Temocillin and piperacillin/tazobactam resistance by disc diffusion as antimicrobial surrogate markers for the detection of carbapenemase-producing Enterobacteriaceae in geographical areas with a high prevalence of OXA-48 producers.
OBJECTIVE
To assess the performance of the agar disc diffusion method for the detection of carbapenemase-producing Enterobacteriaceae (CPE) referred to the national reference laboratories (NRLs) in Belgium and France.


METHODS
All Enterobacteriaceae isolates referred to the NRLs for the confirmation of CPE in 2012 were included. The inhibition zone diameters of meropenem, piperacillin/tazobactam and temocillin using CLSI disc diffusion methodology were recorded. Phenotypic and molecular detection of carbapenemases was performed on all isolates.


RESULTS
A total of 1354 Enterobacteriaceae isolates, including 435 (32.1%) confirmed CPE isolates [OXA-48 (n = 323), KPC (n = 60), VIM (n = 32) and NDM (n = 20)] and 919 carbapenemase-negative isolates, were tested. Using recommended interpretative criteria, non-susceptibility to meropenem had poor sensitivity (52.0% by CLSI susceptibility breakpoint and 80.0% by EUCAST screening breakpoints), while non-susceptibility to piperacillin/tazobactam (according to CLSI breakpoint) or to temocillin (according to Fuchs, Barry, Thornsberry et al. Eur J Clin Microbiol 1985; 4: 30-3) was highly sensitive (99.8% and 98.2%, respectively) but poorly specific (29.4% and 42.9%, respectively) for the detection of CPE. Temocillin diameters <12 mm alone had high specificity (90.0%) and the combination of temocillin diameters ≥12 mm with piperacillin/tazobactam diameters ≥16 mm observed in 40% of all referred isolates displayed excellent negative predictive value (99.2%).


CONCLUSIONS
In geographical areas with a high prevalence of OXA-48 producers, recommended meropenem susceptibility or screening breakpoints failed to detect CPE in a large proportion of isolates. The combination of modified zone diameter cut-offs for piperacillin/tazobactam (≥16 mm) and temocillin (≥12 mm) can be used to rule out the presence of carbapenemase and avoid unnecessary additional testing for confirmation of CPE.
National Reference Laboratory for Monitoring of Antimicrobial Resistance in Gram-negative Bacteria, CHU Mont-Godinne, Université Catholique de Louvain (UCL), 1 Avenue Docteur Gaston Therasse, 5530 Yvoir, Belgium.
Te-Din
TD
Huang
Laurent
L
Poirel
Pierre
P
Bogaerts
Catherine
C
Berhin
Patrice
P
Nordmann
Youri
Y
Glupczynski
D001426:Bacterial Proteins / Q000096:biosynthesis*; D001530:Belgium / Q000453:epidemiology; D015415:Biomarkers / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000502:physiology*; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology* / Q000302:isolation & purification; D005602:France / Q000453:epidemiology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010406:Penicillins / Q000008:administration & dosage*; D010878:Piperacillin / Q000008:administration & dosage; D000077725:Piperacillin, Tazobactam Drug Combination; D015995:Prevalence; D001618:beta-Lactamases / Q000096:biosynthesis*
D001426:Bacterial Proteins; D015415:Biomarkers; D010406:Penicillins; C031367:temocillin; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D001618:beta-Lactamases; C063912:carbapenemase; C108449:oxacillinase; D010878:Piperacillin
OXA-48; breakpoints; meropenem