Very low cefotaxime concentrations select for hypermutable Streptococcus pneumoniae populations.
A mixed culture of an hypermutable hexA Streptococcus pneumoniae mutant strain and its hexA(+) isogenic ancestor was challenged with low cefotaxime concentrations. Despite identical original cefotaxime MICs, the hexA mutant population was significantly selected at very low concentrations, and all of the tested selected variants harbored the Thr550-->Ala mutation in pbp2x. Since cefotaxime selects hypermutators, the risk of secondary acquisition of antibiotic resistance is increased; as expected, the cefotaxime-resistant mutants had a mutation frequency 10 times higher in response to to ciprofloxacin. The present study presents a model (not necessarily reflecting the clinical setting) illustrating the risk of selection of mutators in the evolution of multiple resistance.
Negri
María-Cristina
MC
Servicio de Microbiología, Hospital Ramón y Cajal, Madrid, Spain.
Morosini
María-Isabel
MI
Baquero
María-Rosario
MR
del Campo
Rosa
R
Blázquez
Jesús
J
Baquero
Fernando
F
D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000235:genetics; D002439:Cefotaxime / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000187:drug effects*; D046915:Penicillin-Binding Proteins; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics
D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D004268:DNA-Binding Proteins; C084499:HexA protein, bacteria; D046915:Penicillin-Binding Proteins; C072223:PBP 2x protein, Streptococcus; D002439:Cefotaxime