Gerding D N
Lakeside Division, VA Chicago Healthcare System, Northwestern University Medical School, Illinois 60611, USA.
Infect Control Hosp Epidemiol. 2000 Jan;21(1 Suppl):S12-7. doi: 10.1086/503168.
Several discrete strategies have been suggested to prevent or reduce microbial resistance to antimicrobials, including optimal use of the agents (also known as good stewardship); control, removal, or restriction of antimicrobials; use of antimicrobials in combination; and rotational or cyclic use of antimicrobials. The latter strategy is attractive because it periodically removes from the institutional environment certain classes or specific agents that could induce or select resistance. Hospitalwide studies of aminoglycoside substitution employed from the late 1970s through the early 1990s, although not originally intended to test cycling or rotation of aminoglycosides, serendipitously provided data that may be useful in designing future studies. In particular, one 10-year study at the Minneapolis Veterans' Affairs Medical Center (MVAMC) rotated amikacin and gentamicin use over cycles of 12 to 51 months' duration. Significantly reduced resistance to gentamicin was found when amikacin was used, but resistance to gentamicin returned with the first gentamicin recycle. This was followed by reintroduction of amikacin a second time with decreased resistance to gentamicin and, finally, a second reintroduction of gentamicin without resistance to it recurring. Thus, some evidence of proof of principal can be garnered, albeit subject to considerable criticism. Critical examination of the design of the aminoglycoside rotation study and the unforeseen pitfalls is provided as a 13-element guidance list for design of future rotational studies. Rotational usage practices are likely to be most appropriate for drugs active against gram-negative bacilli because of the wide choices available for rotation. Future availability of new agents active against resistant gram-positive organisms will present the opportunity to cycle these agents as vancomycin substitutes. Careful monitoring of clinical outcomes and resistance will be required. Multicenter controlled trials that follow carefully designed protocols are most likely to produce statistically significant and clinically meaningful results.
为预防或减少微生物对抗菌药物的耐药性，人们提出了几种不同的策略，包括抗菌药物的优化使用（也称为良好的管理）；控制、去除或限制抗菌药物；联合使用抗菌药物；以及抗菌药物的轮换或循环使用。后一种策略很有吸引力，因为它会定期从医疗机构环境中去除某些可能诱导或选择耐药性的类别或特定药物。从20世纪70年代末到90年代初进行的全院范围内氨基糖苷类药物替代研究，虽然最初并非旨在测试氨基糖苷类药物的循环或轮换，但意外地提供了可能有助于设计未来研究的数据。特别是，明尼阿波利斯退伍军人事务医疗中心（MVAMC）的一项为期10年的研究，在12至51个月的周期内轮换使用阿米卡星和庆大霉素。使用阿米卡星时，对庆大霉素的耐药性显著降低，但在首次循环使用庆大霉素时，对庆大霉素的耐药性又恢复了。随后再次引入阿米卡星，对庆大霉素的耐药性降低，最后再次引入庆大霉素，其耐药性未再次出现。因此，尽管受到相当多的批评，但可以获得一些主要原则的证据。对氨基糖苷类药物轮换研究的设计和意外陷阱进行了批判性审查，并提供了一份13项要素的指导清单，用于未来轮换研究的设计。由于可供轮换的选择广泛，轮换使用方法可能最适用于对革兰氏阴性杆菌有效的药物。未来针对耐药革兰氏阳性菌的新型药物的出现，将提供将这些药物作为万古霉素替代品进行循环使用的机会。需要仔细监测临床结果和耐药性。遵循精心设计方案的多中心对照试验最有可能产生具有统计学意义和临床意义的结果。
