A new Cochrane Review has found that the use of the blood infection marker procalcitonin to guide antibiotic treatment in patients with acute respiratory infections improves survival and reduces antibiotic exposure and side effects.
Procalcitonin is a protein associated with the body's response to a bacterial infection. High levels of procalcitonin in the blood suggest a bacterial infection, while low levels indicate a viral infection.
In addition, studies have shown that procalcitonin concentrations fall rapidly during recovery from acute bacterial infections, which makes them a useful measure for monitoring the clinical course of an infection. As a result, the use of procalcitonin as a biomarker has emerged over the last decade as a tool for guiding antibiotic therapy in patients with acute respiratory infections.
In February 2017, the US Food and Drug Administration (FDA) approved the use of a rapid procalcitonin test to help clinicians determine if antibiotics should be started or stopped in patients with lower respiratory tract infections, such as community-acquired pneumonia, and stopped in patients with sepsis. The test, which can provide results in as little as 20 minutes, is meant to be used as an adjunct to clinical judgement and traditional diagnostic parameters.
But while several previous studies have reported reduced antibiotic use of up to 30% when procalcitonin tests were used to guide antibiotic treatment in patients with respiratory infections, evidence for procalcitonin-guided treatment's impact on clinical outcomes has been less conclusive, and questions still remain about its safety across different clinical settings. The intent of the review, which was conducted by an international team of researchers and physicians and published simultaneously in The Lancet Infectious Diseases, was to assess the safety of the approach in patients in different clinical settings and with different types of respiratory infections.
Trials show reduced mortality, antibiotic use
The meta-analysis of individual patient data included 26 randomized controlled trials involving 6,708 patients with an acute respiratory infection who had been assigned to a procalcitonin-guided care group or a control group. The reviewers were primarily looking at all-cause mortality and treatment failure within 30 days of randomization. The secondary end point was antibiotic use.
The trials were conducted in 12 countries and included patients with acute upper and lower respiratory infections such as pneumonia and bronchitis in primary settings, emergency departments, medical wards, and intensive care units (ICUs). The procalcitonin-based algorithms used in the different trials were similar in concept, basing initiation or continuation of antibiotic therapy on procalcitonin cutoff levels.
Among the 3,336 procalcitonin-guided patients in the trials, 286 (8.6%) died within 30 days of randomization, compared with 336 deaths (10%) in the 3,372 control patients—a 14% reduction in relative mortality (adjusted odds ratio [aOR]: 0.83). Treatment failure in the procalcitonin-guided patients was also lower, but not significantly (23% vs. 24.9%, aOR: 0.90). The results were similar when broken down by clinical setting and type of respiratory infection.
The meta-analysis also showed that procalcitonin-based guidance was associated with a 2.4-day reduction in antibiotic exposure compared with the control group (5.7 days vs 8.1 days) and a lower risk of antibiotic side effects (16.3% vs. 22.1%, aOR: 0.68). Length of hospital stay (19 days) and ICU stay (39 days), however, were similar in both groups.
"When embedded in clinical algorithms, the use of procalcitonin has the potential to inform and improve care of patients with acute respiratory infections by reducing antibiotic exposure and the associated risk of developing subsequent antibiotic resistance and more importantly improving clinical outcomes," the authors write in The Lancet.
The findings of the Cochrane Review, considered the gold standard in evidence-based medicine, could aid efforts to reduce antibiotic use in respiratory infections, which are a significant driver of antibiotic prescribing. The US Centers for Disease Control and Prevention estimates that about 44% of outpatient antibiotic prescriptions are written for patients with acute respiratory infections. Yet because respiratory infections are frequently caused by viruses, roughly half of these prescriptions are unnecessary.
The unnecessary use of antibiotics for these viral conditions, along with unnecessarily prolonged antibiotic therapy in patients with bacterial infections, is contributing to the development of antibiotic resistance. That's why strategies to reduce antibiotic prescribing and duration for acute respiratory infections are seen as a critical element of antibiotic stewardship efforts.
Brad Spellberg, MD, an infectious disease specialist at the University of Southern California, says the review is important because it not only reinforces that procalcitonin reduces antibiotic duration, but also shows that patients do better when procalcitonin-guided therapy is used. He suggests that more widespread use of the blood infection marker to guide antibiotic treatment in patients with respiratory infections could be one element of a wider stewardship strategy.
"Overprescribing antibiotics is harmful to patients. It's about time we do something about it," Spellberg told CIDRAP News. "Procalcitonin can get us part of the way there."
The authors of an accompanying commentary in Lancet Infectious Diseases note that procalcitonin alone will not solve antibiotic overuse in patients who have acute respiratory infections, since patient and disease characteristics, along with a physician's experience, will often take precedence in antibiotic-related decisions. Still, they say, it is a strategy that can mitigate the problem.
"Thus, if procalcitonin can safely decrease unnecessary antibiotic use in different settings, even if imperfectly, it is already worthwhile," they write.
Oct 13 Lancet Infect Dis study
Oct 13 Cochrane Review
Oct 13 Lancet Infect Dis commentary