Active Ingredient: Ciprofloxacin
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Unless stated otherwise, all other reagents were of analytic grade and purchased form E.
Bearing in mind the results obtained at pH 7, the four drugs were less active against L. All MICs, however, were still lower than the maximal serum concentrations observed in healthy volunteers Cmax, see Table 1. Extracellular and intracellular activities of quinolones The activity of the four quinolones was then examined against extracellular and intracellular forms of L.
In the first series of experiments Figure 1, all drugs were compared at a fixed post-phagocytosis time point 5 h for L. We observed that the growth of L.
On examining the extracellular activities of quinolones, we see that these were only slightly bactericidal towards L.
In contrast, they were highly bactericidal against S. However, when considering activities against intracellular bacteria, a global analysis of the results showed that these were always significantly lower than what was seen against extracellular bacteria, the difference being, however, smaller for L.
In the next series of experiments, we examined the influence of varying the concentrations of the quinolones.
We concentrated on garenoxacin, for which no previous data were available, and used levofloxacin as a comparator the results of similar studies with ciprofloxacin and moxifloxacin have been reported previously 8, 13, 15.
Figure 2 shows the change in bacterial counts observed in broth left panels and in cells right panels at 5 h for L. On examining L. Garenoxacin was significantly more effective than levofloxacin, reflecting their differences of MIC. In sharp contrast, activity against S.
Interestingly, the ratio of intracellular to extracellular activities remained almost constant at all concentrations above 0.
The difference between garenoxacin and levofloxacin was not statistically significant when examined globally ANCOVA, although the plateau of activity in broth was obtained at a two-fold lower concentration for garenoxacin compared with levofloxacin, reflecting their differences of MIC.
In the last series of experiments, we examined the time-dependency of the killing activities of the quinolones towards L.
Figure 3 shows that there was no significant difference in extracellular and intracellular growth of L. Accumulation of quinolones in uninfected and infected cells Table 2 compares the apparent cellular accumulations of the four quinolones in both uninfected and infected cells, under the conditions used for the experiments described in Figure 1.
Differences between data obtained at 5 and 24 h in uninfected cells were either not significant ciprofloxacin, moxifloxacin or small levofloxacin, garenoxacin, indicating that an apparent steady state had been reached or was close to being obtained.