Heifets L B, Iseman M D, Lindholm-Levy P J
National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Drugs Exp Clin Res. 1987;13(9):529-38.
The aim of this study was to search for new drugs active against the Mycobacterium avium complex and to re-examine the activity of some conventional antituberculosis drugs against these species. This progress report describes the protocol and phases of in vitro experiments in a search which included 57 different compounds tested against numerous strains of M. avium clinical isolates. The preliminary screening and MIC determination of these drugs were conducted in 7H12 broth by the radiometric method (BACTEC system). Of the total of 57 drugs, 23 were discarded after preliminary screening and 17 after MIC determination. The remaining 17 drugs were considered sufficiently promising for more detailed in vitro studies. These, now in progress, include MIC determination by two additional methods (in broth by sampling and plating and in 7H11 agar plates), MBC determination and drug combination studies. The following drugs are currently undergoing these detailed studies: isoniazid, rifampin, rifabutine (ansamycin LM427), amikacin, streptomycin, ethambutol, ethionamide, cycloserine, clofazimine (CF), CF derivative B746, CF derivative B1865, ofloxacin, ciprofloxacin, cephalosporin BMY 28142, trimethoprim-sulfamethoxazole, spectinomycin derivative U6633F(B), and dihydromycoplanecin.
本研究的目的是寻找对鸟分枝杆菌复合群有活性的新药,并重新检验一些传统抗结核药物对这些菌的活性。本进展报告描述了体外实验的方案和阶段,该研究包括对57种不同化合物针对大量鸟分枝杆菌临床分离株进行测试。这些药物的初步筛选和最低抑菌浓度(MIC)测定通过放射测量法(BACTEC系统)在7H12肉汤中进行。在总共57种药物中,23种在初步筛选后被淘汰,17种在MIC测定后被淘汰。其余17种药物被认为有足够的前景进行更详细的体外研究。目前正在进行的研究包括通过另外两种方法测定MIC(在肉汤中取样和接种平板以及在7H11琼脂平板上)、最低杀菌浓度(MBC)测定和药物联合研究。以下药物目前正在进行这些详细研究:异烟肼、利福平、利福布汀(安莎霉素LM-427)、阿米卡星、链霉素、乙胺丁醇、乙硫异烟胺、环丝氨酸、氯法齐明(CF)、CF衍生物B746、CF衍生物B1865、氧氟沙星、环丙沙星、头孢菌素BMY 28142、甲氧苄啶-磺胺甲恶唑、壮观霉素衍生物U6633F(B)和二氢霉菌平面菌素。