California labs commonly use outdated CRE detection practices

Many hospital laboratories in California are using outdated practices to detect carbapenem-resistant Enterobacteriaceae, or CRE, leading to false reports of susceptibility that could impact patient care and hinder the detection of outbreaks, researchers said.

CRE are difficult to treat due to a high level of resistance to antibiotics and may kill up to 50% of infected patients, leading the CDC to deem them “nightmare bacteria.” These organisms include Klebsiella spp. and Escherichia coli.

According to a study published in Clinical Infectious Diseases, among 128 hospital laboratories in California that responded to a voluntary survey about their testing practices, 28% reported using outdated minimum inhibitory concentration (MIC) breakpoints for CREs.

In June 2010, when the Clinical and Laboratory Standards Institute (CLSI) issued updated breakpoints for CREs, the Infectious Diseases Society of America encouraged members to review them, “assess their impact on patient management, and work with the laboratory to implement” them for optimal treatment of patients.

According to James A. McKinnell, MD, infectious disease specialist at LA BioMed and assistant professor of medicine at the David Geffen School of Medicine at UCLA, and colleagues, one of the causes of carbapenem resistance among Enterobacteriaceae may be the presence of a carbapenemase enzyme that can hydrolyze the antibiotics. Most labs that did in-house testing for carbapenemase reported using the Modified Hodge Test, which McKinnell and colleagues said is associated with “significant performance issues,” including false-negative and false-positive results.

The spread of carbapenemase-producing CRE (CP-CRE) — a more virulent form of the bacteria — is thought to be driven by the movement of patients through the health care system.

“Failure to implement the current breakpoints has potential to not only negatively impact patient care, but also impede infection control and public health endeavors to limit the spread of these organisms,” McKinnell and colleagues wrote.

In the fall of 2015 and spring of 2016, McKinnell and colleagues surveyed 392 hospitals and long-term acute-care hospitals in California using online software. They received responses from 264 hospitals that used a total of 129 laboratories between them. Among the 129 labs, 72% said they were using current CLSI carbapenem breakpoints for Enterobacteriaceae, McKinnell and colleagues reported. It took them an average of 41 months for these labs to implement the breakpoints.

McKinnell and colleagues also examined MIC results from 237 CP-CRE isolates that were tested by a UCLA lab between 2013 and 2015 to determine their susceptibility as measured by outdated vs. current breakpoints. According to the results, using old breakpoints resulted in susceptibility rates of 8.9%, 18.6% and 18.6% to Invanz (ertapenem, Merck), imipenem and meropenem, respectively, whereas using current breakpoints resulted in susceptibility rates of less than 1% to ertapenem or imipenem and 2.6% to meropenem. K. pneumonia carbapenemase (KPC) were the most common carbapenemase encountered, accounting for 88% of the UCLA isolates, McKinnell and colleagues reported.

“Laboratories and clinicians need to understand the implications of not using current CLSI breakpoints, which in our study would have resulted in up to 20% of KPCs being categorized as falsely meropenem susceptible,” they wrote. “Such miscategorization could lead to administration of inappropriate antibiotics and subsequent poor patient outcomes, as well as undetected spread of CRE. Regulatory agencies need to develop a more streamlined process for [antimicrobial susceptibility test] manufacturers that allow them and clinical microbiology laboratories to rapidly adopt new breakpoints.” – by Gerard Gallagher

References:

Humphries RM, et al. Clin Infect Dis. 2017;doi:10.1093/cid/cix942.

IDSA. Alert: antimicrobial susceptibility testing. 2010. http://www.idsociety.org/Topics_of_Interest/Antimicrobial_Resistance/Professionals/Antimicrobial_Susceptibility_Testing/. Accessed November 10, 2017.

Disclosures: McKinnell reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.