Still unclear if procalcitonin can aid in antibiotic prescribing for lower respiratory tract infection
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Researchers said it remains unclear whether low procalcitonin levels can be used to safely withhold antibiotics in patients with lower respiratory tract infection.
“The study was prompted by a few factors — first is the overuse of antibiotics and the contribution this makes to worsening antimicrobial resistance; second is the availability of a biomarker, procalcitonin, to help discriminate bacterial from viral infection; third is that prior studies of procalcitonin showed it could safely reduce unnecessary antibiotic use although physicians could overrule the test recommendations and give antibiotics anyway,” Ephraim L. Tsalik, MD, PhD, chief scientific officer for infection disease diagnostic at Danaher Diagnostics and adjunct professor at the Duke University Medical Center, told Healio.
“As a result, no one has ever shown that low levels of this biomarker (suggesting the absence of a bacterial infection) can be safely used to limit antibiotic exposure. We conducted this trial to directly answer that question,” he said.
Tsalik and colleagues performed a randomized, placebo-controlled, double-blind, noninferiority trial at five U.S. health centers, consisting of adults aged 18 years or older with clinically suspected nonpneumonia lower respiratory tract infection and symptom duration from 24 hours to 28 days.
The researchers randomly assigned participants with a procalcitonin concentration of 0.25 ng/mL or less in a 1:1 ratio to receive over-encapsulated oral azithromycin 250 mg or matching placebo. The primary outcome was efficacy of azithromycin placebo in terms of clinical improvement at day 5 in the intention-to-treat population.
Between Dec. 8, 2017, and March 9, 2020, 499 patients were enrolled with 249 randomly assigned to receive azithromycin and 250 placebo.
Clinical improvement at day 5 was observed in 63% (95% CI, 54%-71%) of 238 participants with full data in the placebo group and 69% (95% CI, 61%-77%) of 227 participants with full data in the azithromycin group in the intention-to-treat analysis, rendering a between-group difference of 6% (95% CI, –15% to 2%) which did not meet the noninferiority margin, according to the study.
Tsalik added that at day 11, treatment with placebo was considered noninferior despite those treated with antibiotics seemingly improving faster at day 5.
Additionally, adverse events and the severity of adverse events were not significantly different between groups at day 5, except for increased abdominal pain associated with azithromycin (23%; 95% CI, 18%-29%) compared with placebo (16%; 95% CI, 12%-21%).
“Decisions about whether to use this biomarker to guide antibiotic use should account for the need to maximize rates of clinical improvement (as in those with severe comorbidities at baseline) while minimizing antibiotic related side effects and trying to decrease unnecessary antibiotic use,” Tsalik said.
[Editor’s note: The headline and lead paragraph of this story were updated to better reflect the study findings.]
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