There has been a growing interest regarding the utility of procalcitonin to guide appropriate initiation and duration of antibiotic therapy in critically ill patients. Two randomized controlled studies in critically ill patients suspected to have bacterial infections arrived at disparate conclusions (De Jong et al. 2016; Bouadma et al. 2010).
In patients presenting with acute exacerbation of chronic obstructive pulmonary disease (COPD), it is often difficult to clinically ascertain whether bacterial infection is the precipitating factor. Previous studies that evaluated the utility of procalcitonin in this setting involved less severely ill patients, with relatively few who required treatment in the intensive care unit. Against this background, Daubin et al. carried out a multicentre randomized controlled study in the intensive care unit of 11 hospitals in France to investigate the utility of procalcitonin-guided antibiotic therapy in acute exacerbations of COPD (Daubin et al. 2018).
The authors hypothesized that (1) procalcitonin-guided treatment would reduce antibiotic exposure and (2) mortality will not be different with a lower antibiotic exposure. To demonstrate non-inferiority, a cut off of 12% was considered as the excess mortality permissible with procalcitonin guidance.
Procalcitonin levels were measured in all patients at inclusion, 6 hours later, and on days 1, 3, and 5 after inclusion. In the intervention group, the initiation and duration of antibiotic therapy followed an algorithm based on procalcitonin levels. In the control group, antibiotic therapy was commenced and continued for an appropriate duration based on clinician judgment.
The primary endpoint was mortality at 3 months. At the end of this period, 30 patients (20%) died in the procalcitonin arm compared to 21 (14%) in the control arm, with a confidence interval of −0.3 to 13.5 %. As the upper limit of the confidence interval exceeded the pre-determined cut off of 12% mortality, the study failed to establish non-inferiority of procalcitonin-guided therapy. Mortality with procalcitonin-guided therapy was significantly higher in patients who were not on antibiotics at inclusion. Besides, there was no difference in secondary endpoints including the requirement for vasopressor or dialytic support, the incidence of acute respiratory distress syndrome, ICU-acquired pneumonia or other infections, and multiorgan failure. The duration ventilation, ICU and hospital stay were also not significantly different between groups.
In contrast to previous studies in acute exacerbation of COPD that showed reduced antibiotic usage with procalcitonin guidance, the present study included patients with a relatively higher severity of illness; 87% of patients required non-invasive or invasive mechanical ventilation. Vasopressor support was required in 17.2% of patients, while 5.6% of patients underwent dialysis. The number of patients who received antibiotics was significantly less in the procalcitonin group throughout the first 6 days of the study. This may suggest that procalcitonin levels may have been falsely low and failed to identify infection in some patients.
There were more patients on home oxygen and non-invasive ventilation in the procalcitonin group, which may indicate a more severe illness that may have contributed to mortality. There is no data available on the time to commencement of antibiotics in either group, which may also have affected outcomes.
The bottom line is that in critically ill patients with acute exacerbation of COPD, procalcitonin guidance may fail to identify patients who may have bacterial infection as the precipitating cause. Early antibiotics based on clinical judgment may be more appropriate in such patients. I must confess that I am not a procalcitonin fan; the results of this study is no surprise to me. Our practice of initiation and continuance of antibiotic treatment based on clinician judgment shall remain unchanged.
References:
- Bouadma, Lila, Charles-Edouard Luyt, Florence Tubach, Christophe Cracco, Antonio Alvarez, Carole Schwebel, Frédérique Schortgen, et al. 2010. “Use of Procalcitonin to Reduce Patients’ Exposure to Antibiotics in Intensive Care Units (PRORATA Trial): A Multicentre Randomised Controlled Trial.” Lancet (London, England)375 (9713): 463–74. https://doi.org/10.1016/S0140-6736(09)61879-1.
- Daubin, Cédric, Xavier Valette, Fabrice Thiollière, Jean-Paul Mira, Pascal Hazera, Djillali Annane, Vincent Labbe, et al. 2018. “Procalcitonin Algorithm to Guide Initial Antibiotic Therapy in Acute Exacerbations of COPD Admitted to the ICU: A Randomized Multicenter Study.” Intensive Care Medicine44 (4): 428–37. https://doi.org/10.1007/s00134-018-5141-9.
- Jong, Evelien de, Jos A. van Oers, Albertus Beishuizen, Piet Vos, Wytze J. Vermeijden, Lenneke E. Haas, Bert G. Loef, et al. 2016. “Efficacy and Safety of Procalcitonin Guidance in Reducing the Duration of Antibiotic Treatment in Critically Ill Patients: A Randomised, Controlled, Open-Label Trial.” The Lancet. Infectious Diseases16 (7): 819–27. https://doi.org/10.1016/S1473-3099(16)00053-0.
