a Infectious Diseases Division , Santa Maria Misericordia Hospital , Udine , Italy.
Expert Opin Drug Saf. 2018 Jul;17(7):669-680. doi: 10.1080/14740338.2018.1488962. Epub 2018 Jun 22.
Infections due to multidrug-resistant (MDR) bacteria are burdened by high mortality rates. The development of new compounds to face the global threat of resistance is urgently needed. Combination regimens including "old" high-dose antimicrobials are currently limited by the risk of toxicity, resistance selection, and reduced efficacy. Following the Infectious Diseases Society of America call to develop 10 new antibacterials by 2020, new molecules are currently under development or have become available for use in clinical practice.
We have reviewed safety characteristics and tolerability of old antimicrobials that are currently employed in combination regimens as well as new antimicrobials, including beta-lactams/beta-lactamase inhibitors, new cephalosporins, quinolones, and aminoglycosides.
The availability of new compounds that show in vitro efficacy against MDR represents a unique opportunity to face the threat of resistance and to optimize the current use of antimicrobials, potentially reducing toxicity. Agents that are potentially active against MDR Gram-negatives are ceftozolane/tazobactam, new carbapenems and cephalosporins, the combination of avibactam with ceftazidime, and plazomicin. Further data from clinical trials and post-marketing studies for drugs targeting MDR pathogens are crucial to confirm their efficacy and safety.
由耐多药（MDR）细菌引起的感染死亡率很高。急需开发新的化合物来应对全球耐药性的威胁。包括“旧”高剂量抗生素在内的联合治疗方案目前受到毒性、耐药性选择和疗效降低的风险的限制。在美国传染病学会呼吁到 2020 年开发 10 种新的抗菌药物之后，新的分子目前正在开发中或已可用于临床实践。
我们回顾了目前用于联合治疗方案中的旧抗生素以及新抗生素的安全性特征和耐受性，包括β-内酰胺/β-内酰胺酶抑制剂、新型头孢菌素、喹诺酮类和氨基糖苷类。
具有体外抗 MDR 活性的新化合物的出现为应对耐药性威胁和优化当前抗生素的使用提供了一个独特的机会，有可能降低毒性。对 MDR 革兰氏阴性菌具有潜在活性的药物包括头孢唑肟/他唑巴坦、新型碳青霉烯类和头孢菌素类、阿维巴坦与头孢他啶的联合应用以及泊沙康唑。针对 MDR 病原体的药物的临床试验和上市后研究的进一步数据对于证实其疗效和安全性至关重要。
