LAUSR

Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are a significant cause of morbidity and mortality worldwide. CRE are defined by the Centers for Disease Control and Prevention (CDC) as those Enterobacteriaceae that are resistant in vitro to any carbapenem antimicrobial. This means a minimum inhibitory concentration (MIC) of 2 mg/ml for ertapenem, or an MIC 4 mg/ml for doripenem, meropenem, or imipenem. In addition, those Enterobacteriaceae that are documented to produce a carbapenemase are also considered CRE, regardless of carbapenem MIC. For Enterobacteriaceae species that have intrinsic imipenem resistance – such as Morganella morganii, Proteus spp. and Providencia spp – resistance to carbapenems other than imipenem is required. This phenotypic definition includes both carbapenemase-producing Enterobacteriaceae (CPE or CP-CRE) as well as non-carbapenemaseproducing CRE. A retrospective study evaluating the impact of carbapenemase production on outcomes after monomicrobial CRE bloodstream infections (BSI) found that patients infected with CP-CRE were at increased risk of dying within 14 d as compared with patients with non-carbapenemase-producing CRE (adjusted odds ratio, 4.92; 95% confidence interval 1.01–24.81). The authors speculated that increased virulence of CP-CRE rather than patient factors were the cause of this observation. Similar to carbapenem-susceptible Enterobacteriaceae, CRE have been reported to be the cause of many different types of infections. In most reports, urinary tract infections (UTI) are the most commonly observed infection type with CRE. While less common than UTI, CRE BSI and CRE pneumonia tend to be associated with the highest mortality rates. Also similar to other Enterobacteriaceae is the difficulty in distinguishing infection from colonization in patients with clinical CRE isolates that are obtained from non-sterile sites such as urine, sputum and wounds. In research settings, investigators often defer to surveillance definitions such as those outlined by the CDC to distinguish between infected and colonized patients. However, these definitions were designed with a different objective in mind, which is something to be considered when reading the CRE literature. In any case, it is clear that many patients, who would be considered “colonized” with CRE when applying the CDC definitions, are being treated with antibiotics for presumed infection by their clinicians. This is an especially common situation in asymptomatic bacteriuria. This often unnecessary treatment is associated with healthcare costs, drug adverse reactions, and subsequent resistance development. Various carbapenemases may cause carbapenem resistance in Enterobacteriaceae. The most common enzymatic cause of carbapenem resistance is the family of Klebsiella pneumoniae carbapenemases (KPC). KPC are class A, serine-based b-lactamases. Of these, KPC-2 and KPC-3 are most frequently encountered. Another important class of carbapenemases is class B of metallob-lactamases. This class includes the New Delhi Metallob-lactamase (NDM) family. A third common cause of carbapenem resistance in Enterobacteriaceae is the class D OXA-48-like carbapenemases. The global epidemiology of CRE is discussed by van Duin and Doi. Unfortunately, reliable estimates of the incidence and prevalence of CRE infections from many areas in the world are not available. Only a few states in the United States have mandatory reporting of CRE which facilitates a more complete knowledge of the epidemiology of CRE infections in those states. For the remainder of the US, estimates are limited to the occurrence of specific carbapenemases in those states as reported by the CDC. The epicenter of the CRE epidemic in the US appears to have been the New York area, although there is evidence that incidence in that