Peptide Nucleic Acid Fluorescent In Situ Hybridization for Hospital-Acquired Enterococcal Bacteremia: Delivering Earlier Effective Antimicrobial Therapy

Abstract

Hospital-acquired vancomycin-resistant enterococcal bacteremia has been associated with increased hospital costs, length of stay, and mortality. The peptide nucleic acid fluorescent in situ hybridization (PNA FISH) test for Enterococcus faecalis and other enterococci (EFOE) is a multicolor probe that differentiates E. faecalis from other enterococcal species within 3 h directly from blood cultures demonstrating gram-positive cocci in pairs and chains (GPCPC). A quasiexperimental study was performed over two consecutive years beginning in 2005 that identified GPCPC by conventional microbiological methods, and in 2006 PNA FISH was added with a treatment algorithm developed by the antimicrobial team (AMT). The primary outcome assessed was the time from blood culture draw to the implementation of effective antimicrobial therapy before and after PNA FISH. The severity of illness, patient location, and empirical antimicrobial therapy were measured. A total of 224 patients with hospital-acquired enterococcal bacteremia were evaluated, with 129 in the preintervention period and 95 in the PNA FISH period. PNA FISH identified E. faecalis 3 days earlier than conventional cultures (1.1 versus 4.1 days; P < 0.001). PNA FISH identified Enterococcus faecium a median 2.3 days earlier (1.1 versus 3.4 days; P < 0.001) and was associated with statistically significant reductions in the time to initiating effective therapy (1.3 versus 3.1 days; P < 0.001) and decreased 30-day mortality (26% versus 45%; P ‫؍‬ 0.04). The EFOE PNA FISH test in conjunction with an AMT treatment algorithm resulted in earlier initiation of appropriate empirical antimicrobial therapy for patients with hospital-acquired E. faecium bacteremia.Enterococcal bacteremia is the fourth most common cause of hospital-acquired bacteremia within the United States and the fifth most common in Europe according to the SENTRY antimicrobial surveillance program (2). The predominant enterococcal species that cause these infections are Enterococcus faecalis and Enterococcus faecium (28,38). Vancomycin-resistant enterococci (VRE) have emerged as a major problem and have progressively increased over the last decade. The most recent surveillance data from SENTRY showed that E. faecium resistance to vancomycin had increased from 40% to 61% in 2002, while the Surveillance and Control of Pathogens of Epidemiologic Importance survey also found 40% vancomycin-resistant E. faecium in 2002 (2, 38). At many tertiary-care medical centers, E. faecium is approaching nearly 100% vancomycin resistance (1,22,40). In contrast, E. faecalis has maintained susceptibility to ampicillin with a relatively small increase in vancomycin resistance (1, 37).

Clinical and laboratory considerations for the rapid detection of carbapenem-resistant Enterobacteriaceae

“…85 CDSSs can take many forms, including comprehensive computerized disease management systems that can integrate clinical data, medication orders, and laboratory and microbiology results to suggest anti-infective therapy and alert clinicians about potential suboptimal management of infections. [86][87][88][89] Several studies of rapid blood culture diagnostics report favorable outcomes when rapid test results are reported together with CDSSs that provide actionable guidance for clinicians through antimicrobial stewardship team oversight [90][91][92][93][94][95][96][97] or even templated comments contained within the result report. 84 Increasingly, electronic health records platforms such as Epic and Cerner are incorporating CDSSs to enhance antimicrobial stewardship.…”

Antibiotic Utilization Improvement with the Nanosphere Verigene Gram-Positive Blood Culture Assay

“…Overall, we found that patients in the post-BC-GP group obtained the fi rst dose of optimal antibiotics 19 hours faster; additionally, more of these patients received optimal antibiotics. Other studies have shown that rapid identifi cation of organisms in blood cultures has many benefi ts, such as faster time to optimal antimicrobials (5-7), decreased length of hospital stay (7), and decreased overall hospital costs (5,7,8).…”

AntibioDx

“…The results were ascribed to better effective therapy by ruling out the potential of contamination. Similarly, in patients with VRE bacteremia, Forrest et al showed that implementation of E. faecalis/OE PNA FISH™ (AdvanDx) reduced the time for switching from initial inadequate therapy (as reported by Ibrahim [3]) to targeted effective therapy from 3.1 to 1.3 days, thereby reducing the 30-day mortality rate from 45 to 26% [14]. Other studies have demonstrated that the use of a PNA FISH test for distinguishing C. albicans from non-C. albicans candidemia reduced antifungal costs by US$1700/patient without compromising patient safety by encouraging earlier de-escalation from broad-spectrum echinocandin to generic fluconazole for the treatment of C. albicans [15].…”