Clinical Utility of Molecular Tests for Guiding Therapeutic Decisions in Bloodstream Staphylococcal Infections: A Meta-Analysis

Abstract

Background: Treatment of bloodstream staphylococcal infections (BSI) necessitates the prompt initiation of appropriate antimicrobial agents and the rapid de-escalation of excessive broad-spectrum coverage to reduce the risk of mortality. We, therefore, aimed to demonstrate the diagnostic accuracy of nucleic acid amplification tests (NAAT) for the identification of methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) in clinically suspected patients.Methods: Until November 23, 2020, databases including PubMed, Scopus, Embase, and Web of Science were scanned for eligible studies. A bivariate random-effects model was used for meta-analysis of the 33 included studies obtained from 1606 citations, and pooled summary estimates with 95% confidence intervals (CI) were generated.Results: Twenty-three studies (n = 8,547) assessed NAAT accuracy for MSSA detection, while three studies (n = 479) evaluated MRSA detection in adults. The pooled NAAT sensitivity and specificity for MRSA in adults was higher [sensitivity: 0.83 (95% CI 0.59–0.96), specificity: 0.99 (95% CI 0.98–1.0)] as compared to MSSA [sensitivity: 0.76 (95% CI 0.69–0.82), specificity: 0.98 (95% CI 0.98–0.99)]. Similarly, eight studies (n = 4,089) investigating MSSA in pediatric population reported higher NAAT accuracy [sensitivity: 0.89 (95% CI 0.76–0.96), specificity: 0.98 (95% CI 0.97–0.98)] compared to adults. Among NAA tests, SeptiFast (real-time PCR, commercial) was frequently applied, and its diagnostic accuracy corresponded well to the overall summary estimates. A meta-regression and subgroup analysis of study design, sample condition, and patient selection method could not explain the heterogeneity (P > 0.05) in the diagnostic efficiency.Conclusions: NAAT could be applied as the preferred initial tests for timely diagnosis and BSI management.

Molecular Tools for Guiding Therapy in Patients With Staphylococcal Bone and Joint Infections: A Diagnostic Test Accuracy Meta-analysis

“…Since it gives fast results and can identify dead microbes, we suggest utilizing NAAT in principle to diagnose staphylococcal BJI. In comparison to previously published systematic reviews, we found that the metaanalysis by Chen et al reported on the greater diagnostic value of NAAT for staphylococcal strains in LRT specimens (22) and blood specimens (23), which is consistent with the findings of this study. However, these reviews focused solely on the detection of MSSA or MRSA in fluids other than osteoarticular samples.…”

“…Previously, a few studies showed that NAAT was accurate in the diagnosis of staphylococcal pneumonia and pediatric sepsis ( 22 , 23 ); however, to the best of our knowledge, there is no published information on the functioning of the NAAT test for the identification of pathogens in BJI. NAAT, which usually have a faster reaction time and are unaffected by antibiotic exposure, may assist in the development of an etiological diagnosis to help guide patient treatment.…”

Clinical Relevance of Xpert MRSA/SA in Guiding Therapeutic Decisions for Staphylococcal Infections: A Diagnostic Test Accuracy Analysis

“…Applicability concern in the patients’ selection domain was not a concern as all publications used samples from patients with possible infections, signaling a low risk of bias. Regarding index tests, all studies did not report about blinding of index tests except for three studies [ 65 – 67 ]; therefore, the risk of bias in the index test domain was considered unclear. The index test's applicability for all studies was considered unclear since there is not a globally accepted test methodology.…”

Development of a Multiplex Polymerase Chain Reaction-Based DNA Lateral Flow Assay as a Point-of-Care Diagnostic for Fast and Simultaneous Detection of MRSA and Vancomycin Resistance in Bacteremia

“…This may alter the patient’s microbiome leading to opportunistic infections, subject the patient to drug-related toxicity, and increase the cost of hospitalization. In addition, improper antibiotic use can select for resistant strains [ 28 , 51 ]. Using the developed MBDLFA on DNA extracted from positive blood cultures will also save the time required for traditional testing of MRSA and vancomycin resistance.…”

“…Quantitative real-time PCR helps better interpret positive results, as the low abundance of bacteria usually characterizes contamination [ 28 ]. It is always a good practice to make parallel use of blood culture as the gold-standard method for diagnosis of bacteremia with PCR-based assays [ 51 ]. This will allow for the rapid detection of bacteremia with a high blood bacterial load and commencement of proper treatment within the first 2 h of sampling.…”