Infectious disease/original research
Procalcitonin Test in the Diagnosis of Bacteremia: A Meta-analysis

https://doi.org/10.1016/j.annemergmed.2006.10.020Get rights and content

Study objective

We seek to evaluate the diagnostic performance of the procalcitonin test for the diagnosis of bacteremia in the emergency department (ED) population.

Methods

We conducted a search of MEDLINE, bibliographies of previous systemic reviews, and pertinent national meeting research abstracts. We included studies that assessed the diagnostic accuracy of procalcitonin for bacteremia, with blood culture as the reference standard. We included prospective investigations of adults and children with suspected infection studied in the ED or at admission. Two authors independently extracted data and assessed study quality; consensus was reached by conference. The analysis was based on the I2 statistic for heterogeneity, unweighted summary receiver-operating characteristic curve, and random-effects pooled sensitivity and specificity across studies using the same test threshold.

Results

The search yielded 348 publications and 1 unpublished study. Seventeen studies met the inclusion criteria and provided a sample of 2,008 subjects. There was a substantial degree of inconsistency (I2=64%). The unweighted summary receiver-operating characteristic curve provided the best overall estimate of test performance, with an area under the curve of 0.84 (95% confidence interval [CI] 0.75 to 0.90). Sensitivity analysis based on study quality did not significantly change the results. Subgroup analysis including only studies that used a test threshold of 0.5 or 0.4 ng/mL yielded pooled estimates for sensitivity and specificity of 76% (95% CI 0.66 to 0.84) and 70% (95% CI 0.60 to 0.79), respectively.

Conclusion

We found the diagnostic performance of the procalcitonin test for identifying bacteremia in ED patients to be moderate. Future research designed to determine the utility of the procalcitonin test as a diagnostic tool used in isolation for detecting bacteremia in ambulatory patients is needed before widespread clinical use.

Introduction

Procalcitonin is a prohormone of calcitonin that was first reported to be present in increased levels in the blood of infected patients by Assicot et al.1 Since this sentinel report, numerous authors have investigated its role in differentiating and risk-stratifying infectious and noninfectious disease processes.2, 3 Despite extensive investigation, the procalcitonin test has not gained widespread use as a diagnostic tool in any patient population.4

The ability to accurately and rapidly identify patients with bacteremia is an important management issue for emergency physicians. One of the potential uses of the procalcitonin test in the emergency department (ED) is as a screening test for bacteremia. The availability of such a screening test would have utility in several clinical scenarios. A large area of potential utility is in the febrile pediatric population, particularly those at risk for occult bacteremia. Young children are often unable to localize their infection and the management, disposition, and prognosis all change according to the presence or absence of bacteremia.5, 6 In the adult population, approximately 50% of patients evaluated in the ED with undifferentiated hypotension or hypotension of uncertain cause are ultimately diagnosed with sepsis.7 Many of these patients will have normal body temperature and WBC counts, making the diagnosis even more nebulous.8 The importance of early detection in these cases is underscored by research documenting an unfavorable prognosis for adults with sepsis and bacteremia.9

At least 1 previous report asserted that a low serum procalcitonin level accurately rules out the diagnosis of bacteremia in adults.10 This meta-analysis evaluates the test characteristics of the procalcitonin test in the diagnosis of bacteremia in the ED setting.

Section snippets

Materials and Methods

The research question was, what is the diagnostic accuracy (eg, sensitivity and specificity) of the procalcitonin test in the diagnosis of bacteremia in the ambulatory population with suspected infection?

MEDLINE (January 1, 1970, through August 2005) was searched for English-language clinical studies assessing the diagnostic performance of procalcitonin test in the diagnosis of bacteremia. The search was updated in September 2006. The electronic search used the following terms or MeSH subject

Results

The comprehensive search yielded a total of 342 publications and 1 unpublished study. In the updated search (September 2006), 6 additional potentially relevant studies were identified, and after independent review they were all excluded (Figure 1 and Table 1).

After the relevance search (blinded interobserver agreement, κ=0.7), a complete article review was performed on the remaining 150 articles. Seventeen studies were included in the final analysis, providing a sample of 2,008 subjects (Han et

Limitations

Although our search was comprehensive, we did not search EMBASE or include foreign language studies.43, 44 Systematic reviews that include EMBASE and foreign language studies may yield slightly smaller estimates of effect for interventions; therefore, it is possible that our CIs are too small and our estimates of test performance are overly optimistic. Although we may have missed some articles, we used a comprehensive search using independent reviewers. Moreover, an updated search was completed

Discussion

This meta-analysis evaluates the test characteristics of the procalcitonin test in the diagnosis of bacteremia in ambulatory patients. Using pooled data from 17 studies comprising 2,008 subjects, we found the area under the summary receiver-operating characteristic to be 0.84, with the lower limit 95% CI of 0.75, indicating modest predictive ability of procalcitonin to diagnose bacteremia. Using the pooled sensitivity and specificity for the studies that used a test threshold of 0.5 or 0.4

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    Supervising editor: Brian H. Rowe, MD, MSc

    Author contributions: AEJ and JAK conceived and designed the study. AEJ, JFF, JJB and JAK collected the data. AEJ and MDB analyzed the data. AEJ drafted the article, and all authors contributed to the final manuscript. AEJ takes responsibility for the paper as a whole.

    Funding and support: The authors report this study did not receive any outside funding or support and there were no other conflicts of interest to declare. See the Manuscript Submission agreement form, published each month, for details of covered relationships.

    Available online December 11, 2006.

    Reprints not available from the authors.

    1

    Dr. Fiechtl is currently affiliated with the Department of Emergency Medicine, Vanderbilt University, Nashville, TN.

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