Is Procalcitonin the Key to Discriminating Bacterial from Viral Lower Respiratory Infections?

Abstract & Commentary

Source: Christ-Crain M et al. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomized, single-blinded intervention trial. Lancet 2004; 363:600-607.

Procalcitonin concentrations have been shown to be elevated in severe bacterial infections, but remain low in viral infections and non-specific inflammatory diseases. The objective of this study was to assess the capability of a new, rapid, and sensitive procalcitonin assay to identify bacterial lower respiratory tract infections needing antimicrobial treatment.

The study design was a prospective, cluster-randomized, controlled, single-blinded intervention trial. A total of 243 patients who were suspected of having lower respiratory infections were recruited from an academic, tertiary care hospital emergency department (ED). Appropriate exclusion criteria (e.g., immunocompromised patients) were employed. Patients were assigned randomly either standard care or procalcitonin-guided treatment. In the procalcitonin-guided group, the treating physician was advised either to use or withhold antibiotics depending upon the serum procalcitonin level (one of four categories), although the final decision was at the discretion of the treating physician. On the basis of the procalcitonin level, the use of antibiotics was strongly discouraged (0.1 mcg/L or less suggests absence of bacterial infection), discouraged (0.1-0.25 mcg/L suggests bacterial infection unlikely), recommended (0.25-0.5 mcg/L suggests bacterial infection likely), or strongly recommended (0.5 mcg/L or greater suggests presence of bacterial infection). The primary endpoint was the use of antibiotics, and analysis was by intention to treat.

In the procalcitonin-guided treatment group, the adjusted relative risk of antibiotic exposure was 0.49 (95%; CI: 0.44-0.55; p < 0.0001) compared with the standard group. Antibiotic use was reduced significantly in all diagnostic subgroups, including those with community-acquired pneumonia, bronchitis, chronic obstructive pulmonary disease (COPD) exacerbation, and asthma. Clinical and laboratory outcomes were similar in both groups, including frequency and length of hospitalization, need for intensive care, death, and rate of re-exacerbation and re-admission of patients with acute COPD after six months. This study showed that a procalcitonin level could reduce the use of antibiotics in patients with lower respiratory tract infections by 50%, which translated into 39 fewer antibiotic courses per 100 patients. Withholding antibiotics was safe and did not compromise clinical outcome.

Commentary by Stephanie B. Abbuhl, MD, FACEP

This study also confirms that most respiratory tract infections are due to viral etiologies, with serologic evidence of acute infections reported in 81% of tested patients and IgM-positive in most. Overall, bacterial cultures were grown from sputum or bronchoalveolar lavage fluid in 21% of patients, and from blood in 7%. It is interesting to note that the highest number of positive sputum cultures was found in patients with acute exacerbations of COPD (45%), and in the procalcitonin group this percentage was the same for patients with and without antibiotic treatment. Yet antibiotics were prescribed in only 38% of the patients in the procalcitonin group, compared with 83% in the standard group, with similar outcomes in both groups. This underscores the limitation of using sputum cultures in COPD patients to decide the need for antibiotics.

This study has limitations. The study protocol allowed for the physician in charge to overrule the procalcitonin algorithm, and antibiotics were given in a small group of patients with low procalcitonin levels. In another group of patients in the procalcitonin group, antibiotics that were withheld initially were given later due to rising procalcitonin levels or at the physician’s discretion. It is unclear just how many patients may have received antibiotics at a later time. While the results from this study are encouraging, further studies will need to be done to more clearly define the sensitivity and specificity of the procalcitonin assay for predicting bacterial infections. However, in light of the current overuse of antibiotics in what are self-limited often, viral respiratory infections, the potential of a rapid test to aid in the clinical decision-making is worth more investigation.

Dr. Abbuhl, Medical Director, Department of Emergency Medicine, The Hospital of the University of Pennsylvania; Associate Professor of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, is on the Editorial Board of Emergency Medicine Alert.