Killing kinetics of minocycline, doxycycline and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae

Abstract

Macrolide-resistant Mycoplasma pneumoniae (MRMP) has emerged and is increasing worldwide. In a 2011 outbreak of MRMP infections in Japan, symptoms failed to improve in many patients who initially received macrolides; the therapeutic agent was then changed to minocycline (MIN), doxycycline (DOX) or tosufloxacin (TFX). In this study, the bactericidal effects of these three agents against MRMP were evaluated. Time–kill kinetics against MRMP and macrolide-susceptible M. pneumoniae (MSMP) were determined for 5 days at concentrations corresponding to the respective minimum inhibitory concentration (MIC) and 2 × MIC, i.e. 1 µg/mL and 2 µg/mL for MIN, 0.5 µg/mL and 1 µg/mL for DOX, and 0.5 µg/mL and 1 µg/mL for TFX. The post-antibiotic effects (PAE) of these agents in culture against MRMP were also examined based on their pharmacokinetic parameters in children. Following exposure of MRMP and MSMP to up to twice the respective MICs of MIN, DOX and TFX, viable cells initially numbering 106 CFU/mL had decreased similarly to 103 CFU/mL after 4 days. Clarithromycin and azithromycin showed good bactericidal action against MSMP but not against MRMP. PAEs against MRMP appeared superior with MIN and DOX compared with TFX. In infection with M. pneumoniae having a generation time exceeding 6 h, a therapeutic agent must be selected in consideration of pharmacokinetic parameters, not MICs alone.