Abstract
Bacterial and viral infections often present with similar symptoms. Etiologic misdiagnosis can alter the trajectory of patient care, including antibiotic overuse. A host-protein signature comprising tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) was validated recently for differentiating bacterial from viral disease. However, a focused head-to-head comparison of its diagnostic performance against other biomarker candidates for this indication was lacking in patients with respiratory infection and fever without source. We compared the signature to other biomarkers and prediction rules using specimens collected prospectively at two secondary medical centers from children and adults. Inclusion criteria included fever > 37.5 °C, symptom duration ≤ 12 days, and presentation with respiratory infection or fever without source. Comparator method was based on expert panel adjudication. Signature and biomarker cutoffs and prediction rules were predefined. Of 493 potentially eligible patients, 314 were assigned unanimous expert panel diagnosis and also had sufficient specimen volume. The resulting cohort comprised 175 (56%) viral and 139 (44%) bacterial infections. Signature sensitivity 93.5% (95% CI 89.1–97.9%), specificity 94.3% (95% CI 90.7–98.0%), or both were significantly higher (all p values < 0.01) than for CRP, procalcitonin, interleukin-6, human neutrophil lipocalin, white blood cell count, absolute neutrophil count, and prediction rules. Signature identified as viral 50/57 viral patients prescribed antibiotics, suggesting potential to reduce antibiotic overuse by 88%. The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial respiratory infections and fever without source. Future utility studies are warranted to validate potential to reduce antibiotic overuse.
Highlights
Clinicians often encounter the diagnostic challenge of distinguishing between bacterial and viral etiologies in a febrile patient [1]
Routine cultures may aid in determining infectious etiology but their utility can be limited by lengthy time to result, low yield, and contamination [4]
For 16 out of the 98 patients initially presenting with fever without source, a specific clinical diagnosis was recorded at discharge (Table 1), including bacteremia, meningitis, peritonitis, and lymphadenitis
Summary
Clinicians often encounter the diagnostic challenge of distinguishing between bacterial and viral etiologies in a febrile patient [1]. Misdiagnosis of disease etiology may alter the trajectory of patient care, including over and under use of antibiotics, with fundamental individual and global health consequences. To aid in accurate clinical decision-making, various laboratory tests are regularly requested [1]. Routine cultures may aid in determining infectious etiology but their utility can be limited by lengthy time to result, low yield, and contamination [4]. Pathogen-based tests are inherently limited by requirement to sample the infection focus, which is especially challenging in lower respiratory infections and fever without source. There is pressing need for new reliable and rapid testing to aid the clinician in discriminating between bacterial and viral infections
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