, TNFB and IL1RA and TLR2,4 associated with PTB susceptibility and cytokine levels but not LNTB (p &lt; 0.05). Similarly, genetic variants in LTA4H, P2RX7, DCSIGN and SP110 showed susceptibility to LNTB and not PTB. Pathway analysis showed abundance of cytokine related variants for PTB and apoptosis related variants for LNTB. Conclusions: PTB and LNTB outcomes of TB infection have a genetic component and should be considered for any future susceptibility and functional studies.

The lungs of tuberculosis (TB) patients contain a spectrum of granulomatous lesions ranging from solid and well vascularized cellular granulomas, to avascular caseous granulomas. In solid granulomas, current therapy kills actively replicating (AR) intracellular bacilli, while in low vascularized caseous granulomas the low oxygen tension stimulates aerobic and microaerophilic AR bacilli to transit into non-replicating (NR), drug-tolerant, extracellular stages. These stages, which do not have genetic mutations and are often referred to as persisters, are difficult to eradicate due to low drug penetration inside caseum and mycobacterial cell walls. The sputum of TB patients contains also viable bacilli called differentially detectable (DD) cells that, unlike persisters, grow in liquid, but not in solid media. This review provides a comprehensive update on drug combinations killing in vitro AR and drug-tolerant bacilli (persisters and DD cells), and sterilizing Mycobacterium tuberculosis-infected BALB/c and caseum-forming C3HeB/FeJ mice. These observations have been important for testing new drug combinations in noninferiority clinical trials, in order to shorten duration of current regimens against TB. In 2022, the World Health Organization, based on one of this trial, supported the use of a 4-month regimen for treatment of drug-susceptible TB as a possible alternative to the current 6-month regimen.

Objective: To analyze prevalence of tuberculosis among the people who presented PIMS with complaints of fever, cough, difficulty in breathing during COVID pandemic.Study Design: Retrospective/ Cross-sectional study.Place and Duration: Department of Radiology, Pakistan Institute of Medical Sciences, Islamabad. 2020-2023. Methods: Total 17121 patients who presented PIMS during COVID pandemic with complaints of high grade fever, cough, difficulty in breathing ,were included in this study. Following the acquisition, the HRCT scans were conducted by a skilled and experienced technician and researcher, utilizing GE Healthcare equipment for HRCT Chest procedures. The scans covered the lung apices to the bases and were executed with maximal inspiration, employing a CT scanner from Toshiba Aquilion. Frequency of TB among all cases was recorded. SPSS 21.0 was used to analyze all data.Results: This study incorporated a total of 17,121 patients, comprising 9,961 (58.1%) males and 7,160 (41.8%) females. The mean age of the enrolled cases was 49.11±7.67 years, demonstrating consistency with the findings of a prior study [33]. This study also examined the prevalence of Tuberculosis in different years based on imaging findings of HRCT chest as follows: in 2020, 582 cases out of 2,450, equivalent to 23.7%; in 2021, 2,377 cases out of 9,584, equivalent to 24.8%; in 2022, 1,099 cases out of 3,913, equivalent to 28.1% and in 2023, 295 cases out of 1,174, equivalent to 25.1%. The average prevalence of TB cases from 2020 to 2023 was determined to be 4,353 cases out of 17,121, which is equal to 25.42%.Conclusion: As per the National Tuberculosis Program (NTP) in Pakistan, the prevalence rate of tuberculosis stands at 340 cases per 100,000 population, equivalent to 0.34%. However, our study reveals an exceptionally high frequency of TB cases. Specifically, the prevalence of Tuberculosis in 2020 was 23.7% (582 out of 2,450), in 2021 it was 24.8% (2,377 out of 9,584), in 2022 it surged to 28.1% (1,099 out of 3,913), and in 2023 it was 25.1% (295 out of 1,174). The average prevalence of TB cases over the period from 2020 to 2023 was calculated at 25.4% (4,353 out of 17,121). Consequently, our findings suggest the presence of a substantial tuberculosis burden in Pakistan, equating to a TB Tsunami in Pakistan.

We have developed a family of N-alkyl-nitrobenzamides that exhibit promising antitubercular ac-tivities. These compounds are a simplification of the structure of known inhibitors of DprE1, an essential Mtb enzyme and an emergent anti-TB target. The compounds were obtained by a simple synthetic methodology and their antitubercular, cyto-toxicity and stability were studied. The most active compounds were the 3,5-dinitro and the 3-nitro-5-trifluoromethyl derivatives. Lipophilicity was shown to be a main parameter modulating activity within each family. The most active compound presented MIC of 16 ng/mL and had in-termediate lipophilicities. The activity was also studied in a macrophage model of infection. In this model the compounds with chain lengths of 6 and 12 carbon atoms presented the best results, ex-hibiting activity profiles comparable to isoniazid. Docking studies performed suggested that the fit of our highly active compounds to the DprE1 binding pocket was very similar to the literature compounds. Furthermore, the metrics used in the analysis were able to distinguish between the families of the highly and least active compounds. Assessment of susceptibility over multiple species and computational together with the structure of the compounds are complementary information that supports DprE1 as a likely target of action for this type of compounds.

Human tuberculosis (TB) is caused mainly by Mycobacterium tuberculosis (MTB) and M. africanum (MAF) remains a major global health threat. The varying response of different host to contact with the TB bacteria, indicates the importance of host genetics in susceptibility to TB disease. We explored the association among selected human/host genomic variants and disease caused by the two causative pathogens in Ghana through a case control study. MTBC isolates (323) recovered from pulmonary TB patients recruited between 2016 and 2018 were genotyped using spoligotyping. A selection of 29 SNPs from MTB-related genes with high frequency among African populations were genotyped using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Associations between MTBC lineages and host variables were assessed using univariate and multivariate logistic regression. The prevalence of MTB and Maf among the participants were 79% and 21% respectively. Association analysis between the controls and MAF showed that rs2695342 variant on the SIC11A1 gene have the propensity to confer susceptibility to MAF infections (P = 0.093, OR = 8.35, 95% CI = 0.70 – 99.24) whilst the rs17048476 (P = 0.088, OR = 1.57, 95% CI = 0.93 – 2.63) and rs1482868 (P = 0.095, OR = 0.60, 95% CI = 0.33 – 1.09) were observed to be only suggestive. Our findings implicate SLC11A1 as a potential susceptibility gene of substantial interest for TB caused by MAF which is an important pathogen in West Africa and highlight the need for in-depth host pathogen studies in West Africa.

Mycobacterium tuberculosis was responsible for 1.3 million deaths worldwide in 2022. Bacillus Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB); however, it has limited protective efficacy in adults. In this study, we constructed a recombinant vaccinia virus expressing Ag85B from M. tuberculosis using a novel attenuated vaccinia virus (KVAC103). We then analyzed the immunogenicity of prime-boost inoculation strategies using recombinant KVAC103 expressing Ag85B (rKVAC85B) compared to BCG. In both the rKVAC85B prime-boost and the BCG prime-rKVAC85B boost inoculation regimens, rKVAC85B induced the generation of specific IgG and the secretion of IFN-γ by immune cells. In vitro analysis of Mycobacterium growth inhibition revealed a comparable immune-mediated pattern of outcomes. Furthermore, bacterial loads in the lungs were significantly lower in mice inoculated with the BCG prime-rKVAC85B boost, than in the BCG-only group following a rechallenge infection with both H37Rv and HN878 strains of M. tuberculosis. These findings collectively suggest that KVAC103, incorporated into a viral vector, is a promising candidate for a novel TB vaccine platform that is effective against multiple TB strains, including H37Rv and HN878, and that rKVAC85B effectively stimulates immune responses against TB infection.

The global burden of bacterial resistance remains one of the most serious public health concerns. Infections caused by multiresistant (MDR) bacteria in critically ill patients require immediate empirical treatment, which may not only be ineffective due to the resistance of MDR bacteria to multiple classes of antibiotics, but may also contribute to the selection and spread of antimicrobial resistance. Both the WHO and the ECDC consider carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) to be the highest priority. The ability to form biofilm and the acquisition of multiple drug resistance, in particular to carbapenems, have made these pathogens particularly difficult to treat. They are a growing cause of healthcare-associated infections and a significant threat to public health, associated with a high mortality rate. Moreover, co-colonization with these pathogens in critically ill patients was found to be a significant predictor for in-hospital mortality. Importantly, they have the potential to spread resistance using mobile genetic elements. Given the current situation, it is clear that finding new ways to combat antimicrobial resistance can no longer be delayed. The aim of this review was to evaluate the literature on how these pathogens contribute to the global burden of AMR. The review also highlights the importance of the rational use of antibiotics and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, the review discusses the advantages and limitations of alternative therapies for the treatment of infections caused by these "titans" of antibiotic resistance.

