Antimicrobial cycling: Lessons learned from the aminoglycoside experience

Several discrete strategies have been suggested to prevent or reduce microb ial resistance to antimicrobials, including optimal use of the agents (also known as good stewardship); control, removal, or restriction of antimicrob ials; 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 agen ts that could induce or select resistance. Hospitalwide studies of aminogly coside substitution employed from the late 1970s through the early 1990s, a lthough not originally intended to test cycling or rotation of aminoglycosi des, serendipitously provided data that may be useful in designing future s tudies. In particular, one 10-year study at the Minneapolis Veterans' Affai rs Medical Center (MVAMC) rotated amikacin and gentamicin use over cycles o f 12 to 51 months' duration. Significantly reduced resistance to gentamicin was found when amikacin was used, but resistance to gentamicin returned wi th the first gentamicin recycle. This was followed by reintroduction of ami kacin a second time with decreased resistance to gentamicin and, finally, a second reintroduction of gentamicin without resistance to it recurring. Th us, some evidence of proof of principal can be garnered, albeit subject to considerable criticism. Critical examination of the design of the aminoglyc oside rotation study and the unforeseen pitfalls is provided as a 13-elemen t guidance list for design of future rotational studies. Rotational usage p ractices are likely to be most appropriate for drugs active against gram-ne gative bacilli because of the wide choices available for rotation. Future a vailability of new agents active against resistant gram-positive organisms will present the opportunity to cycle these agents as vancomycin substitute s. 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 (Infect Control Hosp Epidemiol 2000;21(Suppl.):S12-S17).