Investigation of the Efficacy of an Administration Plan for Tazobactam/Piperacillin (TAZ/PIPC) and the Incidence of Kidney and Hepatic Disorders

Abstract

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 signiˆcant increases of AST ( p＝0.0121). The patients who exhibited low albumin levels before administration, exhibited signiˆcant decreases in renal function ( p ＝0.0041). In the case of a breakpoint (BP) of 64 mg/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 formˆnding and a ％TAM＞50％ (maximal bactericidal action).

Investigation of tazobactam/piperacillin– or meropenem–induced liver injury based on retrospective observational study and the FDA Adverse Event Reporting System

“…Liver injury was de ned as an elevation of ALT grade on the basis of the CTCAE version 4.0 (Supplementary Table S4) after the initiation of TZP or MEM therapy 50 . The possibility of TZP-or MEM-induced liver injury was evaluated using the RUCAM (0 or less indicate that the drug is "excluded" as a cause; 1 to 2 that it is "unlikely"; 3 to 5 "possible"; 6 to 8 "probable"; and greater than 8, "highly probable") 50 . The total score consists of points for 8 separate factors in 7 categories that help de ne the "signature" of the drug induced liver injury.…”

“…Tazobactam/piperacillin (TZP), which is a combination of a β-lactam antibiotic and a β-lactamase inhibitor, and meropenem (MEM), which is a carbapenem, are commonly used as an empiric treatment in ICU patients with severe bacterial infections 4,5 and are associated with a signi cantly increased incidence of liver injury 6 . However, the frequency of severe antibiotic-related hepatotoxicity is lower than that of antibiotic-related nephrotoxicity (liver injury vs. renal dysfunction: TZP, 5-6% vs. 9%; MEM, 4% vs. 21%) 7,8 . Therefore, it remains di cult to assess the cause of TZP-or MEM-induced hepatotoxicity.…”