title: The ecology of antibiotic use in the ICU: homogeneous prescribing of cefepime but not tazocin selects for antibiotic resistant infection.
abstract: BACKGROUND
  Antibiotic homogeneity is thought to drive resistance but in vivo data are lacking. In this study, we determined the impact of antibiotic homogeneity per se, and of cefepime versus antipseudomonal penicillin/β-lactamase inhibitor combinations (APP-β), on the likelihood of infection or colonisation with antibiotic resistant bacteria and/or two commonly resistant nosocomial pathogens (methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa). A secondary question was whether antibiotic cycling was associated with adverse outcomes including mortality, length of stay, and antibiotic resistance.
  
  
  METHODS
  We evaluated clinical and microbiological outcomes in two similar metropolitan ICUs, which both alternated cefepime with APP-β in four-month cycles. All microbiological isolates and commensal samples were analysed for the presence of antibiotic-resistant bacteria including MRSA and P. aeruginosa.
  
  
  RESULTS
  Length of stay, mortality and overall antibiotic resistance were unchanged after sixteen months. However, increased colonisation and infection by antibiotic-resistant bacteria were observed in cefepime cycles, returning to baseline in APP-β cycles. Cefepime was the strongest risk factor for acquisition of antibiotic-resistant infection.
  
  
  CONCLUSIONS
  Ecological effects of different β-lactam antibiotics may be more important than specific activity against the causative agents or the effect of antibiotic homogeneity in selection for antibiotic resistance. This has important implications for antibiotic policy.
authors: Centre for Infectious Diseases and Microbiology, Westmead Hospital, Sydney, New South Wales, Australia.
authors: Andrew N
authors: AN
authors: Ginn
authors: Agnieszka M
authors: AM
authors: Wiklendt
authors: Heather F
authors: HF
authors: Gidding
authors: Narelle
authors: N
authors: George
authors: James S
authors: JS
authors: O'Driscoll
authors: Sally R
authors: SR
authors: Partridge
authors: Brian I
authors: BI
authors: O'Toole
authors: Rita A
authors: RA
authors: Perri
authors: Joan
authors: J
authors: Faoagali
authors: John E
authors: JE
authors: Gallagher
authors: Jeffrey
authors: J
authors: Lipman
authors: Jonathan R
authors: JR
authors: Iredell
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000077723:Cefepime; D002511:Cephalosporins / Q000494:pharmacology*; D011307:Drug Prescriptions; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009305:Nasopharynx / Q000382:microbiology; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D015996:Survival Rate
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077725:Piperacillin, Tazobactam Drug Combination; D000077723:Cefepime; D010397:Penicillanic Acid; D010878:Piperacillin