4: The Lack of Utility of Acute Phase Reactant Testing for Predicting Occult Bacteremia In the Well-Appearing Febrile Infant: A Meta-Analysis and Bayesian Evaluation of Hematologic Testing In the Vaccine Era

Article Outline

• Study Objectives
• Methods
• Results
• Conclusions
• Copyright

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Study Objectives 

The diagnosis and treatment of occult bacteremia (OB) in the well-appearing febrile infant is commonly based on acute phase reactant (APR) testing including WBC (white blood cell count), ANC (absolute neutrophil count), CRP (c-reactive protein), and PCT (procalcitonin). The utility of such testing, as defined by predictive value, changes with disease prevalence. This prevalence has dramatically decreased over the last two decades following widespread use of the PCV and Hib vaccines.

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Methods 

We perfomed a meta-analysis of published OB prevalence data as well as hematologic, APR test sensitivities and specificities from studies evaluating febrile patients younger than 36 months for OB.

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Results 

The meta-analysis of applicable studies yields a prevalence of 0.38% (95% CI: 0.27% - 0.49%). Point estimates for APR sensitivities and specificities ranged from 77-86% and 57-78% respectively. Given the prevalence estimate produced by the meta-analysis the “best case scenario” negative and positive predictive values were 99.9% and 3% respectively. Our analysis found that for any increase in sensitivity beyond 50% the added negative predictive value was negligible. Additionally, to achieve even moderate positive predictive values, at this disease prevalence, specificity must exceed 99.75%.

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Conclusions 

A comparative mathematical analysis of these predictive values, adjusted for the declining prevalence, strongly suggests that APR testing no longer has clinically meaningful discriminatory value and should be abandoned. At the current rates of OB sensitivity has become irrelevant and required specificities are impossible to achieve with APRs. Continued over-testing and over-treatment has serious implications for medical resource utilization and increasing resistance rates.