Effect of low-level resistance on subsequent enrichment of fluoroquinolone-resistant Streptococcus pneumoniae in rabbits.
BACKGROUND
We measured the effect of low-level fluoroquinolone resistance in Streptococcus pneumoniae on the development of high-level resistance within the context of the mutant selection window.


METHODS
Rabbits infected with S. pneumoniae were treated with ciprofloxacin or moxifloxacin concentrations that simulated pharmacokinetics in treated humans; bacteria obtained from lungs were examined for fluoroquinolone susceptibility.


RESULTS
Ciprofloxacin enriched resistant mutants from a wild-type strain; moxifloxacin did not. However, moxifloxacin enriched resistant mutants from a parC mutant; the drug concentration at the top of the selection window was determined.


CONCLUSIONS
A parC resistance mutation facilitates the enrichment of high-level resistance, as was predicted by in vitro measurements.
Etienne
Manuel
M
Service des Maladies Infectieuses, Hopital du Bocage, Dijon, France.
Croisier
Delphine
D
Charles
Pierre-Emmanuel
PE
Lequeu
Catherine
C
Piroth
Lionel
L
Portier
Henri
H
Drlica
Karl
K
Chavanet
Pascal
P
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001372:Aza Compounds / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000627:therapeutic use; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D024841:Fluoroquinolones / Q000494:pharmacology*; D008168:Lung / Q000382:microbiology; D000077266:Moxifloxacin; D009154:Mutation; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D011804:Quinolines / Q000627:therapeutic use; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002939:Ciprofloxacin; D027101:DNA Topoisomerase IV; D000077266:Moxifloxacin