piperacillin--tazobactam-drug-combination and Chemical-and-Drug-Induced-Liver-Injury

Tazobactam/piperacillin (TAZ/PIPC) is widely used in the treatment of infectious disease. In this study, three hundred and sixty-three patients who were treated with the recommended dose of TAZ/PIPC were investigated for the proportion of time above the minimum inhibitory concentration (%TAM) and the frequency of renal and liver dysfunction. Of the whole patient population, 5.23%, exhibited increased creatinine levels, 9.37% and 8.82% exhibited increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, respectively. The patients who exhibited high serum creatinine (SCr) levels before administration, exhibited significant increases of AST (p=0.0121). The patients who exhibited low albumin levels before administration, exhibited significant decreases in renal function (p=0.0041). In the case of a breakpoint (BP) of 64 μg/mL, the arrival probabilities of %TAM of 30% and 50% were 99.4% and 76.9%, respectively. We suggested that the dose of TAZ/PIPC should be adjusted according to the interview form finding and a %TAM>50% (maximal bactericidal action).

Topics: Aged; Aged, 80 and over; Alanine Transaminase; Aspartate Aminotransferases; Biomarkers; Chemical and Drug Induced Liver Injury; Creatinine; Drug Administration Schedule; Female; Humans; Incidence; Kidney Diseases; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Treatment Outcome

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

To describe a patient who developed acute interstitial nephritis, hepatitis and serum sickness-like syndrome after receiving piperacillin-tazobactam (zosyn) therapy.. A 30-year-old woman received a 7-day course of piperacillin-tazobactam as empiric treatment for pneumonia. The patient's kidney function worsened and she turned anuric needing dialysis. She also developed fever and a rash. Laboratory analysis showed elevated liver function and leukocytosis. Kidney biopsy showed acute interstitial nephritis. The patient responded well to steroids; white blood cell count normalized and her liver and kidney function improved over a period of one month.. Piperacillin-tazobactam is one of the most commonly used antibiotics in the hospital setting. It has rarely been associated with acute interstitial nephritis, hepatic injury, or serum sickness-like reactions. Steroids have improved the outcome in most of the cases of interstitial nephritis.. Clinicians should be aware of piperacillin-tazobactam as a drug capable of causing interstitial nephritis, hepatitis and serum sickness-like syndrome. It is essential that we monitor for these rare but severe complications.

Topics: Adult; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Female; Humans; Nephritis, Interstitial; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pneumonia; Serum Sickness