Killing of Streptococcus pneumoniae by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin using drug minimum inhibitory concentrations and mutant prevention concentrations

Abstract

Streptococcus pneumoniae continues to be a significant respiratory pathogen, and increasing antimicrobial resistance compromises the use of β-lactam and macrolide antibiotics. Bacterial eradication impacts clinical outcome, and bacterial loads at the site of infection may fluctuate. Killing of two macrolide- and quinolone-susceptible clinical S. pneumoniae isolates by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin against varying bacterial densities was determined using the measured minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). For kill experiments, 106–109 CFU/mL were exposed to the drug and were sampled at 0, 0.5, 1, 2, 3, 4, 6, 12 and 24h following drug exposure. The log10 reduction and percent reduction (kill) of viable cells was recorded. MICs and MPCs (mg/L) for azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin were 0.063–0.125/0.5–1, 0.031–0.063/0.25–0.5, 0.063/0.25–0.5, 0.008/0.016 and 0.031/0.25, respectively. Killing 106–109 CFU/mL of bacteria by the drug MIC yielded incomplete killing, however log10 reductions occurred by 12h and 24h for all drugs. Exposure of 106–109 CFU/mL to MPC drug concentrations resulted in the following log10 reduction by 6h of drug exposure: azithromycin, 1.3–3.9; clarithromycin, 1.9–5.8; erythromycin, 0.8–4.7; telithromycin, 0.3–1.7; and gemifloxacin, 1.8–4.2. Bacterial loads at the site of infection may range from 106 to 109, and kill experiments utilising a higher bacterial inoculum provided a more accurate measure of antibiotic performance in high biomass situations. Killing was slower with telithromycin. Kill was greater and fastest with MPC versus MIC drug concentrations.