Due to nutritional benefits and perceived humane ways of treating the animals, the demand for antibiotic-free pastured poultry chicken has continued to be on a steady rise. However, despite non-usage of antibiotics in pastured poultry broiler production, antibiotic resistance (AR) is reported in zoonotic poultry pathogens. However, actors that drive multidrug resistance (MDR) in pastured poultry are not known. In this study, we used machine learning and deep learning approaches to predict farm management practices, and physicochemical properties of feces and soil that drive MDR in zoonotic poultry pathogens. Antibiotic use in agroecosystems is known to contribute to resistance. Evaluation of the development of resistance in environments that are free of antibiotics such as the all-natural antibiotic-free, pastured poultry production systems described here is critical to understand the background AR. We analyzed 1,635 preharvest (feces and soil) samples collected from forty-two pastured poultry flocks and eleven farms in the Southeastern United States. CDC National Antimicrobial Resistance Monitoring System guidelines were used to determine antimicrobial/multidrug resistance profiles of Salmonella, Listeria and Campylobacter. A combination of two traditional machine learning (RandomForest and XGBoost) and three deep learning (Multi-layer Perceptron, Generative Adversarial Network, and Auto-Encoder) approaches, identified critical farm/environmental variables that drive multidrug resistance in poultry pathogens, in broiler production systems that represents background resistance. This study enumerates management practices that contribute to AR and recommendations to potentially mitigate multidrug resistance and prevalence of Salmonella and Listeria in pastured poultry.

Pathogenic Neisseria gonorrhoeae causes the sexually-transmitted infection gonorrhea. N. gonorrhoeae has evolved high levels of antimicrobial resistance (AR) leading to therapeutic failures even in dual-therapy treatment with azithromycin and ceftriaxone. AR mechanisms can be acquired by genetic transfer from closely related species, such as naturally-competent commensal Neisseria species. At present, little is known about the antimicrobial resistance profiles of commensal Neisseria. Here, we characterized the phenotypic resistance profile of four commensal Neisseria species (N. lactamica, N. cinerea, N. mucosa, and N. elongata) against 10 commonly used antibiotics, and compared their profiles to 4 N. gonorrhoeae strains, using disk diffusion and minimal inhibitory concentration assays. Overall, we observed that 3 of the 4 commensals were more resistant to several antibiotics than pathogenic N. gonorrhoeae strains. Next, we compared the penicillin-binding-protein 2 (PBP2) sequences between commensal and N. gonorrhoeae strains. We found mutations in PBP2 known to confer resistance in N. gonorrhoeae also present in commensal Neisseria sequences. Our results suggest that commensal Neisseria have unexplored antibiotic resistance gene pools that may be exchanged with pathogenic N. gonorrhoeae, possibly impairing drug development and clinical treatment.

Multidrug resistant (MDR) bacteria have become a severe problem for public health. Developing new antibiotics for MDR bacteria is difficult, from inception to the clinically approved stage. Here, we have used a new approach; we have modified the antibiotic, ciprofloxacin (CFX), with triphenylphosphonium (TPP, PPh3) moiety via ester- (CFX-ester-PPh3) and amide-coupling (CFX-ester-PPh3), to target bacterial membranes. In this study, we have evaluated the antibacterial activities of CFX and its derivatives against 16 species of bacteria, including MDR bacteria, using minimum inhibitory concentration (MIC) assay, morphological monitoring, and expression of resistance-related genes. TPP-conjugated CFX, CFX-ester-PPh3 and CFX-amide-PPh3 showed significantly improved antibacterial activity against Gram-positive bacteria, Staphylococcus aureus, including MDR S. aureus (MRSA) strains. The MRSA ST5 5016 strain showed high antibacterial activity, with an MIC values of 11.12 µg/mL for CFX-ester-PPh3 and 2.78 µg/mL for CFX-amide-PPh3. The CFX derivatives inhibited biofilm formation in MRSA by more than 74.9% of CFX-amide-PPh3. In the sub-MIC, CFX derivates induced significant morphological changes in MRSA, including irregular deformation and membrane disruption, accompanied by a decrease in the level of resistance-related gene expression. With these promising results, this method is very likely to combat MDR bacteria, through a simple TPP moiety modification of known antibiotics, which can be readily prepared at clinical sites.

The concerning rise in emergence and prevalence of resistant strains to drugs of M. tuberculosis has ,the prompted researchers to look for new and effective treatments. With this motive, biscoumarins were identified as the lead molecules on a whole-cell-based screening of several less explored low molecular weight bioactive compounds against M. tuberculosis strains. Among the screened biscoumarins, the highest dock score derivatives were synthesized (a-h) using a programmable microwave synthesizer for better yields and reaction control. The synthesized derivatives were evaluated against H37Rv, H37Ra, M. smegmatis, an MDR surrogate model, and other bacterial strains for the structure-activity response. Assessment of the synthesized library against mycobacterial strains led to the identification of compounds (f and d) as lead anti-tuberculosis agents. Compounds (f and d) exhibited less toxicity against human cell lines. At the same time, it displayed enjoyable activity wherein MIC concentrations were observed to be 16- and 32 µg/mL against the susceptible H37Rv, and H37Ra strains of M. tuberculosis and MIC value of 128 µg/mL for M. smegmatis, respectively. For mechanistic insights and identification of drug binding targets, molecular docking and dynamic simulations were employed for a panel of 16 mycobacterial enzymes essential for mycobacterial growth and survival. These in silico studies revealed the DprE1 enzyme as a druggable target for the anti-tuberculosis activity of the selected biscoumarins derivatives. Further investigation is underway in our laboratory, leading to its development as an anti-tuberculosis drug (animal model studies).

Despite the existing effective treatment methods, tuberculosis (TB) is the second most deadly infectious disease globally, its carriers in the latent and active phases accounting for more than 20% of the world population. An effective method to control TB and reduce the mortality is regular population screening and diagnosis of the latent form of TB in order to take preventive and curative measures. Numerous methods allow diagnosing TB and directly detecting Mycobacterium tuberculosis (M.tb) biomarkers, including M.tb DNA, proteins, and specific metabolites, as well as antibodies produced by the host immune system in response to M.tb. PCR, ELISA, immunofluorescence and immunochemical analyses, flow cytometry, and other methods allow the detection of M.tb biomarkers or the host immune response to M.tb by recording the optical signal of fluorescent or colorimetric dyes included in the diagnostic tools. Current research in biosensors is aimed at increasing the sensitivity of detection, which can be achieved by using brighter and more photostable optical tags containing fluorescent quantum dots. Here, we review current methods for detection of M.tb biomarkers using optical sensor systems, primarily quantum dot–based nanosensors, and summarize M.tb biomarkers whose detection can be made significantly more sensitive by using quantum dot–based nanosensors.

Hemophagocytic lymphohistiocytosis (HLH) is a serious haematologic condition that can be re-lated to various diseases, including tuberculosis (TB). The patient is a previously healthy 26-years-old man, originally from Western Africa, admitted to hospital for fever and weight loss. Given the results of computed tomography (CT) scan, ocular examination and microbiologic tests, a miliary TB with pulmonary, lymph nodal and ocular involvement was diagnosed. Following introduction of antitubercular treatment (ATT) an increase in inflammation indexes and severe pancytopenia were observed; at this point the patient presented six of eight diagnostic criteria for HLH and the diagnosis of HLH secondary to TB was raised. Therefore, HLH treatment with high dose of dexamethasone was started with a good clinical response. We performed a literature re-view of TB-related HLH, which shows a high mortality rate; ATT is necessary to ensure patient survival to remove the antigenic driver. Our patients developed HLH after initiation of ATT as a paradoxical reaction, that may be linked to the release of antigens due to the bactericidal effect of ATT.

