Phenotypic detection of carbapenemase-producing organisms from clinical isolates

Abstract

The rapid spread of multidrug-resistant Gram-negative organisms constitutes one of the greatest challenges to global health. While Gram-negative organismshave developed several mechanisms to avert the bactericidal effects of commonly prescribed antibiotic agents, the increasing prevalence of carbapenemase-producing organisms (CPO) is particularly concerning given the rapid spread of mobile genetic elementscontaining carbapenemase genes, the limited treatment options for infections caused bythese organisms, and the high mortality rates associated with CPO infections. Understanding if an organism is carbapenemase producing and, if so, the class of carbapenemase(s) produced has treatment implications, as some agents preferentially have activity against specific carbapenemases. Furthermore, CPO disseminate between patientswith greater ease than non-CP-carbapenem-resistant organisms and warrant more intensive infection control measures than would be employed in the absence of carbapenemase production. Phenotypic assays currently used in clinical practice to detect CPOconsist of the following: (i) growth-based assays which measure carbapenem resistancebased on organism growth in the presence of a carbapenem antibiotic (e.g., modifiedHodge test and modified carbapenem inactivation method), (ii) hydrolysis methodswhich detect carbapenem degradation products (e.g., Carba NP test and matrix-assistedlaser desorption-ionization time of flight mass spectrometry), and (iii) lateral flow immunoassays which detect carbapenemase enzymes through the use of specific antibodies.Although there is no single phenotypic test that meets all specifications of the ideal test,as we describe in this review, there are a number of tests that are user-friendly, affordable, accurate, and feasible for implementation in clinical microbiology laboratories of allsizes.