Lai Chengcheng, Ma Zijun, Zhang Jun, Wang Junjun, Wang Jinghui, Wu Zhuanghao, Luo Yonggang
Department of General Practice, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Syst Rev. 2024 Dec 19;13(1):309. doi: 10.1186/s13643-024-02695-x.
For resistant Gram-positive bacteria, evidence suggests that combination therapy is more effective. However, for resistant Gram-negative bacteria, no consensus has been reached. This study aims to comprehensively summarize the evidence and evaluate the impact of combination versus monotherapy on infections caused by carbapenem-resistant Gram-negative bacteria (CRGNB).
A systematic search was conducted in PubMed, Cochrane library, Web of Science, and Embase up to June 15, 2024, to identify relevant studies. This study included comparisons of monotherapy and combination therapy for treating infections caused by CRGNB. Topical antibiotics (i.e., inhalational or intratracheal administration) and monotherapy with sulbactam/relebactam was excluded. The primary outcome was mortality, and the secondary outcomes were clinical success and microbiological eradication. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated in order to systematically assess effect of treatment on mortality, clinical success and microbiological eradication. Subgroup analyses, publication bias tests, and sensitivity analyses were also performed.
A total of 62 studies, including 8342 participants, were analyzed, comprising 7 randomized controlled trials and 55 non-randomized studies. Monotherapy was associated with higher mortality (OR = 1.29, 95%CI: 1.11-1.51), lower clinical success (OR = 0.74, 95%CI: 0.56-0.98), and lower microbiological eradication (OR = 0.71, 95%CI: 0.55-0.91) compared to combination therapy for CRGNB infections. Specifically, patients with carbapenem-resistant Enterobacteriaceae (CRE) infections receiving monotherapy had higher mortality (OR = 1.50, 95%CI: 1.15-1.95), comparable clinical success (OR = 0.57,95%CI: 0.28-1.16), and lower microbiological eradication (OR = 0.48,95%CI:0.25-0.91) than those receiving combination therapy. For carbapenem-resistant Acinetobacter baumannii (CRAB) infections, no significant differences were observed in mortality (OR = 1.15.95%CI: 0.90-1.47), clinical success (OR = 0.95,95%CI: 0.74-1.24) and microbiological eradication (OR = 0.78,95%CI: 0.54-1.12).
Monotherapy or combination therapy is controversial. The systematic review and meta-analysis suggested that monotherapy is associated with higher mortality, lower clinical success, and lower microbiological eradication for treating infection caused by CRGNB. The available evidence suggests that treatment should be selected based on the specific bacteria and antibiotic used. Monotherapy for CRE infections may lead to adverse outcomes. For CRAB infections, no significant differences were found between combination therapy and monotherapy.
PROSPERO CRD42022331861.
对于耐药革兰氏阳性菌，有证据表明联合治疗更有效。然而，对于耐药革兰氏阴性菌，尚未达成共识。本研究旨在全面总结证据，并评估联合治疗与单一疗法对碳青霉烯类耐药革兰氏阴性菌（CRGNB）所致感染的影响。
截至2024年6月15日，在PubMed、Cochrane图书馆、科学网和Embase中进行系统检索，以识别相关研究。本研究纳入了治疗CRGNB所致感染的单一疗法与联合疗法的比较。排除局部用抗生素（即吸入或气管内给药）以及舒巴坦/瑞来巴坦单一疗法。主要结局为死亡率，次要结局为临床成功率和微生物清除率。计算合并比值比（OR）和95%置信区间（CI），以便系统评估治疗对死亡率、临床成功率和微生物清除率的影响。还进行了亚组分析、发表偏倚检验和敏感性分析。
共分析了62项研究，包括8342名参与者，其中有7项随机对照试验和55项非随机研究。与CRGNB感染的联合治疗相比，单一疗法与更高的死亡率（OR = 1.29，95%CI：1.11 - 1.51）、更低的临床成功率（OR = 0.74，95%CI：0.56 - 0.98）以及更低的微生物清除率（OR = 0.71，95%CI：0.55 - 0.91）相关。具体而言，接受单一疗法的碳青霉烯类耐药肠杆菌科（CRE）感染患者的死亡率更高（OR = 1.50，95%CI：1.
