Where Do We Go From Here?

Since 2004, European investigators have published at least 14 clinical trials that support the measurement of serum procalcitonin (PCT) levels in patients with respiratory tract infections [1–3]. The results consistently show that elevated serum PCT levels are encountered in patients with a clinical syndrome of bacterial pneumonia and that low levels correlated with a picture of viral pneumonia or noninfectious causes of pulmonary infiltrates. In a Cochrane review, European colleagues systematically reviewed studies of PCT-guided treatment algorithms that suggest whether to start or stop empirical antibiotic therapy in patients with 1 or 2 low initial PCT values [4]. The authors concluded that PCTguided therapy was not associated with an increase in mortality or clinical failures. Further, they called for non-European studies to confirm the published results [4]. A valid concern with the published trials is the paucity of data that associate the microbiologic etiology of respiratory tract infections with PCT levels. One exception is a modestly sized retrospective study of children in German emergency departments, wherein low PCT levels reliably distinguished between documented viral and bacterial respiratory tract infections [5]. Data generated by investigators at the University of Rochester in this issue of The Journal of Infectious Diseases are pertinent to the topic [6]. The Rochester studies by Branche et al are based on 3 assumptions: (1) traditional cultures of sputum and blood specimens, plus probing urine samples for the antigens of Streptococcus pneumoniae and Legionella species, do not identify the role of viral pathogens; (2) measurement of serum PCT levels would assist in separating viral from bacterial invasive infections and in clarifying whether an identified bacteria was invading or colonizing; and (3) the combination of aggressive attempts at pathogen detection and PCT levels would enhance antibiotic stewardship. In an earlier study by the Rochester investigators, with extensive testing for viral, bacterial, and atypical pathogens, a microbiologic diagnosis was made in 76 of 134 patients (56%) with acute exacerbations of chronic obstructive pulmonary disease (COPD) [7]. That study documented a high frequency of pathogenic viruses, either alone, in 26 of 76 patients, or in combination with bacterial pathogens, in 21 of 76 patients. PCT levels were low with pure viral infection, but PCT levels rose in patients with mixed viral and bacterial infections or only bacterial infections. With this foundation, plus the ability to diagnose an increased number of respiratory virus targets via multiplex polymerase chain reaction (PCR) platforms, the Rochester group reasoned that it was possible, within 2–3 hours of admission (or study enrollment), to inform physicians whether a pathogenic virus was present or absent. In addition, the study intervention provided physicians with the patient’s serum PCT concentration. It was postulated that the combination of pathogen identification and PCT levels would remove most of the uncertainties among physicians that prevent withholding or de-escalating antibiotic therapy in patients with viral lower respiratory tract infections [8]. Branche et al randomly assigned patients with lower respiratory tract infections, most of which involved acute exacerbations of COPD, to receive either standard care or treatment based on algorithms involving findings from a combination of multiplex viral PCR platforms and serum PCT levels [6]. A viral etiology was found in 63 of the 150 patients in the intervention group, with an associated low PCT level in 49. The duration of antibiotic therapy was shortened by 2 days in these patients (P = .002). Further, fewer days of antibiotic therapy were seen in virus-positive patients with low PCT levels. It is encouraging that fewer patients from this latter group were discharged receiving antibiotics. As in many previous PCT studies, there were no adverse consequences as a result of following the intervention PCT algorithm. In short, the current study Received and accepted 21 April 2015; electronically published 24 April 2015. Correspondence: David N. Gilbert, MD, Department of Infectious Diseases, Providence Portland Medical Center, Ste 540, 5050 NE Hoyt St, Portland, OR 97213 (david. [email protected]). The Journal of Infectious Diseases 2015;212:1687–9 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/infdis/jiv253