Medical Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania.
Infectious Disease Department, Victor Babes University Hospital Craiova, 200515 Craiova, Romania.
Int J Mol Sci. 2024 Sep 4;25(17):9574. doi: 10.3390/ijms25179574.
Antimicrobial resistance is increasingly concerning, causing millions of deaths and a high cost burden. Given that carbapenemase-producing Enterobacterales are particularly concerning due to their ability to develop structural modifications and produce antibiotic-degrading enzymes, leading to high resistance levels, we sought to summarize the available data on the efficacy and safety regarding the combination of meropenem-vaborbactam (MV) versus the best available therapy (BAT). Articles related to our objective were searched in the PubMed and Scopus databases inception to July 2024. To assess the quality of the studies, we used the Cochrane risk-of-bias tool, RoB2. The outcomes were pooled as a risk ratio (RR) and a 95% confidence interval (95%CI). A total of four published studies were involved: one retrospective cohort study and three phase 3 trials, including 432 patients treated with MV and 426 patients treated with BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, colistin, and tigecycline; or ceftazidime-avibactam; or piperacillin-tazobactam). No significant difference in the clinical response rate was observed between MV and the comparators at the TOC (RR = 1.29, 95%CI [0.92, 1.80], = 0.14) and EOT (RR = 1.66, 95%CI [0.58, 4.76], = 0.34) visits. MV was associated with a similar microbiological response as the comparators at TOC (RR = 1.63, 95%CI [0.85, 3.11], = 0.14) and EOT assessment (RR = 1.16, 95%CI [0.88, 1.54], = 0.14). In the pooled analysis of the four studies, 28-day all-cause mortality was lower for MV than the control groups (RR = 0.47, 95%CI [0.24, 0.92], = 0.03). MV was associated with a similar risk of adverse events (AEs) as comparators (RR = 0.79, 95%CI [0.53, 1.17], = 0.23). Additionally, MV was associated with fewer renal-related AEs than the comparators (RR = 0.32, 95%CI [0.15, 0.66], = 0.002). MV was associated with a similar risk of treatment discontinuation due to AEs (RR = 0.76, 95%CI [0.38, 1.49], = 0.42) or drug-related AEs (RR = 0.56, 95%CI [0.28, 1.10], = 0.09) as the comparators. In conclusion, MV presents a promising therapeutic option for treating CRE infections, demonstrating similar clinical and microbiological responses as other comparators, with potential advantages in mortality outcomes and renal-related AEs.
抗菌药物耐药性日益令人担忧，导致数百万人死亡和高昂的负担。鉴于产碳青霉烯酶肠杆菌科由于其能够进行结构修饰和产生抗生素降解酶而特别令人关注，导致高水平的耐药性，我们旨在总结有关美罗培南-法硼巴坦（MV）与最佳可用治疗（BAT）联合治疗的疗效和安全性的现有数据。在 2024 年 7 月之前，在 PubMed 和 Scopus 数据库中搜索了与我们的目标相关的文章。为了评估研究的质量，我们使用了 Cochrane 风险偏倚工具 RoB2。结果以风险比（RR）和 95%置信区间（95%CI）进行汇总。共有四项已发表的研究涉及：一项回顾性队列研究和三项 3 期试验，包括 432 名接受 MV 治疗的患者和 426 名接受 BAT 治疗的患者（多粘菌素、碳青霉烯类、氨基糖苷类、粘菌素和替加环素的单药/联合治疗；或头孢他啶-阿维巴坦；或哌拉西林-他唑巴坦）。在 TOC（RR=1.29，95%CI[0.92，1.80]， =0.14）和 EOT（RR=1.66，95%CI[0.58，4.76]， =0.34）就诊时，MV 与对照药物在临床反应率方面无显著差异。MV 与对照药物在 TOC（RR=1.63，95%CI[0.85，3.11]， =0.14）和 EOT 评估（RR=1.16，95%CI[0.88，1.54]， =0.14）时的微生物学反应相似。在四项研究的汇总分析中，MV 组 28 天全因死亡率低于对照组（RR=0.47，95%CI[0.24，0.92]， =0.03）。MV 与对照药物的不良事件（AE）风险相似（RR=0.79，95%CI[0.53，1.17]， =0.23）。此外，MV 组与对照组相比，肾相关 AE 较少（RR=0.32，95%CI[0.15，0.66]， =0.002）。MV 与对照组因 AE（RR=0.76，95%CI[0.38，1.49]， =0.42）或药物相关 AE（RR=0.56，95%CI[0.28，1.10]， =0.09）停药的风险相似。总之，MV 为治疗 CRE 感染提供了一种有前景的治疗选择，与其他对照药物相比，MV 具有相似的临床和微生物学反应，在死亡率和肾相关 AE 方面具有潜在优势。
