title: Emergence of resistance to ceftazidime during therapy for Enterobacter cloacae infections.
abstract: The mechanism of resistance to ceftazidime in two clinical isolates of Enterobacter cloacae that emerged during therapy with broad-spectrum beta-lactam antibiotics was studied. Both isolates acquired broad resistance to advanced-spectrum beta-lactam drugs other than imipenem. Biotyping confirmed strain identity in both cases, and no new plasmids were detected in the resistant isolates. Both resistant isolates produced beta-lactamase constitutively. Slow but definite hydrolysis of ceftazidime was demonstrated by using purified beta-lactamase in a spectrophotometric assay. Further evidence that beta-lactamase is responsible for resistance in these organisms was provided by the demonstration that cefoxitin, a potent inducer of beta-lactamase, antagonized the activity of ceftazidime against these isolates. This antagonism could be prevented by inhibition of derepression of beta-lactamase with clindamycin. Clindamycin also prevented regrowth of ceftazidime-treated cells in time-kill studies and markedly reduced production of beta-lactamase in induced cultures at concentrations as low as 2 micrograms/ml.
mesh_terms: D000328:Adult; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D002440:Cefoxitin / Q000494:pharmacology; D002442:Ceftazidime / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D002981:Clindamycin / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004754:Enterobacter / Q000032:analysis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D004755:Enterobacteriaceae / Q000187:drug effects*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010957:Plasmids; D001618:beta-Lactamases / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D002981:Clindamycin; D002440:Cefoxitin; D002442:Ceftazidime; D001618:beta-Lactamases