Despite the efforts made to stop the tuberculosis (TB) epidemic, it still remains one of the leading causes of death from an infectious disease. Previous work in the group uncovered a new family of amides which showed promising activities against Mycobacterium tuberculosis. A closer look at the literature showed that these compounds are structurally related to the DNB family of DprE1 inhibitors, so, we decided to study a wide range of substituted amides and determine their activity, focusing on unexplored structures related to the dinitrobenzamides (DNB) found in the literature. To synthesize our library of compounds we started from 3,5-dinitrobenzoic acid to form the nitroaromatic core that is characteristic of the DNB’s, to which we then added linear or cyclic amine moieties. Additionally, the impact of terminal aromatic moieties was also assessed for some derivatives, via an ether, ester, or amide bond. In order to obtain the desired derivatives, multiple synthetic approaches were used, mainly focused on nucleophilic addition/elimination reactions, SN2 reactions and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of the linker. The most interesting compounds exhibited activities comparable to isoniazid and DNB1. Computational studies were also performed aimed at understanding their possible interactions with DprE1. The most active compounds are a good starting point for further development, and we plan to study an extended family of compounds based in those structures.

Infectious illnesses have always posed a threat to human health, with tuberculosis being a major concern. The use of various drugs in the fight against such TB has led to the emergence of drug-resistant tuberculosis, which has become increasingly difficult to manage. While there have been a few studies and proposed conceptual models on how to manage and prevent various drug-resistant TB mutations and lineages, a model aimed at limiting and controlling such mutations in rural areas burdened with tuberculosis is lacking. This study seeks to map a model that is to be used to bridge the gap by facilitating the exchange of knowledge among healthcare professionals in healthcare facilities, diagnostic laboratories, and research institutes, particularly for underprivileged communities in the Eastern Cape. The model information is based on three published manuscripts; therefore, this is a follow-up study. The model will also serve as a practical guide to monitor and evaluate epidemiological TB management plans.

Infectious illnesses have always posed a threat to human health, with tuberculosis being a major concern. The use of various medications and antibiotics in the fight against such TB has led to the emergence of drug-resistant tuberculosis, which has become increasingly difficult to manage. While there have been a few studies and proposed conceptual models on how to manage and prevent various drug-resistant TB mutations and lineages, a model aimed at limiting and con-trolling such mutations in rural areas burdened with tuberculosis is lacking. This study seeks to map a model that is to be used to bridge the gap by facilitating the exchange of knowledge among healthcare professionals in healthcare facilities, diagnostic laboratories, and research institutes, particularly for underprivileged communities in the Eastern Cape. The model will also serve as a guide to monitor and evaluate epidemiological TB management plans.

The lethal combination involving TB and HIV, known as 'syndemic’ diseases synergistically act upon one another to magnify the disease burden. Individuals on ART are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The underlying inflammatory complication includes the rapid restoration of immune responses following ART eventually leading to exaggerated inflammatory responses to MTB antigens. TB-IRIS continues to be a cause of morbidity and mortality among HIV/TB coinfected patients initiating ART, and although significant quantum of knowledge has been acquired on the pathogenesis of IRIS, the underlying pathomechanisms and identification of a sensitive and specific diagnostic markers still remain a grey area of investigation. Here, we reviewed the latest research developments in IRIS immunopathogenesis, and outlined the modalities to prevent and manage strategies for better clinical and diagnostic outcomes for IRIS.

Aim. To identify factors associated with mortality with tuberculosis diagnosis in the indigenous population in Peru 2015-2019. Methods. Case-control study nested in a retrospective cohort, using the registry of persons belonging to indigenous peoples of the National Tuberculosis Prevention and Control Strategy of the Ministry of Health of Peru. A descriptive analysis was applied, and then bivariate and multiple logistic regression was used to evaluate associations between the variables and the outcome (live-deceased), the results were presented as OR with their respective 95% confidence intervals. Results. The mortality rate of the total indigenous population of Peru was 1.75 deaths per 100,000 indigenous people diagnosed with TB. The community of Kukama kukamiria - Yagua reported 505 (28.48%) individuals. The final logistic model showed that indigenous men (OR=1.93; 95% CI: 1.001-3.7), with a history of HIV prior to TB (OR=16.7; 95% CI: 4.7-58.7) and indigenous people in old age (OR=2.95; 95% CI: 1.5-5.7), are factors associated with a greater chance of dying from TB. Conclusions. It is important to reorient health services among indigenous populations, especially those related to improving the timely diagnosis and early treatment of TB-HIV co-infection, to ensure comprehensive care for this population, considering that they are vulnerable groups.

Background: Women in rural districts of Pakistan face numerous barriers to healthcare, rendering gender-responsive health programming important, including for Tuberculosis (TB). This study was conducted to assess the general understanding of TB and of access to healthcare for women, as a first step towards implementation of a gender responsive TB programme in TandoAllayar, a rural district of Pakistan. Methods: A total of 36 participants were interviewed. The focus group discussion guide comprised of questions on: (1) family/household dynamics (2) community norms (3) healthcare system (4) women’s access to healthcare (5) TB Awareness;, and (6) women’s access to TB Care. Results: Limited autonomy in household financial decision-making, disapproval of unassisted travel, long travel time, lack of prioritization of spending on women’s health and inadequate presence of female health providers, were identified as barriers to access of healthcare for women, higher in younger women. Facilitators to access of TB care included a reported lack of TB-related stigma, moderate knowledge about TB disease, and broad understanding of tuberculosis as a curable disease. Other suggested facilitators include health facilities closer to the villages and the availability of higher quality services. Conclusion: Significant barriers are faced by women in access to TB care in rural districts of Pakistan. Programme implementers in high burden countries, should shift towards improved gender-responsive TB programming.

Tuberculosis (TB) is an airborne infectious disease caused by organisms in the Mycobacterium tuberculosis (Mtb) complex. In many low and middle-income countries, TB remains a major cause of morbidity and mortality. Once a patient has been diagnosed with TB, it is critical that healthcare workers make the most appropriate treatment decision given the individual conditions of the patient and the likely course of the disease based on medical experience. Depending on the prognosis, delayed or inappropriate treatment can result in unsatisfactory results including the exacerbation of clinical symptoms, poor quality of life, and increased risk of death. This work benchmarks machine learning models to aid TB prognosis using a Brazilian health database of confirmed cases and deaths related to TB in the State of Amazonas. The goal is to predict the probability of death by TB thus aiding the prognosis of TB and associated treatment decision making process. In its original form, the data set comprised 36,228 records and 130 fields but suffered from missing, incomplete, or incorrect data. Following data cleaning and preprocessing, a revised data set was generated comprising 24,015 records and 38 fields, including 22,876 reported cured TB patients and 1,139 deaths by TB. To explore how the data imbalance impacts model performance, two controlled experiments were designed using (1) imbalanced and (2) balanced data sets. The best result is achieved by the Gradient Boosting (GB) model using the balanced data set to predict TB-mortality, and the ensemble model composed by the Random Forest (RF), GB and Multi-layer Perceptron (MLP) models is the best model to predict the cure class.

Molecular studies regarding regulatory elements such as small ncRNAs and their mechanisms are poorly understood in infectious diseases. Tuberculosis is one of the oldest infectious diseases of humanity, and it is still a challenge to prevent and treat it. The control of the infection as well as its diagnosis are still complex, and treatments used are linked to several side effects. This study aimed to investigate miRNA’s expression profile to identify possible biomarkers for tuberculosis. We applied NGS techniques to investigate miRNA’s global expression profile from blood samples of infected patients with tuberculosis, their respective healthy physicians, and external healthy individuals as controls. Samples from 22 individuals run through a differential expression, target genes, gene set enrichment, and miRNA-gene network analysis. We observed 153 altered miRNAs, among which, only three DEmiRNAs (hsa-let-7g-5p, hsa-miR-486-3p and hsa-miR-4732-5p) were found between the investigated patients and their respective physicians. These DEmiRNAs are suggested to play an important role in granuloma regulation and their immune physiopathology. Our results propose that miRNAs may be involved in immune modulation, regulating the repertoire of genes expressed in the immune system’s cells. Our findings encourage the application of miRNAs as potential biomarkers for tuberculosis.

