title: The use of cefepime for treating AmpC β-lactamase-producing Enterobacteriaceae.
abstract: BACKGROUND
  AmpC β-lactamase-producing organisms are associated with significant morbidity and mortality. Induction of resistance to third-generation cephalosporins after exposure to these agents complicates treatment options and carbapenems are considered optimal therapy. The role of cefepime, however, remains unclear. Our objective was to compare clinical outcomes for patients receiving cefepime compared with meropenem for invasive infections caused by organisms expressing AmpC β-lactamases.
  
  
  METHODS
  Hospitalized patients with blood, bronchoalveolar lavage, or intra-abdominal fluid cultures growing Enterobacter spp, Serratia spp, or Citrobacter spp were evaluated using the cefotetan-boronic acid disk test and the cefotetan-cloxacillin Etest to identify organisms with AmpC β-lactamase production from February 2010 to January 2011. In patients with organisms hyperproducing AmpC β-lactamases (positive by both methods), clinical outcomes for patients receiving cefepime or meropenem therapy were compared. To minimize the possibility of treatment selection bias, 1:1 nearest neighbor propensity score matching was performed prior to regression analysis.
  
  
  RESULTS
  Of 399 patients meeting eligibility criteria, 96 (24%) had confirmed infections with AmpC β-lactamase-producing organisms. Propensity score matching of patients infected with AmpC β-lactamase-positive organisms treated with cefepime or meropenem yielded 32 well-balanced patient pairs with no difference in 30-day mortality (odds ratio, 0.63; 95% confidence interval [CI], .23-2.11; P = .36) or length of hospital stay after infection (relative risk, 0.96; 95% CI, .79-1.26; P = .56) between the 2 groups.
  
  
  CONCLUSIONS
  Cefepime may be a reasonable option for the treatment of invasive infections due to AmpC β-lactamase-producing organisms, particularly when adequate source control is achieved.
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, MHS Johns Hopkins Medical Institutions, 200 N Wolfe St, Baltimore, MD 21287, USA. ptamma1@jhmi.edu
authors.forename: Pranita D
authors.initials: PD
authors.lastname: Tamma
authors.forename: Sonya C T
authors.initials: SC
authors.lastname: Girdwood
authors.forename: Ravindra
authors.initials: R
authors.lastname: Gopaul
authors.forename: Tsigereda
authors.initials: T
authors.lastname: Tekle
authors.forename: Ava A
authors.initials: AA
authors.lastname: Roberts
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Harris
authors.forename: Sara E
authors.initials: SE
authors.lastname: Cosgrove
authors.forename: Karen C
authors.initials: KC
authors.lastname: Carroll
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000096:biosynthesis*; D000077723:Cefepime; D002511:Cephalosporins / Q000627:therapeutic use*; D015331:Cohort Studies; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D006760:Hospitalization; D006801:Humans; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D057216:Propensity Score; D013845:Thienamycins / Q000627:therapeutic use; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D013845:Thienamycins; D000077723:Cefepime; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; D000077731:Meropenem
keywords: AmpC β-lactamases; Enterobacter; boronic acid; cefepime; gram-negative resistance