Introduction

Gram-negative nosocomial pneumonia (NP), including hospital-acquired bacterial pneumonia (HABP), ventilated HABP (vHABP), and ventilator-associated bacterial pneumonia (VABP), is a significant cause of morbidity and mortality. Common pathogens, including Enterobacterales and Pseudomonas aeruginosa, are prevalent in healthcare settings and have few effective treatment options due to high rates of antibacterial resistance. Resistant pathogens are associated with significantly worse outcomes, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials of patients with NP. This review aims to collate data on C/T use for HABP/vHABP/VABP infections in real-world clinical practice.

Methods

This systematic literature review searched online biomedical databases for real-world studies of C/T used to treat Gram-negative respiratory tract infections (RTIs) between January 2009 and June 2020.

Results

Thirty-three studies comprising 658 patients were identified. Pneumonia was the most common infection treated with C/T (85%), with a smaller number of unspecified RTIs (9%) and tracheobronchitis (5%) reported. The majority of patients had respiratory infections caused by P. aeruginosa (92.8%), of which 88.1% were multidrug-resistant. Examination of these studies demonstrated an increase in the percentage of patients receiving the recommended dose of C/T for respiratory infections (3 g q8h or renal impairment-adjusted) over time (36.8% of patients in 2017 to 71.5% in 2020). Clinical success rates ranged from 51.4 to 100%, with 10 studies (55.6% of studies reporting clinical success) reporting clinical success rates of > 70%; microbiological success rates ranged from 57.0 to 100.0%, with three studies (60.0% of studies reporting microbiological success) reporting microbiological success rates of > 70%. Thirty-day mortality ranged from 0.0 to 33.0%, with nine studies (90% of studies reporting mortality) reporting 30-day mortality of < 30%.

Conclusions

The studies identified in this review demonstrate that C/T shows similar outcomes as those seen in clinical trials, despite the higher frequency of multidrug-resistant pathogens, and comorbidities that may have been excluded from the trials.

中文翻译：

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Ceftolozane/他唑巴坦治疗呼吸道感染的真实世界证据的系统文献综述

介绍

革兰氏阴性医院获得性肺炎 (NP)，包括医院获得性细菌性肺炎 (HABP)、机械通气 HABP (vHABP) 和呼吸机相关细菌性肺炎 (VABP)，是发病率和死亡率的重要原因。常见的病原体，包括肠杆菌属和铜绿假单胞菌，在医疗机构中很普遍，但由于抗菌药物耐药率很高，因此几乎没有有效的治疗选择。相对于易感感染的患者，耐药病原体与显着更差的结果相关。头孢唑烷/他唑巴坦 (C/T) 在 NP 患者的临床试验中已确立疗效。本综述旨在整理真实世界临床实践中 C/T 用于 HABP/vHABP/VABP 感染的数据。

方法

这篇系统性文献综述在在线生物医学数据库中搜索了 2009 年 1 月至 2020 年 6 月期间用于治疗革兰氏阴性呼吸道感染 (RTI) 的 C/T 的真实世界研究。

结果

确定了包括 658 名患者的 33 项研究。肺炎是用 C/T 治疗的最常见感染 (85%)，报告了较少数量的未指定 RTIs (9%) 和气管支气管炎 (5%)。大多数患者患有由铜绿假单胞菌引起的呼吸道感染(92.8%)，其中 88.1% 为多重耐药。对这些研究的检查表明，随着时间的推移，接受推荐剂量的 C/T 治疗呼吸道感染（3 g q8h 或肾功能损害调整后）的患者百分比随时间增加（2017 年为 36.8%，2020 年为 71.5%）。临床成功率从 51.4% 到 100% 不等，其中 10 项研究（55.6% 的研究报告临床成功）报告临床成功率 > 70%；微生物学成功率从 57.0% 到 100.0% 不等，其中三项研究（60.0% 的研究报告微生物学成功）报告微生物学成功率 > 70%。30 天死亡率范围为 0.0% 至 33.0%，其中 9 项研究（90% 的研究报告死亡率）报告 30 天死亡率 < 30%。

结论

本综述中确定的研究表明，C/T 显示出与临床试验相似的结果，尽管耐多药病原体的频率较高，并且可能已被排除在试验之外的合并症。