Introduction Tuberculosis is common in Pakistan. Due to various factors including socioeconomic factors, compliance is poor to anti-tuberculosis drugs, leading to resistance. We aim to determine the prevalence of Multidrug resistance (MDR) tuberculosis in Pakistani population.Methods A prospective observational study was conducted from April 1, 2019, to December 31, 2019, in the Pulmonology department of a tertiary care hospital in Pakistan. Culture and sensitivity were assessed using a sputum sample or, in cases of an absent sputum sample, from Broncho alveolar lavage.ResultsApproximately 71.3% percent patients who had tuberculosis were found to be resistant to Isoniazid and around 48.6% did not respond to Rifampin. Multi-drug resistant was found in 29.4% participants.ConclusionMulti-drug resistance tuberculosis is very prevalent in Pakistan, which may increase burden on health care system and may lead to various complications of tuberculosis.

Multidrug resistant bacteria pose a significant threat to global health, particularly in healthcare settings. This study aimed to explore the potential of aminoglycoside consumption and resistance data to correlate with multidrug resistance in Acinetobacter baumannii and Klebsiella pneumoniae. Data on aminoglycoside consumption and antibiotic resistance indices (ARI) were collected from 2010 to 2023. Descriptive statistics and Pearson correlation analyzes were performed to examine both immediate and delayed (one-year delay) correlations between aminoglycoside use (amikacin, tobramycin, gentamicin) and resistance patterns. The results indicated that the consumption of amikacin was consistently high and correlated with resistance in both bacterial species. Tobramycin and gentamicin showed variable resistance patterns, with negative correlations in some cases. Delayed effect analysis revealed that amikacin and tobramycin consumption had a slight delayed positive impact on multidrug resistance in A. baumannii, while gentamicin use was associated with a delayed reduction in resistance. In K. pneumoniae, gentamicin showed a strong delayed positive correlation with multidrug resistance, while amikacin and tobramycin had weaker associations. These findings highlight the complex and species-specific relationships between aminoglycoside consumption and resistance development, emphasizing the need for customized antibiotic management strategies that account for the immediate and delayed effects of antibiotic use.

Background: While it is established that intravenous catheter placement duration is strongly linked to the risk of catheter colonization and bloodstream infections, there are still substantial knowledge gaps concerning the varying durations of PICC placement that lead to either infection or colonization by common pathogens, particularly MDR pathogens. The present study aims to compare the dwell time required for MDR pathogens to colonize with the time required to cause Central Line-Associated Bloodstream Infections (CLABSIs) in critically ill patients with PICCs and compares it with non-MDR pathogens, shedding light on the significance of preventive procedures to control MDR infections in clinical settings. Methods: Data from critically ill patients with PICCs admitted consecutively to «Metropolitan» Hospital in Athens, Greece, from May 2017 to May 2020 were retrospectively analysed. Results: In this study, 86 hospitalized patients, consisting of 56 (65.1%) males and 30 (34.9%) females, with a mean age of 55.67±21.1 years (range 16-91 years), presented with both CLABSIs and colonization following PICC placements. Specifically, 42 (48.8%) of them presented with CLABSIs, while 44 (51.2%) presented with colonization. Among the total participants, an MDR pathogen was isolated from 26 (30.2%) PICCs, while other pathogens were isolated from 60 (69.8%). The mean duration of catheter dwell time for all participants was 20.94±14.22 days (range 3-72 days). When analysed separately for each group, the dwell time for PICCs with CLABSIs was 25.73±16.19 days and 16.36±10.28 days for those with colonization (T test, p=0.002). Additionally, the mean dwell time for PICCs infected by non-MDROs was 22.48±15.64 days whereas for PICCs with MDROs, it was 17.38±9.5 days (T test, p=0.005). In PICCs with CLABSIs, the mean indwelling time for MDR pathogens was 21.50±12.31 days, while for non-MDROs, it was 27.73±16.98 days (T test, p=0.417). In PICCs with colonization, the mean dwell time for MDR pathogens was 15.55±7.73 days, while for non-MDROs, it was 16.92±11.85 days (T test, p=0.124). Among PICCs with MDR pathogens (n=26), the mean duration in CLABSIs events (n=18) was 21.5±12.31 days and in colonization events 15.55±7.73 days, (n=8) (T test, p=0.146). Conclusions: The present study reveals that colonization of PICCs exhibited a shorter dwell time compared to those with CLABSIs. Moreover, PICCs infected by MDROs had a shorter mean dwell time than those with non-MDROs. These findings underscore the importance of considering infection status and microbial resistance patterns when evaluating PICC dwell times.

Urinary tract infections (UTIs) are a prevalent bacterial infection in both community and healthcare settings. They account for approximately 40% of all bacterial infections and require around 15% of all antibiotic prescriptions. Although antibiotics have traditionally been used to treat UTIs for several decades, the significant increase in antibiotic resistance in recent years has made many previously effective treatments ineffective. Biofilm on medical equipment in healthcare settings creates a reservoir of pathogens that can be easily transmitted to patients. Urinary catheter infections are frequently observed in hospitals and are caused by microbes that form a biofilm after the catheter is inserted into the bladder. Managing infections caused by biofilms is challenging due to the emergence of antibiotic resistance. Biofilms enable pathogens to evade the host's innate immune defences, resulting in long-term persistence. The incidence of sepsis caused by urinary tract infections that have spread to the bloodstream is increasing, and drug-resistant infections may be even more prevalent. While the availability of upcoming tests to identify the bacterial cause of infection and its resistance spectrum is critical, it alone will not solve the problem; innovative treatment approaches are also needed. This review analyses the main characteristics of biofilm formation and drug resistance in recurrent uropathogen-induced UTI. The importance of innovative and alternative therapies to combat biofilm-caused UTI is emphasised.

ATP-binding cassette (ABC) transporters, acting as cellular "pumps," facilitate solutes translocation through membranes via ATP hydrolysis. Their overexpression is closely tied to multidrug resistance (MDR), a major obstacle in chemotherapy and neurological disorder treatment, hampering drug accumulation and delivery. Extensive research has delved into the intricate interplay between ABC transporter structure, function, and potential inhibition for MDR reversal. Cryo-electron microscopy has been instrumental in unveiling structural details of various MDR-causing ABC transporters, encompassing ABCB1, ABCC1, ABCG2, as well as recently revealed ABCC3 and ABCC4 structures. The newly obtained structural insight has deepened our understanding of substrate and drug binding, translocation mechanisms, and inhibitor interactions. Given the growing body of structural information available for human MDR transporters and their associated mechanisms, we believe it is timely to compile a comprehensive review of these transporters and compare their functional mechanisms in the context of multidrug resistance. Therefore, this review primarily focuses on the structural aspects of clinically significant human ABC transporters linked to MDR, with the aim of providing valuable insights to enhance the effectiveness of MDR reversal strategies in clinical therapies.

The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics, contributes to cancer drug resistance and the development of gout. In this work we have analyzed the effects of selected variants, residing in a structurally unresolved cytoplasmic region (a.a. 354-367) of ABCG2, on the function and trafficking of this protein. A cluster of four lysines (K357-360) and the phosphorylation of a threonine (T362) residue in this region have been previously suggested to significantly affect the cellular fate of ABCG2. Here we report that the naturally occurring K360del variant in human cells increased ABCG2 plasma membrane expression and accelerated cellular trafficking. The variable alanine replacements of the neighboring lysines had no significant effect on transport function, and the apical localization of ABCG2 in polarized cells has not been altered by any of these mutations. Moreover, in contrast to previous reports, we found that the phosphorylation incompetent T362A, or the phosphorylation mimicking T362E variants in this loop, had no measurable effects on the function or expression of ABCG2. Molecular dynamics simulations indicated an increased mobility of the mutant variants with no major effects on the core structure of the protein. These results may help to decipher the potential role of this unstructured region within this transporter.

Antibiotic resistance among bacterial pathogens is recognized as a major threat to human health worldwide. The emergence of multidrug-resistant bacteria can also be found in the community settings, apart from hospital environment, which indicates that reservoirs of antibiotic resistance genes do exist outside the hospital. The growth of antibiotic resistance is a consequence of bacterial adaptations in response to selective pressures. To survive in this hostile environment, bacteria develop defence mechanisms such as chemical modification of antibiotics, enzyme-catalysed antibiotic degradation, altered permeability, antibiotic efflux, mutation of target sites and biofilm formation, resulting in resistance to nearly all currently available antibiotics used in the clinical practice. The present review summarizes insights into the molecular mechanisms underlying the antibiotic resistance which is useful for planning strategies to combat antibiotic resistance and devise innovative therapeutic tools to fight against multidrug-resistant bacterial species.

