Original Contribution
C-reactive protein as predictor of bacterial infection among patients with an influenza-like illness,☆☆,

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Abstract

Objective

During the influenza season patients are labeled as having an influenza-like illness (ILI) which may be either a viral or bacterial infection. We hypothesize that C-reactive protein (CRP) levels among patients with ILI diagnosed with a bacterial infection will be higher than patients diagnosed with an influenza or another viral infection.

Methods

We enrolled a convenience sample of adults with ILI presenting to an urban academic emergency department from October to March during the 2008 to 2011 influenza seasons. Subjects had nasal aspirates for viral testing, and serum CRP. Bacterial infection was determined by positive blood cultures, radiographic evidence of pneumonia, or a discharge diagnosis of bacterial infection. Receiver operating characteristic curve, analysis of variance, and Student t test were used to analyze results.

Results

Over 3 influenza seasons there were 131 total patients analyzed (48 influenza infection, 42 other viral infection and 41 bacterial infection). CRP values were 25.65 mg/L (95% CI, 18.88-32.41) for influenza, 18.73 mg/L (95% CI, 12.97-24.49) for viral and 135.96 mg/L (95% CI, 99.38-172.54) for bacterial. There was a significant difference between the bacterial group, and both the influenza and other viral infection groups (P < .001). The receiver operating characteristic curve for CRP as a determinant of bacterial infection had an area under the curve of 0.978, whereby a CRP value of <20 had a sensitivity of 100% and >80 had a specificity of 100%.

Conclusion

C-reactive protein is both a sensitive and specific marker for bacterial infection in patients presenting with ILI during the influenza season.

Introduction

During the influenza season, there is a sharp increase in the number of patients presenting to the emergency department (ED) with respiratory complaints. However, the percentage of these patients with influenza infection varies anywhere from 5% to 35% [1]. The remainder of these patients are infected with another respiratory virus in circulation at that time or by a bacterial process such as pneumonia. Given that pneumonia is the leading infectious cause of death in the United States with mortality rates exceeding 5% and age adjusted rates as high as 22%, it is crucial to identify such patients so that they can receive timely antibiotic therapy [2], [3].

Most symptoms traditionally associated with bacterial infection (such as fever, cough, and rigors) are not predictive of a bacterial process and are indistinguishable from influenza [4], [5]. During the influenza season, patients presenting with such symptoms are grouped as to having an influenza-like illness (ILI) [6]. Physicians therefore rely heavily on the presence of an infiltrate on chest x-ray (CXR) to help make the diagnosis of bacterial pneumonia. However, the absence of an infiltrate does not preclude the diagnosis of bacterial pneumonia, as roughly 21% to 33% of patients admitted for community acquired pneumonia will have a normal chest x-ray [7], [8]. White blood cell (WBC) count has widely been used to distinguish severe bacterial infection from viral infections; however, it lacks both sensitivity and specificity to do so [9], [10]. Ultimately, the diagnosis of bacterial infection rests on the clinician using information pooled from history, physical, laboratory, and radiological data. Differentiating a bacterial infection, from influenza or other viral infection, is therefore challenging in the acute setting.

Biomarkers have been gaining recognition as an important tool in the diagnosis of bacterial infection. An ideal biomarker would aid the emergency physician in rapidly and reliably making the diagnosis of bacterial infection in patients with ILI. C-reactive protein (CRP), an acute phase protein produced by the liver in response to infection, is potentially such a biomarker. CRP in healthy individuals are considered less than 0.5 mg/L, and when these levels are elevated it can be helpful in establishing the etiology of some infections [11]. Elevated CRP (>20 mg/L) has been shown to be present in the majority (>97%) of patients admitted to the hospital with community acquired pneumonia [12]. However, there is limited evidence evaluating the use of CRP in the ED evaluation [4].

The primary aim of our study was to compare CRP levels among patients with ILI, diagnosed with either a bacterial infection, influenza infection, or another viral infection. Secondarily, we aimed to determine the sensitivity and specificity of CRP at determining the presence of bacterial infection in ILI patients; and also to compare CRP to the white blood cell count and differential and patient-driven symptom scores. We hypothesized that CRP levels would be significantly higher in bacterial infection. Further, if CRP levels are established to be sensitive and specific of bacterial infection, this biomarker could aid in distinguishing bacterial infections from viral in patients with ILI, potentially helping to both reduce unnecessary antibiotic use and reduce the misdiagnosis of viral infection when a bacterial one is present.

Section snippets

Study design and setting

This is a prospective, observational study of patients presenting to the ED with symptoms of ILI, which included a cough and a fever. The study setting was an urban academic Level 1 trauma center with an annual census greater than 100000 patients. This study was conducted over 3 influenza seasons. The first season spanned the months of January through March of 2009 and included subjects with seasonal influenza infection. The second and third influenza seasons spanned the months of October

Characteristics of study subjects

A total of 250 patients were screened over 3 influenza seasons, October through March in the years of 2008 through 2011. A total of 172 patients were enrolled. Of those patients, 41 (23.8%) were excluded from final analysis leaving a final total of 131 patients. Reasons for subsequent exclusion included patients being lost to follow-up (75.6%), taking immunosuppressant medication (9.8%), active liver disease (4.9%), inability to get a nasal wash sample (7.3%), and finally inability to draw

Limitations

Our study has several limitations. First, there was a difference in enrollment procedures from the first year of this study and the subsequent 2 years. During the 2008-2009 influenza season, there was a rapid point of care influenza antigen test which was used to screen patients to enroll only influenza-positive patients. The original design of this study was to look at differences in influenza-positive-only patients compared to bacterial infection group. With the emergency of the H1N1 strain

Discussion

This investigation is the first to demonstrate that CRP is a capable adjunct to help distinguish bacterial infection in a subset of patients with ILI. CRP was significantly elevated in bacterial infection and was both sensitive and specific for bacterial infection. Our data demonstrated that with a CRP value less that 20 mg/L, the sensitivity of the test approached 100%, whereas a CRP value of greater than 80 mg/L had a specificity approaching 100% for bacterial infection. This provides useful

References (19)

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Funding: This study was designed and carried out at Rhode Island Hospital/Brown University and was supported by an intradepartmental grant through the Department of Emergency Medicine.

☆☆

Meetings: Presented at the Society for Academic Emergency Medicine (SAEM) Annual Meeting, Boston, MA, June 6, 2011 (Lightning Oral Presentation) Academic Emergency Medicine, Volume 18, number 5, p s141, May 2001.

Presented at SAEM New England Emergency Medicine Research Directors (NERDS) Regional Meeting, Worcester, MA, April 6, 2011 (Oral Presentation).

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