Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
Adelphi Values PROVE, Adelphi Mill, Bollington, Cheshire, UK.
Antimicrob Resist Infect Control. 2021 Apr 8;10(1):68. doi: 10.1186/s13756-021-00933-8.
Antibacterial-resistant gram-negative infections are a serious risk to global public health. Resistant Enterobacterales and Pseudomonas aeruginosa are highly prevalent, particularly in healthcare settings, and there are limited effective treatment options. Patients with infections caused by resistant pathogens have considerably worse outcomes, and incur significantly higher costs, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials. This review aimed to collate data on C/T use in clinical practice.
This systematic literature review searched online biomedical databases for real-world studies of C/T for gram-negative infections up to June 2020. Relevant study, patient, and treatment characteristics, microbiology, and efficacy outcomes were captured.
There were 83 studies comprising 3,701 patients were identified. The most common infections were respiratory infections (52.9% of reported infections), urinary tract infections (UTIs; 14.9%), and intra-abdominal infections (IAIs; 10.1%). Most patients included were seriously ill and had multiple comorbidities. The majority of patients had infections caused by P. aeruginosa (90.7%), of which 86.0% were antimicrobial-resistant. C/T was used as both a 1.5 g q8h and 3 g q8h dose, for a median duration of 7-56 days (varying between studies). Outcome rates were comparable between studies: clinical success rates ranged from 45.7 to 100.0%, with 27 studies (69%) reporting clinical success rates of > 70%; microbiological success rates ranged from 31 to 100%, with 14 studies (74%) reporting microbiological success rates of > 70%. Mortality rates ranged from 0 to 50%, with 31 studies (69%) reporting mortality rates of ≤ 20%. In comparative studies, C/T was as effective as aminoglycoside- or polymyxin-based regimens, and in some instances, significantly more effective.
The studies identified in this review demonstrate that C/T is effective in clinical practice, despite the diverse group of seriously ill patients, different levels of resistance of the pathogens treated, and varying dosing regimens used. Furthermore, comparative studies suggest that C/T offers a successful alternative to standard of care (SoC).
抗菌耐药革兰氏阴性感染对全球公共健康构成严重威胁。耐药肠杆菌科和铜绿假单胞菌的感染率很高，特别是在医疗保健环境中，且有效治疗选择有限。与敏感感染患者相比，感染耐药病原体的患者预后明显更差，且医疗费用显著更高。头孢他啶/他唑巴坦（C/T）在临床试验中已证实疗效。本综述旨在汇总 C/T 治疗革兰氏阴性感染的临床实践数据。
本系统文献综述对截至 2020 年 6 月的 C/T 治疗革兰氏阴性感染的真实世界研究进行了在线生物医学数据库检索。收集了相关研究、患者和治疗特征、微生物学和疗效结果。
共纳入 83 项研究，包含 3701 例患者。最常见的感染是呼吸道感染（52.9%的报告感染）、尿路感染（14.9%）和腹腔内感染（10.1%）。大多数患者病情严重，合并多种合并症。大多数患者的感染由铜绿假单胞菌引起（90.7%），其中 86.0%对抗菌药物耐药。C/T 剂量为 1.5 g q8h 和 3 g q8h，疗程中位数为 7-56 天（不同研究间存在差异）。各研究间的治疗结局相当：临床治愈率为 45.7%-100.0%，27 项研究（69%）报告的临床治愈率 >70%；微生物学治愈率为 31%-100%，14 项研究（74%）报告的微生物学治愈率 >70%。死亡率为 0%-50%，31 项研究（69%）报告的死亡率 ≤20%。在对照研究中，C/T 与氨基糖苷类或多黏菌素类药物方案同样有效，某些情况下疗效更优。
本综述中纳入的研究表明，C/T 在临床实践中是有效的，尽管患者病情严重，病原体耐药程度不同，且使用的剂量方案各异。此外，对照研究表明 C/T 是标准治疗（SoC）的有效替代方案。
