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Case Report

Community-Acquired Klebsiella pneumoniae KPC Invasive Infection: Argentine Case Report

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09 July 2024

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09 July 2024

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Abstract
The incidence of infections due to carbapenemase-producing Enterobacteriaceae (CPE) is rising worldwide. We present the case of a 48-year-old female patient, diabetic, with previous episodes of urinary tract infections that was admitted due to pyelonephritis, later identified to be caused by KPC and ESBL-producing Klebsiella pneumoniae. Both the patient and her family had no strong epidemiological link with the healthcare system, and for this reason, this case stands out in regional literature since similar reports are scarce and therefore constitutes a reason for alert in health institutions. Further studies are needed in order to ascertain the real incidence of these infections in community settings in Latin America and the Caribbean.
Keywords: 
Subject: Medicine and Pharmacology  -   Epidemiology and Infectious Diseases

Introduction

Worldwide, there has been an increase in the incidence of infections due to carbapenemase-producing Enterobacteriaceae (CPE), even in countries where shortage of diagnostic resources could be underestimating its true incidence [1].
COVID-19 pandemic accelerated this process, and multiple reports were published worldwide [2,3] and in Latin America in particular [4,5]. This has been linked to excessive antibiotic consumption [6] and high patient-caregiver ratio [7], among other factors.
CPE infectious typically present as healthcare-associated infections and condition higher costs and mortality [8]. Moreover, CPE acquisition usually occurs during hospital stay, specially in patients with invasive devices, Intensive Care unit admission, carbapenem consumption and prolonged hospital stays [9,10,11].
In our health institution, a tertiary-care level center in the city of Santa Fe (Argentina), we described an increase of 2.5 times in the incidence of infections due to carbapenem-resistant bacteria during the COVID-19 pandemic [12].
We present a case of an invasive infection caused by community-acquired KPC carbapenemase and extended spectrum betalactamase (ESBL)-producing Klebsiella pneumoniae during December 2022, that is to our knowledge the first published case in Latin America and the Caribbean of community-onset CPE infection without a strong epidemiological link to healthcare institutions. Afterwards, we review the available international literature in Pubmed -including Medline and PMC-, Lilacs, Scielo and Cochrane Library up to January 2023 regarding such infections.

Case Report

The patient had no history of substance abuse and had a medical history of diabetes mellitus type 2, hypertension, hypothyroidism and repeated urinary tract infections, with a maximum of two episodes a year, with seldom visits to healthcare centers. She had never been hospitalized.
The last referred episode of pyelonephritis was 8 months prior to admission, for which she received a 5-day course of ciprofloxacin, subsequently visiting an emergency room -within a secondary-level care center- due to the persistence of low back pain. There, she stayed for less than 6 hours in observation and received analgesia.
Now, her chief complaint was an abdominal pain that has lasted more than 2 days and that was focused on the left flank and iliac fossa and radiated to the homolateral lumbar area. She described it as continuous, with an increasing intensity reaching 10/10. She denied digestive symptoms, and referred irritative urinary symptoms.
On physical examination, she was hemodynamically stable and presented with fever and abdominal distension, which showed selective tenderness and defense on palpation -but no rebound- in the left hemiabdomen. Positive left lumbar fist percussion.
On admission, blood tests showed leukocytosis (WBC 16910 cells/mm3), neutrophilia (88,4%), increased erythrosedimentation rate (59 mm/h), hyperglycemia (3,79 g/L), acute kidney failure (urea 0,30 mg/dL, creatinine 1,85 mg/dL, urine density 1025) and a negative test for HIV. An urinalysis showed a leukocyte-covered field, negative nitrites.
A preliminary diagnosis of pyelonephritis was made. Therefore, we requested a urine sample for culture and prescribed empiric antibiotic therapy with ciprofloxacin, since her last use of antibiotics dated back to 6 months previous to consultation and reported no history of infections caused by multidrug-resistant bacteria or use of urinary tract devices.
On kidney ultrasound, she had a mild left pyelic ectasia, without urinary lithiasis. A CT urography was performed, which ruled out urinary lithiasis.
48 hours after admission, she developed hemodynamic instability. In the context of sepsis, blood culture samples were collected. At the same time, the Microbiology laboratory reported growth in the urine culture of mucous colonies with Blue-carba test positive Gram-negative bacilli. The empirical antibiotic was switched to a combined regimen of amikacin and fosfomycin, based on local epidemiology.
Microbiological Identification: The midstream urine sample sent to the laboratory, presented with abundant leukocytes and red blood cells on microscopic examination. The sample was cultured in CLED agar and incubated at 37°C. A significant growth was obtained at 24 hs, with a count of over 100.000 UFC/mL Gram-negative bacilli with positive Blue-Carba test. Identification and sensitivity tests were carried out with the Vitek 2C system (bioMérieux, Argentina). The result was the isolation of Klebsiella pneumoniae, which was sensitive to amikacin (CIM <2 ug/mL), tigecycline (CIM 0.25 ug/mL) and nitrofurantoin (CIM <16 ug/mL), but showed a carbapenem-resistance profile (imipenem CIM 8 ug/mL and meropenem CIM >16 ug/mL) and resistance to ciprofloxacin (CIM >4 ug/mL), piperacillin-tazobactam (CIM >128 ug/mL), gentamicin (CIM >16 ug/mL) and trimethoprim-sulfamethoxazole (>320 ug/mL). It was also sensitive to colistin (tested by colistin pre-diffusion method with Rosco Neosensitabs; 25 mm) and to fosfomycin (tested by disk diffusion method, 21mm)
Carbapenem disks were confronted to phenyl-boronic acid and EDTA and the synergy between aztreonam-boronic acid and EDTA-Ceftazidime Avibactam was assessed, obtaining as a result positive synergies with boronic acid in both plates, which indicated the presence of KPC carbapenemase. Moreover, we found a positive synergy test between ceftazidime -as well as cefotaxime- and amoxicillin-clavulanate disks, which phenotypically confirmed the presence of ESBL alerted by the VITEK 2C System (bioMérieux, Argentina).
Blood culture samples were incubated in the BactAlert system (bioMérieux, Argentina), which detected significant growth after 15.8 hrs. Gram-negative bacilli were observed, the identification and sensitivity of which matched the findings in the urine sample.
Epidemiological link: The patient lives no further than 3.5 km from our healthcare center, in a house with all basic needs met. There, she lives with her daughter and her male partner. The latter manifested that he had no recent hospitalizations, that he works in a slaughterhouse in the production of charcuterie, and that he has no contact with the poultry industry. Both the patient and her daughter said that their regular line of work consisted of housemaid chores, not related to caring for elders, and that they had no contact with people undergoing illnesses or recently hospitalized. They also mentioned that their employers were a retired physician and a biochemist working in the private sector.
Evolution: The patient completed a 10-day course of intravenous amikacin (fosfomycin was suspended after the definite antibiogram) and remained in strict contact isolation. She evolved with no fever and the rest of her symptoms improved. After this, she was successfully discharged. During routinary surveillance swabs, we did not identify the spread of this resistant strain within the institution.

