Kenny G E, Cartwright F D
Department of Pathobiology, School of Public Health and Community Medicine, University of Washington, Seattle 98195.
Antimicrob Agents Chemother. 1994 Nov;38(11):2628-32. doi: 10.1128/AAC.38.11.2628.
The glycylcyclines are new tetracycline derivatives that include the N,N-dimethylglycylamido derivative of minocycline (DMG-MINO) and the N,N-dimethylglycylamido derivative of 6-demethyl-6-deoxytetracycline (DMG-DMDOT). The susceptibilities of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum to DMG-MINO, DMG-DMDOT, tetracycline, doxycycline, and minocycline were determined by the agar dilution method. The glycylcyclines with MICs at which 50% of the isolates are inhibited of 0.25 to 0.5 micrograms/ml for M. pneumoniae were two- to fourfold more active than tetracycline and had the same activity as minocycline and doxycycline. Tetracycline-susceptible M. hominis strains were four- to eightfold more susceptible to the glycylcyclines (0.12 to 0.25 micrograms/ml) than to tetracycline. Strains of M. hominis known to be resistant to tetracycline, doxycycline, and minocycline because of the tet(M) determinant were as susceptible to the glycylcyclines as the tetracycline-susceptible strains. For tetracycline-susceptible U. urealyticum strains, the glycylcyclines showed the same activity as tetracycline (MICs at which 50% of the isolates are inhibited of 1 to 2 micrograms/ml). Tetracycline-resistant strains of U. urealyticum were resistant to doxycycline and minocycline and showed variable susceptibility to the glycylcyclines (range, 0.5 to 32 micrograms/ml). In view of the increasing resistance of M. hominis and U. urealyticum strains to tetracyclines, the glycylcyclines have promise, pending assessment of their pharmacokinetic and safety profiles.
甘氨酰环素是新型四环素衍生物,包括米诺环素的N,N - 二甲基甘氨酰胺衍生物(DMG - MINO)和6 - 去甲基 - 6 - 脱氧四环素的N,N - 二甲基甘氨酰胺衍生物(DMG - DMDOT)。采用琼脂稀释法测定了肺炎支原体、人型支原体和解脲脲原体对DMG - MINO、DMG - DMDOT、四环素、多西环素和米诺环素的敏感性。对于肺炎支原体,50%分离株被抑制的MIC为0.25至0.5微克/毫升的甘氨酰环素,其活性比四环素高2至4倍,与米诺环素和多西环素活性相同。对四环素敏感的人型支原体菌株对甘氨酰环素(0.12至0.25微克/毫升)的敏感性比对四环素高4至8倍。已知因tet(M)决定簇而对四环素、多西环素和米诺环素耐药的人型支原体菌株对甘氨酰环素的敏感性与对四环素敏感的菌株相同。对于对四环素敏感的解脲脲原体菌株,甘氨酰环素显示出与四环素相同的活性(50%分离株被抑制的MIC为1至2微克/毫升)。解脲脲原体的四环素耐药菌株对多西环素和米诺环素耐药,对甘氨酰环素的敏感性各不相同(范围为0.5至32微克/毫升)。鉴于人型支原体和解脲脲原体菌株对四环素的耐药性不断增加,在对其药代动力学和安全性进行评估之前,甘氨酰环素具有应用前景。