Activities of the glycylcyclines N,N-dimethylglycylamido-minocycline and N,N-dimethylglycylamido-6-demethyl-6-deoxytetracycline against Nocardia spp. and tetracycline-resistant isolates of rapidly growing mycobacteria

Abstract

Susceptibilities to the new semisynthetic tetracycline (Tet) compounds N,N-dimethylglycylamido-minocycline (DMG-MINO) and N,N-dimethylglycylamido-6-demethyl-6-deoxytetracycline (DMG-DMDOT) were compared with those to doxycycline, minocycline, and Tet for 198 Tet-resistant (Tetr) and 33 Tet-susceptible (Tets) clinical isolates of rapidly growing mycobacteria (RGM) including the Mycobacterium fortuitum group, Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium mucogenicum and 68 isolates belonging to six taxa of Nocardia spp. All Tetr RGM were highly susceptible to the glycylcyclines. The MICs at which 50 and 90% of isolates are inhibited were < or = 0.125 and < or = 0.25 microgram/ml, respectively, for DMG-DMDOT and < or = 0.25 and 1 microgram/ml, respectively, for DMG-MINO. The MIC of DMG-DMDOT at which 50% of Tetr strains are inhibited was the same as that for Tets strains for each of the four taxa of RGM. The new agents were less active against Nocardia spp. MICs of DMG-DMDOT were comparable to those of minocycline except for the MICs for Nocardia brasiliensis sensu stricto, the new taxon Nocardia pseudobrasiliensis, and some isolates of Nocardia nova, against which they were four- to eightfold more active. The MICs of DMG-DMDOT were consistently lower than those of DMG-MINO for RGM. This class of drugs offers exciting therapeutic potential for RGM and for selected species of Nocardia.