PreprintArticleVersion 1This version is not peer-reviewed
Early-Stage IM Treatment with the Host-Derived Immunostimu-Lant CPDI-02 Increases Curative Protection of Healthy Outbred Mice Against Subcutaneous Infection with CA-MRSA USA300
Version 1
: Received: 2 October 2024 / Approved: 3 October 2024 / Online: 4 October 2024 (08:12:03 CEST)
How to cite:
Vetro, J. Early-Stage IM Treatment with the Host-Derived Immunostimu-Lant CPDI-02 Increases Curative Protection of Healthy Outbred Mice Against Subcutaneous Infection with CA-MRSA USA300. Preprints2024, 2024100290. https://doi.org/10.20944/preprints202410.0290.v1
Vetro, J. Early-Stage IM Treatment with the Host-Derived Immunostimu-Lant CPDI-02 Increases Curative Protection of Healthy Outbred Mice Against Subcutaneous Infection with CA-MRSA USA300. Preprints 2024, 2024100290. https://doi.org/10.20944/preprints202410.0290.v1
Vetro, J. Early-Stage IM Treatment with the Host-Derived Immunostimu-Lant CPDI-02 Increases Curative Protection of Healthy Outbred Mice Against Subcutaneous Infection with CA-MRSA USA300. Preprints2024, 2024100290. https://doi.org/10.20944/preprints202410.0290.v1
APA Style
Vetro, J. (2024). Early-Stage IM Treatment with the Host-Derived Immunostimu-Lant CPDI-02 Increases Curative Protection of Healthy Outbred Mice Against Subcutaneous Infection with CA-MRSA USA300. Preprints. https://doi.org/10.20944/preprints202410.0290.v1
Chicago/Turabian Style
Vetro, J. 2024 "Early-Stage IM Treatment with the Host-Derived Immunostimu-Lant CPDI-02 Increases Curative Protection of Healthy Outbred Mice Against Subcutaneous Infection with CA-MRSA USA300" Preprints. https://doi.org/10.20944/preprints202410.0290.v1
Abstract
Background/Objectives: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) greatly complicates treatment of skin and soft tissue infections (SSTI). It was previ-ously found that subcutaneous (SQ) treatment with the mononuclear phagocyte (MP)-selective activator, complement peptide-derived immunostimulant-02 (CPDI-02; formerly EP67), increases prophylaxis of outbred CD-1 mice against SQ infection with CA-MRSA. Here, we determined if treatment with CPDI-02 also increases curative protection. Methods: Female CD-1 mice were challenged SQ with CA-MRSA USA300 LAC then CPDI-02 or inactive scCPDI-02 was administered by a topical, SQ, IM, or IV route at 6- or 24-hrs post-challenge. Dermal abscess sizes were compared over 10 days and CA-MRSA burden, neutrophils, MP, and pro-inflammatory cytokines were compared in dermal abscesses. CPDI-02 PK and distribution in female CD-1 mice were compared after IM or IV dosing and CPDI-02 toxicity was determined by IM dose escalation and repeat IM dosing in male and female CD-1 mice. Results: Repeat IM treatment with CPDI-02 starting at 6-hrs post-challenge decreased maximum abscess surface area, CA-MRSA burden, and time to resolu-tion, whereas repeat treatment by the topical, SQ, or IV route had no effect. Starting CPDI-02 treatment at 24-hrs post-challenge was ineffective regardless of route. Single IM treatment with CPDI-02 starting at 6-hrs post-challenge was as effective as repeat IM treatment, increased systemic exposure, and decreased initial levels of IL-1β and increased MP in dermal abscesses. CPDI-02 was tolerated to between 130-170 mg/kg for single IM dosing and 65-130 mg/kg for repeat IM dosing with males being more tolerant. Conclusions: Single early-stage IM treatment with CPDI-02 may increase curative protection against SSTI caused by CA-MRSA or other pathogens controlled by activated MP.
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
