title: Comparative susceptibility of clinical isolates producing extended spectrum beta-lactamases to ceftibuten: effect of large inocula.
abstract: BACKGROUND
  Infections caused by Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) are a growing clinical problem. However, there is wide variation in the level of resistance to third generation beta-lactams conferred by these enzymes.
  
  
  METHODS
  We studied 33 Klebsiella pneumoniae and 4 Escherichia coli isolates producing ESBLs obtained from outbreaks in 14 different hospitals and a nursing home in the United States. Microdilution testing with standard (10(4-5) colony-forming units/ml) and large (10(6-7) colony-forming units/ml) inocula, was used to compare the minimum inhibitory concentrations (MICs) of ceftibuten, a novel oral oxyimino beta-lactam, with those of other third generation beta-lactams (cefotaxime, ceftazidime, aztreonam, cefixime, cefpodoxime and cefoxitin).
  
  
  RESULTS
  Twenty-seven of the clinical isolates had well-characterized ESBLs of 10 different types, 7 of which produced TEM-1; 1 isolate also produced LXA-1. Two strains produced more than 1 ESBL. The remaining 10 strains produced 8 as yet uncharacterized types of ESBL. With large inocula 73% tested susceptible to ceftibuten, whereas 8 to 22% tested susceptible to the other third generation beta-lactam antibiotics. Ceftibuten MICs increased with higher inocula when tested against strains producing SHV-4 or SHV-5 and, to a lesser extent, strains producing multiple beta-lactamases. Only cefoxitin showed a smaller inoculum effect.
  
  
  CONCLUSIONS
  Ceftibuten merits clinical evaluation in infections caused by bacteria that produce ESBLs.
authors.affiliation: Miriam Hospital, Providence, RI 02906, USA. antone-medeiros@brown.edu
authors.forename: A A
authors.initials: AA
authors.lastname: Medeiros
authors.forename: J
authors.initials: J
authors.lastname: Crellin
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000077722:Ceftibuten; D002511:Cephalosporins / Q000494:pharmacology*; D004196:Disease Outbreaks; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000378:metabolism*; D006761:Hospitals; D007525:Isoelectric Focusing; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000378:metabolism*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D009735:Nursing Homes; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D001618:beta-Lactamases; D000077722:Ceftibuten