BacteriologyReal-world performance of a microarray-based rapid diagnostic for Gram-positive bloodstream infections and potential utility for antimicrobial stewardship
Introduction
Gram-positive bacteria account for over 50% of all nosocomial bloodstream infections in the United States, with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) accounting for roughly 25% of all isolates (Wisplinghoff et al., 2004). Overall mortality in patients with Gram-positive bacteremia ranges from 10% to 40%, with delays in effective antimicrobial therapy leading to a dramatic increase in mortality (Lautenbach et al., 1999, van Hal et al., 2012). Patients with Gram-positive bacteremia also often suffer from substantial long-term morbidity as a result of prolonged hospitalization and generalized deconditioning.
Relying exclusively on traditional microbiological techniques, final identification and antimicrobial susceptibility testing can take 2–3 days following Gram stain identification of a Gram-positive bacterial isolate. Patients with Gram-positive bacteremia are therefore often treated with broad-spectrum antimicrobial agents, such as vancomycin, until the final sensitivity results are known. While this strategy provides an antibiotic that is active against the most likely causative agents, patients with methicillin-susceptible S. aureus (MSSA) treated with vancomycin are known to have increased mortality in comparison to those treated with a β-lactam (Lodise et al., 2007, Stryjewski et al., 2007).
Rapid diagnostic tests (RDTs) are an increasingly common method by which clinical microbiology laboratories improve on the time delays associated with traditional culture methodologies. Additionally, hospital-based antimicrobial stewardship teams are able to utilize the results of RDTs to increase the efficacy of antibiotics, while minimizing toxicity and decreasing the overall cost of care (Goff et al., 2012, MacDougall and Polk, 2005). Several RDTs have entered routine clinical use, including matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), peptide nucleic acid fluorescence in situ hybridization, polymerase chain reaction (PCR), or other molecular-based tests. The Verigene Gram-positive blood culture (BC-GP) assay (Nanosphere, Northbrook, IL, USA) uses a microarray-based technology that allows for species-level identification and identification of resistance gene determinants for the most common clinically relevant Gram-positive bacteria, with a turnaround time of roughly 2.5 hours (Buchan et al., 2013). BC-GP includes targets for species-level identification of Enterococcus faecalis, Enterococcus faecium, S. aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus anginosus group, Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes as well as genus-level identification of other staphylococci, streptococci, and Listeria. Additionally, the panel detects the resistance genes mecA, vanA, and vanB. The ability of the BC-GP to supplement routine antimicrobial stewardship efforts is largely unknown. We performed a prospective cohort study to establish the real-world performance characteristics of BC-GP in comparison to routine clinical microbiological work-up and to establish the potential role of BC-GP in antimicrobial stewardship.
Section snippets
Patient identification and eligibility
Hospitalized patients with blood cultures submitted as part of routine clinical care to a 650-bed tertiary care hospital were eligible for inclusion in this study. All blood cultures with Gram stain identification of Gram-positive cocci between October and December 2013 were prospectively screened for eligibility. To be included in the study, patients were required to be inpatients aged >18 years of age at the time of screening. Patients were excluded from the study if they had previously been
Concordance of the BC-GP with routine clinical testing
A total of 143 patients with 155 organisms were included in the analysis, including 136 monomicrobial blood cultures and 7 polymicrobial cultures. A summary of the BC-GP results compared to conventional work-up for monomicrobial cultures is presented in Table 1 and polymicrobial cultures in Table 2. Organisms not present on the BC-GP panel but identified during the course of this study by routine laboratory methods included Micrococcus spp. (4, 2.5%), diphtheroids (3, 1.9%), Bacillus spp. (2,
Discussion
Rapid diagnostic testing dramatically decreases time to organism identification (Goff et al., 2012, van Belkum et al., 2013). Use of these tests is an increasingly important component of antimicrobial stewardship service and routine clinical microbiology (Perez et al., 2013). Studies evaluating the use of rapid diagnostic tests in patients with Gram-positive bacteremia have demonstrated consistent benefits in clinical outcomes and cost, primarily when combined with active antimicrobial
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2016, Diagnostic Microbiology and Infectious DiseaseCitation Excerpt :The immediate identification of the pathogen directly from a BC bottle should have a positive impact on targeting the antibiotic treatment within a shorter time (Aitken et al., 2015; Hill et al., 2014). Several recent studies have investigated the sensitivity and specificity of the Verigene tests, but only few reports evaluated them in the context of the development of treatment algorithms (Aitken et al., 2015; Alby et al., 2013; Hill et al., 2014; Roshdy et al., 2015). We have demonstrated that based on the local epidemiology of antibiotic resistances, Verigene results allow the recommendation of a targeted therapy in the report to the clinician.