A Study of Antibiotic Tolerance to Levofloxacin and Rifampin in Staphylococcus aureus Isolates Causing Prosthetic Joint Infections: Clinical Relevance and Treatment Challenges
Abstract
Background: Antibiotic tolerance in Staphylococcus aureus biofilms poses a major clinical challenge in prosthetic joint infections (PJIs). This study aimed to characterize the antibiotic tolerance of clinical S. aureus isolates recovered from cases of PJI under different stress conditions, including biofilm formation and antibiotic exposure. The correlation between tolerance level, the presence of specific tolerance-related genes, and clinical outcome was also evaluated. Methods: Twelve clinical S. aureus isolates were analyzed. To assess tolerance, the TDtest was used on exponentially growing bacteria, 48 h biofilms, and biofilms treated with levofloxacin and/or rifampin. Whole-genome sequencing was performed to identify tolerance-associated genes. Results: All isolates were phenotypically susceptible to rifampin and levofloxacin. Although all strains exhibited basal tolerance levels, biofilm formation led to heightened antibiotic tolerance, particularly those treated with rifampin as compared to levofloxacin: 29.5 vs. 17 (p = 0.01). Rifampin tolerance in biofilm-embedded bacteria was significantly higher in isolates from patients with treatment failure (p sspA and leuS in biofilm isolates, and between rifampin tolerance and prs and pgm. Conclusions: In this study, clinical S. aureus strains isolated from prosthetic joint infections exhibited considerable inter-strain variability in antibiotic tolerance, particularly under biofilm conditions. Elevated rifampin tolerance in…
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