Measuring Carbapenem-Resistant Enterobacteriaceae in the United States: A Critical Step for Control.

Carbapenem-resistant Enterobacteriaceae (CRE)may be the most concerning contemporary antibiotic resistance threat. Enterobacteriaceae comprise a large group of bacteria, including Escherichia coli and Klebsiella pneumoniae, and are commoncauses of health care–associatedandcommunity-acquiredinfections.Carbapenems,suchasimipenem,meropenem,ertapenem,anddoripenem areamongthebroadest-spectrumandmostpotentβ-lactamantibiotics.Fordecades, carbapenemswere reliablyactiveagainst Enterobacteriaceae, and thuswere frequently selected for empirical treatmentofsuspectedseriousgram-negative infections. Significant carbapenem resistance in Enterobacteriaceae was first described in 2001 in a US strain of K pneumoniae that produced an enzyme, termed “K pneumoniae carbapenemase” that was able to destroy all β-lactam antibiotics, including carbapenems.1 Infections due to K pneumoniae carbapenemase–producingCREareoverwhelminghealthcare– associated infections, andmortality related tobloodstream infections is substantial, with an estimated case fatality rate of more than 50%.1,2 This appears to be due more to delayed or inadequateantibiotic therapy for thesemultidrug-resistantorganisms than to increased bacterial virulence.2,3 Reports of K pneumoniae carbapenemase increased rapidly after 2005, and several new carbapenemases were identified,mostnotablyNewDelhimetallo-β-lactamase andOXA48-like oxacillinase.1 Carbapenemase-producing CRE have since spread globally, including into the community in developing countries,1 although long-term reduction in incidence has been achieved in regions inwhich aggressivemultimodal interventions were introduced early after CRE emergence.4 Carbapenem resistance canbedue tomechanismsother than carbapenemase production; however, CRE that do not produce a carbapenemase are of lesser epidemiological importance because these organisms have not demonstrated the same potential for rapid transmission and regional spread.1 In this issueof JAMA,Guhandcolleagues5 reportonacritical step toward control of CRE in theUnited States. The investigators conducted active, laboratory-based surveillance through the US Centers for Disease Control and Prevention (CDC) Emerging Infections Program (EIP) Multi-site Gramnegative Surveillance Initiative. Threemetropolitan EIP sites (inGeorgia,Minnesota, andOregon) participated in 2012, and 4 additional sites (in Colorado, Maryland, New Mexico, and New York) joined in 2013, covering a total population of 13.2 million. All incident cases underwentmedical record review. Standardized incidence ratios adjusted for age and race were calculated for each catchment area to facilitate comparisons between sites. The result is the most comprehensive evaluation to date of the burden of CRE in the United States. As Guh et al5 report, during 2012-2013, 599 incident CRE caseswereidentifiedin481individualsacrossthe7EIPsites,with CREdetectedinurinein520casesandinbloodin68cases.Overall, 51 patients (9.0%) with incident CRE infection died. These findings suggest both bad news and perhaps some good news. The bad news is that CREwere identified in every surveillance site in theMulti-site Gram-negative Surveillance Initiative network (rangeofstandardized incidenceratiosper 100 000population, 0.35 [95%CI, 0.14-0.74] in 2012 in Oregon to 4.80 [95% CI,3.89-5.85] in2013 inMaryland),with incidencerates insome regionshighenoughtosuggest thatCREareendemic.Thegood newsis thatevenintheregionwiththehighestnumberofcases, the estimated crude incidence rate of CRE was relatively low (4.68per 100 000population inGeorgia). Theoverall crude incidence rate of CRE in the network was estimated at 2.93 per 100 000. As noted by the authors, this rate ismuch lower than population-based estimates for established health care– associated pathogens, such as methicillin-resistant Staphylococcus aureus (25.1 per 100 000) or Clostridium difficile (147.2 per100 000),andsuggeststhat interventionsimplementednow to control CRE could have a sizeable effect.4,6 ThestudybyGuhetal reliedondatageneratedbylocalclinical laboratories, which resulted in some limitations. For instance, because knowledge of the mechanism of carbapenem resistance is not needed for treatment decisions, clinical laboratories usually do not characterize themechanism of carbapenem resistance in CRE, thus, it was not known for most isolates. Susceptibility testing methods likely differed among laboratories, and the accuracy of laboratory results could not be guaranteed. Not all commercial laboratories in catchment areasparticipated in surveillance,whichcouldhave resulted in incomplete case ascertainment. Inaboutone-thirdofcases, isolateswereavailableandanalyzed in a CDC laboratory. The only carbapenemase detected was K pneumoniae carbapenemase (90/188 isolates; 47.9% [95% CI, 40.6%-55.1%]), but this percentage may not be representativebecause thesampleof isolateswasnot random. Ideally, so that themost effective infectionpreventionefforts can be instituted, the specific mechanism of carbapenem resistance inCREshouldbedetermined,particularlywhenCREare Related article page 1479 Opinion