Escherichia coli (E. coli) is a common pathogen in veterinary clinical infections, typically not causing disease. However, under certain conditions, it can cause severe diarrhea, septicemia, and respiratory infections in domestic animals. Here, we report a large-scale mortality event in young donkeys, caused by E. coli infection in a farm with a herd of 340 donkeys, of which over 100 were under 4 months old. The characteristics of the E. coli strain were determined through clinical observation, complete blood count, blood biochemical analysis, H&E staining, histopathological examination, 16S rRNA analysis, and antibiotic sensitivity testing. A mice experiment using the isolated bacteria was also conducted, resulting in the onset of clinical and pathological symptoms similar to those observed in the donkeys. Molecular Evolutionary Genetic Analysis (MEGA) showed that the isolated bacteria, named CEG-GZL20, shared 99.98% sequence identity with E. coli. CEG-GZL20 exhibited high antibiotic resistance and only showed sensitivity to two antibiotics, Tetracycline and Gentamicin. As E. coli is a key component of the gut microbiota, responsible for digestion, nutrient absorption, and immune health, diseases and mortality caused by E. coli have significant implications for animal husbandry and human health.

Antibiotics are released into the environment either directly in an unchanged form or in a partially metabolized form. The discharge is usually through untreated waste or industrial treatment effluents. The potential concern is the uptake of these antibiotics by crops irrigated by treated wastewater. This study collected wastewater from eight points at the Pagla, Kadamtali, Dhaka treatment plant. Here we consider three crucial antibiotics, Doxycycline, Ciprofloxacin, and Tetracycline, used mainly during the last two years of the pandemic. A PDA detector was used in high-performance liquid chromatography (HPLC) analysis to determine the raw and processed effluent antibiotics. The most frequently seen antibiotics in natural wastewater were Doxycycline and Ciprofloxacin, with the highest concentration of 0.23µgL-1and 0.20 µgL-1(raw water), respectively. Tetracycline was not detected in natural water. Contrarily, Doxycycline was discovered in the Pagla plant's completed water and had the highest concentration (0.12 gL-1), whereas Ciprofloxacin and Tetracycline were not found in the dead water. The findings of this study showed that Doxycycline was still present in both the raw and processed effluent. Both natural and finished wastewater was subjected to a microbial-resistant test in the presence of all three antibiotics. The results revealed that the samples detected both heterotrophic bacteria and total coliform. The viable aerobic heterotrophic bacteria ranged between 5.421 and 4.754 log cfu/ml. Total bacteria load gradually decreased in the finished wastewater.

The aim of this study was to establish the blood glucose response to different cooking methods of pasta. Participants consumed three identical meals in a random order that were freshly cooked (hot), cooled and reheated. Blood glucose concentrations were assessed before, and every 15 minutes after ingestion of each meal for 120 minutes. There was a significant interaction between temperature and time (F_{(8.46-372.34)} = 2.75, p = 0.005), with the reheated (90 minutes) condition returning to baseline faster than both cold (120 minutes) and hot conditions. Blood glucose AUC was significantly lower in the reheated (703 ± 56 mmol L^-1 min^-1) compared with the hot condition (735 ± 77 mmol L^-1 min^-1, t(92) = -3.36, pbonferroni = 0.003), with no significant difference with the cold condition (722 ± 62 mmol L^-1 min^-1). To our knowledge, the current study is the first to show that reheating pasta causes changes in post-prandial glucose response, with a quicker return to fasting levels in both the reheated and cooled conditions compared with the hot condition. The mechanisms behind the changes in post-prandial blood glucose seen in this study are most likely related to changes in starch structure and how these changes influence glycaemic response.

Triple negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger containing transcription factor), was capable of sensitizing preclinical models of triple negative breast cancer to chemotherapy, in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with inhibition of the P-glycoprotein efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump, in a manner consistent with inhibition of pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in triple negative breast cancer, that has not yet been successfully addressed by clinical efforts.

The emergence of drug-resistant strains of M. tuberculosis (Mtb) and the phenomenon of phe-notypic tolerance to drugs challenge the goal of tuberculosis (TB) elimination worldwide. By using the ex vivo cultures of alveolar macrophages obtained from lung tissues of TB patients after intensive antimicrobial chemotherapy before surgery, different subpopulations of multi-drug-tolerant Mtb with a spectrum of phenotypic and growth features were identified in the same TB lesions. Our results indicative of not only passive mechanisms generating nonheritable resistance of Mtb to antibiotics, which are associated mainly with a lack of Mtb growth, but also some active mechanisms of Mtb persistence, such as cell wall and metabolic pathway remod-eling. In one of the subpopulations, non-acid-fast Mtb have undergone significant repro-gramming with the restoration of acid-fastness, lipoarabinomannan expression and replication in host cells of some patients after withdrawal of anti-TB drugs. Our data indicate the universal stress protein Rv2623 as a clinically relevant biomarker of Mtb that have lost acid-fastness in human lungs. The studies of Mtb persistence, dormancy, and resumption and the identification of biomarkers characterizing these phenomena are very important to develop vaccines and drug regimens with the individualized management of patients for overcoming the re-sistance/tolerance crisis in anti-TB therapy.

Background Candida auris is an emerging multidrug-resistant fungal pathogen that represents a serious threat to healthcare settings currently. Objective: Its objective was to determine the prevalence of C. auris in the hospital since its initial detection in late 2019. Methods: Using an adapted risk assessment tool, we reviewed the charts. and medical files of all suspected? and confirmed cases of C. auris cases reported at King Khalid University Hospital, Riyadh between November 2019 and December 2022. Anonymized data were retrieved in a pre-established datasheet and analyzed to determine the epidemiological characteristics of C. auris infection in our facility. We established our initial prevalence by age, gender, risk factors, and according to sampling source. Results: Of the 53 confirmed cases positive for C. auris during the study period, 33 (62%) were males. Their ages ranged between 15 and 98; most positive cases occurred in 50 and above. Only one of the confirmed cases was hospital-acquired. All patients had at least one risk factor, and Urine samples yielded the greatest number of positive cases while admission to healthcare facilities constituted the highest risk in our study. Conclusion: Establishing a local prevalence could serve as our baseline/benchmark to compare with regional and international benchmarks.

Nose mask is a fomite and its usage was mandatory during the COVID-19 outbreak. Its effectiveness has been established; however, as a fomite, it can harbor opportunistic respiratory pathogens such as Streptococcus spp., which could complicate COVID-19 infections. This study profiled Streptococcus species resident on nose masks obtained from consenting participants. Phenotypic assays and 16S rRNA sequencing were used to identify Streptococcus spp. resident on the interior and exterior of 100 nose masks analyzed. Antibiotic resistance (AMR) was determined with disc diffusion and broth microdilution assays. AMR and virulence makers were profiled with primer-specific PCR amplification. 23% of the analyzed samples had Streptococcus isolates. The isolates were highly resistant to the antimicrobials, including conventional, last-resort antibiotics, disinfectants and antiseptics. All the isolates are multidrug resistant with 80-100% levels of AMR to the 16 antibiotics tested with a Multiple-Antibiotic Resistance index greater than 0.2, indicative of potential pathogens. The isolates harbored tetB, ermB, pbp2B, pbp2b1 (resistance) and lytA, lytA1, ply1, cbpA, lytA, pavA (virulence) markers, which might constitute a serious public health risk. Overall, the study emphasizes the need to assess mask usage and the risks associated with opportunistic pathogens that are resident on frequently used nose masks in the COVID-19 era.

