Article Figures & Data
Figures
- FIG. 1.
(A) Dose-response relationship between levofloxacin and changes in S. pneumoniae (strain AMC-058) density in thigh muscles (mean ± 1 standard deviation) following ∼108-CFU/thigh inoculation. In this evaluation, all doses were given on a once-daily basis. In neither experiment (A and B) were any drug-resistant mutants recovered by direct plating on levofloxacin-contaning plates. (B) Dose fractionation experiments were performed (QD refers to the whole dose given once; BID refers to half the dose given every 12 h twice; QID refers to one-quarter of the dose given every 6 h). The data are displayed with the AUC/MIC ratio as the independent variable. The peak/MIC ratio and time > MIC are also evaluated as independent variables, but AUC/MIC displayed the best fit of the model to the data. The inoculum was 6.5 log10 CFU/thigh. When tested by analysis of variance, no difference was seen between q24h (the whole dose once), q12h (a half dose q12h), and q6h (a quarter dose q6h) administration of the same total daily dose.
- FIG. 2.
Comparison of efflux rates of EtBr from the parent strain (AMC-058) and its isogenic efflux-mediated-resistance daughter (RC2). The change in fluorescence is normalized to the initial observed levels for direct comparison of initial EtBr efflux rates. The time scale is in seconds. The error bars indicate standard deviations.
- FIG. 3.
In vivo outcome study results for S. pneumoniae AMC-058 with pharmacodynamically equivalent exposures to ciprofloxacin (CIP) and levofloxacin (LVX). Total bacterial population densities (black) enumerated on drug-free plates and drug-resistant-subpopulation (CIPr and LVXr) densities (gray) isolated on 3 × MIC-containing plates are shown for ciprofloxacin (A) and levofloxacin (B). Levofloxacin-exposed organisms were plated on levofloxacin-containing plates, and ciprofloxacin-exposed organisms were plated on ciprofloxacin-containing plates. In panel B, no clones resistant to levofloxacin were isolated; this is displayed by plotting at the detection limit. The error bars indicate standard deviations.
- FIG. 4.
In vivo outcome study results for S. pneumoniae RC2 exposed to pharmacodynamically equivalent exposures of ciprofloxacin (CIP) and levofloxacin (LVX). Total bacterial population densities (black) enumerated on drug-free plates and drug-resistant-subpopulation (CIPr and LVXr) densities (gray) isolated on 3 × MIC-containing plates are shown for ciprofloxacin (A) and levofloxacin (B). Levofloxacin-exposed organisms were plated on levofloxacin-containing plates, and ciprofloxacin-exposed organisms were plated on ciprofloxacin-containing plates. The error bars indicate standard deviations.
