Clinical significance of inhibition kinetics for Streptococcus pyogenes in response to penicillin

Objectives: The antibiotic mode of action against clinical isolates of Streptococcus pyogenes and physiological factors involved in modifying the inhibitory response to the antibiotic were investigated. Methods: We developed high-resolution respirometry for continuous monitoring of bacterial growth and inhibition kinetics. One hundred and ten clinical isolates from 90 paediatric patients were tested, including 48 isolates obtained from 28 patients with eradication failure. Respirometric inhibition curves were monitored at 4 mg/L penicillin G over a short 30 min period, corresponding to the drug's serum half-life. Results: None of the clinical isolates exhibited penicillin tolerance. Latency in the respirometric response of S. pyogenes to penicillin increased significantly with decreasing strain-specific respirometric growth rate. No difference in inhibition kinetics was found in vitro for isolates from patients with or without bacteriological treatment failure. Conclusions: In streptococcal pharyngotonsillitis, tolerance is not a relevant concept to explain bacteriological treatment failure. Definitions of tolerance should be reconsidered in the framework of growth-dependent antibiotic susceptibility.