Evidera, The Ark, 201 Talgarth Road, Hammersmith, London W6 8BJ UK.
2Klinikum Peine, Academic Hospital of Medical University Hannover, Hannover, Germany.
Antimicrob Resist Infect Control. 2019 Dec 21;8:204. doi: 10.1186/s13756-019-0652-x. eCollection 2019.
The rising incidence of resistance to currently available antibiotics among pathogens, particularly Gram-negative pathogens, in complicated intra-abdominal infections (cIAIs) has become a challenge for clinicians. Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose antibiotic approved in Europe and the United States for treating (in combination with metronidazole) cIAI in adult hospitalised patients who have limited or no alternative treatment options. The approval was based on the results of RECLAIM, a Phase III, parallel-group, comparative study (RECLAIM 1 [NCT01499290] and RECLAIM 2 [NCT01500239]). The objective of our study was to assess the cost-effectiveness of CAZ-AVI plus metronidazole compared with 1) ceftolozane/tazobactam plus metronidazole and 2) meropenem, as an empiric treatment for the management of cIAI in Italy.
A sequential, patient-level simulation model, with a 5-year time horizon and 3% annual discount rate (applied to both costs and health benefits), was developed using Microsoft Excel® to demonstrate the clinical course of the disease. The impact of resistant pathogens was included as an additional factor.
In the base-case analysis, the CAZ-AVI sequence (CAZ-AVI plus metronidazole followed by a colistin + tigecycline + high-dose meropenem combination after treatment failure), when compared to sequences for ceftolozane/tazobactam (ceftolozane/tazobactam plus metronidazole followed by colistin + tigecycline + high-dose meropenem after treatment failure) and meropenem (meropenem followed by colistin + tigecycline + high-dose meropenem after treatment failure), had better clinical outcomes with higher cure rates (93.04% vs. 91.52%; 92.98% vs. 90.24%, respectively), shorter hospital stays (∆ = - 0.38 and ∆ = - 1.24 days per patient, respectively), and higher quality-adjusted life years (QALYs) gained per patient (4.021 vs. 3.982; 4.019 vs. 3.960, respectively). The incremental cost effectiveness ratio in the CAZ-AVI sequence was €4099 and €15,574 per QALY gained versus each comparator sequence, respectively, well below the willingness-to-pay threshold of €30,000 per QALY accepted in Italy.
The model results demonstrated that CAZ-AVI plus metronidazole could be a cost-effective alternative when compared with other antibiotic treatment options, as it is expected to provide better clinical benefits in hospitalised patients with cIAI in Italy.
目前,病原体(尤其是革兰氏阴性病原体)对现有抗生素的耐药性不断上升,这给复杂性腹腔内感染(cIAI)的临床医生带来了挑战。头孢他啶/阿维巴坦(CAZ-AVI)是一种固定剂量抗生素,已在欧美获得批准,用于治疗患有复杂性腹腔内感染的住院成人患者(联合使用甲硝唑),这些患者的治疗选择有限或没有其他选择。该批准基于 III 期、平行组、对照研究 RECLAIM 的结果(RECLAIM 1[NCT01499290]和 RECLAIM 2[NCT01500239])。我们的研究目的是评估 CAZ-AVI 加甲硝唑与 1)头孢他啶/他唑巴坦加甲硝唑和 2)美罗培南相比,作为意大利治疗复杂性腹腔内感染的经验性治疗的成本效益。
使用 Microsoft Excel®开发了一个连续的患者水平模拟模型,具有 5 年的时间范围和 3%的年度贴现率(同时应用于成本和健康效益),以展示疾病的临床过程。将耐药病原体的影响作为附加因素包括在内。
在基础案例分析中,CAZ-AVI 方案(CAZ-AVI 加甲硝唑,然后在治疗失败后使用粘菌素+替加环素+高剂量美罗培南联合治疗)与头孢他啶/他唑巴坦方案(头孢他啶/他唑巴坦加甲硝唑,然后在治疗失败后使用粘菌素+替加环素+高剂量美罗培南联合治疗)和美罗培南方案(治疗失败后使用粘菌素+替加环素+高剂量美罗培南联合治疗)相比,具有更好的临床结果,治愈率更高(93.04% vs. 91.52%;92.98% vs. 90.24%),住院时间更短(每位患者分别减少 0.38 和 1.24 天),每位患者获得的质量调整生命年(QALY)更高(4.021 vs. 3.982;4.019 vs. 3.960)。CAZ-AVI 方案的增量成本效益比分别为每个 QALY 增加 4099 欧元和 15574 欧元,而每个比较方案的增量成本效益比分别为每个 QALY 增加 4099 欧元和 15574 欧元,远低于意大利接受的每 QALY 30000 欧元的意愿支付阈值。
模型结果表明,CAZ-AVI 加甲硝唑可能是一种具有成本效益的替代方案,因为与其他抗生素治疗方案相比,它有望为意大利患有复杂性腹腔内感染的住院患者提供更好的临床获益。