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Dutta et al1 reported impressive results using universal primer 16S rRNA polymerase chain reaction (PCR) to diagnose sepsis among 242 patients in a level III neonatal intensive care unit (NICU). However, because 2 of 52 bacteremic patients (4%) had falsely negative results, DeCamp et al,2 in the accompanying commentary, were unenthusiastic, concluding that “universal PCR is still not accurate enough to justify withholding antibiotic therapy in neonates being evaluated for sepsis.”
We believe DeCamp and colleagues' conclusion may be too pessimistic. In the NICU setting of the study by Dutta et al, the pretest probability of sepsis was 21.5% and a negative test (likelihood ratio, 0.04) reduced the probability of sepsis to about 1.1%. One could argue that it is worth treating at least 100 patients with antibiotics for each one who really needs them; therefore, in a NICU setting with such a high pretest probability of sepsis, the conclusion that the test is not sensitive enough to affect management is reasonable. However, in a normal newborn nursery setting, the pretest probability of sepsis among infants being evaluated with a complete blood count and blood culture is much lower—about 1% in those with risk factors but no symptoms.3 - 4 If the PCR test performs as well in these low-risk infants as in the study of Dutta et al (which seems a reasonable assumption), then a negative result would reduce the probability from 1% to about 0.04% (ie, 1 in 2500), a level at which observation, rather than empirical antibiotics, is a reasonable option. On the other hand, a positive result (likelihood ratio, 26.1) would lead to a posttest probability of 21%, which surely is high enough to start treatment.
The general point is that whether the result of a test should affect management decisions depends not on the sensitivity or specificity of the test, but on the posttest probability, which in turn depends on the pretest probability. The closer the patient's pretest probability is to the treatment threshold, the more likely a diagnostic test is to affect management decisions.5 If the PCR test described by Dutta et al can be made rapid and inexpensive, it could be very useful in a setting where the pretest probability of sepsis is low.
Correspondence: Dr Newman, Departments of Epidemiology & Biostatistics and Pediatrics, University of California–San Francisco, 185 Berry St, Lobby 5, Ste 5700, San Francisco, CA 94107-1762 (newman@epi.ucsf.edu).
Author Contributions:Study concept and design: Newman and Kohn. Drafting of the manuscript: Newman. Critical revision of the manuscript for important intellectual content: Kohn. Statistical analysis: Newman.
Financial Disclosure: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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