Adjunctive rifampicin increases antibiotic efficacy in group A streptococcal tissue infection models
Objectives: Biofilm has recently been highlighted as a complicating feature of necrotizing soft tissue infections (NSTI) caused by Streptococcus pyogenes ( i.e. group A streptococcus ; GAS) contributing to a persistence of bacteria in tissue despite prolonged antibiotic therapy. Here we assessed the standard treatment of benzylpenicillin and clindamycin with or without rifampicin in a tissue-like setting. Methods: Antibiotic efficacy was evaluated by colony forming units determination in a human organotypic skin model infected for 24 or 48 hours with GAS strains isolated from NSTI patients. Antibiotic effect was also evaluated by micro-calorimetric metabolic assessment in in vitro infections of cellular monolayers providing continuous measurements over time. Results: Adjunctive rifampicin resulted in enhanced antibiotic efficacy of bacterial clearance in an organotypic skin tissue model: 97.5% vs. 93.9% (p=0.006). Through microcalorimetric measurements, adjunctive rifampicin resulted in decreased metabolic activity and extended lag phase for all clinical GAS strains tested (p<0.05). In addition, a case report is presented of adjunctive rifampicin treatment in an NSTI case with persistent GAS tissue infection. Conclusion: The findings of this study demonstrate that adjunctive rifampicin enhances clearance of GAS biofilm in an in vitro tissue infection model.