Background and objectives: Due to resistance and lack of treatment options, hospital-acquired Acinetobacter baumannii (A. baumannii) infections are associated with high mortality. The aim of this study was to identify the characteristics and outcomes of patients with infections caused by multidrug resistant A. baumannii in a tertiary-care teaching hospital and to determine the risk factors for in-hospital mortality. Materials and methods: A retrospective cohort study including 196 patients with A. baumannii strains isolated from different clinical specimens in the Hospital of the Lithuanian University of Health Sciences in 2016, 2017 and 2020, 2021 was conducted. Data on patients’ characteristics, comorbid diseases, treatment, length of hospital and ICU stay, outcome were collected. To determine risk factors for in-hospital mortality, logistic regression analysis was performed. Results: There were 60 (30.6%) women 136 (69.4%) men with a mean age of 61.7 ± 16.6 years (range, 52–74). More than three-fourths (76.5%, n = 150) of the patients had at least one comorbid disease. The highest number of A. baumannii strains were isolated from patients hospitalized in ICUs (43.4%, n = 85). A. baumannii strains producing three types of β-lactamases were more frequently isolated from women than men (77.8 % vs. 22.2%, p = 0.006). Infections caused by A. baumannii strains producing two types of β-lactamases were significantly more often treated with combination therapy than infections caused by strains producing one type of β-lactamase (78.9% vs. 60.0%, p = 0.019). Patients with A. baumannii strains producing two different types of β-lactamases (AmpC plus KPC, AmpC plus ESBL, or ESBL plus KPC) stayed significantly shorter at the ICU compared to patients with A. baumannii strains not producing β-lactamases (median of 9, IQR 2–18, vs. median of 26, IQR 7–38, p = 0.022). Death occurred in 58.7% (n = 115) of patients. Logistic regression analysis showed that combination therapy, length of hospital stay of < 10 days after A. baumannii infection, age of > 58 years, and absence of co-infection were independent predictors of in-hospital mortality. Conclusions: Patients with infection caused by A. baumannii strains producing two different types of β-lactamases were more frequently treated with combination therapy. Mortality of patients with multidrug resistant A. baumannii infection was high, and it was associated with patient’s age, length of hospital stay after the diagnosis of A. baumannii infection, absence of co-infection, and combination treatment.

Enterococcus faecalis is a growing cause of nosocomial and antibiotic-resistant infections. Treating drug-resistant E. faecalis requires novel approaches. The use of bacteriophages (phages) against multidrug-resistant (MDR) bacteria has recently garnered global attention. Biofilms play a vital role in E. faecalis pathogenesis as they enhance antibiotic resistance. Phages eliminate biofilms by producing lytic enzymes, including depolymerases. In this study, Enterococcus phage vB_Efs8_KEN04 (ФKEN04), isolated from a sewage treatment plant in Nairobi, Kenya, was tested against clinical strains of MDR Enterococcus faecalis. This phage had a broad host range against 100% (26/26) of MDR E. faecalis clinical isolates and cross-species activity against Enterococcus faecium. It was able to withstand acidic and alkaline conditions, from pH 3 to 11, as well as temperatures between -80ᵒC and 37ᵒC. It could inhibit and disrupt the biofilms of MDR E. faecalis. Its linear double-stranded DNA genome of 142,402 bp contains 238 coding sequences with a G+C content and coding gene density of 36.01% and 91.46%, respectively. Genomic analyses showed that ФKEN04 belongs to the genus Kochikohdavirus in the family Herelleviridae. It lacked antimicrobial resistance, virulence, and lysogeny genes, and its stability, broad host range, and cross-species lysis indicate strong potential for the treatment of Enterococcus infections.

The aberrant glycosylation is a hallmark of cancer progression and chemoresistance. It is also an immune therapeutic target for various cancers. Tunicamycin (TM) is one of the potent nucleo-side antibiotics and an inhibitor of aberrant glycosylation in various cancer cells, including breast cancer, gastric cancer, and pancreatic cancer, parallel with inhibition of cancer cell growth and progression of tumors. Thus, TM can be considered a potent antitumor drug in various cancers and may promote chemosensitivity. Mechanistically, TM impedes the role of the UDP-HexNAc enzyme in the biosynthesis of oligosaccharides, specialized macromolecules instrumental in N-linked glycosylation. Further, like chemotherapies such as doxorubicin (DOX), 5'fluorouracil, etoposide, and Cisplatin, TM induces the unfolded protein response (UPR) by blocking aberrant glycosylation. Despite TM's antitumor effectiveness, its lack of cell-type specific cytotoxicity impedes its anticancer efficacy. Thus, various nanoencapsulation techniques and materials have been considered for use in experiments to reduce TM's cytotoxicity and improve efficacy as a targeted therapy. The current review is a profound audit of the benefits and pitfalls of TM in various cancers, focusing on breast, colon, and pancreatic cancers. Additional progressive studies have also discussed the use of TM in immune checkpoints and other unique pathways. Cytotoxicity and other possibly adverse effects of TM are highlighted based on the data from in vitro and in vivo assays. In addition, the recent advances in nano-based drug delivery systems regarding TM have been emphasized. However, the potential of this nucleoside inhibitor re-quires thorough investigation and research to determine its likeliness as a viable chemotherapeutic.

Epidemiologic studies have shown an association between tuberculosis and lung cancer. The al-tered tumor microenvironment after tuberculosis infection appears to contribute to cancer pro-gression. Pleural effusions are enriched in exosomes, which act as mediators of intercellular communication. We hypothesized that tuberculous pleural effusion (TPE)-derived exosomes mediate intercellular communication. Then we examined the interaction between TPE-derived exosomes and cancer cells. Exosomal miRNA profiling of TPE was performed using a microRNA array. An in vitro lung cancer cell experiment and an in vivo mouse xenograft tumor model were used to evaluate the effects of select exosomal microRNAs. TPE-derived exosome treatment en-hanced the growth of A549 cells both in vitro and in a nude mouse xenograft model. Neighboring cancer cells were observed to take up TPE-derived exosomes, which promoted cancer cell inva-sion. Exosome-mediated transfer of select microRNAs, including miR-130b-3p and miR-423-5p, to A549 lung cancer cells activated cyclin D1 signaling and increased the expression of phos-phorylated p65, a cyclin D1 transcription factor. Inhibitors of miR-130b and miR-423-5p sup-pressed the promotion of lung cancer by TPE derived exosomes and reduced the expression of p65 and cyclin D1. These results suggest that TBE-derived exosomal miRNAs can serve as a novel therapeutic target in tuberculous fibrosis-induced lung cancer.

Tuberculosis (TB) is an infectious disease declared a global emergency by the World Health Organization and continues as one of the world’s top ten causes of death. TB diagnosis is more critical in developing countries where demanded infrastructure for detection, and treatment complicates the efforts against the disease. These aspects related to limited resources are significant, especially in areas away from the main cities, with few mechanisms to make a timely diagnosis that contributes to successfully addressing the possible patients. Artificial intelligence has begun to be essential in providing additional strategies in the diagnosis processes for health professionals’ support. This paper uses natural language processing (NLP) and machine learning (ML) techniques to create models that can supply TB diagnosis when the needed infrastructure is unavailable. Two different sources were explored: text extracted from electronic medical records (EMR) and patient clinical data (CD). Four proposals using five different machine learning models were implemented. The first two models employed ML and each data source independently. Then, two additional approaches developed a data fusion from both sources. This strategy’s employment was analyzed with physicians according to their pertinence in the process and understanding of the EMR. Finally, the results of the data fusion were compared to each source, obtaining better performance at using only the CD, where an area under the ROC curve of 69.9±2.3% was obtained. However, the advantage of analyzing physician’s reports is the availability of this information contrasted to clinical-specific data, which can be more useful in places far from the main cities without enough basic structure for its obtaining.

Tuberculosis (TB) remains a significant public health challenge in Nigeria, with high rates of transmission and low case detection rates. This paper presents the challenges of TB screening and the existing gaps in Contact Investigation (CI). This descriptive qualitative study was conducted in 8 local government areas with high TB burdens in Oyo and Osun States, Nigeria. Twenty-four focus group discussions and 27 key informant interviews were conducted among TB patients, household TB contacts, and government TB staff, among others. Respondents' ages ranged from 17-85 years with a mean of 42.08±14.9 years, and (4.0%) had a postgraduate degree. The unwillingness of the majority of TB contacts who tested negative for TB to be placed on TB preventive therapy because of the belief that only a sick person should take drugs and hostility from the TB contacts to the contact tracers during the house-to-house screening of presumptive TB cases due to community stigma associated with TB were some of the existing gaps reported in TB contact investigations. The findings emphasize the importance of tailored approaches in TB prevention and control, addressing challenges in testing and contact investigations; this necessitates investments in community engagement strategies to enhance the cooperation of TB contacts.

