Correlation between in vitro and in vivo activity of levofloxacin and moxifloxacin against pneumococcal strains with different susceptibilities to fluoroquinolones.
In vitro and in vivo models were developed to evaluate the efficacy of levofloxacin and moxifloxacin against three serotype 3 pneumococcal strains with different susceptibilities to fluoroquinolones (wild-type, parC mutant, and parC, parE and gyrA mutant). Levofloxacin and moxifloxacin reduced the bacterial burden in the in vitro pharmacodynamic and animal models for the wild-type strain but had very little activity against the fully resistant strain (parC, parE and gyrA mutant). Levofloxacin showed very little activity both in the in vitro pharmacodynamic model and in the animal model for the strain having a mutation in parC (levofloxacin and moxifloxacin minimum inhibitory concentrations, 2mg/L and 0.25mg/L, respectively). However, moxifloxacin still had a significant in vitro and in vivo activity against this strain.
Huelves
Lorena
L
Unit for Research in Medical Microbiology and Antimicrobial Chemotherapy, Fundación Jiménez Díaz-UTE, Avenida de Reyes Católicos 2, 28040 Madrid, Spain.
Sevillano
David
D
Martínez-Marín
Carmina
C
López-Casla
María Teresa
MT
Gracia
Matilde
M
Alou
Luis
L
del Carmen Ponte
María
M
Prieto
José
J
Soriano
Francisco
F
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001372:Aza Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D015169:Colony Count, Microbial; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial / Q000235:genetics; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D064704:Levofloxacin; D008297:Male; D051379:Mice; D008954:Models, Biological; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology*; D011008:Pneumococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D011804:Quinolines / Q000493:pharmacokinetics / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016019:Survival Analysis
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D000077266:Moxifloxacin