Development of an algorithm for phenotypic screening of carbapenemase-producing Enterobacteriaceae in the routine laboratory

BMC Infect Dis. 2017 Jan 17;17(1):78. doi: 10.1186/s12879-016-2174-y.

Abstract

Background: Carbapenemase-producing Enterobacteriaceae (CPE) are difficult to identify among carbapenem non-susceptible Enterobacteriaceae (NSE). We designed phenotypic strategies giving priority to high sensitivity for screening putative CPE before further testing.

Methods: Presence of carbapenemase-encoding genes in ertapenem NSE (MIC > 0.5 mg/l) consecutively isolated in 80 French laboratories between November 2011 and April 2012 was determined by the Check-MDR-CT103 array method. Using the Mueller-Hinton (MH) disk diffusion method, clinical diameter breakpoints of carbapenems other than ertapenem, piperazicillin+tazobactam, ticarcillin+clavulanate and cefepime as well as diameter cut-offs for these antibiotics and temocillin were evaluated alone or combined to determine their performances (sensitivity, specificity, positive and negative likelihood ratios) for identifying putative CPE among these ertapenem-NSE isolates. To increase the screening specificity, these antibiotics were also tested on cloxacillin-containing MH when carbapenem NSE isolates belonged to species producing chromosomal cephalosporinase (AmpC) but Escherichia coli.

Results: Out of the 349 ertapenem NSE, 52 (14.9%) were CPE, including 39 producing OXA-48 group carbapenemase, eight KPC and five MBL. A screening strategy based on the following diameter cut offs, ticarcillin+clavulanate <15 mm, temocillin <15 mm, meropenem or imipenem <22 mm, and cefepime <26 mm, showed 100% sensitivity and 68.1% specificity with the better likelihood ratios combination. The specificity increased when a diameter cut-off <32 mm for imipenem (76.1%) or meropenem (78.8%) further tested on cloxacillin-containing MH was added to the previous strategy for AmpC-producing isolates.

Conclusion: The proposed strategies that allowed for increasing the likelihood of CPE among ertapenem-NSE isolates should be considered as a surrogate for carbapenemase production before further CPE confirmatory testing.

Keywords: Algorithm; Carbapenemase; Disk diffusion method; Enterobacteriaceae; Screening.

MeSH terms

  • Algorithms*
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / analysis*
  • Bacterial Proteins / metabolism
  • Carbapenems / metabolism*
  • Carbapenems / pharmacology
  • Cefepime
  • Cephalosporins / pharmacology
  • Clavulanic Acids / pharmacology
  • Drug Resistance, Bacterial*
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / genetics
  • Enterobacteriaceae / metabolism*
  • Enterobacteriaceae / physiology
  • Ertapenem
  • Humans
  • Imipenem / metabolism
  • Imipenem / pharmacology
  • Meropenem
  • Microbial Sensitivity Tests
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / pharmacology
  • Penicillins / pharmacology
  • Tazobactam
  • Thienamycins / metabolism
  • Thienamycins / pharmacology
  • Ticarcillin / pharmacology
  • beta-Lactamases / analysis*
  • beta-Lactamases / metabolism
  • beta-Lactams / metabolism
  • beta-Lactams / pharmacology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • Cephalosporins
  • Clavulanic Acids
  • Penicillins
  • Thienamycins
  • beta-Lactams
  • temocillin
  • Imipenem
  • Cefepime
  • ticarcillin-clavulanic acid
  • Penicillanic Acid
  • beta-Lactamases
  • carbapenemase
  • Ticarcillin
  • Meropenem
  • Ertapenem
  • Tazobactam