Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada.
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA; Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Chest. 2021 Mar;159(3):1041-1054. doi: 10.1016/j.chest.2020.10.039. Epub 2020 Oct 23.
Previous meta-analyses suggested that treating hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), with empiric carbapenems was associated with lower mortality rates but higher rates of clinical failure for pseudomonal pneumonia. This study was an updated meta-analysis with sensitivity analyses and meta-regression to better understand the impact of carbapenem use in HAP/VAP.
What is the efficacy of carbapenems for empiric treatment of nosocomial pneumonia?
Databases were searched for randomized controlled studies evaluating empiric treatment for HAP and/or VAP, and studies were included comparing carbapenem- vs non-carbapenem-containing regimens. The primary outcome was all-cause mortality. Secondary outcomes included subgroup stratification and resistance development.
Of 9,140 references, 20 trials enrolling 5,489 patients met inclusion criteria. For mortality, carbapenem use had a risk ratio (RR) of 0.84 (95% CI, 0.74-0.96; P = .01). Stratified according to VAP proportion (< 33%, 33%-66%, and > 66%), RRs were 0.95 (95% CI, 0.77-1.17; P = .66), 0.78 (95% CI, 0.57-1.07; P = .13), and 0.81 (95% CI, 0.65-0.99; P = .04), respectively. Stratified according to severity, only groups with Acute Physiology and Chronic Health Evaluation II scores < 14 and between 14 and 17 showed mortality benefit (RRs of 0.64 [95% CI, 0.45-0.92; P = .01] and 0.77 [95% CI, 0.61-0.97; P = .03]). Meta-regression did not show an association between Pseudomonas prevalence and mortality (P = .44). Carbapenem use showed a trend toward developing resistance (RR, 1.40; 95% CI, 0.95-2.06; P = .09) and a 96% probability of resistance emergence.
Carbapenem-based empiric regimens were associated with lower mortality rates compared with non-carbapenems, largely driven by trials of VAP. The mortality effect was not observed in trials with high disease severity and was not associated with Pseudomonas. The mortality difference was observed mainly in studies that used ceftazidime as control. There was a trend toward increasing resistance associated with carbapenems.
International Prospective Register of Systematic Reviews; No. CRD42018093602; URL: https://www.crd.york.ac.uk/prospero/.
先前的荟萃分析表明，经验性使用碳青霉烯类药物治疗医院获得性肺炎（HAP），包括呼吸机相关性肺炎（VAP），可降低死亡率，但铜绿假单胞菌肺炎的临床失败率更高。本研究是一项更新的荟萃分析，包括敏感性分析和荟萃回归，以更好地了解 HAP/VAP 中碳青霉烯类药物使用的影响。
碳青霉烯类药物经验性治疗医院获得性肺炎的疗效如何？
检索数据库，以评估 HAP 和/或 VAP 的经验性治疗的随机对照研究，并纳入比较碳青霉烯类与非碳青霉烯类药物治疗方案的研究。主要结局是全因死亡率。次要结局包括亚组分层和耐药性发展。
在 9140 篇参考文献中，有 20 项试验纳入了 5489 名患者，符合纳入标准。碳青霉烯类药物的使用与死亡率的风险比（RR）为 0.84（95%CI，0.74-0.96；P=0.01）。根据 VAP 比例（<33%、33%-66%和>66%）分层，RR 分别为 0.95（95%CI，0.77-1.17；P=0.66）、0.78（95%CI，0.57-1.07；P=0.13）和 0.81（95%CI，0.65-0.99；P=0.04）。根据严重程度分层，只有急性生理学和慢性健康评估 II 评分<14 和 14-17 分的组显示出死亡率获益（RR 分别为 0.64[95%CI，0.45-0.92；P=0.01]和 0.77[95%CI，0.61-0.97；P=0.03]）。荟萃回归未显示铜绿假单胞菌流行率与死亡率之间存在关联（P=0.44）。碳青霉烯类药物的使用与耐药性的发展呈趋势（RR，1.40；95%CI，0.95-2.06；P=0.09），耐药性出现的概率为 96%。
与非碳青霉烯类药物相比，碳青霉烯类药物经验性治疗方案与较低的死亡率相关，这主要归因于 VAP 试验。在疾病严重程度高的试验中未观察到死亡率效应，且与铜绿假单胞菌无关。死亡率差异主要见于使用头孢他啶作为对照的研究中。碳青霉烯类药物的使用与耐药性的发展呈趋势相关。
国际前瞻性系统评价注册库；编号 CRD42018093602；网址：https://www.crd.york.ac.uk/prospero/。