Discussion

Antimicrobial resistance is a dynamic and adaptive process of microorganisms.
The main antimicrobials used in ambulatory human and animal health condition the most common resistance mechanisms: at the community level, the higher spectrum resistance is the methicillin-resistance and the production of ESBL [13,14]. Hospitals make up a niche for the development of multidrug-resistant microorganisms.
There are very few reported cases in international literature of infections caused by CPE in the absence of previous contact with the healthcare system [15,16]. These cases pose a threat for hospital outbreaks, since these patients may not present criteria for rectal screening [15].
A revision of 15 markedly heterogeneous studies, which included an Argentinean study (Villar et al., 2013), found a prevalence of 4.9% of CPB intestinal carrying in 164 samples from non-hospitalized patients, but at the expense of non-fermenting Gram-negative bacilli [17].
A surveillance study carried out in 2012-2013 in the county of Michigan (USA) found 102 isolates of CPE, among which 65% met the criteria for community-acquisition. However, most of these patients had been recently hospitalized in acute or long-term acute care settings [18].
In 2016, a study from Taiwan showed that 29,5% of 78 infections due to CPE had their onset in the community setting [19]. Meanwhile, a Spanish study reported that from 780 CPE isolated in clinical samples 20% were community-acquired, but 71,4% of these had been hospitalized in the 90 days prior symptom onset and up to 86,6% the previous year [20]. Afterwards, in 2020 there were 68 reports of infections documented by CPE in 4 years in a hospital in China, 22.1% of those were community-acquired [21]. The same year, the SMART surveillance study in Taiwan presented a report of 1294 Gram-negative bacilli isolations, among which only 20 belonged to CPB. However, 4/20 were community-acquired [22].
The observation of community-acquired cases in these reports by far exceeds the Argentinean experience, where nosocomial acquisition predominates.
In Spain, in 2022, an infection caused by KPC Klebsiella pneumoniae with ceftazidime-avibactam resistance was reported, with community onset and no link to the healthcare system [23].
To our knowledge, a case of an invasive infection caused by a community-acquired CPE -co-carrying ESBL- with no link to the healthcare system, has not been published within Latin American or Caribbean literature. Regarding this patient, she presented a community-onset infection and declared no contact with the healthcare system for over 6 months. Even if her short stay (<6 hs) in the emergency department of a secondary-care hospital 8 months prior to consultation was taken into consideration, colonization with CPE significantly declines after 6 months [24,25,26], and the risk of infection after colonization significantly declines after 1 month [27]. Risk factors for persistence include prolonged hospital stays, intercurrent admissions and Clostridium difficile infections, none of which this patient presented [24,25,26].
This puts forward questions about the spreading of CPE from hospitals to the environment. Sewage may be one of the main sources of spreading. An Austrian study carried out in 2011 found three CPE isolations in sewage waste through microbiological surveillance [28]. KPC isolations in sewage had been reported four years before in Brazil and concomitantly in rivers in Portugal [29,30]. Later, it was found in river water in Croatia [31]. More recently, a Swiss study found a 10% positivity for CPE in water samples and with a wider diversity of genetic resistance mechanisms [32].
A review showed that even when the isolation of CPE in water samples is a worldwide phenomenon, most of the research comes from Europe and the highest caseload comes from the United States, Brazil and Asia, while there are no Argentinean reports [33].
Recently, in Swiss veterinary clinics, they detected not only invasive infections and rectal colonizations caused by CPE in hospitalized animals, but also the rectal carrying of the same epidemic clones in vets [34].
The high caseload of hospitalized patients during the COVID-19 pandemic together with the rise in CPE infections incidence in hospital settings in Argentina, as well as worldwide, provided an uncontrolled and unassessed source of CPE-colonized patients to the community. Moreover, since these infections are not yet of mandatory reporting, there is no data regarding the approximate caseload in our country or how many of these patients may represent community-acquired or community-onset healthcare-associated infections. No studies have been performed to assess CPE colonization in community settings.
Further studies are needed in order to ascertain the real incidence of these infections in community settings in Latin America and the Caribbean.

Funding

The present report did not receive any financial support.

Conflicts of Interest

The authors declare no conflicts of interest.

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