Background: Microbial cultures for diagnosis of neonatal sepsis suffer from low sensitivity and reporting delay. Advances in molecular microbiology have fostered new molecular assays that are rapid and may improve neonatal outcomes.
Objectives: We assessed whether molecular assays have sufficient sensitivity (>0.98) and specificity (>0.95) to replace microbial cultures in the diagnosis of neonatal sepsis and explored heterogeneity by use of subgroup analyses based on the type of assay, gestational age of the neonate, and type of sepsis onset.
Methods: We performed the systematic review as recommended by the Cochrane Diagnostic Test Accuracy Working Group. Electronic bibliographic databases, conference abstracts, personal files, and reference lists of identified articles were searched. We included studies of case-control or consecutive series design, which evaluated molecular assays (index test) in neonates with suspected sepsis (participants) in comparison with microbial cultures (reference standard). Two reviewers independently assessed the methodologic quality of the studies and extracted data.
Results: A bivariate random-effects model was used for meta-analysis of the 23 included studies, and summary estimates of sensitivity and specificity with 95% confidence intervals (CIs) were generated. Mean sensitivity and specificity were 0.90 (95% CI: 0.78-0.95) and 0.96 (95% CI: 0.94-0.97), respectively. Real-time polymerase chain reaction (PCR) and broad-range conventional PCR had higher sensitivity and specificity than other assays. Sufficient data were not available to evaluate gestational-age and sepsis-type subgroups.
Conclusion: Molecular assays do not have sufficient sensitivity to replace microbial cultures in the diagnosis of neonatal sepsis but may perform well as "add-on" tests.