Procalcitonin-Guided Care Cut Antibiotic Use in Acute Pancreatitis

Using procalcitonin-based algorithms reduced the use of antibiotics in patients with acute pancreatitis, with no increased risk of infection or harm, a randomized trial in the U.K. showed.

In an intention-to-treat analysis involving 260 patients, 45% of those who received procalcitonin-guided care plus usual care were prescribed antibiotics compared with 63% of those who received usual care alone (P=0.0071), with an odds ratio of 0.49 (95% CI 0.29-0.83) for the treatment effect, reported Ajith Siriwardena, MD, of the Manchester Royal Infirmary in England, and colleagues.

Despite this, there were no significant differences in the number of clinical infections or hospital-acquired infections between the groups, the authors noted in Lancet Gastroenterology & Hepatology.

There were also no significant differences in adverse events, length of hospital stay, readmissions, quality of life, mortality, or costs, they pointed out.

"These are important findings because decision making around antibiotic prescribing in patients with acute pancreatitis is difficult," Siriwardena and team wrote. "Although the International Association of Pancreatology/American Pancreatic Association guideline states that antibiotics should be avoided in the early stages of all acute pancreatitis, this is a difficult policy to follow in the setting of an ill, often febrile patient with leukocytosis and a raised C-reactive protein concentration."

Clinicians use increased procalcitonin levels to differentiate inflammation from bacterial infection due to their sensitivity compared with other biomarkers, Siriwardena's group noted. Procalcitonin measurements based on algorithms can distinguish between bacterial sepsis and a systemic inflammatory response, which could lead to more appropriate antibiotic use.

"The results of this study are likely to lead to modifications of current practice and of recommendations in guidelines," wrote Gabriele Capurso, MD, PhD, of Vita-Salute San Raffaele University in Milan, and Enrique de-Madaria, MD, PhD, of Miguel Hernández University in Alicante, Spain, in an accompanying editorial.

Among the patients included in the study, 58% had mild acute pancreatitis, 22% had moderate disease, and 21% had severe disease.

"Although there was no statistically significant interaction between disease severity and antibiotic use, the sensitivity analysis showed a reduced risk of antibiotic use among patients with mild acute pancreatitis; however, there was no risk difference for antibiotic use for patients with moderate or severe disease," Capurso and de-Madaria noted. "This finding can be explained by the smaller proportion of patients with moderate to severe disease and their expected higher incidence of infections."

"Future studies aiming to validate these results should also focus on the accuracy of procalcitonin for the detection of infection in patients with moderate to severe disease and on whether the procalcitonin-based algorithm should be used in all patients or only in some subgroups," they concluded.

For this study, Siriwardena and colleagues enrolled 260 patients with acute pancreatitis (mean age 51, 51% men) from the Manchester Royal Infirmary between July 29, 2018 to Nov. 13, 2020. Patients were blinded and randomized to receive procalcitonin-guided care in addition to usual care (n=132) or usual care only (n=128). Randomization was stratified by disease severity and admission pathway (direct admission or tertiary transfer).

Most patients (86%) were directly admitted to the hospital. Prior to admission, all had abdominal pain, three-quarters were vomiting, and 14% had a prior diagnosis of acute pancreatitis. About half of the patients had no comorbidities, 35% had hypertension, and 22% had hyperlipidemia.

Procalcitonin testing was done at 0, 4, and 7 days, and then weekly. Under procalcitonin-guided care, stopping or not starting antibiotics was recommended for patients with procalcitonin values below 1.0 ng/mL, while those with values of 1.0 ng/mL and higher initiated or continued antibiotics.

Four patients in the procalcitonin-guided group and three in the usual care group died within 90 days, with all deaths related to severe acute pancreatitis.

Siriwardena and team noted that their study took place at a single center, and the results may not be generalizable to different settings.

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