含磷霉素方案治疗重症患者中由产KPC肺炎克雷伯菌和耐碳青霉烯鲍曼不动杆菌引起的严重感染的疗效。
Efficacy of fosfomycin-containing regimens in treating severe infections caused by KPC-producing klebsiella pneumoniae and carbapenem-resistant acinetobacter baumannii in critically ill patients.
作者信息
Oliva A, Curtolo A, Falletta A, Sacco F, Lancellotti F, Carnevalini M, Ceccarelli G, Roma G, Bufi M, Magni G, Raponi G M, Venditti M, Mastroianni C M
机构信息
Department of Public Health and Infectious Diseases, Sapienza University of Rome.
Department of Public Health and Infectious Diseases, Sapienza University of Rome; Department of Infectious Diseases, Provincial Hospital of Bolzano (SABES-ASDAA), Bolzano-Bozen, Italy; teaching Hospital of the Paracelsus Medial University.
出版信息
Int J Antimicrob Agents. 2024 Dec;64(6):107365. doi: 10.1016/j.ijantimicag.2024.107365. Epub 2024 Oct 28.
BACKGROUND
Fosfomycin (FOS) is gaining increasing importance as part of combination therapy for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) and KPC-producing Klebsiella pneumoniae (KPC-Kp), thanks to its in vitro synergism with several antibiotics, high tissue distribution and good tolerability. We analyzed the effect on 30-day survival of FOS-containing regimens compared to non-FOS-containing regimens in critically ill patients admitted to the intensive care unit with CRAB or KPC-Kp infections. Secondary objectives were to evaluate clinical cure and microbiologic eradication in the FOS vs. the NO-FOS group.
METHODS
This was a monocentric retrospective observational study including SARS-Cov2-negative critically ill patients with KPC-Kp or CRAB infection treated with combination antibiotic therapy with or without FOS for ≥48 h (FOS vs. NO-FOS groups, respectively). The primary outcome was 30-day mortality; secondary outcomes were clinical cure and microbiological eradication.
RESULTS
Of the 78 patients analyzed, 26 (33.3%) were men, with a median (IQR) age and Charlson Comorbidity Index (CCI) of 67 years (53-74) and 4 (2-5), respectively. Septic shock was present in 18 patients (23.1%); 37 (47.4%) were receiving FOS, 41 (52.6%) were not receiving FOS; CRAB and KPC-Kp were isolated in 44 (56.4%) and 34 (43.6%) of patients, respectivley. Compared to NO-FOS, patients receiving FOS had a higher clinical cure (89.2% vs. 65.9%, P = 0.017), early (<72 h) improvement (78.4% vs. 52.2%, P = 0.018), microbiological eradication (87.5% vs 62.2%, P = 0.027), and lower 7-, 14- and 30-day mortality (0% vs. 4.6%, P =0.027; 2.7% vs 22%, P = 0.016; and 13.5% vs. 34.2%, P = 0.039, respectively). This effect was particularly evident for infections sustained by KPC-Kp. On multivariable analysis, receiving FOS was independently associated with survival (hazard ratio = 0.29, 95% CI = 0.09-0.93, P = 0.038), confirmed after IPTW (HR = 0.501 95% CI = 0.25-0.98 P = 0.042).
CONCLUSIONS
FOS-containing regimens exhibited a higher clinical cure, higher microbiological eradication and reduced mortality compared with regimens not containing FOS in critically ill patients with CRAB and KPC-Kp infections.
背景
由于磷霉素（FOS）与多种抗生素具有体外协同作用、组织分布广泛且耐受性良好，它在耐碳青霉烯鲍曼不动杆菌（CRAB）和产肺炎克雷伯菌碳青霉烯酶肺炎克雷伯菌（KPC-Kp）的联合治疗中发挥着越来越重要的作用。我们分析了在重症监护病房收治的患有CRAB或KPC-Kp感染的重症患者中，含FOS方案与不含FOS方案对30天生存率的影响。次要目标是评估FOS组与非FOS组的临床治愈情况和微生物清除情况。
方法
这是一项单中心回顾性观察研究，纳入了SARS-CoV2阴性的重症患者，这些患者患有KPC-Kp或CRAB感染，接受含或不含FOS的联合抗生素治疗≥48小时（分别为FOS组和非FOS组）。主要结局是30天死亡率；次要结局是临床治愈和微生物清除。
结果
在分析的78例患者中，26例（33.3%）为男性，年龄中位数（IQR）为67岁（53 - 74岁），查尔森合并症指数（CCI）中位数为4（2 - 5）。18例患者（23.1%）出现感染性休克；37例（47.4%）接受FOS治疗，41例（52.6%）未接受FOS治疗；分别在44例（56.4%）和34例（43.6%）患者中分离出CRAB和KPC-Kp。与非FOS组相比，接受FOS治疗的患者临床治愈率更高（89.2%对65.9%，P = 0.017），早期（<72小时）改善率更高（78.4%对52.2%，P = 0.018），微生物清除率更高（87.5%对62.2%，P = 0.027），7天、14天和30天死亡率更低（0%对4.6%，P = 0.027；2.7%对22%，P = 0.016；13.5%对34.2%，P = 0.039）。这种效应在KPC-Kp引起的感染中尤为明显。多变量分析显示，接受FOS治疗与生存独立相关（风险比 = 0.29，95%置信区间 = 0.09 - 0.93，P = 0.038），逆概率加权法（IPTW）后得到确认（HR = 0.501，95%置信区间 = 0.25 - 0.98，P = 0.042）。
结论
在患有CRAB和KPC-Kp感染的重症患者中，与不含FOS的方案相比，含FOS的方案具有更高的临床治愈率、更高的微生物清除率和更低的死亡率。
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