Can procalcitonin guide decisions about antibiotic management?

ACUTE RESPIRATORY TRACT INFECTION

The Procalcitonin Guided Antibiotic Therapy and Hospitalisation in Patients With Lower Respiratory Tract Infections (ProHOSP) trial⁴ randomized 1,381 patients to antibiotic therapy guided by procalcitonin levels or standard guidelines. Most patients had community-acquired pneumonia, while the rest had exacerbations of COPD, acute bronchitis, or other lower respiratory tract infections.

In the study algorithm, starting or continuing antibiotics was discouraged if procalcitonin levels were 0.25 ng/mL or less, and strongly discouraged if less than 0.1 ng/mL. Starting or continuing antibiotics was encouraged if levels were greater than 0.25 ng/mL, and strongly encouraged if greater than 0.5 ng/mL.

The algorithm recommended stopping antibiotics if procalcitonin levels fell below 0.25 ng/mL or decreased by 80%, and strongly recommended stopping them if procalcitonin fell below 0.1 ng/mL or decreased by 90%.

The treating physician could override the algorithm if the patient was unstable, was in an ICU, or had Legionella infection.

Antibiotic use was less in the procalcitonin-guided arm (75.4% vs 87.7%; mean duration 5.7 days vs 8.7 days), as was the rate of adverse effects from antibiotics (19.8% vs 28.1%). Rates of recurrence or rehospitalization were also lower with procalcitonin guidance (3.7% vs 6.5%), presumably because of fewer antibiotic-related side effects or better diagnostic accuracy. Rates of death and ICU admission were similar in the 2 groups. These findings were similar to those of PRORATA and SAPS, demonstrating that guidance with procalcitonin levels decreased antibiotic utilization, with other outcomes either improved or unchanged.

Schuetz et al,⁵ in a 2018 meta-analysis, collected data on 6,708 patients from 26 trials in 12 countries and found that procalcitonin guidance decreased antibiotic exposure by 2.4 days and reduced the rate of antibiotic-related side effects (16% vs 22%). Although there was skepticism about the mortality benefit reported in the SAPS trial, a similar mortality benefit was found in this meta-analysis (30-day mortality rates were 9% vs 10%), suggesting that measuring procalcitonin not only reduces unnecessary antibiotic exposure, but also saves lives.

Although decreasing antibiotic exposure may not confer a survival benefit, procalcitonin guidance likely clarifies the diagnosis and thus expedites proper treatment in patients with sepsis-like syndromes that are actually due to a noninfectious pathology (eg, pulmonary embolism, myocardial infarction, adrenal insufficiency).

Negative findings in ProACT

The Procalcitonin Antibiotic Consensus Trial (ProACT)⁶ subsequently reported findings discordant with those above but was flawed in that adherence to the procalcitonin guideline by physicians was only 62% in the subgroup of patients with low procalcitonin results, which accounted for almost 90% of patients. Overall adherence by physicians to the procalcitonin guideline was 65%, much lower than in other trials (ProHOSP had over 90% adherence).⁴ Further, ProACT was done in American centers unfamiliar with procalcitonin, and it seems they did not trust low procalcitonin values as a reason to stop or avoid antibiotics.

ACUTE EXACERBATIONS OF COPD

Multiple small randomized controlled trials and subgroups of larger studies like ProHOSP have studied the use of procalcitonin in acute exacerbations of COPD. Most studies used a design similar to the algorithm in ProHOSP.

Mathioudakis et al,⁷ in a meta-analysis of 8 trials with a total of 1,062 patients with acute exacerbation of COPD, found that with procalcitonin guidance, prescription of antibiotics on admission decreased by almost one-half, and courses of antibiotics were approximately 4 days shorter without any statistically significant difference in rates of treatment failure, length of hospital stay, recurrence, rehospitalization, or overall mortality.

However, the quality of the studies included in the meta-analysis was deemed only low to moderate, and thus the authors concluded, “Procalcitonin-based protocols appear to be clinically effective; however, confirmatory trials with rigorous methodology are required.”⁷ Nonetheless, given the lack of data supporting current practices for patient selection for antibiotics in COPD exacerbations, a strategy involving procalcitonin seems to be reasonable.