Data Sheet 1_Factors affecting the effectiveness and safety of colistin in treating drug-resistant gram-negative bacterial infections: a meta-analysis.zip

PurposeAs an important antibiotic for treating infections caused by drug-resistant Gram-negative bacteria, colistin’s clinical efficacy and safety might be influenced by multiple factors. This meta-analysis aimed to identify the key factors affecting the effectiveness and safety of colistin in treating these infections. The results of this study provide a reference for clinicians to choose treatment methods. At the same time, the rational use of colistin can prevent the occurrence of adverse drug reactions (AKI), improve the cure rate of patients, and delay the development of bacterial resistance.
MethodsThe overall mortality rate was designated as the primary effectiveness outcome, with clinical response rate and bacterial eradication rate serving as the secondary outcomes. The incidence of acute kidney injury (AKI) was evaluated as a safety endpoint. Key analytical variables included colistin dose (high-dose≥4.2 mg/kg/day and low-dose< 4.2 mg/kg/day), ACCI (low <5, moderate = five to six, high >6), co-therapy (carbapenems/tigecycline/fosfomycin, etc.), microbial species (Acinetobacter baumannii/Pseudomonas aeruginosa/Enterobacteriaceae, etc.), and administration methods (aerosolized plus intravenous colistin vs. intravenous colistin alone).
ResultsA total of 74 studies (N = 8,889 participants) were included in our analysis. Mortality was lower in the high-dose group compared to the low-dose group (34.09% vs. 41.08%, p = 0.09). In ACCI score subgroups (low, moderate, high), mortality rates were 27.11% vs. 44.69% vs. 47.11% (p < 0.01). Monotherapy was associated with a higher mortality rate compared to co-therapy (42.97% vs. 33.10%, p < 0.01). Although no statistical differences were observed among different pathogenic bacteria species, infection caused by A. baumannii exhibited the highest mortality rate at 43.75%. Mortality rates for aerosolized plus intravenous colistin versus intravenous colistin alone were 40.81% vs. 32.84% (p = 0.09). The incidence of AKI was significantly higher in the loading dose group, high-ACCI group, and group receiving concomitant nephrotoxic drugs while being notably lower in the Pseudomonas aeruginosa infection group.
ConclusionLoading dose, co-therapy (carbapenems or quinolones), microbial factors, and ACCI are the main factors associated with the effectiveness of colistin. Additionally, loading dose, microbial factors, ACCI, and co-therapy are associated with an increased risk of colistin-associated AKI.
Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/search, identifier CRD420250655507.

目的：作为治疗耐药革兰阴性菌感染的重要抗生素，黏菌素的临床疗效与安全性可能受多种因素影响。本荟萃分析旨在明确影响黏菌素治疗此类感染的疗效与安全性的关键因素。本研究结果可为临床医师选择治疗方案提供参考。同时，合理使用黏菌素可预防药品不良反应（急性肾损伤，acute kidney injury, AKI）的发生，提升患者治愈率，并延缓细菌耐药性的发展。
方法：将总死亡率设为主要疗效结局指标，临床应答率与细菌清除率作为次要结局指标。以急性肾损伤（acute kidney injury, AKI）的发生率作为安全性评价终点。关键分析变量包括黏菌素剂量（高剂量≥4.2 mg/kg/日，低剂量<4.2 mg/kg/日）、ACCI（低危<5分，中危5~6分，高危>6分）、联合治疗（碳青霉烯类、替加环素、磷霉素等）、微生物菌种（鲍曼不动杆菌、铜绿假单胞菌、肠杆菌科等）以及给药方式（雾化吸入联合静脉输注黏菌素 vs 单纯静脉输注黏菌素）。
结果：本分析共纳入74项研究，共计8889名受试者。高剂量组死亡率低于低剂量组（34.09% vs 41.08%，p=0.09）。在ACCI评分亚组（低危、中危、高危）中，死亡率分别为27.11%、44.69%、47.11%（p<0.01）。单药治疗组死亡率高于联合治疗组（42.97% vs 33.10%，p<0.01）。尽管不同致病菌菌种间未观察到统计学差异，但鲍曼不动杆菌感染所致死亡率最高，达43.75%。雾化吸入联合静脉输注黏菌素组与单纯静脉输注黏菌素组的死亡率分别为40.81%与32.84%（p=0.09）。负荷剂量组、高ACCI评分组及合并使用肾毒性药物患者的AKI发生率显著升高，而铜绿假单胞菌感染组的AKI发生率则显著降低。
结论：负荷剂量、联合治疗（碳青霉烯类或喹诺酮类）、微生物学因素及ACCI评分是影响黏菌素疗效的主要因素。此外，负荷剂量、微生物学因素、ACCI评分及联合治疗与黏菌素相关AKI的发病风险升高相关。
系统评价注册：https://www.crd.york.ac.uk/PROSPERO/search，注册号CRD420250655507。