EFFECT OF QUINOLONES AGAINST SLOWLY GROWING BACTERIA

Bacteria growing in vivo multiply much more slowly than in vitro. If t he bactericidal activity of quinolones may be affected by an increase in generation time (g) was studied in batch cultures as well as under the well-controlled conditions of a continuous flow culture. By limiti ng the nutrient supply, generation times were lengthened from approxim ately 0.45 to 1.5 h up to 3.9 h. Three recent clinical isolates each o f Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa w ere exposed to twice the MIC of ciprofloxacin, norfloxacin, fleroxacin and ofloxacin. The 'killing rates' were calculated in analogy to the growth rate. The bactericidal activity of the quinolones tested agains t E. coli was minimally influenced by the reduced generation time and the effect against S. aureus was moderate. As compared to their rapidl y growing counterparts (g = 0.4 h) slowly growing (g = 1.3 h) P. aerug inosa were killed even more effectively by ciprofloxacin (176% increas e) fleroxacin (48% increase) norfloxacin (36% increase) and ofloxacin (86% increase). These changes may likely be due to adaptive responses of the outer membranes of the bacteria to the limited nutrient supply thereby sensitizing the bacteria to the bactericidal activity of quino lones.