Bacteriology
Value of serum procalcitonin, neopterin, and C-reactive protein in differentiating bacterial from viral etiologies in patients presenting with lower respiratory tract infections

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Abstract

The values of procalcitonin (PCT), neopterin, and C-reactive protein (CRP) alone and in combination to differentiate bacterial from viral etiology in patients with lower respiratory tract infections (LRTIs) were evaluated. Sera obtained on the day of hospitalization for LRTI from 139 patients with confirmed bacterial etiology and 128 patients with viral etiology were examined. A further 146 sera from healthy Chinese subjects with no infection were included as controls. The area under the receiver operating characteristic (ROC) curve (area under curve [AUC]) for distinguishing bacterial from viral infections was 0.838 for CRP and 0.770 for PCT (P < 0.05). The AUC for distinguishing viral from bacterial infections was 0.832 for neopterin (P < 0.05). When the markers were used in combination, AUC of ROC (CRP/neopterin) was 0.857, whereas (CRP × PCT)/neopterin was 0.856. Combination of 2 or all 3 of the biomarkers may improve the discriminatory power in delineating bacterial versus viral etiology in LRTI.

Introduction

Lower respiratory tract infections (LRTIs) account for a 6.9% global mortality (World Health Report, WHO 2004), drain already stretched health care resources, and can bring down a country's health service and economy. Differentiating viral from bacterial causes of LRTI is important so that, first, optimal treatment is started, second, inappropriate antibiotic treatment and subsequent resistance is prevented, and third, patients with mixed infection are not cohorted together.

Antibiotic resistance is a global concern, and strategies that use biomarkers to delineate bacterial from viral etiologies have been applied to aid more judicious use of antibiotics. Serum procalcitonin (PCT) is a marker of bacterial infection (Simon et al., 2004), and a newly developed assay (Kryptor PCT; BRAHMS, Hennigsdorf, Germany) has been introduced and used to guide the appropriate use of antibiotics in patients with LRTIs (Christ-Crain et al., 2004) and community-acquired pneumonia (CAP) (Christ-Crain et al., 2006). Prompt initiation of appropriate antibiotic therapy improves outcome, and a delay of more than 4 h in bacterial CAP has been associated with increased mortality (Meehan et al., 1997). The potential use of biomarker(s) to accurately include or exclude bacterial and viral infection will improve the management of LRTI.

In this study, we evaluated assays for PCT, neopterin, and C-reactive protein (CRP) alone and in combination to differentiate bacterial from viral causes of LRTI.

Section snippets

Patient subjects

Ethical approval was obtained to conduct a prospective study of consecutive patients admitted to the Prince of Wales Hospital (PWH), Hong Kong, through our emergency department with LRTI/CAP between January 1 and December 31, 2004. Sera were obtained from all patients on the day of hospitalization for suspected LRTI and were used for the evaluation of 3 markers: PCT, neopterin, and CRP. PWH is a 1350-bed teaching hospital and tertiary referral center for the New Territories of the Hong Kong

Patient characteristics

The mean age of the patients with LRTI in the 2 groups with bacterial and viral etiology was both 69.7 years (the range for the 2 groups was 20–103 years and 15–91 years, respectively), and the female-to-male ratio was 1:1.15. In thecontrol group, the mean age was 61.9 years (range, 19–91 years) with a female-to-male ratio of 3.1:1.

CRP, neopterin, and PCT levels

In patients with LRTI of bacterial etiology, serum CRPconcentrations were raised above the normal range (>10 mg/L) in 132 (95%) of 139 patients compared with 6

Discussion

This study shows that CRP >10 and PCT >0.1 may be used to rule in bacterial infection in 60% to 95% cases of bacterial infection, whereas neopterin >10 may be used to rule in viral infection in 97% cases. PCT is a reliable marker of sepsis as applied in the intensive care setting (Müller et al., 2000), and PCT has been shown to be sensitive and specific for differentiating bacterial from viral etiology in children admitted with CAP (Moulin et al., 2001). However, in adults with CAP, PCT was

Acknowledgment

The authors thank the Research Department of BRAHMS, Hennigsdorf, Berlin, and in.vent diagnostica, Hennigsdorf, Berlin, for donation of Neopterin ELISA kits and Kryptor PCT®. This study was supported in part by the Small Entrepreneur Research Assistance Programme (SERAP, S/P895/05B), and by Dr. George W.H. Cautherley of R&C Biogenius, Hong Kong.

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    CRP and PCT are the most frequently evaluated and indicative biomarkers for identifying bacterial infections in children because their levels are higher in bacterial infections than in viral infections [15,33–36]. Although CRP and PCT can be used with great accuracy to detect many pediatric infections such as pneumonia and meningitis [37–43], some studies have shown inconsistent results [44], and this undermines their reliability as a sole predictor. The large range of CRP values is especially a weakness with regard to differential diagnosis [14].

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