Tekes-Manuva Dorit, Babich Tanya, Kozlovski Dror, Elbaz Michal, Yahav Dafna, Halperin Erez, Leibovici Leonard, Avni Tomer
Internal Medicine Department, Maayenei Hayeshua Medical Center, Bnei-Brak, Israel; Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel; Research Authority, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.
Clin Microbiol Infect. 2025 May;31(5):740-752. doi: 10.1016/j.cmi.2024.12.036. Epub 2024 Dec 31.
Severe infections caused by Pseudomonas aeruginosa are associated with significant morbidity and mortality, particularly in hospitalized and immunocompromised patients. Determining the optimal definitive monotherapy for these infections is critical. The main objective was to compile the evidence of subgroups of patients with Pseudomonas aeruginosa infection from randomized control trials (RCTs) evaluating different definite antipseudomonal monotherapies for severe P. aeruginosa infection.
Systematic review and meta-analysis of RCTs that assessed monotherapy with an antipseudomonal drug versus another antipseudomonal for definite treatment, and reported on the subgroup of patients with P. aeruginosa infection. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, LILACS and the reference lists of included trials. Eligibility criteria included RCTs enrolling hospitalized adults (≥18 years) with microbiologically confirmed severe P. aeruginosa infections. Studies were excluded if they included >20% of patients receiving combination therapy or if patients had resistant P. aeruginosa strains at recruitment. Antipseudomonal drugs evaluated included cephalosporins, carbapenems, penicillins, quinolones and aztreonam. The primary outcome was 30-day mortality. Risk of bias was assessed using the Cochrane tool. Results were pooled using fixed-effects and random-effects models as appropriate. Relative risk (RR) and 95% CIs were calculated. Sensitivity analyses and subgroup analyses were performed when data were available.
A total of 76 RCTs and 1681 patients with pseudomonal infection were included. Due to the low number of studies which reported our outcomes of interest, all subgroup analyses were underpowered. No difference in all-cause mortality was found for any direct antibiotic comparison. Higher clinical failure rates of carbapenems versus piperacillin-tazobactam were observed for pneumonia in two RCTs (RR, 2.55; 95% CI, 1.29-5.03; I = 0%, n = 2), and higher microbiological failure rates with carbapenems versus other comparators (RR, 1.24; 95% CI, 1.02-1.51; I = 0%, n = 23). Patients treated with imipenem were more likely to develop resistance to the study drug versus comparators (RR, 2.33; 95% CI, 1.61-3.38; I = 0%, n = 7).
In this systematic review and meta-analysis of definite antipseudomonal monotherapy for P. aeruginosa infection, we found no evidence of clinical benefit differences among direct antibiotic comparisons, but all subgroup analyses were underpowered to detect significant differences.
铜绿假单胞菌引起的严重感染与显著的发病率和死亡率相关，尤其是在住院患者和免疫功能低下的患者中。确定针对这些感染的最佳确定性单药治疗至关重要。主要目的是汇总来自评估不同确定性抗铜绿假单胞菌单药治疗严重铜绿假单胞菌感染的随机对照试验（RCT）中铜绿假单胞菌感染患者亚组的证据。
对评估使用一种抗铜绿假单胞菌药物与另一种抗铜绿假单胞菌药物进行确定性治疗的单药治疗，并报告铜绿假单胞菌感染患者亚组情况的RCT进行系统评价和荟萃分析。我们检索了Cochrane对照试验中央登记册（CENTRAL）、MEDLINE、拉丁美洲和加勒比卫生科学数据库（LILACS）以及纳入试验的参考文献列表。纳入标准包括招募住院成年患者（≥18岁）且经微生物学确诊为严重铜绿假单胞菌感染的RCT。如果研究中接受联合治疗的患者超过20%，或者患者在入组时感染的是耐药铜绿假单胞菌菌株，则将其排除。评估的抗铜绿假单胞菌药物包括头孢菌素、碳青霉烯类、青霉素类、喹诺酮类和氨曲南。主要结局是30天死亡率。使用Cochrane工具评估偏倚风险。根据情况使用固定效应模型和随机效应模型汇总结果。计算相对风险（RR）和95%置信区间（CI）。当有数据时进行敏感性分析和亚组分析。
共纳入76项RCT和1681例铜绿假单胞菌感染患者。由于报告我们感兴趣结局的研究数量较少，所有亚组分析的效能均不足。在任何直接抗生素比较中，全因死亡率均无差异。在两项RCT中，肺炎患者使用碳青霉烯类药物的临床失败率高于哌拉西林 - 他唑巴坦（RR，2.55；95% CI，1.29 - 5.03；I² = 0%，n = 2），使用碳青霉烯类药物的微生物学失败率高于其他对照药物（RR，1.24；95% CI，1.02 - 1.51；I² = 0%，n = 23）。与对照药物相比，接受亚胺培南治疗的患者对研究药物产生耐药的可能性更大（RR，2.33；95% CI，1.61 - 3.38；I² = 0%，n = 7）。
在这项针对铜绿假单胞菌感染的确定性抗铜绿假单胞菌单药治疗的系统评价和荟萃分析中，我们未发现直接抗生素比较之间存在临床获益差异的证据，但所有亚组分析的效能均不足以检测到显著差异。
