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CP-CRE carriers infected with different genotype face sixfold greater mortality risk

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January 17, 2019

Researchers found that patients colonized with carbapenem-producing carbapenem-resistant Enterobacteriaceae, or CP-CRE, who are subsequently infected with a different CP-CRE genotype are at a six times higher risk for dying.

“Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging threat to health care communities globally, with an increase in health care burden and costs,” Wen Kai Chen, MBBS, MPH, of the department of epidemiology at Singapore General Hospital, and colleagues wrote. “Resistance to carbapenems is a result of two main mechanisms — firstly through the production of extended-spectrum beta-lactamases and/or Amp C cephalosporinase combined with altered membrane permeability or secondly through the production of carbapenemase.”

According to Chen and colleagues, patients infected with CP-CRE can introduce the bacteria to the hospital, causing contamination that could lead to subsequent spread to other patients and suggesting the possibility that patients with CP-CRE are infected with CP-CRE carrying another type of carbapenemase gene.

Using data collected from January 2012 through December 2016, Chen and colleagues conducted a small retrospective cohort study to determine whether CP-CRE carriers who developed infection with another genotype had a higher risk for mortality. They analyzed clinical isolates of CP-CRE in patients who had developed an infection during their hospital stay and compared CP-CRE carriers who developed clinical isolates of another genotype with those whose clinical isolates were the same genotype that they originally had.

In total, 73 CP-CRE carriers who developed infections were included. Findings showed that 15.4% (n = 10) of the carriers who developed an infection with isolates of the same CP-CRE genotype died after 14 days, whereas 62.5% (n = 5) of the patients who developed an infection with clinical isolates of a different genotype died after 14 days (adjusted RR = 6.36; 95% CI, 1.75-23.06).

“We present the first finding of an increased mortality risk to CP-CRE carriers, when

infected by another genotype of CP-CRE,” the authors concluded. “We hope that our study would spur more research into this premise. We are also mindful that greater debate is needed, revolving around the ethics involved in balancing the public health importance of reducing CP-CRE transmission, vs. the increased individual mortality risk of the cohorted patient.” – by Caitlyn Stulpin

Disclosures: The authors report no relevant financial disclosures.

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This article demonstrates the complexity of the epidemiology of carbapenem-resistant organisms. In short, among patients colonized with CP-CRE, subsequent CP-CRE infections are not “created equal” with regard to clinical outcomes. Patients who had infections due to CP-CRE that were of a different carbapenemase genotype than their colonizing strain had a greater than sixfold increased risk for 14-day mortality than did patients with infections due to the same genotype as their colonizing strain. An important question that this study raises is whether “cohorting” of patients with CP-CRE is safe. Cohorting involves placing patients colonized with CP-CRE together on the same hospital unit and, in some cases, in the same room. This type of intervention is effective in decreasing CP-CRE spread to patients who are not colonized. However, this study raises the possibility that cohorting might place CP-CRE subjects at increased risk for becoming infected with a CP-CRE strain of a different genotype, and potentially at risk for poor clinical outcomes. Although the findings of this study alone are not strong enough (because of the its small size, retrospective nature, presence of notable potential residual clinical and molecular confounding) to deem the cohorting of patients with CP-CRE to be unsafe, the results are thought-provoking. A prospective study conducted in settings where cohorting of patients colonized with CP-CRE is in place (and possibly compared with settings where cohorting is not used) would be informative.

Keith S. Kaye, MD, MPH

Infectious Disease News Editorial Board member
Professor of internal medicine
Director of clinical research, division of infectious diseases
University of Michigan Medical School

Disclosure: Kaye reports no relevant financial disclosures.


Jason Burnham, MD

Carbapenemase production by Enterobacteriaceae is an infectious diseases nightmare. Carbapenemases can be transferred on mobile genetic elements to other commensal organisms, resulting in future carbapenem-resistant infections and spread of carbapenem resistance within and between patients. With few effective antibiotics remaining for these organisms, morbidity and mortality for these infections are high. The study by Chen and colleagues has important implications for contact precautions in patients with CRE infections. At present, many institutions already have protocols for permanent contact isolation for patients with CP-CRE infections. This study supports this practice. What it means for routine rectal screening to look for CP-CRE remains to be seen. The number of patients in the study by Chen and colleagues is small, and the CIs for increased mortality in patients with different genotypes of CP-CRE are wide, reinforcing that their findings need to be externally validated. Another unanswered question from this study is why a different genotype of CRE would be associated with increased mortality. The authors postulate that it is because of increased virulence, but this is conjecture and requires further testing.

Jason Burnham, MD

Instructor in medicine
Division of infectious diseases
Washington University School of Medicine

Disclosure: Burnham reports no relevant financial disclosures.