Abstract and Introduction
Abstract
Objective To summarize evidence for the diagnostic accuracy of procalcitonin (PCT) tests for identifying secondary bacterial infections in patients with influenza.
Methods Major databases, including MEDLINE, EMBASE, and the Cochrane Library, were searched for studies published between January 1966 and May 2009 that evaluated PCT as a marker for diagnosing bacterial infections in patients with influenza infections and that provided sufficient data to construct two-by-two tables.
Results Six studies were selected that included 137 cases with bacterial coinfection and 381 cases without coinfection. The area under a summary ROC curve was 0·68 (95% CI: 0·64–0·72). The overall sensitivity and specificity estimates for PCT tests were 0·84 (95% CI: 0·75–0·90) and 0·64 (95% CI: 0·58–0·69), respectively. These studies reported heterogeneous sensitivity estimates ranging from 0·74 to 1·0. The positive likelihood ratio for PCT (LR+ = 2·31; 95% CI: 1·93–2·78) was not sufficiently high for its use as a rule-in diagnostic tool, while its negative likelihood ratio was reasonably low for its use as a rule-out diagnostic tool (LR− = 0·26; 95% CI: 0·17–0·40).
Conclusions Procalcitonin tests have a high sensitivity, particularly for ICU patients, but a low specificity for identifying secondary bacterial infections among patients with influenza. Because of its suboptimal positive likelihood ratio and good negative likelihood ratio, it can be used as a suitable rule-out test but cannot be used as a standalone rule-in test.
Introduction
Coinfections with bacterial pathogens in patients with influenza pneumonia have been well documented for the 1918–19 influenza pandemic and have been shown to be a major cause of influenza-related deaths. Post-mortem autopsies uniformly showed severe pathological changes compatible with bacterial pneumonia in patients who had died from influenza in 1918. In the spring of 2009, a novel influenza A virus (H1N1) of swine origin was identified in the USA and Mexico, which rapidly led to a worldwide pandemic. During this pandemic, the incidence of bacterial coinfections was estimated to be 20–30%. However, owing to the poor sensitivities of culture methods to identify respiratory bacterial etiologies, this figure may well have been an underestimate.
The early identification of secondary bacterial infections among patients with influenza infections may enable the early administration of antibiotics and, possibly, improve patient outcomes. However, clinical variables, such as patient characteristics, chest radiographic findings, or routine laboratory results, are unreliable for distinguishing between viral and bacterial lower respiratory tract infection, which may coexist influenza.
Procalcitonin (PCT) is a precursor protein of calcitonin whose production is stimulated by endotoxin and pro-inflammatory cytokines, such as interleukin-one beta and tumor necrosis factor-alpha. Unlike C-reactive protein (CRP), PCT production is inhibited by interferon-gamma, a cytokine that is produced during viral infections. Because of this characteristic, PCT has been shown to differentiate between bacterial and viral infections in many pediatric studies. Recently, several studies have examined its ability to differentiate influenza pneumonia from mixed bacterial and viral infections. However, the relatively small sample sizes in these studies have limited its generalizability.
The aim of our study was to systemically review and qualitatively summarize the current evidence for the diagnostic role of PCT in discriminating between viral and mixed pneumonia among patients with influenza infections.