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Molecular assays not accurate enough for definitive diagnosis of neonatal sepsis

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – The sensitivity of currently available PCR-based assays for diagnosing sepsis in newborns is not yet high enough to replace microbial cultures, according to the results of a meta-analysis reported in Pediatrics for October.

“However, molecular assays have a faster turnaround time and may perform well as add-on tests,” the authors suggest.

Dr. Mohan Pammi, with Texas Children’s Hospital and Baylor College of Medicine in Houston, and colleagues point out that while blood cultures are the standard for diagnosing neonatal bacteremia, sensitivity can be low and results may not be available for up to 72 hours. Molecular assays, on the other hand, can be completed in less than 12 hours and may have better sensitivity.

The authors performed a systematic review and meta-analysis of the literature to see if various molecular assays, based on polymerase chain reaction (PCR) amplification of targeted regions in the microbial genome, were sensitive and specific enough to replace cultures in the diagnosis of neonatal sepsis.

“We arbitrarily set minimum limits of sensitivity at 0.11197, considering that neonates with sepsis should not be missed, and specificity at 0.95 because false-positives and overtreatment are not life-threatening,” Dr. Pammi and colleagues explain.

They identified 23 studies that met inclusion criteria. Their meta-analysis of the pooled data gave an estimated mean sensitivity of 0.90 and a mean specificity of 0.96 for molecular assays, the investigators report.

Therefore, the accuracy of these assays is not sufficient to substitute for microbial cultures, they conclude. They calculate that, based on these numbers, in a theoretical cohort of 1000 VLBW infants, molecular assays would miss two cases of early-onset sepsis and 20 culture-positive cases of late-onset sepsis.

However, the authors point out, molecular assays may be useful as “add-on” tests. “Molecular assays may be performed concurrently with the gold standard (cultures). Results of molecular assays will be available in 6 to 8 hours and may contribute to the optimization of clinical therapy.”

And looking to the future, Dr. Pammi and colleagues conclude, “Advancement of technologies in molecular microbiology may bring about newer assays with sensitivity and specificity sufficient to replace microbial cultures in the diagnosis of neonatal sepsis.”

Reference:Molecular Assays in the Diagnosis of Neonatal Sepsis: A Systematic Review and Meta-analysis

Pediatrics 2011;128:e973–e985.