A study in the New England Journal of Medicine casts doubt on the role of procalcitonin (PCT) testing in tamping down on unnecessary antibiotic prescriptions. Applying this testing to nearly 1,700 patients with lower respiratory tract infections, investigators found that doctors were more influenced by clinical symptoms than the test results. The study authors presented their results at the American Thoracic Society’s annual meeting in San Diego.

Physicians have a tendency to overprescribe antibiotics for lower respiratory tract infections, a condition whose origin is difficult to ascertain as viral or bacterial. PCT is a peptide that typically increases in the presence of a bacterial infection, but not a viral infection. Following a series of European trials which found that PCT could safely reduce antibiotic use for these types of infections, the U.S. Food and Drug Administration (FDA) in 2017 approved a PCT test to help guide clinical decisions on antibiotics in the emergency department and the hospital.

Not many studies have looked at this topic in the United States, whose institutions may have different prescribing patterns than those in Europe. As Clinical Laboratory News reported in June, PCT testing strategies are catching on in Europe, but labs in the United States continue to debate its value in enhancing antimicrobial stewardship.

The Procalcitonin Antibiotic Consensus Trial (ProACT) investigated whether using PCT testing to guide antibiotic prescribing would reduce antibiotic exposure more effectively than standard care.

The trial included 1,656 adult patients from 14 academic centers who presented to emergency departments and were diagnosed with suspected acute lower respiratory tract infections. All participants received PCT testing and then were randomly divided into two cohorts: 826 for procalcitonin-guided antibiotic prescription treatment and 830 for usual care. Only those physicians assigned to the PCT group got to see the test results. Antibiotics were strongly encouraged among patients with PCT levels above 0.5 µg/L and strongly discouraged at less than 0.1 µg/L.

“We hypothesized that within 30 days after enrollment the total antibiotic days would be lower—and the percentage of patients with adverse outcomes would not be more than 4.5 percentage points higher—in the PCT group than in the usual-care group,” the researchers wrote. However, that did not turn out to be the case. Investigators did not find notable differences between the two cohorts as far as antibiotic days were concerned. Both groups after 1 month were exposed to approximately 4 days of antibiotics, each experiencing comparable rates of adverse outcomes.

Clinical features of infection seemed to influence a doctor’s decision to prescribe antibiotics more so than the PCT test results. Prescription decisions didn’t seem to vary among doctors who knew their patients’ test result versus those who didn’t.

“In other words, it seems likely that physicians already commonly withheld antibiotics based on clinical signs alone, and, therefore, instead of the magic bullet I and many others hoped PCT [testing] might be, it offered only limited incremental value over clinical judgment,” said lead author David Huang, MD, MPH, associate professor with the University of Pittsburgh’s critical care medicine and emergency medicine departments, in a statement.

Investigators did find that in patients with acute bronchitis antibiotic prescribing was half in the PCT group versus the usual care group. Although a statistically robust finding, this was nonetheless one of many secondary analyses, Huang told CLN Stat.

For laboratories, the study’s biggest takeaway is, at least in hospitals similar to those that participated in ProACT, providing PCT guidance in the emergency department and hospital as currently approved by FDA will have minimal if any impact on overall antibiotic use, Huang said.

He couldn’t speculate whether the study results would influence future use of PCT as a guide for antibiotics prescribing in hospitals. “The impact of research on policy and clinical practice is always hard to predict,” he said.