Efficacy and safety of oral fosfomycin trometamol for the treatment of lower urinary tract infections caused by multi drug resistant bacteria：an open-label, uncontrolled, multicenter study

目的：了解目前国内磷霉素氨丁三醇对于多重耐药细菌所致下尿路感染的药敏情况以及临床疗效和细菌学疗效。方法本研究为前瞻性、非对照、开放、多中心临床试验。选取2011年1—12月就诊于12家临床研究中心泌尿外科的非发热性下尿路感染患者。共入组356例，其中临床资料完整病例350例，男120例（34．3％），女230例（65．7％）。年龄（49．9±16．6）岁。以磷霉素氨丁三醇散3g口服，隔日1次，共3剂疗程治疗。以第1次培养阳性的致病菌株为肠杆菌科细菌、金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌和屎肠球菌的142例患者为进一步研究对象，评价该治疗方案对于多重耐药细菌所致的下尿路感染的药敏情况及疗效。结果142例培养阳性患者中，革兰阴性菌104株，其中产超广谱β内酰胺酶的多重耐药菌株52株（50．0％）；革兰阳性菌38株，其中葡萄球菌20株（包括甲氧西林耐药者11株），肠球菌18株。药敏试验结果显示，磷霉素氨丁三醇对于多重耐药菌的敏感率为85．7％（54／63），对多重耐药细菌所致下尿路感染的临床疗效为96．4％（53／55），细菌学疗效为87．5％（42／48）。临床不良反应发生率为5．6％（20／356），主要为腹泻，未发生与药物相关的严重不良事件。结论国内目前常见的尿路感染病原菌中多重耐药细菌比例高，磷霉素氨丁三醇散3g口服，隔日1次，共3剂的给药方案用于治疗非多重耐药、多重耐药细菌引起的非发热性下尿路感染患者疗效良好，不良反应轻微，可用于此类尿路感染的经验治疗。Objective To assess the efficacy and safety of oral fosfomycin trometamal in patients with lower urinary tract infections ( UTIs) caused by multi drug resistant ( MDR) bacteria in the clinical setting in China.Methods Multicenter study was conducted from January 2011 to December 2011 in 12 hospitals in China.Three hundred and fifty-six patients with non-fever lower UTls were treated by fosfomycin trometamal 3 g once daily.Three hundred and fifty cases with complete data were further evaluated .One hundred and twenty ( 34.3%) were male and 230 ( 65.7%) were female.The average age was ( 49.9 ± 16.6) years.Depending of the results of urine culture at the first visit ,142 patients with E.coli, Klebsiella pneumonia, proteus, Staphylococcus aureus, Staphylococcus epidermidis and entercocous were analyzed.The susceptibility of MDR bacteria to fosfomycin trometamol were calculated . The clinical efficacy , bacteriological efficacy of fosfomycin trometamol to these patients was evaluated .Results For the gram-negative bacteria detected by culture , among the E.coli, Klebsiella pneumonia and proteus, 50%(52/104) were Extended-Spectrum β-lactamases producing organisms . For the gram-positive bacteria ( n =38 ) detected by culture, methicillin-resistant staphylococcus accounts for 55%(11/20) of all the Staphylococcus and the other gram-positive bacteria were Enterococcus ( n=18 ) .Higher susceptibility rates to fosfomycin trometamol were observed among MDR bacteria (85.7%) and the clinical effective rate and bacteriological effective rate of fosfomycin trometamol were 96.4%( 53/55 ) and 87.5%( 42/48 ) , respectively .The incidence of drug-related adverse events (AEs) was 5.6%(20/356).The most common AE was diarrhea. No drug-related serious adverse events were found .Conclusions The distributions of uropathogens in China are complicated. The detection rate of MDR uropathogens is high . The dosing regimen of fosfomycin trometamal 3 g once daily is effective and tolerable for the patients with lower UTIs caused by MDR bacteria . It may represent good options for the empiric therapy for the patients with lower UTIs .中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)10777-7813