Is Procalcitonin Testing Sensitive Enough to be a Rule-Out Test?

Many antibiotic prescriptions in the United States are inappropriate. Antimicrobial stewards use procalcitonin concentrations, which increase in response to bacterial infections, are used as an indicator when determining whether antibiotic use is appropriate. However, there are some concerns about procalcitonin’s sensitivity.

The investigators of a new study in Open Forum Infectious Diseases have shared what they call a “cautionary tale” about procalcitonin sensitivity. In their study, 38% of inpatients with bacteremia at an academic medical center had low (<0.5 µg/L) procalcitonin values. These low concentrations were associated with a delay of antibiotic therapy.

The study team conducted a retrospective chart review of electronic health records at St. Joseph’s Hospital and Medical Center in Phoenix, Arizona. Patients were eligible if they were admitted between July 1, 2018 and June 30, 2019.

Patients included in the study were required to have ≥ 1 positive blood culture within 24 hours of hospital admission and procalcitonin testing within 48 hours of the first blood draw.

The procalcitonin value of <0.5 µg/L was selected to align with the recommendation of “antibiotics discouraged” in previous sepsis studies of procalcitonin.

There were 1289 adult inpatients with positive blood cultures during the study period. Of these patients, 332 met inclusion criteria.

The sensitivity of procalcitonin for bacteremia was 62% at 0.5 µg/L, 76% at a threshold of 0.25 µg/L, and 92% at 0.1 µg/L.

Of the 125 patients with low procalcitonin levels, 8 received repeat testing within 48 hours. Among these patients, only 2 increased above the 0.5 µg/L “antibiotics discouraged” standard.

Patients with low procalcitonin values were more likely to have Staphylococcus aureus infections, with S aureus making up 39% of infections in that group versus 21% of the rest of the study group. Procalcitonin was 70% sensitive for gram-negative bacteremia but only 56% sensitive for gram-positive bacteremia.

The study team explained that the sensitivity problem could be lost in analysis by previous studies.

“When the pre-test probability of bacterial infection is low in a population, the number of false negatives may be obscured by the large number of true negatives, resulting in an artificially high negative predictive value despite low sensitivity,” the study authors wrote.

Higher procalcitonin concentrations were associated with higher mortality, ICU admission, and vasopressor or ventilator support. It is possible that procalcitonin concentrations may still be useful as one of several biomarkers. But the investigators clarified that even these associations present a sensitivity problem.

“…a sizeable proportion of patients in the low procalcitonin group also appeared critically ill, representing approximately 20% of all included patients requiring ICU admission and vasopressor support,” the study authors wrote.

The area with the most support for procalcitonin concentration testing is in lower respiratory infection. Yet guidelines in this field have also discouraged using procalcitonin as a rule-out test.

Procalcitonin could still be one of several indicators. Antimicrobial stewardship always involves some tradeoff and risk, and the study team did not discourage all use of procalcitonin testing. However, with these results antimicrobial stewards may be better situated to assess these tradeoffs and risks.