title: Risk factors for piperacillin/tazobactam-resistant Gram-negative infection in hematology/oncology patients with febrile neutropenia.
abstract: OBJECTIVE
  Febrile neutropenia (FN) is a life-threatening complication of cancer therapy, and initial ineffective therapy is associated with poor outcomes. Piperacillin/tazobactam (PTZ) is a commonly used empiric antibiotic for the treatment of FN, but resistance among Gram-negative pathogens is well described. We conducted a retrospective case-control study to identify risk factors for PTZ-resistant (PTZ-R) Gram-negative isolates.
  
  
  METHODS
  Hematology/oncology patients with FN from November 2007 to November 2013 with a positive culture for Gram-negative bacilli were divided into two groups: PTZ-sensitive (PTZ-S) and PTZ-R. A multivariable model using logistic regression was constructed to identify risk factors for PTZ-R.
  
  
  RESULTS
  A total of 171 patients were included (25 PTZ-R, 146 PTZ-S), yielding a 14.6 % resistance rate. Thirty-day all-cause mortality was significantly higher in the PTZ-R group (29 vs 11 %, P = 0.024). Multivariable analysis yielded intensive care unit (ICU) status (odds ratio (OR) 20.18; 95 % confidence interval (CI) 1.03-397.35; P = 0.048), antibiotics for > 14 days in the previous 90 days (OR 6.02; CI 1.17-30.93; P = 0.032), and respiratory source (OR 13.65; CI 1.14-163.57; P = 0.039) as significant risk factors for PTZ-R, and the receiver operating characteristic area under the curve of the model was 0.894. Among PTZ-R isolates, 88 % were sensitive to meropenem and 100 % were sensitive to amikacin.
  
  
  CONCLUSIONS
  Given the high mortality rates in the PTZ-R group, a risk-factor-guided approach driven by this multivariable model may help identify patients that could benefit from amikacin combination therapy to help optimize empiric therapy in this setting.
authors.affiliation: Department of Pharmacy Services and Clinical Sciences, University of Michigan Health System and College of Pharmacy, 1111 E. Catherine St., Rm 300, Ann Arbor, MI, 48109, USA.
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Marini
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Hough
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Gregg
authors.forename: Haya
authors.initials: H
authors.lastname: Abu-Seir
authors.forename: Jerod L
authors.initials: JL
authors.lastname: Nagel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D024901:Drug Resistance, Multiple, Bacterial; D064147:Febrile Neutropenia / Q000188:drug therapy / Q000382:microbiology*; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology*; D019337:Hematologic Neoplasms / Q000382:microbiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000382:microbiology*; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010403:Penicillin Resistance; D010878:Piperacillin / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin