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Abstract：
Background This study was designed to evaluate the current in vitro susceptibility of clinical isolates to broad-spectrum β-lactam antibiotics. Methodology Bacterial isolates, cultured from 180 non-repetitive clinical samples between April and November 2022 at three hospitals in India, were used to evaluate the minimum inhibitory concentration (MIC) of broad-spectrum β-lactam antibiotics using the Epsilometer test (E-test) method. Test antibiotics were ceftriaxone and ceftriaxone in combination with β-lactamase inhibitors (BLIs) sulbactam and tazobactam. Comparator antibiotics included amoxicillin + BLI clavulanic acid, piperacillin + tazobactam, cefotaxime, and cefepime. The MIC values obtained were used to assess the susceptibility of the isolates and to compute the efficacy ratios (ERs) of the antibiotics. Results Among the 180 clinical isolates, ~89% were gram-negative bacteria, the most prevalent ones being Escherichia coli and Klebsiella pneumoniae. Of the gram-negative isolates, ~37% were susceptible/intermediately susceptible to ceftriaxone, and ~29% were susceptible to ceftriaxone + BLIs. The test antibiotics had ER >10 against 85%-95% E. coli isolates, whereas comparator antibiotics had ER >10 against 31%-68% isolates. The differences between the test antibiotics and piperacillin + tazobactam or cefotaxime were statistically significant. Ceftriaxone, ceftriaxone + sulbactam, and ceftriaxone + tazobactam had ER >10 against 78%, 100%, and 90% of K. pneumoniae isolates, while the corresponding percentages for cefotaxime, piperacillin + tazobactam, and cefepime were 100%, 64%, and 80%, respectively. The difference between ceftriaxone + BLIs and piperacillin + tazobactam was statistically significant. Ceftriaxone + BLIs had ER >10 against all E. coli isolates producing extended-spectrum β-lactamases (ESBLs); the percentage of isolates was significantly higher than that for piperacillin + tazobactam. Ceftriaxone + tazobactam had ER >10 against all ESBL-producing K. pneumoniae isolates; ceftriaxone and ceftriaxone + sulbactam had ER ranging 6-10. Conclusions Ceftriaxone and ceftriaxone in combination with sulbactam and tazobactam are promising antibiotics to explore against prevalent infectious microorganisms such as E. coli and K. pneumoniae. Ceftriaxone + tazobactam also holds promise against ESBL-producing variants.
摘要：
背景本研究旨在评估临床分离株对广谱β-内酰胺抗生素的体外敏感性。方法学细菌分离，2022年4月至11月在印度三家医院从180个非重复临床样本中培养出来，使用Epsilometer测试（E-test）方法评估广谱β-内酰胺抗生素的最低抑制浓度（MIC）。试验抗生素为头孢曲松和头孢曲松联合β-内酰胺酶抑制剂(BLIs)舒巴坦和他唑巴坦。比较抗生素包括阿莫西林+BLI克拉维酸，哌拉西林+他唑巴坦,头孢噻肟,还有头孢吡肟.获得的MIC值用于评估分离株的敏感性并计算抗生素的功效比（ER）。结果180例临床分离株中,~89%是革兰氏阴性菌，最普遍的是大肠杆菌和肺炎克雷伯菌。革兰氏阴性分离株中，~37%易感/中度易感头孢曲松，约29%的人对头孢曲松+BLIs敏感。试验抗生素对85%-95%大肠杆菌分离株的ER>10，而对照抗生素对31%-68%的分离株的ER>10。试验抗生素与哌拉西林他唑巴坦或头孢噻肟之间的差异有统计学意义。头孢曲松,头孢曲松+舒巴坦,头孢曲松+他唑巴坦的ER>10对78%，100%,和90%的肺炎克雷伯菌分离株，而头孢噻肟的相应百分比，哌拉西林+他唑巴坦,头孢吡肟100%,64%,80%,分别。头孢曲松+BLIs与哌拉西林+他唑巴坦的差异有统计学意义。头孢曲松+BLIs对所有产超广谱β-内酰胺酶(ESBLs)的大肠杆菌分离株的ER>10;分离株的百分比显著高于哌拉西林+他唑巴坦。头孢曲松他唑巴坦对所有产ESBL的肺炎克雷伯菌分离株的ER>10；头孢曲松和头孢曲松舒巴坦的ER范围为6-10。结论头孢曲松和头孢曲松联合舒巴坦和他唑巴坦是有前途的抗生素，可用于探索针对大肠杆菌和肺炎克雷伯菌等流行的感染性微生物。头孢曲松+他唑巴坦对产生ESBL的变体也有希望。
