Abstract：
BACKGROUND: The role of intravenous fosfomycin (iv-FOS), as a part of combination therapy for Gram-negative bacteria bloodstream infections (GNB-BSI), needs to be evaluated in clinical practice as in vitro data show a potential efficacy.
METHODS: All consecutive patients with a GNB-BSI from January 1st, 2021, to April 1st, 2023, were included. Primary outcome was 30-day mortality. A Cox- regression analysis was used to identify predictors of mortality. Moreover, an inverse-probability of treatment-weighting (IPTW) analysis was also performed.
RESULTS: Overall, 363 patients were enrolled: 211 (58%) males, with a median (q1-q3) age of 68 (57-78) years, and a median Charlson-comorbidity index of 5 (3-7). At GNB-BSI onset, median SOFA score was 5 (2-7), 122 (34%) presented with septic shock. Pathogens involved were principally K. pneumoniae (42%), E. coli (28%), and P. aeruginosa (17%); of them 36% were carbapenem-resistant. The therapy included carbapenems (40%), cephalosporins (37%) and beta-lactams/beta-lactamases-inhibitors (19%); combination with iv-FOS was used in 98 (27%) cases at a median dosage of 16 (16-18) gr/daily. Use of iv-FOS was not associated with reduced crude mortality (21% vs 29%, p-value=0.147). However, at multivariable Cox-regression combination therapy with iv-FOS resulted protective for mortality (aHR=0.51, 95%CI=0.28-0.92), but not other combo-therapies (HR=0.69, 95%CI=0.44-1.16). This result was also confirmed at the IPTW-adjusted-Cox-model (aHR=0.52, 95%CI=0.31-0.91). Subgroup analysis suggested a benefit in severe infections (SOFA>6, PITT≥4) and when iv-FOS was initiated within 24 hours from GNB-BSI onset.
CONCLUSIONS: Fosfomycin in combination therapy for GNB-BSI may have a role to improve survival. These results justify the development of further clinical trials.
METHODS: All consecutive patients with a GNB-BSI from January 1st, 2021, to April 1st, 2023, were included. Primary outcome was 30-day mortality. A Cox- regression analysis was used to identify predictors of mortality. Moreover, an inverse-probability of treatment-weighting (IPTW) analysis was also performed.
RESULTS: Overall, 363 patients were enrolled: 211 (58%) males, with a median (q1-q3) age of 68 (57-78) years, and a median Charlson-comorbidity index of 5 (3-7). At GNB-BSI onset, median SOFA score was 5 (2-7), 122 (34%) presented with septic shock. Pathogens involved were principally K. pneumoniae (42%), E. coli (28%), and P. aeruginosa (17%); of them 36% were carbapenem-resistant. The therapy included carbapenems (40%), cephalosporins (37%) and beta-lactams/beta-lactamases-inhibitors (19%); combination with iv-FOS was used in 98 (27%) cases at a median dosage of 16 (16-18) gr/daily. Use of iv-FOS was not associated with reduced crude mortality (21% vs 29%, p-value=0.147). However, at multivariable Cox-regression combination therapy with iv-FOS resulted protective for mortality (aHR=0.51, 95%CI=0.28-0.92), but not other combo-therapies (HR=0.69, 95%CI=0.44-1.16). This result was also confirmed at the IPTW-adjusted-Cox-model (aHR=0.52, 95%CI=0.31-0.91). Subgroup analysis suggested a benefit in severe infections (SOFA>6, PITT≥4) and when iv-FOS was initiated within 24 hours from GNB-BSI onset.
CONCLUSIONS: Fosfomycin in combination therapy for GNB-BSI may have a role to improve survival. These results justify the development of further clinical trials.
摘要：
背景：静脉注射磷霉素（iv-FOS）的作用，作为革兰氏阴性菌血流感染（GNB-BSI）联合治疗的一部分，需要在临床实践中进行评估，因为体外数据显示了潜在的疗效。
方法：从1月1日起，所有连续患有GNB-BSI的患者，2021年至4月1日2023年，包括。主要结果是30天死亡率。Cox回归分析用于确定死亡率的预测因子。此外，我们还进行了治疗加权逆概率(IPTW)分析.
结果：总体而言，纳入363例患者：211例（58%）男性，年龄中位数（q1-q3）为68（57-78）岁，Charlson-合并症指数中位数为5（3-7）。在GNB-BSI发作时，中位SOFA评分为5（2-7），122（34%）出现感染性休克。涉及的病原体主要是肺炎克雷伯菌（42%），大肠杆菌（28%），和铜绿假单胞菌（17％）；其中36％对碳青霉烯耐药。治疗包括碳青霉烯类（40%），头孢菌素（37％）和β-内酰胺/β-内酰胺酶抑制剂（19％）；98例（27％）病例中使用了静脉内FOS，中位剂量为每天16（16-18）gr。使用静脉FOS与降低粗死亡率无关(21%vs29%，p值=0.147)。然而,在多变量Cox回归联合治疗与iv-FOS导致保护死亡率（aHR=0.51，95CI=0.28-0.92），而不是其他组合疗法（HR=0.69，95CI=0.44-1.16）。该结果也在IPTW调整的Cox模型中得到证实(aHR=0.52,95CI=0.31-0.91)。亚组分析显示，严重感染（SOFA>6，PITT≥4）和在GNB-BSI发病后24小时内开始iv-FOS时获益。
结论：磷霉素联合治疗GNB-BSI可能具有提高生存率的作用。这些结果证明了进一步临床试验的发展。
方法：从1月1日起，所有连续患有GNB-BSI的患者，2021年至4月1日2023年，包括。主要结果是30天死亡率。Cox回归分析用于确定死亡率的预测因子。此外，我们还进行了治疗加权逆概率(IPTW)分析.
结果：总体而言，纳入363例患者：211例（58%）男性，年龄中位数（q1-q3）为68（57-78）岁，Charlson-合并症指数中位数为5（3-7）。在GNB-BSI发作时，中位SOFA评分为5（2-7），122（34%）出现感染性休克。涉及的病原体主要是肺炎克雷伯菌（42%），大肠杆菌（28%），和铜绿假单胞菌（17％）；其中36％对碳青霉烯耐药。治疗包括碳青霉烯类（40%），头孢菌素（37％）和β-内酰胺/β-内酰胺酶抑制剂（19％）；98例（27％）病例中使用了静脉内FOS，中位剂量为每天16（16-18）gr。使用静脉FOS与降低粗死亡率无关(21%vs29%，p值=0.147)。然而,在多变量Cox回归联合治疗与iv-FOS导致保护死亡率（aHR=0.51，95CI=0.28-0.92），而不是其他组合疗法（HR=0.69，95CI=0.44-1.16）。该结果也在IPTW调整的Cox模型中得到证实(aHR=0.52,95CI=0.31-0.91)。亚组分析显示，严重感染（SOFA>6，PITT≥4）和在GNB-BSI发病后24小时内开始iv-FOS时获益。
结论：磷霉素联合治疗GNB-BSI可能具有提高生存率的作用。这些结果证明了进一步临床试验的发展。
