[Mutation window for the "pneumococcus-fluoroquinolone" couple. Contribution of experimental models].
Low-level resistance to fluoroquinolones (in vitro susceptible but with topoisomerase mutation, parC) is currently rare among pneumococci in France. However, this resistance is more frequently observed in previously exposed patients and therapeutic failure has been reported. These issues were investigated by using a humanized model of experimental pneumonia induced by pneumococci exhibiting this low-level resistance profile. The results are as follows: 1) when the pneumonia is due to a wild type pneumococcus, humanized ciprofloxacin treatment is not effective because of resistant mutants with parC mutation; moreover, levoflaxin treatment is less bactericidal than gatiflo- or moxifloxacin (-4 vs -6 log CFU/g); 2) when an efflux strain is used, levo-treatment is not efficient but there are no mutants, a gatiflo-treatment is combined when mutants appear and moxiflo-treatment is effective; 3) when the pneumonia is induced with susceptible parC strains, treatment with either levo, or gati, or moxifloxacin is completely ineffective because resistant mutants appear (acquisition of another gyrA mutation). Measure of the mutation prevention concentration (MPC) allows anticipating these results since the mutation window can be determined. These results stress the necessity to identify patients with such pneumococcal strains in order to avoid therapeutic failure and the emergence of fluoroquinolone resistant mutants.
Chavanet
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Laboratoire des maladies infectieuses, LQRF-EA 562, service des maladies infectieuses, hôpital du Bocage, CHU de Dijon, faculté de médecine de Dijon, BP 77908, 21000 Dijon, France. pascal.chavanet@chu-dijon.fr
Croisier
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D023421:Models, Animal; D009154:Mutation; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics*
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones