N ucleic acid amplification testing (NAAT) for viral etiologies of central nervous system (CNS) infections provides rapid diagnosis for optimization of therapy (1, 2). However, this testing can be costly and may not always be used judiciously (3). In this era of cost containment, with a growing emphasis on the optimal use of diagnostic tests (4-8), we assessed ordering practices for viral NAAT with cerebrospinal fluid (CSF) specimens. Our objective was to develop criteria to reduce unnecessary testing.Herpes simplex virus 1 (HSV-1) is the most common treatable cause of viral encephalitis (9), while three of the most commonly identified causes of aseptic meningitis are herpes simplex virus 2 (HSV-2), varicella-zoster virus (VZV), and enteroviruses (EV) (10, 11). In addition, cytomegalovirus (CMV) infections of the CNS may be of clinical concern among immunocompromised individuals (12). NAAT has become the gold standard for diagnosis of most viral CNS infections (1, 2).Viral CSF NAAT has several important benefits. First, early diagnosis enables adequate administration of antiviral treatment for HSV-1/2, VZV, and CMV, if necessary. Second, while no targeted EV therapies currently exist, utilization of NAAT for EV diagnosis has been correlated with reductions in length of stay, ancillary testing, antibiotic utilization, and costs in pediatric populations (13, 14). However, utilization of viral NAAT assays in cases with low pretest probability may unnecessarily increase costs while decreasing the positive predictive value of the testing (13, 15). Several previous studies evaluated the implementation of laboratory screening criteria to reduce superfluous CSF NAAT for HSV-1/2 (16, 17). However, those studies were restricted to HSV-1/2 and had limited sample sizes.Herein we describe a retrospective study of nearly 11,000 CSF NAAT assays and we propose screening criteria for HSV-1/2, VZV, CMV, and EV testing. Using data from 2008 to 2012, we identified CSF characteristics with very high negative predictive values for HSV-1/2, VZV, CMV, and EV. We then retrospectively applied those screening criteria to CSF requests for a 1-year period (2013), to assess the cost savings and impact of the proposed algorithm. Finally, we describe the impact of implementation of the acceptance criteria described herein.(This work was presented in part at the 49th Annual Meeting of the Academy of Clinical Laboratory Physicians and Scientists, San Francisco, CA, May 30, 2014.)
MATERIALS AND METHODSStudy overview. Barnes-Jewish Hospital (BJH) is an urban, adult, tertiary care hospital in St. Louis, MO. Data on all HSV-1/2, VZV, CMV, and EV NAAT studies ordered at BJH between January 1, 2008, and December 31, 2013, were obtained from the laboratory information system. Data on laboratory CSF characteristics and immune status were collected for all subjects with positive NAAT results and either twice as many randomly selected subjects with negative results (2008-2012 cohort) or 10% of all subjects with negative results (2013 cohort). Subjects wi...