In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point.
A dose-decreasing immunocompetent sepsis mouse model was used to evaluate the in vivo effect of levofloxacin, moxifloxacin and gemifloxacin, using a ciprofloxacin/levofloxacin susceptible serotype 6B strain (ciprofloxacin MIC: 1 mg/l) and two resistant serotype 14 and 19F strains with gyrA and parC point mutations (ciprofloxacin MICs of 32 and 64 mg/l, respectively). Significant higher in vivo activity was found for moxifloxacin and gemifloxacin than for levofloxacin against strains 1 and 2, and for gemifloxacin versus moxifloxacin or levofloxacin against strain 3. Gemifloxacin treatment resulted in 100% survival against strains 1 and 2(AUC0-24 h/MIC of 30 and 62) but against strain 3, survival was 60-80% (AUC0-24 h/MIC of 93). Similar AUC0-24 h/MIC values produced different therapeutic results suggesting that in vitro parameters other than the MIC could influence efficacy predictions based on in vitro susceptibility tests (MICs) or pharmacodynamic parameters (AUC0-24 h/MIC).
Alkorta
M
M
Servicio de Microbiología, Hospital Donostia, Po del Doctor Beguiristain s/n, 20014 San Sebastián, Spain. malkorta@hcru.osakidetza.net
Giménez
M J
MJ
Vicente
D
D
Aguilar
L
L
Pérez-Trallero
E
E
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001372:Aza Compounds / Q000494:pharmacology / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000494:pharmacology; D027081:DNA Gyrase / Q000235:genetics*; D027101:DNA Topoisomerase IV / Q000235:genetics*; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology / Q000627:therapeutic use*; D000077735:Gemifloxacin; D064704:Levofloxacin; D051379:Mice; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D009287:Naphthyridines / Q000494:pharmacology / Q000627:therapeutic use; D015242:Ofloxacin / Q000494:pharmacology / Q000627:therapeutic use; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D017354:Point Mutation; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D009287:Naphthyridines; D011804:Quinolines; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D000077735:Gemifloxacin; D000077266:Moxifloxacin