Department of Infectious Diseases, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy.
Department of Infectious Diseases, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy.
Int J Antimicrob Agents. 2024 May;63(5):107134. doi: 10.1016/j.ijantimicag.2024.107134. Epub 2024 Mar 5.
To investigate the efficacy of intravenous (IV) fosfomycin as combination therapy for treatment of difficult-to-treat (DTT) acute and subacute infections with multi-drug-resistant (MDR) Gram-negative bacteria (GNB), and risk factors associated with 90-day mortality.
A retrospective, observational, monocentric study enrolled patients treated with IV fosfomycin in combination regimens (≥72 h) for proven DTT-MDR-GNB infection. Multi-variate regression analysis identified independent risk factors for 90-day mortality. A propensity score for receiving fosfomycin was performed to control for confounding factors.
In total, 70 patients were included in this study: 54.3% had carbapenem-resistant isolates, 31.4% had ceftazidime/avibactam-resistant isolates and 28.6% had ceftolozane/tazobactam-resistant isolates. The main pathogens were Pseudomonas aeruginosa (57.1%) and Klebsiella pneumoniae (22.9%). The most prevalent infections were nosocomial pneumonia (42.9%), osteomyelitis (17.1%) and intra-abdominal infections. All-cause 30- and 90-day mortality were 15.7% and 31.4%, respectively (18.9% and 50% considering acute DTT-MDR-GNB infections alone). Relapse at 30 days occurred in 22.9% of cases (29% with emergence of fosfomycin resistance). Mortality at 90 days was independently associated with septic shock and ceftolozane/tazobactam resistance. The relationship between resistance to ceftolozane/tazobactam and 90-day mortality was confirmed to be significant after adjustment by propensity score analysis (hazard ratio 5.84, 95% confidence interval 1.65-20.68; P=0.006).
Fosfomycin seems to be a promising salvage, combination treatment in DTT-MDR-GNB infections. Resistance to ceftolozane/tazobactam seems to be independently associated with treatment failure. Randomized clinical trials focusing on pathogen and infection sites are needed urgently to demonstrate the superiority of fosfomycin in combination with other agents for the resolution of DTT-MDR-GNB infections.
研究静脉注射（IV）磷霉素作为联合治疗方案治疗多药耐药（MDR）革兰氏阴性菌（GNB）所致治疗困难（DTT）的急性和亚急性感染的疗效，以及与 90 天死亡率相关的危险因素。
这是一项回顾性、观察性、单中心研究，纳入了使用磷霉素联合治疗方案（≥72 小时）治疗确诊为 DTT-MDR-GNB 感染的患者。多变量回归分析确定了 90 天死亡率的独立危险因素。为了控制混杂因素，进行了接受磷霉素治疗的倾向评分。
共有 70 例患者纳入本研究，其中 54.3%的患者分离出碳青霉烯类耐药菌，31.4%的患者分离出头孢他啶/阿维巴坦耐药菌，28.6%的患者分离出头孢唑肟/他唑巴坦耐药菌。主要病原体为铜绿假单胞菌（57.1%）和肺炎克雷伯菌（22.9%）。最常见的感染为医院获得性肺炎（42.9%）、骨髓炎（17.1%）和腹腔内感染。全因 30 天和 90 天死亡率分别为 15.7%和 31.4%（仅考虑急性 DTT-MDR-GNB 感染，死亡率分别为 18.9%和 50%）。30 天复发率为 22.9%（出现磷霉素耐药者占 29%）。90 天死亡率与感染性休克和头孢唑肟/他唑巴坦耐药独立相关。经倾向评分分析校正后，头孢唑肟/他唑巴坦耐药与 90 天死亡率的关系仍具有统计学意义（危险比 5.84，95%置信区间 1.65-20.68；P=0.006）。
磷霉素似乎是治疗治疗困难的多药耐药革兰氏阴性菌感染的一种有前途的挽救性联合治疗药物。头孢唑肟/他唑巴坦耐药似乎与治疗失败独立相关。迫切需要开展针对病原体和感染部位的随机临床试验，以证明磷霉素联合其他药物在治疗多药耐药革兰氏阴性菌感染方面的优越性。
