Very Low Cefotaxime Concentrations Select for Hypermutable Streptococcus pneumoniae Populations

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 selec...

Activities against Streptococcus pneumoniae of amoxicillin and cefotaxime at physiological concentrations: in vitro pharmacodynamic simulation.

An in vitro model simulating amoxicillin and cefotaxime concentrations in human serum (after standard doses) was used to explore the activities of these drugs over time against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae strains. An initial inoculum reduction percentage of > or = 90% was obtained with amoxicillin and maintained for 2 to 8 h, regardless of the strain...

Genomic analysis and reconstruction of cefotaxime resistance in Streptococcus pneumoniae.

OBJECTIVES To identify non-penicillin-binding protein (PBP) mutations contributing to resistance to the third-generation cephalosporin cefotaxime in Streptococcus pneumoniae at the genome-wide scale. METHODS The genomes of two in vitro S. pneumoniae cefotaxime-resistant isolates and of two transformants serially transformed with the genomic DNA of cefotaxime-resistant mutants were determined ...

Bactericidal activities of ceftizoxime and cefotaxime against Streptococcus pneumoniae.

Patel et al. (4) compared the serum bactericidal titers (SBTs) and the time serum drug concentrations remained above the MICs (T . MIC) of ceftizoxime and cefotaxime against three intermediately penicillin-resistant Streptococcus pneumoniae isolates. MICs were # 1.0 mg/ml, SBTs were . 1:2, and T . MIC exceeded 50% of dosage intervals. They concluded that ceftizoxime’s longer T . MIC compensates...

Importance of using current NCCLS breakpoints to interpret cefotaxime and ceftriaxone MICs for Streptococcus pneumoniae.