Metronidazole-associated pancreatitis

OBJECTIVE: To report a case of acute reversible pancreatitis associated with metronidazole-treated aspiration pneumonia. CASE SUMMARY: A 61-year-old white woman requiring coronary artery bypass surgery developed acute pancreatitis following treatment with metronidazole for suspected postsurgical aspiration pneumonia. The patient developed moderate to severe bilateral upper quadrant abdominal pain; laboratory studies revealed elevated amylase and lipase concentrations four days following the initiation of metronidazole therapy. After discontinuation of metronidazole, the patient's abdominal pain subsequently improved, and both amylase and lipase concentrations immediately declined and were within normal limits within one week. DISCUSSION: An acute attack of pancreatitis is characterized by moderate to severe abdominal pain that may radiate to the back, accompanied by increased concentrations of pancreatic enzymes and few morphologic changes in the pancreas. Metronidazole is reported as having a probable association with acute pancreatitis, although the mechanism of drug-induced pancreatitis is not known. One speculative mechanism of metronidazole-induced pancreatitis is that, under aerobic conditions, metronidazole may undergo redox cycling and yield hydrogen peroxide, superoxide, and other free radicals. Such redox-active compounds are toxic to pancreatic beta-cells, and oxygen-centered free radicals have been implicated in the induction of pancreatitis. Other suggested mechanisms include immune-mediated inflammatory response, pancreatic duct constriction, and metabolic effects. CONCLUSIONS: Very few cases of metronidazole-associated pancreatitis have been reported, and the long-term sequelae are unknown. However, if metronidazole or any other drug is suspected as the causative agent in pancreatitis, it should be discontinued and rechallenge should be avoided.