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Abstract：
BACKGROUND: Treatment of carbapenem-resistant Enterobacterales (CRE) infections in low-resource settings is challenging particularly due to limited treatment options. Colistin is the mainstay drug for treatment; however, nephrotoxicity and neurotoxicity make this drug less desirable. Thus, mortality may be higher among patients treated with alternative antimicrobials that are potentially less efficacious than colistin. We assessed mortality in patients with CRE bacteremia treated with colistin-based therapy compared to colistin-sparing therapy.
METHODS: We conducted a cross-sectional study using secondary data from a South African national laboratory-based CRE bacteremia surveillance system from January 2015 to December 2020. Patients hospitalized at surveillance sentinel sites with CRE isolated from blood cultures were included. Multivariable logistic regression modeling, with multiple imputations to account for missing data, was conducted to determine the association between in-hospital mortality and colistin-based therapy versus colistin-sparing therapy.
RESULTS: We included 1 607 case-patients with a median age of 29 years (interquartile range [IQR], 0-52 years) and 53% (857/1 607) male. Klebsiella pneumoniae caused most of the infections (82%, n=1 247), and the most common carbapenemase genes detected were blaOXA-48-like (61%, n=551), and blaNDM (37%, n=333). The overall in-hospital mortality was 31% (504/1 607). Patients treated with colistin-based combination therapy had a lower case fatality ratio (29% [152/521]) compared to those treated with colistin-sparing therapy 32% [352/1 086]) (p=0.18). In our imputed model, compared to colistin-sparing therapy, colistin-based therapy was associated with similar odds of mortality (adjusted odds ratio [aOR] 1.02; 95% confidence interval [CI] 0.78-1.33, p=0.873).
CONCLUSIONS: In our resource-limited setting, the mortality risk in patients treated with colistin-based therapy was comparable to that of patients treated with colistin-sparing therapy. Given the challenges with colistin treatment and the increasing resistance to alternative agents, further investigations into the benefit of newer antimicrobials for managing CRE infections are needed.
METHODS: We conducted a cross-sectional study using secondary data from a South African national laboratory-based CRE bacteremia surveillance system from January 2015 to December 2020. Patients hospitalized at surveillance sentinel sites with CRE isolated from blood cultures were included. Multivariable logistic regression modeling, with multiple imputations to account for missing data, was conducted to determine the association between in-hospital mortality and colistin-based therapy versus colistin-sparing therapy.
RESULTS: We included 1 607 case-patients with a median age of 29 years (interquartile range [IQR], 0-52 years) and 53% (857/1 607) male. Klebsiella pneumoniae caused most of the infections (82%, n=1 247), and the most common carbapenemase genes detected were blaOXA-48-like (61%, n=551), and blaNDM (37%, n=333). The overall in-hospital mortality was 31% (504/1 607). Patients treated with colistin-based combination therapy had a lower case fatality ratio (29% [152/521]) compared to those treated with colistin-sparing therapy 32% [352/1 086]) (p=0.18). In our imputed model, compared to colistin-sparing therapy, colistin-based therapy was associated with similar odds of mortality (adjusted odds ratio [aOR] 1.02; 95% confidence interval [CI] 0.78-1.33, p=0.873).
CONCLUSIONS: In our resource-limited setting, the mortality risk in patients treated with colistin-based therapy was comparable to that of patients treated with colistin-sparing therapy. Given the challenges with colistin treatment and the increasing resistance to alternative agents, further investigations into the benefit of newer antimicrobials for managing CRE infections are needed.
摘要：
背景：在低资源环境中治疗耐碳青霉烯的肠杆菌（CRE）感染具有挑战性，特别是由于治疗选择有限。粘菌素是治疗的主要药物；然而，肾毒性和神经毒性使该药物不太理想。因此，在接受替代抗菌药物治疗的患者中,死亡率可能高于粘菌素.我们评估了基于粘菌素的治疗与保留粘菌素治疗相比的CRE菌血症患者的死亡率。
方法：我们从2015年1月至2020年12月，使用来自南非国家实验室的CRE菌血症监测系统的次要数据进行了一项横断面研究。包括在监测前哨地点住院的患者，从血液培养物中分离出CRE。多变量逻辑回归模型，通过多种估算来解释丢失的数据，本研究旨在确定院内死亡率与基于粘菌素的治疗与保留粘菌素治疗之间的相关性.
结果：我们纳入了1607例患者，中位年龄为29岁（四分位距[IQR]，0-52岁）和53%（857/1607）男性。肺炎克雷伯菌引起大部分感染（82%，n=1.247),最常见的碳青霉烯酶基因是blaOXA-48样（61%，n=551),和blaNDM(37%，n=333）。总体住院死亡率为31%(504/1607)。与使用粘菌素保留疗法32％[352/1086]治疗的患者相比，使用基于粘菌素的联合疗法治疗的患者病死率较低（29％[152/521]）（p=0.18）。在我们估算的模型中，与保留粘菌素疗法相比，基于粘菌素的治疗与相似的死亡率相关(校正比值比[aOR]1.02;95%置信区间[CI]0.78~1.33,p=0.873).
结论：在我们资源有限的环境中，以粘菌素为主的治疗患者的死亡风险与保留粘菌素治疗患者的死亡风险相当.鉴于粘菌素治疗的挑战和对替代药物的耐药性不断增加，需要进一步研究新型抗菌药物对治疗CRE感染的益处.
方法：我们从2015年1月至2020年12月，使用来自南非国家实验室的CRE菌血症监测系统的次要数据进行了一项横断面研究。包括在监测前哨地点住院的患者，从血液培养物中分离出CRE。多变量逻辑回归模型，通过多种估算来解释丢失的数据，本研究旨在确定院内死亡率与基于粘菌素的治疗与保留粘菌素治疗之间的相关性.
结果：我们纳入了1607例患者，中位年龄为29岁（四分位距[IQR]，0-52岁）和53%（857/1607）男性。肺炎克雷伯菌引起大部分感染（82%，n=1.247),最常见的碳青霉烯酶基因是blaOXA-48样（61%，n=551),和blaNDM(37%，n=333）。总体住院死亡率为31%(504/1607)。与使用粘菌素保留疗法32％[352/1086]治疗的患者相比，使用基于粘菌素的联合疗法治疗的患者病死率较低（29％[152/521]）（p=0.18）。在我们估算的模型中，与保留粘菌素疗法相比，基于粘菌素的治疗与相似的死亡率相关(校正比值比[aOR]1.02;95%置信区间[CI]0.78~1.33,p=0.873).
结论：在我们资源有限的环境中，以粘菌素为主的治疗患者的死亡风险与保留粘菌素治疗患者的死亡风险相当.鉴于粘菌素治疗的挑战和对替代药物的耐药性不断增加，需要进一步研究新型抗菌药物对治疗CRE感染的益处.
