Petrosillo N, Ioannidou E, Falagas M E
National Institute for Infectious Diseases L Spallanzani, Rome, Italy.
Clin Microbiol Infect. 2008 Sep;14(9):816-27. doi: 10.1111/j.1469-0691.2008.02061.x.
Colistin is commonly the last resort for treatment of infections caused by multidrug-resistant Gram-negative bacteria. In clinical practice, it is frequently used as combination therapy in order to improve its antibacterial activity, despite the consequent increase in toxicity. The available evidence from various studies (microbiological, animal and clinical studies, retrieved from the PubMed and Scopus databases) regarding the comparative effectiveness of colistin monotherapy and colistin combination therapy was evaluated. Most of the microbiological studies examined colistin monotherapy vs. combinations with rifampicin (nine studies) or carbapenems (three studies) for Pseudomonas aeruginosa or Acinetobacter baumannii infections. A synergistic effect was detected in all the studies examining the combination of colistin and rifampicin, whereas carbapenems exhibited a synergistic effect in two of three studies. Most of the animal studies examined colistin monotherapy vs. combinations with rifampicin, carbenicillin, piperacillin and imipenem for treatment of P. aeruginosa, A. baumannii or Escherichia coli infections. Mortality rates were significantly lower in the combination treatment arm in three of six relevant studies. However, data from the small number (four) of relevant human studies suggest non-inferiority of colistin monotherapy as compared with combination therapy. In conclusion, microbiological studies suggest superiority of colistin combination treatment, which is in contrast to preliminary data from studies in humans. Results from animal study data are equivocal. There is an urgent need for appropriately designed and powered clinical trials addressing this apparently controversial situation.
黏菌素通常是治疗多重耐药革兰氏阴性菌感染的最后手段。在临床实践中，尽管会导致毒性增加，但为了提高其抗菌活性，它经常被用作联合治疗。我们评估了从PubMed和Scopus数据库检索到的关于黏菌素单药治疗和黏菌素联合治疗比较有效性的各种研究（微生物学、动物和临床研究）的现有证据。大多数微生物学研究比较了黏菌素单药治疗与联合利福平（9项研究）或碳青霉烯类药物（3项研究）治疗铜绿假单胞菌或鲍曼不动杆菌感染的效果。在所有研究黏菌素和利福平联合使用的研究中均检测到协同效应，而在三项研究中有两项研究显示碳青霉烯类药物具有协同效应。大多数动物研究比较了黏菌素单药治疗与联合利福平、羧苄青霉素、哌拉西林和亚胺培南治疗铜绿假单胞菌、鲍曼不动杆菌或大肠杆菌感染的效果。在六项相关研究中的三项研究中，联合治疗组的死亡率显著较低。然而，少量（四项）相关人体研究的数据表明，与联合治疗相比，黏菌素单药治疗并不逊色。总之，微生物学研究表明黏菌素联合治疗更具优势，这与人体研究的初步数据形成对比。动物研究数据的结果并不明确。迫切需要设计合理且样本量充足的临床试验来解决这一明显存在争议的情况。
