Carbapenem resistance and the laboratory: When, how and why?

Manageiro, Vera; Ferreira, Eugénia; Caniça, Manuela

http://hdl.handle.net/10400.18/4228

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Authors

Manageiro, Vera

Ferreira, Eugénia

Caniça, Manuela

Abstract(s)

Carbapenem resistance are intrinsic in a few clinical bacteria, such as Stenotrophomonas maltophilia, Aeromonas sp., and Acinetobacter baumannii due to the production of carbapenemases. In addition, most non-fermenters are naturally resistant only to ertapenem and Serratia sp. and Proteeae have intrinsically low-level resistance to imipenem. Indeed, not all carbapenem-resistant isolates produce a carbapenemase (resistance can be mediated by other mechanisms, such as the combination of ESBL plus AmpC, plus impermeability) and not all carbapenemase producers are resistant to carbapenems (enzyme expression at low-level). Concerns about carbapenemase-mediated carbapenem resistance, imply that clinically-significant Gram-negative bacteria should be screened routinely for carbapenem susceptibility. However, detection of carbapenemase production can became difficult, because some carbapenemase-producing isolates demonstrate susceptible carbapenem MICs, even closely to intermediate breakpoint [1]. The ECOFF values, defined by EUCAST, can be a good strategy to detect those isolates [2]. Meropenem offers the best compromise between sensitivity and specificity in terms of detecting carbapenemase-producers, while ertapenem has high sensitivity but low specificity, and therefore not recommended for routine use [3]. Hence, following detection of reduced susceptibility to carbapenems in routine susceptibility tests, specific phenotypic methods for carbapenemases should be applied. The combination disk test, using boronic acid, dipicolinic acid and cloxacillin as β-lactamase inhibitors, is a well-validated choice. In addition, other methods may also be considered for detecting carbapenemase producers, such as Modified Hodge Test (MHT), MALDI-ToF or the new biochemical tests Carba NP and Blue-Carba. Further characterization of the carbapenemase-encoding genes, should include molecular biology methods.