Impact of Non-FDA-Approved CLSI Breakpoint Criteria on Laboratory Carbapenem-Resistant Enterobacteriaceae Detection Practices: A State-Wide Assessment

BACKGROUND: Infections due to carbapenem-resistant Enterobacteriaceae (CRE) are associated with high mortality. In 2012, CDC released guidance to help states understand the extent of unrecognized CRE and to control their spread. Surveillance, control, and public reporting efforts will require accurate laboratory CRE detection. Rhode Island surveyed the state's clinical microbiology laboratories to assess current CRE detection practices in the context of new Clinical and Laboratory Standards Institute (CLSI) breakpoints for identification, which were not yet approved by the Food and Drug Administration (FDA).

METHODS: In the summer of 2012, the Rhode Island Department of Health and its Healthcare-Acquired Infection Advisory Subcommittee sent a 20-item questionnaire electronically to the 11 clinical microbiology laboratory supervisors representing all of the state’s 12 acute-care facilities, one acute and long-term facility with psychiatric services, and one commercial laboratory that serves the majority of the state’s long-term care facilities. The questionnaire assessed carbapenem breakpoints, use of a Modified Hodge Test and other secondary testing methods, susceptibility testing verification studies and barriers to conducting them, as well as methods of reporting CRE.

RESULTS: The response rate was 100%. All respondents reported that their laboratories detected at most one CRE each month, despite varying numbers of Modified Hodge Tests performed monthly (range 1-68). Only two respondents (18%) reported documenting intermediate resistance as “non-susceptible.” When CRE was detected, 91% of respondents reported flagging the patient’s chart and informing the facility infection control department. Among the laboratories that tested meropenem, imipenem, or ertapenem susceptibilities, none of the laboratory supervisors reported using the new CLSI breakpoint recommendations in their initial susceptibility testing. None of the laboratories tested doripenem susceptibility. Although 27% of respondents reported interest in conducting the necessary verification studies to modify their automated antibiotic susceptibility testing (AST) system to accommodate the newest breakpoints, none have conducted the verification studies or modified their existing systems. All respondents reported preferring to wait until manufacturers update their AST system breakpoints after the FDA accepts the newest CLSI breakpoints for carbapenems.

CONCLUSIONS: Our findings reveal high testing practice variability and raise concern for undetected CRE, as none of the laboratory supervisors in Rhode Island reported using the current CLSI breakpoints. Given the cost burden to perform the necessary verification study to modify automated AST systems, until the FDA approves the new CLSI breakpoints for manufacturers, inadequate CRE surveillance and control remains a risk, and hinders the potential to develop facility-level public reporting using standardized CRE testing methods.