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Recent Insights in Understanding the Clinical Impact and Burden of Carbapenem-Resistant Enterobacteriaceae

Since 2000, there has been an increase in the rate of carbapenem- resistant Enterobacteriaceae (CRE) in the United States (US). CRE are resistant to a majority of first and second-line antibiotics, sometimes forcing healthcare providers to use last-line therapies that are often toxic, poorly efficacious, or both. 


There has been a steady increase in CRE prevalence, with emergence due, in part, to increased use of carbapenems for the treatment of infections caused by extended spectrum ß-lactamase–producing Enterobacteriaceae.1,2 By 2011, the percentage of Enterobacteriaceae that was not susceptible to at least one carbapenem had risen to 4.2%, with the greatest increase observed among Klebsiella pneumoniae (1.6 to 10.4%).3 The most widely disseminated CRE in the United States are Klebsiella pneumoniae carbapenemase (KPC) producers whereas metallo-ß-lactamase producers remain localized and are often associated with outbreaks.4
In 2013, the Centers for Disease Control and Prevention (CDC) characterized CRE as an urgent threat to public health. Although the CDC cited 9000 infections caused by CRE in the United States annually, and 600 deaths, there was acknowledgement that this assessment is likely an underestimate. These estimates were derived from healthcare-associated infections (HAIs) reported as part of a 2011 Emerging Infections Program (EIP) survey of 11,282 patients in 10 states. Estimates of carbapenem resistance were derived from the National Healthcare Safety Network to predict the number of HAIs due to CRE. Infections occurring outside of acute care hospitals (ACHs) or diagnosed after discharge, as well as infections caused by Enterobacteriaceae other than Klebsiella spp. and Escherichia coli, were not included in this analysis.5
A report by Reuters indicated that due to the small sample size of the EIP survey and the methodology utilized for the 2013 report, the actual estimate of annual death from CRE could be up to twice the current estimate. Upon further collaboration and investigation with the CDC’s National Center for Health Statistics’ Division of Vital Statistics, Reuters predicted that more than 180,000 annual deaths are due to drug-resistant infections overall, compared with the original CDC estimate of 23,000. This new prediction may also be an underestimate due to lack of documentation on death certificates and lack of a unified surveillance system for drug-resistant infections.5,6
A recent estimate of the national prevalence of CRE infections in both the acute care and ambulatory settings was reported at IDWeek 2016 in New Orleans, using a Becton Dickinson & Company (BD) database. Susceptibility data from nonduplicate E. coli, K. pneumoniae, and Proteus mirabilis isolates were reported from 348 hospitals in the United States over one year (2015-2016) and statistical methods were applied to estimate national prevalence.
Although the rate of CRE in this report was 0.7%, the rate ranged from 0.5% in the ambulatory setting to 1.9% in the hospital-onset period. The estimated national prevalence of CRE infections was 53,724, almost 6 times greater than the CDC estimate, and 57% of cases occurred in the ambulatory setting.7 To add to the mounting evidence of CRE in the ambulatory setting, a regional antibiogram from Los Angeles County encompassing 61 acute-care hospitals (ACH) and 9 long-term acute care (LTAC) hospitals determined the incidences of carbapenem-resistant Klebsiella spp. to be approximately 21% and 71% in ACH and LTACs, respectively.8 Despite these reports, the true prevalence of CRE in the United States might be higher due to a lack of implementation of the 2010 revised Clinical Laboratory Standards Institute breakpoints for carbapenems and Enterobacteriaceae.9

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