The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care

Kaul, Karen L.; Sabatini, Linda M.; Tsongalis, Gregory J.; Caliendo, Angela M.; Olsen, Randall J.; Ashwood, Edward R.; Bale, Sherri; Benirschke, Robert; Carlow, Dean; Funke, Birgit H.; Grody, Wayne W.; Hayden, Randall T.; Hegde, Madhuri; Lyon, Elaine; Murata, Kazunori; Pessin, Melissa; Press, Richard D.; Thomson, Richard B.

Antimicrobial susceptibility testing, used to determine whether antibiotic treatment will be successful, is an essential component of the microbiology culture report. Emerging resistance among pathogenic bacteria and new antimicrobial agents require frequent updates to both testing methods and interpretation of the results. Most laboratories use automated instruments to perform minimal inhibitory concentration (MIC) testing to determine whether a patient's isolated bacteria are susceptible, susceptible dose dependent, intermediate, or resistant to a panel of antibiotics. These interpretations are based on FDA breakpoint criteria published at the time of drug approval and periodically updated to respond to the appearance of new resistance mechanisms. 169 The FDA also clears automated instrumentation used to determine MIC values (via the 510k process). 170 Although the MIC testing process may not be changed, new breakpoints added to the instrument software require a revised 510k application. Because the FDA does not have the authority to require manufacturers to submit data for revised breakpoints within a specified time frame, manufacturers may elect to use outdated breakpoints rather than face the expense of a 510K resubmission. A recent example was the 3year delay between the release of updated breakpoints for diagnosing carbapenem-resistant Enterobacteriaceae in 2010 and the ability to use these breakpoints in the clinical laboratory. This delay was used to calculate the potential for additional carriers of multidrug-resistant Enterobacteriaceae in Southern California health-care systems. As many as 1821 additional carriers of MDRO Enterobacteriaceae were estimated to have occurred in Orange County, California because of this delay. 171 The disastrous spread of MDRO Enterobacteriaceae can be mitigated by laboratories validating testing methods that enable use of updated antimicrobial breakpoint interpretations before FDA-cleared testing is available. Specifically, modifying a manufacturer's instructions, including interpreting MIC results using a revised breakpoint other than that listed in the product insert, is a change that renders the procedure an LDP. Without the option of using an LDP, one is left reporting outdated interpretations that miss resistant strains leading to unacceptable patient care.