title: Treatment with a broad-spectrum cephalosporin versus piperacillin-tazobactam and the risk for isolation of broad-spectrum cephalosporin-resistant Enterobacter species.
abstract: Receipt of a broad-spectrum cephalosporin is a strong risk factor for isolation of broad-spectrum cephalosporin-resistant Enterobacter species, and yet the risk from other broad-spectrum beta-lactams hydrolyzed by group 1 beta-lactamases has not been well characterized. We compared the risk conferred by broad-spectrum cephalosporins to that conferred by piperacillin-tazobactam, alone or in combination with an aminoglycoside or a fluoroquinolone. A retrospective cohort was monitored from treatment onset until a broad-spectrum cephalosporin-resistant Enterobacter strain was isolated or the patient was discharged. There were 447 patients in the piperacillin-tazobactam group and 2,341 patients in the broad-spectrum cephalosporin group. Groups were similar in age (mean, 62.5 years). The piperacillin-tazobactam group had a smaller percentage of men (32% versus 44%, P < 0.001) and a lower rate of intensive care unit stay (25% versus 38%, P < 0.001) but a higher rate of surgery (41% versus 26%, P < 0.001). Groups differed in the distribution of comorbidities. Resistant Enterobacter strains were isolated from 62 patients, 2% in each group (hazard ratio [RR] = 1.02 [P = 0.95]). In multivariable analysis, risk was similar among treatment groups (RR = 0.71 [P = 0.32]). Intensive care unit stay and surgery were associated with increased risk (RR = 4.53 [P < 0.001] and RR = 1.97 [P = 0.015], respectively), fluoroquinolones were protective (RR = 0.24 [P = 0.003]), and aminoglycosides did not affect risk (RR = 0.98 [P = 0.95]). The protective effect of fluoroquinolones against isolation of broad-spectrum cephalosporin-resistant Enterobacter spp. and the equivalence in risk associated with piperacillin-tazobactam and broad-spectrum cephalosporins may have important clinical and epidemiologic implications.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston, Massachusetts, USA. mschwabe@caregroup.harvard.edu
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Schwaber
authors.forename: Camilla S
authors.initials: CS
authors.lastname: Graham
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Sands
authors.forename: Howard S
authors.initials: HS
authors.lastname: Gold
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Carmeli
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002442:Ceftazidime / Q000494:pharmacology* / Q000627:therapeutic use; D002443:Ceftriaxone / Q000494:pharmacology* / Q000627:therapeutic use; D015331:Cohort Studies; D004359:Drug Therapy, Combination / Q000494:pharmacology / Q000627:therapeutic use; D004754:Enterobacter / Q000254:growth & development* / Q000302:isolation & purification / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D010878:Piperacillin / Q000494:pharmacology* / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D002443:Ceftriaxone; D010397:Penicillanic Acid; D002442:Ceftazidime; D010878:Piperacillin