Bermudez L E, Young L S, Inderlied C B
Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco 94115.
Antimicrob Agents Chemother. 1994 May;38(5):1200-2. doi: 10.1128/AAC.38.5.1200.
Organisms of the Mycobacterium avium complex (MAC) cause disseminated disease in patients with AIDS, and evidence points to the gastrointestinal tract as the major route of infection. Since MAC can bind to and invade intestinal mucosal cells, we examined whether subinhibitory concentrations of antibiotics which have anti-MAC activity in vitro affect the interaction between MAC and HT-29 intestinal mucosal cells. MAC isolates were exposed to subinhibitory concentrations of rifabutin (MIC, 2.6 micrograms/ml), sparfloxacin (MIC, 8.4 micrograms/ml), or azithromycin (MIC, 32 micrograms/ml) for 30 to 120 min, washed, and incubated with HT-29 cell monolayers for 2 h at 4 degrees C. HT-29 cell monolayers were then washed to remove unbound bacteria and were subsequently lysed. The number of MAC isolates that bound to the HT-29 cells was determined by plating the cell lysate onto 7H10 agar. Preincubation of the MAC isolates with rifabutin at concentrations of 1 and 2 micrograms/ml reduced MAC binding to HT-29 cells by 80 to 90%, while MAC exposed to sparfloxacin at 1 and 7 micrograms/ml inhibited binding by 77 to 93%. Azithromycin at concentrations of 2, 10, and 30 micrograms/ml had no effect on MAC binding to HT-29 cells. Inhibition of MAC binding to the gastrointestinal mucosa may be one underlying mechanism for the prophylactic effects of rifabutin and quinolones.
鸟分枝杆菌复合体(MAC)的微生物可在艾滋病患者中引起播散性疾病,且有证据表明胃肠道是主要感染途径。由于MAC可结合并侵入肠道黏膜细胞,我们研究了体外具有抗MAC活性的抗生素亚抑菌浓度是否会影响MAC与HT - 29肠道黏膜细胞之间的相互作用。将MAC分离株暴露于利福布汀(MIC,2.6微克/毫升)、司帕沙星(MIC,8.4微克/毫升)或阿奇霉素(MIC,32微克/毫升)的亚抑菌浓度下30至120分钟,洗涤后,在4℃下与HT - 29细胞单层孵育2小时。然后洗涤HT - 29细胞单层以去除未结合的细菌,随后进行裂解。通过将细胞裂解物接种到7H10琼脂平板上来确定与HT - 29细胞结合的MAC分离株数量。将MAC分离株与浓度为1和2微克/毫升的利福布汀预孵育可使MAC与HT - 29细胞的结合减少80%至90%,而暴露于浓度为1和7微克/毫升司帕沙星的MAC对结合的抑制率为77%至93%。浓度为2、10和30微克/毫升的阿奇霉素对MAC与HT - 29细胞的结合没有影响。抑制MAC与胃肠道黏膜的结合可能是利福布汀和喹诺酮类药物预防作用的一种潜在机制。