Cefoperazone-Sulbactam Induced Coagulopathy: A Lesson in Pharmacokinetics

Cefoperazone-sulbactam is a widely used antibiotic, but clinicians must remain vigilant about potential side effects. We describe an elderly lady on immunosuppressive therapy admitted with suspected sepsis. She was empirically started on cefoperazone-sulbactam. The International normalized ratio (INR) progressively increased over the next few days. Cefoperazone-sulbactam-induced coagulopathy was suspected. INR normalized after antibiotic discontinuation and vitamin K supplementation. Several factors predispose to cefoperazone sulbactam-induced coagulopathy. Some factors include poor dietary vitamin K intake and intestinal bacterial interference with vitamin K synthesis in broad-spectrum antibiotic therapy. The serum half-life of cefoperazone is increased 2–4 fold in patients with hepatic disease and biliary obstruction. A total daily dosage above 4 g should not be necessary in such patients. Higher dosages in such situations increase the risk of toxicity. Cefoperazone therapy may prolong INR. Monitoring INR is indicated when high doses are used or when there is liver disease/biliary obstruction, renal impairment, or both.