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Complicated intra-abdominal infections usually mandate prompt surgical intervention supplemented by appropriate antimicrobial therapy. The aim of this study was to demonstrate that ertapenem was not inferior to piperacillin-tazobactam for the treatment of community-acquired intra-abdominal infections. A randomized open-label active-comparator clinical trial was conducted at 48 medical centers on four continents from December 2001 to February 2003. Adult patients with intra-abdominal infections requiring surgery were randomized to receive either ertapenem 1 g daily or piperacillin/tazobactam 13.5 g daily in 3-4 divided doses. The primary analysis of efficacy was the clinical response rate in clinically and microbiologically evaluable patients at the test-of-cure assessment 2 weeks after completion of therapy. All treated patients were included in the safety analysis. Patient demographics, disease characteristics, and treatment duration in both treatment groups were generally similar. The most commonly isolated pathogens at baseline were E coli (greater than 50% of cases in each group) and B fragilis ( approximately 9%). Favorable clinical response rates were 107/119 (90%) for ertapenem recipients and 107/114 (94%) for piperacillin/tazobactam recipients. The frequencies of drug-related adverse events, most commonly diarrhea and elevated serum alanine aminotransferase levels, were similar in both treatment groups. Six of 180 ertapenem recipients (3%) and two of 190 piperacillin/tazobactam recipients (1%) had serious drug-related adverse experiences. In this study, ertapenem and piperacillin/tazobactam were comparably safe and effective treatments for adult patients with complicated intra-abdominal infections. [ABSTRACT FROM AUTHOR]

Abstract: The impact of different antimicrobial regimens for intra-abdominal infections on the frequency of bowel colonization with vancomycin-resistant enterococci (VRE) was examined in 2 randomized open-label trials of intra-abdominal infection comparing piperacillin–tazobactam or ceftriaxone/metronidazole with ertapenem. In these short-term studies, overall rates of bowel colonization with VRE were generally comparable after treatment with piperacillin–tazobactam, ceftriaxone/metronidazole, or ertapenem. [Copyright &y& Elsevier]

The first-order degradation rate constant (k deg ) of cytochrome P450 (CYP) enzymes is a known source of uncertainty in the prediction of time-dependent drug-drug interactions (DDIs) in physiologically-based pharmacokinetic (PBPK) modelling. This study aimed to measure CYP k deg using siRNA to suppress CYP expression in primary human hepatocytes followed by incubation over a time-course and tracking of protein expression and activity to observe degradation. The magnitude of gene knockdown was determined by qPCR and activity was measured by probe substrate metabolite formation and CYP2B6-Glo™ assay. Protein disappearance was determined by Western blotting. During a time-course of 96 and 60 h of incubation, over 60% and 76% mRNA knockdown was observed for CYP3A4 and CYP2B6, respectively. The k deg of CYP3A4 and CYP2B6 protein was 0.0138 h -1 (±0.0023) and 0.0375 h -1 (±0.025), respectively. The k deg derived from probe substrate metabolism activity was 0.0171 h -1 (±0.0025) for CYP3A4 and 0.0258 h -1 (±0.0093) for CYP2B6. The CYP3A4 k deg values derived from protein disappearance and metabolic activity were in relatively good agreement with each other and similar to published values. This novel approach can now be used for other less well-characterised CYPs., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)