Surgical treatment of tuberculosis has been applied in the former Soviet Union more frequently than in other countries. On the contrary to the international practice, tuberculoma has been often operated. There has been a decreasing tendency since the last decades; but the surgery rate is still comparatively high. Surgeries were sometimes performed without preceding chemotherapy. Among others, an argument in favour of the early surgery was non-compliance increasing with time. Compulsory treatments of patients with Tb and/or alcoholism are discussed here. The factors predisposing to the use of invasive procedures with questionable indications included the partial isolation from international scientific community, insufficient consideration of the principles of informed consent, professional autonomy and scientific polemics, as well as paternalistic attitude to patients. The message of this preprint is that patients should not undergo operations to comply with doctrines. Evidence-based clinical indications must be determined individually.

Background Nigeria is among the top 5 countries that have the highest gap between people reported as diagnosed and estimated to have developed Tuberculosis (TB). To bridge this gap, there is a need for innovative approaches to identify geographical areas at high risk of TB transmission and targeted Active Case Finding (ACF) interventions. Leveraging community level data together with granular sociodemographic contextual information can unmask local hotspots which could be otherwise missed. This work evaluated if this approach helps to reach communities with higher numbers of undiagnosed TB. Methodology A retrospective analysis of the data generated from an ACF intervention program in 4 south-western states in Nigeria was conducted. Wards (the smallest administrative level in Nigeria) were subdivided into further smaller population clusters. ACF sites and their respective TB screening outputs were mapped to these population clusters. This data was then combined with open-source high resolution contextual data to train a Bayesian inference model. The model predicted TB positivity rates on the community level (population cluster level), and these were visualised on a customised geoportal for use by the local teams to identify communities at high risk of TB transmission and plan ACF interventions. The TB positivity yield (proportion) observed at model-predicted hotspots was compared with the yield obtained at other sites identified based on aggregated notification data. Results The yield in population clusters that were predicted to have high TB positivity rates by the model was at least 1.75 times higher (p-value <0.001) than the yield in other locations in all four states. Conclusion The community level Bayesian predictive model has the potential to guide ACF implementers to high TB positivity areas for finding undiagnosed TB in the communities, thus improving efficiency of interventions.

Menaquinone is one of the major lipoquinones involved in the respiratory chains of bacteria, which includes ubiquinone. Menaquinone is an essential component in the electron transfer process and ATP synthesis especially in some Gram-positive bacteria including Mycobacterium tuberculosis (M. Tb). However, mammals utilize ubiquinone in the analogous electron transfer processes, and do not synthesize menaquinone. In the biosynthesis of menaquinone, MenA is an important enzyme, which is involved in the conversion of 1,4-dihydroxy-2-napthoate to demethylmenaquinone via prenyl transferase activity. Therefore MenA is chosen as a drug target in determining the inhibitor. While designing and screening MenA inhibitors we observed that benzophenone derivatives showed high coordination with enzymes in transition state and interrupted the growth of M. Tb moderately. In addition, diphenyl ether derivatives also showed moderate MIC and IC50 results. Therefore, to improve the biological activity we synthesized a polymeric compound having both benzophenone and diphenyl ether groups. In addition, a hydrophilic functional group was introduced into the polymeric compound to enhance the biological activity. The synthesized polymeric inhibitor showed improved MIC and IC50 values to inhibit the M. tb infection.

Bovine tuberculosis (BTB) is endemic in Ethiopian cattle. BTB is caused by Mycobacterium bovis (M. bovis) and has economic and public health significance. which has significant impact on the health of livestock and human. It has been significantly a cause for great economic loss in animal production. Associated risk factors contributed to the prevalence of the disease in cattle and its transmission. Moreover, the majority of cattle owners lack awareness about the disease and its public health significance. The presence of multiple hosts including wild animals, inefficient diagnostic techniques, absence of defined national controls and eradication programs could impede the control of bovine TB. Awareness rising about the disease, its transmission andzoonotic implication however, in Ethiopia Bovine Tuberculosis in Human-Livestock-Wildlife Interface is not well studied in the country and there were no studies concerning the burden of the disease between human ,animal and wild life which is of great importance for reduction and control measures. This paper aims to review the potential health and economic impact of bovine tuberculosis control in order to safeguard human and animal population in Ethiopia

Disseminated or military tuberculosis (TB) is defined as the presence of at least two non-contiguous sites of Mycobacterium tuberculosis, occurring as a result of progressive primary infection, reactivation and spread of a latent focus or due to iatrogenic origin. Disseminated TB represents a life-threatening condition, especially in at-risk children and when the diagnosis and treatment are delayed. We report on a case of a 3-year old boy who presented with long-lasting unrecognised disseminated TB that was successfully managed in a low-resource setting.

Background: The COVID-19 pandemic has promoted a shortage of filtering facepiece respirators (FFRs) and the emergence of new FFRs brands. We aimed to determine the fit provided by in-use FFRs in Peruvian healthcare workers (HCWs) during the COVID-19 pandemic. Methods: We enrolled 279 HCWs from 37 primary healthcare centers with highest burden of care for TB in Peru, of which 263 were assessed using quantitative fit tests (QNFT). Results were expressed as real-time fit factor (rt-FF) and overall fit factor (overall-FF), which was categorized as ≥100 (optimal result), 50-99, and <50. Results: We identified 3M 1860 FFRs (33.1%), Xiantao Zhong Yi ZYB-11 FFRs (24.7%) and Makrite 9500 FFRs (20.5%), mainly. Eighty-seven HCWs (33.1%) had an optimal overall-FF, 27 (10.3%) between 50-99, and 149 (56.7%) less than 50. Of the 87 HCWs with optimal over-all-FF, 73 (83.9%) were 3M 1860 FFR. Of the 27 participants with overall-FF between 50-99, 7 (25.9%) were Makrite 9500, while of the 149 with overall-FF less than 50, 58 (38.9%), and 47 (31.5%) were Xiantao Zhong Yi ZYB-11 and Makrite 9500, respectively. Conclusion: The Xiantao Zhong Yi and Makrite FFRs do not adapt adequately to the face of Peruvian HCWs, most having fit factors less than 50.

Background Tuberculosis is a type of infectious disease that can cause death if treatment is not completed. the duration of tuberculosis treatment can reach 6 to 8 months so it really requires discipline when doing treatment. This makes tuberculosis patients in dire need of health information and social support which is very helpful in providing motivation, health information, and monitoring treatment from nurses. Aim of this literature review is to provide an overview of the The Role Of Nurses In Providing Social Support In Tuberculosis Treatment: Literature Review. Method is a literature review research, this study uses electronic database searches using keywords according to research questions from the online library PubMed, Content Science, and Science Direct. Result it was found that the role of nurses in the aspect of social support, namely in providing motivation, supervision, comfort, empathy, and information. this is very necessary for patients with tuberculosis at the time of treatment. Conclution social support is needed by tuberculosis patients who are currently undergoing treatment to provide motivation, health information, and as a nurse's supervision of patient adherence to tuberculosis treatment.

Tuberculosis (TB) is a contagious disease, caused by Mycobacterium tuberculosis (MTB) that has infected and killed a lot of people in the past. At present treatments against TB are available at a very low cost. Since these chemical drugs have many adverse effects on health, more attention is now given on the plant-derived phytochemicals as potential agents to fight against TB. In this study, 5 phytochemicals, 4-hydroxybenzaldehyde, benzoic acid, bergapten, psoralen, and p-hydroxybenzoic acid, are selected to test their potentiality, safety, and efficacy against two potential targets, the MTB RNA polymerase and enoyl-acyl carrier protein (ACP) reductase, the InhA protein, using various tools of in silico biology. The molecular docking experiment, drug-likeness property test, ADME/T-test, P450 SOM prediction, pharmacophore mapping, and modeling, solubility testing, DFT calculations, and PASS prediction study had confirmed that all the molecules had the good potentiality to inhibit the two targets. However, two agents, 4-hydroxybenzaldehyde and bergapten were considered as the best agents among the five selected agents and they also showed far better results than the two currently used drugs, that function in these pathways, rifampicin (MTB RNA polymerase) and isoniazid (InhA protein). These two agents can be used effectively to treat tuberculosis.

