Effective Oral Combination Treatment for Extended-Spectrum Beta-Lactamase-Producing Escherichia coli
Effective Oral Combination Treatment for Extended-Spectrum Beta-Lactamase-Producing Escherichia coli
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DOI：
10.1089/mdr.2019.0065
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发表时间：
2019-05-20
影响因子：
2.6
通讯作者：
Saleh, Saiel
中科院分区：
文献类型：
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作者：
Al-Tamimi, Mohammad;Abu-Raideh, Jumana;Saleh, Saiel
背景：产超广谱β-内酰胺酶大肠埃希菌（ESBL-EC）在世界范围内呈上升趋势。治疗ESBLs的首选药物是肠外碳青霉烯类。本研究的目的是评价一种新的口服头孢菌素和阿莫西林/克拉维酸联合治疗ESBL-EC的体外和体内疗效。方法：收集两个转介中心1年以上的ESBL-EC样本共150份。使用圆盘逼近和圆盘置换法在体外进行头孢菌素类和阿莫西林/克拉维酸的协同作用研究。对20名ESBL-EC尿路感染（UTI）患者进行了体内联合治疗评估。结果：150例患者中检出ESBL-EC菌株，平均年龄46.67岁，其中75.2%为女性。药敏试验结果表明，分离株对口服抗生素耐药率高。采用纸片近似法和纸片置换法，头孢噻肟和头孢克肟与阿莫西林/克拉维汀之间的阳性协同作用频率和平均协同作用距离显著高于头孢泊肟、头孢地尼和头孢他啶（p < 0.05）。加用阿莫西林/克拉维汀使头孢克肟的敏感率从8.6%提高到86.3%，显著高于其他头孢菌素（P < 0.0005）。年龄、性别、医院、科室、样本类型或细菌载量不影响头孢克肟和阿莫西林/克拉维汀的协同作用。20例ESBL-EC阳性UTI患者中有18例在完成头孢克肟和阿莫西林/克拉维汀口服治疗疗程后体外协同试验阳性，临床和微生物学完全消退。结论：头孢克肟和阿莫西林/克拉维汀联合治疗ESBL-EC是一种有效的门诊治疗选择。体外协同试验简单，可预测成功治疗。
Background: Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) is increasing worldwide. The drugs of choice for treatment of ESBLs are parenteral carbapenems. The aim of this study was to evaluate the in vitro and in vivo efficacy of a new combination of oral cephalosporins and amoxicillin/clavulanate in treatment of ESBL-EC. Methods: A total of 150 ESBL-EC samples were collected over 1 year from two referral centers. Synergistic studies of cephalosporins and amoxicillin/clavulanate were performed in vitro using disk approximation and disk replacement methods. Combination treatment was assessed in vivo on 20 ESBL-EC urinary tract infection (UTI) patients. Results: ESBL-EC isolates were confirmed in 150 patients with a mean age of 46.67 years, 75.2% of them being women. Antibiotic susceptibility testing of isolates indicated high resistance rate to oral antibiotics. The frequency of positive synergy and mean distance of synergy between cephalosporins and amoxicillin/clavulanate was significantly higher with cefotaxime and cefixime compared with cefpodoxime, cefdinir, and ceftazidime using disk approximation and disk replacement methods (p < 0.05). Addition of amoxicillin/clavulanate enhanced the susceptibility rate with cefixime from 8.6% to 86.3%, significantly higher than with other cephalosporins (p < 0.0005). Cefixime and amoxicillin/clavulanate synergy was not affected by age, gender, hospital, department, sample type, or bacterial load. Eighteen of 20 ESBL-EC-positive UTI patients had a positive in vitro synergy test and complete clinical and microbiological resolution after completion of cefixime and amoxicillin/clavulanate oral treatment course. Conclusions: Cefixime and amoxicillin/clavulanate combination therapy could be an effective oral outpatient treatment option for ESBL-EC. In vitro synergistic testing is simple and predictive of successful treatment.