Risk Factors for Treatment Failure of Polymyxin B Monotherapy for Carbapenem-Resistant Klebsiella pneumoniae Infections
Risk Factors for Treatment Failure of Polymyxin B Monotherapy for Carbapenem-Resistant Klebsiella pneumoniae Infections
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DOI：
10.1128/aac.00510-13
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发表时间：
2013-11-01
影响因子：
4.9
通讯作者：
Mehta, Sapna A.
中科院分区：
文献类型：
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作者：
Dubrovskaya, Yanina;Chen, Ting-Yi;Mehta, Sapna A.
多粘菌素用于抢救耐碳青霉烯类肺炎克雷伯菌(CRKP)引起的感染。尽管多粘菌素与碳青霉烯类或替加环素的联合应用已证实有协同作用，但体外协同试验尚不规范，其临床效果尚不清楚。这项研究描述了接受多粘菌素B单一治疗的CRKP感染患者的结果。我们回顾了2007-2011年间接受多粘菌素B单一治疗的CRKP感染患者的医疗记录。收集了临床、微生物学和抗菌治疗数据。通过Logistic回归分析确定治疗失败的危险因素。40名患者被纳入分析。根据临床医生记录的感染症状和体征的改善，40名患者中有29名(73%)实现了临床治愈，而有随访培养数据的32名患者中有17名(53%)实现了微生物治愈。治疗结束时死亡率为10%，30天内死亡率为28%。在多变量分析中，基线肾功能不全与感染性休克校正后的临床衰竭增加6.0倍相关(优势比[OR]=6.0；95%可信区间[CI]=1.22至29.59)。在治疗期间，3名患者发生了对多粘菌素具有内在耐药性的突破性感染。40名患者中有18名(45%)在最初接受多粘菌素B治疗后出现新的CRKP感染，中位数为23天，其中3名感染对多粘菌素耐药。在这项回顾性研究中，接受多粘菌素B单一疗法治疗的CRKP感染患者的临床治愈率为73%。基线肾功能不全是感染性休克校正后治疗失败的危险因素。对多粘菌素B具有内在耐药性的微生物的突破性感染以及随后的CRKP分离株对多粘菌素B的耐药性的发展令人担忧。
Polymyxins are reserved for salvage therapy of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Though synergy has been demonstrated for the combination of polymyxins with carbapenems or tigecycline, in vitro synergy tests are nonstandardized, and the clinical effect of synergy remains unclear. This study describes outcomes for patients with CRKP infections who were treated with polymyxin B monotherapy. We retrospectively reviewed the medical records of patients with CRKP infections who received polymyxin B monotherapy from 2007 to 2011. Clinical, microbiology, and antimicrobial treatment data were collected. Risk factors for treatment failure were identified by logistic regression. Forty patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved clinical cure as defined by clinician-documented improvement in signs and symptoms of infections, and 17/32 (53%) patients with follow-up culture data achieved microbiological cure. End-of-treatment mortality was 10%, and 30-day mortality was 28%. In a multivariate analysis, baseline renal insufficiency was associated with a 6.0-fold increase in clinical failure after adjusting for septic shock (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 1.22 to 29.59). Breakthrough infections with organisms intrinsically resistant to polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%) patients developed a new CRKP infection a median of 23 days after initial polymyxin B treatment, and 3 of these 18 infections were polymyxin resistant. The clinical cure rate achieved in this retrospective study was 73% of patients with CRKP infections treated with polymyxin B monotherapy. Baseline renal insufficiency was a risk factor for treatment failure after adjusting for septic shock. Breakthrough infections with organisms intrinsically resistant to polymyxin B and development of resistance to polymyxin B in subsequent CRKP isolates are of concern.