The Problem of Carbapenemase-Producing-Carbapenem-Resistant-Enterobacteriaceae Detection

Abstract

The emergence and spread of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are a significant clinical and public health concern. Reliable detection of CP-CRE is the first step in combating this problem. There are both phenotypic and molecular methods available for CP-CRE detection. There is no single detection method that is ideal for all situations.G ram-negative bacteria, specifically Enterobacteriaceae, are common causes of both community-acquired and hospitalacquired infections, including urinary tract, bloodstream, and lower respiratory tract infections. These bacteria can acquire genes encoding multiple antibiotic resistance mechanisms, including extended-spectrum ␤-lactamases (ESBLs), AmpCs, and carbapenemases (1). ␤-Lactam drugs are often the primary therapeutic option for serious infections, and carbapenems in particular are often considered agents of last resort. Thus, the emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) are a significant clinical and public health concern. CRE are often resistant to all ␤-lactam drugs and frequently carry mechanisms conferring resistance to other antimicrobial classes, further limiting treatment options. Although CRE infections are relatively infrequent, they have become more common in the United States since their emergence (2, 3, 4). Infections with these resistant bacteria are associated with higher mortality rates than those for infections caused by carbapenem-susceptible organisms (5).The epidemiologic description and phenotypic detection of CRE are complicated by the fact that Enterobacteriaceae may be nonsusceptible (intermediate or resistant) to carbapenems via a variety of mechanisms. Proteus, Providencia, and Morganella species demonstrate intrinsically elevated MICs to imipenem (6). Enterobacteriaceae can also produce ␤-lactamase enzymes such as AmpCs (chromosomal or acquired) and ESBLs that do not readily inactivate carbapenems on their own but can confer carbapenem resistance when combined with chromosomal porin mutations that prevent accumulation of ␤-lactam agents in the bacteria. Finally, the production of carbapenemase enzymes, typically found on mobile genetic elements, that inactivate carbapenem and other ␤-lactam antibiotics is increasingly common (1, 2). These carbapenemase-producing CRE (CP-CRE) frequently carry multiple resistance mechanisms, which can include redundant ␤-lactamases such as AmpCs and ESBLs and genes conferring resistance to other antimicrobial classes.Among the various types of CRE, CP-CRE have received the most attention because they have the greatest potential to contribute to the overall problem of antimicrobial resistance. Production of a carbapenemase usually confers resistance on its own, without requiring additional chromosomal mutations or accessory mechanisms. Because carbapenemase genes are carried on mobile genetic elements, these genes can be spread horizontally to naive bacteria, thus contributing to the reservoir of resistance in both environmental and clinical Enterob...

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