Metan Gõkhan, Kaynar Leylagül, Yozgat Nuran, Elmali Ferhan, Kürkçüoglu Cemile Altay, Alp Emine, Çetin Mustafa
Departments of Infectious Diseases, Erciyes University Faculty of Medicine, Kayseri, Turkey.
Hematology, Erciyes University Faculty of Medicine, Kayseri, Turkey.
Infez Med. 2017 Mar 1;25(1):33-37.
After experiencing a high rate of carbapenem-resistant Gram-negative bacilli infections in febrile neutropenic patients, a two-stage intervention was introduced in the haematopoietic stem cell transplantation (HSCT) centre. During the first eight months of 2014, carbapenems remained the first choice for the empirical treatment of febrile neutropenia while the use of piperacillin/tazobactam (TZP) was encouraged in patients with stable clinical condition. When blood cultures were reported as negative and the patient was clinically stable the carbapenem/TZP treatment was stopped regardless of continuous fever and neutrophil count. From October 2014, TZP (with prolonged infusion) with or without amikacin replaced carbapenems as the first line therapy of neutropenic fever except for high-risk patients previously known as colonized or infected with extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae, who presented with severe sepsis, septic shock or nosocomial pneumonia, and recently transferred from the intensive care unit with a high endemicity of multidrug-resistant Gram-negative bacilli. Vancomycin or teicoplanin was used when there was suspicion of septic shock or detection of severe mucositis and central-line associated bacteraemia. The antibacterial therapy was escalated or de-escalated in culture-positive patients according to the antimicrobial susceptibility reports and clinical progress. Daily defined dosages (DDD) per 1000 patient days were calculated for all antibiotics by the hospital pharmacist for each year. A total of 913 admissions with 11,544 patient-days were followed in 2013; and 1,072 admissions with 11,843 patient-days were followed in 2014. The rate of ESBL production in Enterobacteriaceae bacteraemia was as 31.8% in 2013 and 47.3% in 2014. All staphylococci isolated from blood culture were methicillin-resistant for both years. All Enterococcus faecium isolates but one from blood cultures were resistant to ampicillin. The number of the patients who died during hospitalization was 24 in 2013, and 17 patients died in 2014. The DDDs/1000 patient days for imipenem, meropenem, vancomycin, teicoplanin, daptomycin, linezolid, colistin, piperacillin/tazobactam and amikacin in 2013 and 2014 were respectively as follows; 201 vs 19 (p<0.001); 1,578 vs 1,092 (p<0.001); 533 vs 251 (p<0.001); 205 vs 159 (p<0.001); 56 vs 14 (p<0.001); 76 vs 26 (p<0.001); 188 vs 154 (p<0.001); 157 vs 254 (p<0.001); and 5 vs 41 (p<0.001). Our study showed that a febrile neutropenia pathway guided by local epidemiology and international guidelines can reduce the use of antibiotics in haematological cancer or HSCT patients. The sustainability of such an intervention requires strong multidisciplinary cooperation.
在发热性中性粒细胞减少患者中出现耐碳青霉烯革兰氏阴性杆菌感染的高发生率后,造血干细胞移植(HSCT)中心引入了两阶段干预措施。在2014年的前八个月,碳青霉烯类药物仍是发热性中性粒细胞减少经验性治疗的首选,而对于临床状况稳定的患者,鼓励使用哌拉西林/他唑巴坦(TZP)。当血培养报告为阴性且患者临床稳定时,无论是否持续发热和中性粒细胞计数如何,均停止碳青霉烯/TZP治疗。从2014年10月起,除了先前已知感染产超广谱β-内酰胺酶(ESBL)肠杆菌科细菌、出现严重脓毒症、感染性休克或医院获得性肺炎且最近从多重耐药革兰氏阴性杆菌高流行的重症监护病房转出的高危患者外,TZP(延长输注)联合或不联合阿米卡星取代碳青霉烯类药物作为中性粒细胞减少发热的一线治疗。当怀疑感染性休克或检测到严重粘膜炎和中心静脉导管相关菌血症时,使用万古霉素或替考拉宁。根据抗菌药物敏感性报告和临床进展,对培养阳性患者的抗菌治疗进行升级或降级。医院药剂师每年计算所有抗生素每1000患者日的每日限定剂量(DDD)。2013年共随访913例入院患者,共11544个患者日;2014年随访1072例入院患者,共11843个患者日。2013年肠杆菌科菌血症中ESBL产生率为31.8%,2014年为47.3%。两年从血培养分离出的所有葡萄球菌均对甲氧西林耐药。从血培养分离出的所有粪肠球菌菌株(除一株外)均对氨苄西林耐药。住院期间死亡患者人数2013年为24例,2014年为17例。2013年和2014年亚胺培南、美罗培南、万古霉素、替考拉宁、达托霉素、利奈唑胺、黏菌素、哌拉西林/他唑巴坦和阿米卡星的DDD/1000患者日分别如下:201对19(p<0.001);1578对1092(p<0.001);533对251(p<0.001);205对159(p<0.001);56对