Comparison of faecal and optimal growth conditions on in vitro pharmacodynamic activity of marbofloxacin against Escherichia coli.
The objective of the study was to compare the in vitro activity of marbofloxacin against Escherichia coli (E. coli) strains with differing marbofloxacin susceptibility levels under optimal growth conditions and under condition mimicking faecal environment in time-kill kinetic studies. Under optimal growth conditions, marbofloxacin exerted a bactericidal concentration-dependent activity against all E. coli strains with bactericidal concentrations equal to 1 or 4 times MIC. Under faecal growth conditions, marbofloxacin maintained a bactericidal concentration-dependent activity but a 4- to 16-fold increase in bactericidal concentration was required to produce a similar magnitude of effect at 8 h. The bactericidal activity decreased between 8 and 24 h and allowed a residual bacterial population to subsist with a significant regrowth for some of them. Under no-growth conditions, marbofloxacin produced a very low decrease of non-dividing bacteria during a short time. No concentration produced a reduction > or = 3log10 in viable count excepted for two susceptible strains at concentration > or = 64 x MIC after 4 h exposure. The pharmacodynamic parameters from time-kill kinetic studies provide a useful means of studying antimicrobial activity. The importance of using different growth conditions is indicated by the difference in the killing of E. coli in the absence of active dividing cells and in the presence of autoclaved faecal content, both of which have a detrimental effect on the activity of marbofloxacin.
Pellet
T
T
Agence Française de Sécurité Sanitaire des Aliments, LERMVD, Unité Pharmacocinétique-Pharmacodynamie, La Haute Marche, BP 90203, 35 302 Fougères, France.
Gicquel-Bruneau
M
M
Sanders
P
P
Laurentie
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000382:microbiology / Q000662:veterinary*; D005243:Feces / Q000382:microbiology; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D011201:Poultry Diseases / Q000382:microbiology*; D015363:Quinolones / Q000493:pharmacokinetics / Q000494:pharmacology*; D013552:Swine; D013553:Swine Diseases / Q000382:microbiology*; D014422:Turkeys
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D015363:Quinolones; C080260:marbofloxacin