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.