Procalcitonin to Initiate or Discontinue Antibiotics in Acute Respiratory Tract Infections

Daphne Stannard, the contributing editor for the Cochrane Review Summary, is the chief nurse researcher and director of the Institute for Nursing Excellence at UCSF Medical Center, San Francisco, California. She is also the director of the UCSF JBI Centre.For questions related to this article, contact Daphne Stannard at daphne.stannard@ucsfmedctr.org.What is the safety and efficacy of using procalcitonin for starting or stopping antibiotics using individual patient data with varying severity of acute respiratory infections (ARIs) and from different clinical settings?Significant morbidity and mortality worldwide are related to ARIs. These infections comprise a large and heterogeneous group of bacterial, viral, and other etiologies. Although the diagnostic gold standard for establishing the presence or absence of ARI has been the use of blood or sputum cultures, these tests lack both sensitivity and specificity, with only around 10% of patients with pneumonia having positive cultures (including some false positives).1Procalcitonin, a prohormone of calcitonin, has emerged in recent years as a promising biomarker for the diagnosis of bacterial infections, as higher levels of procalcitonin are found in severe bacterial infections but remain fairly low in viral infections and nonspecific inflammatory diseases. Procalcitonin is released in multiple tissues in response to bacterial infections through direct stimulation of cytokines, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6. Conversely, procalcitonin production is blocked by interferon γ, a cytokine released in response to viral infections. As such, procalcitonin levels may be used to support tailored clinical decision making for the appropriate initiation and duration of antibiotic therapy in patients with a bacterial ARI.This summary is based on a Cochrane systematic review that included individual patient data from 14 randomized controlled trials (RCTs) with a total of 4211 participants. Inclusion criteria were adult patients with a clinical diagnosis of ARI, as well as patients with sepsis and suspected ARIs. The systematic review and individual patient data meta-analysis of RCTs was undertaken to compare the effects of using procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARIs to patients without procalcitonin measurements. The aim of the analysis was to assess the safety and efficacy of a procalitonin-guided approach to treatment over a large range of patients with varying severity of ARIs. Trials were excluded if they exclusively focused on pediatric participants or if they used procalcitonin to escalate antibiotic therapy. No exclusion was made on the basis of language or clinical setting, and trials from primary care, the emergency department, and medical and surgical intensive care units (ICUs) were included. Primary outcomes included all-cause mortality after randomization up to a follow-up time of 30 days and setting-specific treatment failure. Secondary outcomes included the following:The overall quality of the evidence included in the review was moderate. There were 6 trials with concealed allocation and 5 trials with blinded outcome assessment. All trials achieved complete or near-complete follow-up for mortality. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate hierarchical logistic regression for the co-primary endpoints of mortality from any cause and treatment failure. Linear and logistic regression modeling was used for continuous and binary secondary endpoints, respectively. Multivariable hierarchical logistic regression was used to combine patient data from the different trials, and individual patient data were requested from the investigators of all eligible trials. In meta-analyses with aggregated trial data, summary ORs were calculated using a random-effects model and the Mantel-Haenszel statistical method in RevMan 2011 (Cochrane software, London, UK).This systematic review and meta-analysis of individual patient data from 14 RCTs found no increased risk for mortality or treatment failure when procalcitonin was used to guide initiation and duration of antibiotic treatment in patients with ARIs compared to control patients. In relation to efficacy, procalcitonin-guided patients had a consistent reduction of antibiotic use. It should be noted that most of the trials were conducted in Europe and China and additional high-quality research is needed to confirm the safety of this approach for non-European countries (including the United States).2