کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5667087 1591747 2017 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Piperacillin/tazobactam as an alternative antibiotic therapy to carbapenems in the treatment of urinary tract infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae: an in silico pharmacokinetic study
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروبیولوژی و بیوتکنولوژی کاربردی
پیش نمایش صفحه اول مقاله
Piperacillin/tazobactam as an alternative antibiotic therapy to carbapenems in the treatment of urinary tract infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae: an in silico pharmacokinetic study
چکیده انگلیسی


- Piperacillin/tazobactam for ESBL-PE UTI was evaluated by Monte Carlo simulation.
- Continuous infusion or 4.5 g four times daily as a 4-h infusion appears convenient for mild pyelonephritis.
- Continuous infusion should be preferred for severe pyelonephritis due to ESBL-Kp.

Piperacillin/tazobactam (TZP) as an alternative treatment to carbapenems for infections involving extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) remains debated. In this study, the probabilities of pharmacodynamic (PD) target attainment with different TZP regimens in ESBL-producing Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp) were evaluated in the context of pyelonephritis. Minimum inhibitory concentrations (MICs) of 144 ESBL-Ec and 111 ESBL-Kp from pyelonephritis were measured, and two previously published population pharmacokinetic models were used to determine by Monte Carlo simulation the probabilities of reaching two PD targets (50%fT>MIC and 100%fT>MIC) with TZP doses of 4 g three times daily and 4.5 g four times daily given as short (1 h) or prolonged (4 h) infusions or as 12-18 g/day continuous infusions. Only MICs of the 133 ESBL-Ec and 74 ESBL-Kp strains susceptible to TZP according to inhibition zone diameter were considered for the simulations. Results were similar with the two models, and only prolonged and continuous infusions allowed to reach 50%fT>MIC with a probability of >90% irrespective of bacterial species. Continuous infusion and prolonged infusion combined with the maximum dosage were the only condition allowing to achieve 100%fT>MIC with a probability of >70% with this population of ESBL-Ec. A probability of >90% to reach 100%fT>MIC with ESBL-Kp could be obtained only with the 18 g/day continuous-infusion regimen. TZP may be used for treatment for mild pyelonephritis involving susceptible ESBL-Ec provided that administration modalities are optimised. Conversely, for ESBL-Kp the risk of treatment failure may be higher, supporting the use of continuous infusion.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Antimicrobial Agents - Volume 49, Issue 1, January 2017, Pages 62-66
نویسندگان
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