meropenem and Cholestasis

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Cefepime; Ceftazidime; Cholangitis; Cholestasis; Drug Resistance, Bacterial; Escherichia coli; Humans; Imipenem; Meropenem; Retrospective Studies

Vanishing bile duct syndrome (VBDS) refers to a group of acquired disorders associated with progressive destruction and disappearance of the intrahepatic bile ducts. We report a case of meropenem-induced VBDS in a patient who had undergone surgical repair of a ruptured abdominal aortic aneurysm. Meropenem was used to treat

Topics: Bile Ducts; Bile Ducts, Intrahepatic; Cholestasis; Humans; Liver; Liver Function Tests; Meropenem

β-lactam antibiotics may necessitate higher than licensed drug doses to achieve therapeutic exposures in critically ill patients. Therapeutic drug monitoring can be used to guide dosing so as to maximise therapeutic effect whilst reducing the likelihood of exposure-related toxicity.. A retrospective review of critically ill patients identified those that received higher than licensed doses of either meropenem (3-6 g/day) or piperacillin-tazobactam (16 g-2 g/day) (i.e. high-dose group) guided by therapeutic drug monitoring. β-lactam-associated toxicities were compared with a patient group of similar age, sex, body mass index and admission diagnosis that received licensed doses of either antibiotic.. Mean daily doses were more than 40% higher in the high-dose groups for each antibiotic. There were no significant differences between the high-dose and licensed-dose groups in terms of hepatocellular derangement (17.9% vs. 31.8%, P=0.25 for meropenem and 17.4% vs. 16.0%, P=0.90 for piperacillin-tazobactam), cholestasis (28.0% vs. 13.6%, P=0.32 for meropenem and 13.0% vs. 4.0%, P=0.26 for piperacillin-tazobactam), need for continuous renal replacement therapy (0% vs. 9.1%, P=0.10 for meropenem and 0% vs. 8.0%, P=0.16 for piperacillin-tazobactam), seizure incidence (7.1% vs. 4.5%, P=0.70 for meropenem and nil for either piperacillin-tazobactam group), thrombocytopenia (9.1% vs. 10.7%, P=0.85 for meropenem and 4.0% vs. 4.3% for piperacillin-tazobactam), or neutropenia (4.5% vs. 3.6%, P=0.95 for meropenem and 0.0% vs. 4.3% for piperacillin-tazobactam).. Higher than licensed doses of meropenem and piperacillin-tazobactam guided by therapeutic drug monitoring were not associated with additional toxicities. Larger prospective studies are required to confirm the clinical utility of higher than licensed dosing.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Chemical and Drug Induced Liver Injury; Cholestasis; Critical Illness; Drug Monitoring; Female; Humans; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Renal Replacement Therapy; Retrospective Studies; Seizures; Thienamycins; Thrombocytopenia

Vanishing bile duct syndrome (VBDS) is a rare and potentially life-threatening disorder in which progressive destruction and disappearance of small intrahepatic bile ducts occur, with resultant cholestasis. The mechanism by which biliary epithelial cells are damaged and intrahepatic bile ducts are lost has not been fully elucidated. However, many etiologies have been reported,and several drugs have been implicated. Meropenem is a widely used, well tolerated broad-spectrum carbapenem antibiotic indicated for the treatment of intraabdominal infections, complicated skin and skin structure infections, and pediatric bacterial meningitis. We describe what we believe is the first reported case of meropenem-induced VBDS. A 60-year-old woman was diagnosed with VBDS after being treated with meropenem for a left temporal lobe brain abscess. Three weeks after starting the drug, the patient developed mixed hepatocellular and cholestatic liver injury with jaundice and pruritus.Meropenem-induced liver injury was suspected, and the drug was discontinued. Diagnostic tests ruled out other causes of cholestasis, including infectious and immunologic conditions. A liver biopsy, performed due to persistent liver injury, demonstrated an absence of bile ducts, which, in conjunction with the patient's clinical course, was consistent with the diagnosis of VBDS. Several months after the cessation of meropenem, the patient's liver function test results improved. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6)between the patient's development of VBDS and meropenem therapy. A high index of suspicion is necessary to diagnose VBDS and other types of drug induced liver injury. Clinicians should consider VBDS as a potential diagnosis in patients receiving meropenem who have prolonged cholestasis, especially after other more probable causes have been excluded.

Topics: Anti-Bacterial Agents; Bile Duct Diseases; Bile Ducts, Intrahepatic; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Humans; Jaundice; Liver; Meropenem; Middle Aged; Thienamycins