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Procalcitonin-guided antibiotic protocol could reduce unnecessary prescriptions

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Emily Albers, PharmD

COVID-19 illness with bacterial coinfection can be difficult to identify because coronavirus presents similarly to bacterial infection. Even when properly identified, coinfection is uncommon. Coinfection only occurs in about 8% of patients with COVID-19, but 60% to 80% of patients are prescribed antibiotics as a contingency plan.

Unnecessary, empiric antibiotic administration can lead to antimicrobial resistance and superinfection, affecting health systems’ antibiotic armory in the long run.

To combat high antibiotic prescription rates, researchers have looked toward biological markers as a source of stewardship. One study, published in the April 2023 edition of the CHEST Journal, investigated the use of a procalcitonin-guided antibiotic protocol and the subsequent impact it had on antibiotic administration.

The study found that when hospitals put in place a procalcitonin (PCT)-guided antibiotic protocol, antibiotic prescription rates in hospitalized patients with COVID-19 were reduced, without major safety concerns

Study methods

The multicenter cohort study was based out of the Netherlands in collaboration with the COVIDPredict study group. COVIDPredict is a multicenter initiative in the Netherlands, which collects data on patients hospitalized with COVID-19. While previously there have been retrospective assessments validating the use of PCT levels, this is the first study prospectively evaluating the implementation of a PCT-guided protocol.

Patients were enrolled from October 2020 to July 2021 into three patient groups. The study group included  patients from one set of clinics on antibiotics with PCT-guided protocol. The second group retrospectively analyzed patients from the same clinics treated without PCT guidance. The third group, the control, consisted of patients from three additional COVIDPredict hospitals without PCT guidance.

All study patients were admitted to a hospital, were 18 years or older, and diagnosed with COVID-19 via positive sample test. PCT levels were measured within 24 hours of admission. PCT levels are normally lower than 0.1 μg/L in healthy adults, and only raised in bacterial infections, not viral. In the PCT-guided study group, the protocol used by prescribers was that if PCT levels were lower than 0.25 μg/L, antibiotics were discouraged. If PCT levels were 0.25 to 0.5 μg/L, antibiotics could be considered. If PCT levels were greater than 0.5 μg/L, antibiotics were recommended. A prescriber could override these decisions with rationale.

The primary outcome was the proportion of antibiotic prescriptions during the first 7 days of admission. Secondary outcomes included proportion of antibiotic prescriptions during the total stay, length of hospital stay, admission to ICU, mechanical ventilation, noninvasive ventilation, 30-day all-cause mortality, 90-day all-cause mortality, and readmission within 30 days.


In the first 7 days of admission, 26.8% of PCT-guided protocol patients were prescribed antibiotics. In the non-PCT group, 43.9% of patients were prescribed antibiotics, and 44.7% of the control group were prescribed antibiotics. During their total admission timeframe, 35.2% of patients in the PCT group, 43.9% of the non-PCT group, and 54.5% of the control group were prescribed antibiotics.

There were no significant differences in the secondary outcomes other than readmission within 30 days, which had a higher rate for the PCT-guided group but were mainly noninfectious.

The actual prevalence of bacterial infection in patients with PCT levels above 0.50 μg/L was 10.6%, but the prescription rate in this group was still 26.8%. Prescribers adhered to the protocol 94% of the time in patients with PCT lower than 0.25 μg/L, and 100% in patients with PCT greater than 0.50 μg/L.


This multicenter cohort study shows that a PCT-guided antibiotic protocol can reduce the number of patients with COVID-19 who were treated with antibiotics in the first 7 days of admission. Patients managed with the PCT-guided protocol had fewer antibiotic prescriptions in the first 7 days of admission and throughout their total hospitalization.

The study’s high rate of adherence at multiple sites showed that using a PCT-guided antibiotic protocol is feasible. Even so, antibiotic prescriptions still outnumbered true infections. Follow-up studies should consider using a higher PCT level cutoff. Pharmacists that receive these orders must be diligent antimicrobial stewards.

This study did not compare PCT-guided protocol to standard care. The Infectious Diseases Society of America still describes PCT as an unpredictable biomarker to identify coinfection. A PCT-guided protocol may be used safely in patients with COVID-19 to reduce risk of resistance and superinfection, but may not be superior to clinical judgment and current practice. ■



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