Randomized clinical trials represent the gold standard in therapeutic research. Nevertheless, observational cohorts of patients treated for multidrug-resistant (MDR) or rifampin-resistant (RR) tuberculosis (TB) also play an important role in generating evidence to guide MDR/RR TB Generally, summary exposure classifications (e.g., ‘ever versus never’, ‘exposed at baseline’) have been used to characterize drug exposure, in the absence of detailed longitudinal data on MDR-TB regimen These summary classifications, along with an absence of data on covariates that change throughout the course of treatment, constrain researchers’ ability to answer the most relevant questions while accounting for known This paper highlights the importance of regimen changes in improving inference from observational studies of longer MDR-TB treatment regimens and offers an overview of the data and analytic strategies required to do

Studies on Protein-Protein interactions (PPI) can be helpful for the annotation of unknown protein function and for the understanding of cellular processes, such as specific virulence mechanisms developed by bacterial pathogens. In that context, several methods have been extensively used in recent years for the characterization of Mycobacterium tuberculosis PPI to further decipher TB pathogenesis. This review aims at compiling the most striking results based on in vivo methods (yeast and bacterial two-hybrid systems, protein complementation assays) for the specific study of PPI in mycobacteria. Moreover, newly developed methods, such as in-cell native mass resonance and proximity-dependent biotinylation identification, will have a deep impact on future mycobacterial research, as they are able to perform dynamic (transient interactions) and integrative (multiprotein complexes) analyses.

South Africa is afflicted with the worst epidemic of HIV in the world a legacy of the system of oscillating migrant labour in the region and the consequent social disruption that was the legacy of Apartheid. The initial response from the national government was slow and ineffective but once the magnitude of the epidemic became apparent the government began to respond. The investment in HIV- and TB-related activities in 2013 was R22 Bn or (US$2.5; 2013 exchange rate) of which the South Africa government contributed 80% and the Presidents Emergency Plan for AIDS Relief (PEPFAR) 17%. South Africa now has the more people on anti-retroviral therapy than any other country and treatment is being started much sooner after infection. Much of the best biomedical, virological, immunological, mathematical and social science around the treatment and prevention of HIV and AIDS and the associated epidemic of TB has been done by South African’s and their international collaborators. If the efforts to control the epidemic are maintained South Africa is on track to meet the UNAIDS 90-90-90target by 2020 and to End AIDS by 2030 in spite of the magnitude of the problem. While individual, patient level data are increasingly available, especially in the Western Cape, much greater efforts need to be made to ensure that the information collected in this way is used to give feedback and support to clinic staff, to ensure that health clinics are providing the best possible service, and to individual patients and people living with HIV to ensure that they are receiving the best possible care and support. South Africa needs to make better use of the rich and detailed data that are being collected from individual clinics and their patients to identify problems or difficulties at the clinic level and to ensure that individual patients are retained on treatment, are virally suppressed and receive the best possible care and support.

Plasma osteopontin (OPN) levels are elevated in mycobacterium tuberculosis patients and may involve granuloma formation. New inhibitors using brefelamide, an aromatic amide isolated from Dictyostelium cellular slim molds which may inhibit OPN transcription at concentration of 1M, were synthesized as compounds C, D and E. Their inhibitory activity against OPN synthesis in phorbol 12-myristate 13-acetate (PMA)-stimulated THP-1 cells was confirmed using enzyme-linked immunosorbent assay (ELISA), a multicolor immune-fluorescent microscope and western blot analysis. For the ELISA performed using the full-length OPN, each compound showed significant inhibition. Detailed analysis were done using C and D. They also showed inhibitory activity when used on another ELISA system to detect the immune-related form of OPN and their IC50 were 0.6 and 1.2 M for compounds C and D, respectively. Fluorescent particle count of stained cell numbers by O-17 showed the inhibition. Antibodies for O-17 and 34E3, which recognize OPN N-terminus and thrombin-cleaved site, respectively, detected distinct bands on the western blots following PMA stimulation. The decrease in full-length OPN detected by O-17 in the compound-treated cells was identified via western blot analysis. These newly-developed compounds may therefore be used in clinical trials for cancer and infectious diseases.

The aim of the study was to identify factors associated with non-adherence to tuberculosis (TB) preventive treatment among contacts with latent TB infection of new cases of pulmonary TB cases reported in Catalonia in 2019-2021. All contacts aged 18 years or older with a latent TB infection who received a TB preventive treatment were included in the study. The Chi square test and the odds ratios (OR) were used to assess the association between non-adherence to TB preventive treatment and the study variables, considering a p < 0.05 as statistically significant. Multiple logistic regression analysis was used to detect the in-dependent factors associated with TB preventive treatment non-adherence, considering a p < 0.05 as statistically significant. The percentage of non-adherence to TB preventive treatment found in this study was 23.7%. A multivariable logistic regression analysis determined that the following factors were significantly associated with TB preventive treatment non-adherence among adult contacts: “exposure at school or workplace” (aOR = 3.34), “exposure to an index case without laboratory confirmation of TB” (aOR = 2.07), “immigrant contact” (aOR = 1.81), “male gender” (aOR = 1.75) and “exposure duration <6 hours per week or sporadic exposure” (aOR = 1.60). By contrast, the factor “short-term TB preventive treatment regimen” (aOR = 0.38) was significantly associated with a lower treatment non-adherence. Adherence to TB preventive treatment should be improved among adult contacts of TB pulmonary cases with latent TB infection by recommending short-term treatment regimens and by developing health education activities, with a greater focus on contacts with factors associated with treatment non-adherence.

Background: Resistant hypertension (HTN) is associated with high risk of cardiovascular complications. Our study aimed to assess prevalence, characteristics and treatment of patients with resistant HTN; Methods: We screened 4340 consecutive cardiovascular patients and identified 3762 with HTN. Of them 128 fulfilled criteria for resistant HTN and were included in our study. We matched these patients to 128 hypertensive patients with controlled HTN; Results: Resistant HTN patients were 3.4% of all hypertensives. Most of these patients (67.2%) were at high or very high cardiovascular risk compared to controlled HTN patients (40.6%), p&lt;0001. Resistant HTN patients had more frequently concomitant chronic kidney disease (CKD) (60.9%), overweight/obesity (52.3%), dyslipidemias (35.2%), smoking (27.3%) and diabetes (21.9%) compared to controlled HTN patients (37.5%, 29.7%, 28.1%, 14.1% and 7.8% respectively), p&lt;0.001. Regression analysis showed strongest association of resistant HTN with CKD (OR 6.64), stage III HTN (OR 3.07) and obesity/overweight (OR 2.60). In contrast, single-pill combinations (SPCs) were associated with lower likelihood of uncontrolled HTN (OR 0.58); Conclusions: Resistant HTN represented a small proportion of all hypertensives in our study, but it was characterized by high/very high cardiovascular risk. Optimized therapy including increased usage of SPCs could improve blood pressure control and long-term prognosis of these patients.

The paper provides and comments on the results of studies of the effect of sandstone-based abrasives and quartz sand alone on the wear of martensitic surfaces of wear-resistant steels. The wear process was examined on a ring-on-ring test rig seeking to determine the mass decrement parameter which characterised wear. The tests were conducted for three sandstone varieties: Carboniferous, Permian, and Cretaceous, and they made it possible to determine that the most intense process of deterioration of wear-resistant steels took place in the presence of quartz sand grain, while less intense wear was observed in the case of sandstone-based abrasives. The mass decrement values established in the presence of the sandstones in question did not differ significantly between individual sandstone varieties. Based on a surface damage analysis, the basic damage mechanism was found to be micro-scratching, however, with regard to the sandstones examined, it was also determined that individual grains could be pressed into surface irregularities, as well as that films of soft hematite cement developed in the Permian sandstone and that inclusions of carbonaceous matter were formed in the Carboniferous sandstone. With reference to the wear process observations, a wear model was described for the surface of the steels examined in the presence of sandstone-based abrasives.

Most recent studies of doxycycline PEP have assessed doxycycline's effect on antimicrobial resistance by measuring the proportion of colonies of the target species with AMR as the outcome measure. In this study, we show that this method is insufficiently sensitive to detect shifts in MIC distribution.