Marra F O, Frighetto L O, Marra C A, Sleigh K M, Stiver H G, Bryce E A, Reynolds R P, Jewesson P J
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Canada.
Ann Pharmacother. 1999 Feb;33(2):156-62. doi: 10.1345/aph.17366.
In 1998 we reported the first Canadian double-blind, randomized, clinical trial involving a comparison of piperacillin/tazobactam (P/T) with imipenem/cilastatin (I/C). The present study was conducted to determine the feasibility of replacing I/C at our institution.
To describe the outcome of a pharmacoeconomic analysis of the clinical trial from the perspective of a tertiary acute-care institution.
A total of 150 consenting adults originally prescribed I/C were randomly assigned to receive either P/T 4.5 g i.v. (n = 75) or I/C 500 mg i.v. (n = 75) every six hours. Actual direct medical resources used in relation to the treatment of bacterial infections were prospectively assessed during a clinical trial; these included cost of study and ancillary antibiotics, hospitalization, diagnostic testing (radiology, laboratory assessments), and labor, as well as treatment of adverse drug reactions, antibiotic failures, and superinfections.
While costs for successful treatment courses were similar across treatment arms, hospitalization costs for treatment course failures were higher for P/T recipients. Direct medical costs for treatment courses associated with a superinfection were also higher in the P/T arm. Overall costs for treatment failures with either study drug were at least twofold those observed for successful treatment courses. Mean total management cost per patient in the P/T group was $15,211 ($ CDN throughout) (95% CI $11,429 to $18,993), compared with $14,232 (95% CI $11,421 to $17,043) in the I/C group (p = 0.32), resulting in a mean cost difference of $979. Sensitivity analyses revealed that the superiority of I/C over P/T for successful treatment of serious infections was sensitive to changes in the cost of hospitalization and drug efficacy for either drug.
Based on the results of the clinical trial, P/T and I/C offer similar clinical, microbiologic, and toxicity outcomes in hospitalized patients with serious infections. Under base-case conditions, our pharmacoeconomic analysis showed that I/C was a cost-effective alternative to P/T at the dosage regimens studied. However, this finding was sensitive to plausible changes in both clinical and economic parameters.
1998年我们报道了加拿大首个双盲、随机临床试验，该试验比较了哌拉西林/他唑巴坦（P/T）与亚胺培南/西司他丁（I/C）。本研究旨在确定在我们机构用P/T替代I/C的可行性。
从三级急性护理机构的角度描述该临床试验的药物经济学分析结果。
总共150名最初被处方I/C的成年受试者同意参与研究，他们被随机分配，每6小时接受一次静脉注射4.5 g P/T（n = 75）或静脉注射500 mg I/C（n = 75）。在一项临床试验期间，前瞻性评估了与细菌感染治疗相关的实际直接医疗资源；这些资源包括研究和辅助抗生素的费用、住院费用、诊断检测（放射学、实验室评估）以及人工费用，还有药物不良反应、抗生素治疗失败及二重感染的治疗费用。
虽然各治疗组成功治疗疗程的费用相似，但P/T组治疗疗程失败的住院费用更高。P/T组与二重感染相关的治疗疗程直接医疗费用也更高。两种研究药物治疗失败的总体费用至少是成功治疗疗程观察费用的两倍。P/T组每位患者的平均总管理成本为15,211加元（全程为加元）（95%置信区间为11,429加元至18,993加元），而I/C组为14,232加元（95%置信区间为11,421加元至17,043加元）（p = 0.32），平均成本差异为979加元。敏感性分析显示，I/C在成功治疗严重感染方面优于P/T这一结果对住院费用和两种药物的药物疗效变化敏感。
基于临床试验结果，P/T和I/C在患有严重感染的住院患者中提供了相似的临床、微生物学和毒性结果。在基础病例条件下，我们的药物经济学分析表明，在所研究的剂量方案中，I/C是P/T具有成本效益的替代药物。然而，这一发现对临床和经济参数的合理变化敏感。
