Adjunctive Rifampicin Increases Antibiotic Efficacy in Group A Streptococcal Tissue Infection Models

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 rifampin in a tissue-like setting. Antibiotic efficacy was evaluated by CFU determination in a human organotypic skin model infected for 24 or 48 h with GAS strains isolated from NSTI patients. Antibiotic effect was also evaluated by microcalorimetric metabolic assessment in in vitro infections of cellular monolayers providing continuous measurements over time. Adjunctive rifampin resulted in enhanced antibiotic efficacy of bacterial clearance in an organotypic skin tissue model, 97.5% versus 93.9% (P = 0.006). Through microcalorimetric measurements, adjunctive rifampin 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 rifampin treatment in an NSTI case with persistent GAS tissue infection. The findings of this study demonstrate that adjunctive rifampin enhances clearance of GAS biofilm in an in vitro tissue infection model.