Hadassah University Hospital, Jerusalem, Israel.
Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Clin Infect Dis. 2017 Nov 13;65(11):1819-1828. doi: 10.1093/cid/cix646.
This intercontinental study aimed to study gram-negative rod (GNR) resistance in hematopoietic stem cell transplantation (HSCT).
GNR bacteremias occurring during 6 months post-HSCT (February 2014-May 2015) were prospectively collected, and analyzed for rates and risk factors for resistance to fluoroquinolones, noncarbapenem anti-Pseudomonas β-lactams (noncarbapenems), carbapenems, and multidrug resistance.
Sixty-five HSCT centers from 25 countries in Europe, Australia, and Asia reported data on 655 GNR episodes and 704 pathogens in 591 patients (Enterobacteriaceae, 73%; nonfermentative rods, 24%; and 3% others). Half of GNRs were fluoroquinolone and noncarbapenem resistant; 18.5% carbapenem resistant; 35.2% multidrug resistant. The total resistance rates were higher in allogeneic HSCT (allo-HSCT) vs autologous HSCT (auto-HSCT) patients (P < .001) but similar in community-acquired infections. Noncarbapenem resistance and multidrug resistance were higher in auto-HSCT patients in centers providing vs not providing fluoroquinolone prophylaxis (P < .01). Resistance rates were higher in southeast vs northwest Europe and similar in children and adults, excluding higher fluoroquinolone- and β-lactam/β-lactamase inhibitor resistance rates in allo-HSCT adults. Non-Klebsiella Enterobacteriaceae were rarely carbapenem resistant. Multivariable analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones; noncarbapenem resistance: hospital-acquired infection, breakthrough on noncarbapenems or other antibiotics (excluding fluoroquinolones, noncarbapenems, carbapenems), donor type; carbapenem resistance: breakthrough on carbapenem, longer hospitalization, intensive care unit, previous other antibiotic therapy; multidrug resistance: longer hospitalization, breakthrough on β-lactam/β-lactamase inhibitors, and carbapenems. Inappropriate empiric therapy and mortality were significantly more common in infections caused by resistant bacteria.
Our data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empiric antibiotic protocols. Knowledge of pathogen-specific resistance enables early appropriate empiric therapy. Monitoring of resistance is crucial.
NCT02257931.
本项洲际研究旨在探讨造血干细胞移植（HSCT）后革兰氏阴性杆菌（GNR）耐药性。
前瞻性收集 HSCT 后 6 个月内（2014 年 2 月至 2015 年 5 月）发生的 GNR 菌血症，并分析氟喹诺酮类、非碳青霉烯类抗假单胞菌β-内酰胺类药物（非碳青霉烯类）、碳青霉烯类和多重耐药性的耐药率和危险因素。
来自欧洲、澳大利亚和亚洲 25 个国家的 65 个 HSCT 中心报告了 591 例患者 655 例 GNR 感染和 704 株病原体的数据（肠杆菌科，73%；非发酵菌，24%；其他 3%）。一半的 GNR 对氟喹诺酮类和非碳青霉烯类耐药；18.5%耐碳青霉烯类；35.2%为多重耐药。与自体 HSCT 患者相比，异基因 HSCT（allo-HSCT）患者的总耐药率更高（allo-HSCT 患者 vs 自体 HSCT 患者，P <.001），但社区获得性感染的耐药率相似。在提供与不提供氟喹诺酮类预防用药的中心，自体 HSCT 患者中非碳青霉烯类耐药和多重耐药率更高（P <.01）。与西北欧相比，东南欧的非产酸克雷伯菌的耐碳青霉烯类率更低。多变量分析显示 allo-HSCT 患者的耐药危险因素：氟喹诺酮类耐药：成人、中性粒细胞减少时间延长、氟喹诺酮类突破感染；非碳青霉烯类耐药：医院获得性感染、非碳青霉烯类或其他抗生素突破感染（不包括氟喹诺酮类、非碳青霉烯类、碳青霉烯类）、供者类型；碳青霉烯类耐药：碳青霉烯类突破感染、住院时间延长、重症监护病房、先前其他抗生素治疗；多重耐药：住院时间延长、β-内酰胺/β-内酰胺酶抑制剂和碳青霉烯类突破感染。由耐药菌引起的感染，经验性治疗不当和死亡率明显更高。
我们的数据对氟喹诺酮类预防用药的推荐提出了质疑，并呼吁重新评估当地经验性抗生素方案。了解病原体特异性耐药性可实现早期适当的经验性治疗。监测耐药性至关重要。
NCT02257931。
