Intracellular Activity and Efficacy in a Mouse Model of Septic Arthritis of the Novel Pseudopeptide Pep16 Against Clinical Isolates

Overview

Journal JAC Antimicrob Resist

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2024 Feb 27

PMID 38410249

Authors

Jean-Baptiste Mascary

Valerie Bordeau

Irene Nicolas

Marie-Clemence Verdier

Pierre Rocheteau

Vincent Cattoir

Affiliations

Soon will be listed here.

Abstract

Objectives: Assessing the therapeutic potential of a novel antimicrobial pseudopeptide, Pep16, both and for the treatment of septic arthritis caused by .

Methods: Seven clinical isolates of (two MRSA and five MSSA) were studied. MICs of Pep16 and comparators (vancomycin, teicoplanin, daptomycin and levofloxacin) were determined through the broth microdilution method. The intracellular activity of Pep16 and levofloxacin was assessed in two models of infection using non-professional (osteoblasts MG-63) or professional (macrophages THP-1) phagocytic cells. A mouse model of septic arthritis was used to evaluate the efficacy of Pep16 and vancomycin. A preliminary pharmacokinetic (PK) analysis was performed by measuring plasma concentrations using LC-MS/MS following a single subcutaneous injection of Pep16 (10 mg/kg).

Results: MICs of Pep16 were consistently at 8 mg/L for all clinical isolates of (2- to 32-fold higher to those of comparators) while MBC/MIC ratios confirmed its bactericidal activity. Both Pep16 and levofloxacin (when used at 2 × MIC) significantly reduced the bacterial load of all tested isolates (two MSSA and two MRSA) within both osteoblasts and macrophages. In MSSA-infected mice, Pep16 demonstrated a significant (∼10-fold) reduction on bacterial loads in knee joints. PK analysis following a single subcutaneous administration of Pep16 revealed a gradual increase in plasma concentrations, reaching a peak of 5.6 mg/L at 12 h.

Conclusions: Pep16 is a promising option for the treatment of septic arthritis due to , particularly owing to its robust intracellular activity.

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