Dutta S, Narang A, Chakraborty A, Ray P. Diagnosis of neonatal sepsis using universal primer polymerase chain reaction before and after starting antibiotic drug therapy. Arch Pediatr Adolesc Med 2009;163:6-11.
Question
Among neonates with suspected sepsis, how accurate is a universal primer 16S rRNA gene polymerase chain reaction (PCR) for diagnosis of blood culture–positive neonatal sepsis before and after starting antibiotic drug therapy?
Design
Prospective study of diagnostic tests.
Setting
Level III neonatal intensive care unit.
Participants
Neonates with a fresh episode of clinically suspected sepsis were enrolled; those with major malformations, life expectancy less than 12 hours, or contaminated blood cultures were excluded.
Intervention
Before starting antibiotic drug therapy, PCR (0 hour), blood culture, and sepsis screening (complete blood cell counts, micro-erythrocyte sedimentation rate, and C-reactive protein level) were performed. The PCR was repeated 12, 24, and 48 hours after starting antibiotic drug therapy.
Outcomes
The primary outcomes were the sensitivity and specificity of 0-hour PCR for diagnosing blood culture-positive sepsis, and the secondary outcome was the proportion of 0-hour PCR-positive patients who remained positive after antibiotic drug therapy.
Main Results
Of 306 patients evaluated, 242 were included (mean [SD] gestation, 32.2 [3.1] weeks; and mean [SD] birth weight, 1529.2 [597.2] g). Blood culture was positive in 52 patients and 0-hour PCR in 57. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of PCR were 96.2%, 96.3%, 87.7%, 98.8%, 26.1, and 0.04, respectively. Two patients were blood culture positive but 0-hour PCR negative, whereas 7 were 0-hour PCR positive but blood culture negative. Of the patients in the 0-hour PCR-positive group, 7 remained positive at 12 hours and none at 24 and 48 hours after starting antibiotic drug therapy. In patients in the 0-hour PCR-positive group, no predictors of positive 12-hour PCR were identified.
Conclusions
Universal primer PCR can accurately diagnose neonatal sepsis before, but not after, antibiotic drugs are given.
Commentary
Blood culture remains an imperfect test for prompt and accurate diagnosis of neonatal sepsis. Universal PCR does not depend on bacterial viability, so the authors hypothesized it could identify sepsis in patients exposed to antibiotics with killed bacterial fragments present, but in whom blood culture results could be false negative. The study reports a positive likelihood ratio of 26.1 and a negative likelihood ratio of 0.04 for predicting and excluding sepsis, respectively, with universal PCR used in initial evaluation for sepsis in neonates not exposed to antibiotics. Both values are well beyond the commonly identified thresholds of 10 for ruling in and 0.1 for ruling out disease. Accuracy of universal PCR is greater than that of the commonly used diagnostic adjunct, C-reactive protein.1, 2 Still, the test did not identify all cases of culture-positive sepsis. Additionally, universal PCR was negative after antibiotic administration in nearly all neonates with sepsis. With the results of this study, universal PCR offers some clinical benefit over currently available tests that guide decision-making during initial sepsis evaluation in the neonatal intensive care unit. However, universal PCR cannot inform decision-making when sepsis evaluation is compromised by antibiotic exposure, arguably the clinical situation for which a discriminating test would be more useful.
References
1. 1Malik A, Hui CP, Pennie RA, Kirpalani H. Beyond the complete blood cell count and C-reactive protein: a systematic review of modern diagnostic tests for neonatal sepsis. Arch Pediatr Adolesc Med. 2003;157:511–516. MEDLINE |
CrossRef
2. 2Fowlie PW, Schmidt B. Diagnostic tests for bacterial infections from birth to 90 days-a systematic review. Arch Dis Child Fetal Neonatal Ed. 1998;78:F92–F98. MEDLINE |
CrossRef
University of Michigan, Robert Wood Johnson Clinical Scholars Program, Ann Arbor, Michigan
FULL TEXT