Department of Medical Microbiology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom
Institute of Dentistry, University of Aberdeen, Aberdeen, United Kingdom.
Antimicrob Agents Chemother. 2021 May 18;65(6). doi: 10.1128/AAC.02483-20.
Antimicrobial combination therapy is a time/resource-intensive procedure commonly employed in the treatment of cystic fibrosis (CF) pulmonary exacerbations caused by Ten years ago, the most promising antimicrobial combinations were proposed, but there has since been the introduction of new β-lactam plus β-lactamase inhibitor antimicrobial combinations. The aims of this study were to (i) compare activity of these new antimicrobials with other antipseudomonal agents and suggest their most synergistic antimicrobial combinations and (ii) determine antimicrobial resistance rates and study inherent trends of antimicrobials over 10 years. A total of 721 multidrug-resistant isolates from 183 patients were collated over the study period. Antimicrobial susceptibility and combination testing were carried out using the Etest method. The results were further assessed using the fractional inhibitory concentration index (FICI) and the susceptible breakpoint index (SBPI). Resistance to almost all antimicrobial agents maintained a similar level during the studied period. Colistin (< 0.001) and tobramycin (0.001) were the only antimicrobials with significant increasing isolate susceptibility, while an increasing resistance trend was observed for levofloxacin. The most active antimicrobials were colistin, ceftolozane-tazobactam, ceftazidime-avibactam, and gentamicin. All combinations with β-lactam plus β-lactamase inhibitors produced some synergistic results. Ciprofloxacin plus ceftolozane-tazobactam (40%) and amikacin plus ceftazidime (36.7%) were the most synergistic combinations, while colistin combinations gave the best median SBPI (50.11). This study suggests that effective fluoroquinolone stewardship should be employed for CF patients. It also presents data to support the efficacy of novel combinations for use in the treatment of chronic infections.
抗微生物联合治疗是一种耗时耗资源的程序，常用于治疗囊性纤维化 (CF) 肺部恶化，这些恶化是由假单胞菌引起的。十年前，提出了最有前途的抗微生物联合治疗方案，但此后又引入了新的β-内酰胺加β-内酰胺酶抑制剂抗微生物联合治疗方案。本研究的目的是：(i) 比较这些新的抗微生物药物与其他抗假单胞菌药物的活性，并提出最具协同作用的抗微生物联合治疗方案；(ii) 确定抗微生物药物耐药率，并研究 10 年来抗微生物药物的固有趋势。在研究期间，共从 183 名患者中收集了 721 株多药耐药分离株。使用 Etest 法进行抗微生物药物敏感性和联合检测。使用部分抑菌浓度指数 (FICI) 和敏感断点指数 (SBPI) 进一步评估结果。在研究期间，几乎所有抗微生物药物的耐药率都保持在相似水平。多粘菌素（<0.001）和妥布霉素（0.001）是唯一具有显著增加分离株敏感性的抗微生物药物，而左氧氟沙星的耐药趋势则有所增加。最有效的抗微生物药物是多粘菌素、头孢洛扎他唑巴坦、头孢他啶-阿维巴坦和庆大霉素。所有与β-内酰胺加β-内酰胺酶抑制剂的联合用药都产生了一些协同作用的结果。环丙沙星加头孢洛扎他唑巴坦（40%）和阿米卡星加头孢他啶（36.7%）是最具协同作用的联合用药，而多粘菌素联合用药的中位 SBPI（50.11）最佳。本研究表明，应在 CF 患者中实施有效的氟喹诺酮类药物管理。它还提供了支持新型联合治疗方案用于治疗慢性感染的疗效的数据。
