In vitro activity of trimethoprim and sulfamethoxazole against the nontuberculous mycobacteria.

Trimethoprim (TMP) and sulfamethoxazole (SMZ) were studied alone and in combination (TMP-SMZ) against 141 nontuberculous mycobacteria; an agar dilution method was used. All strains of Mycobacterium kansasii (8), Mycobacterium marinum (16), and Mycobacterium scrofulaceum (3); 97% (63 of 65) of strains of Mycobacterium fortuitum; and 27% (3 of 11) of strains of Mycobacterium avium-intracellulare were inhibited by less than or equal to 32 micrograms of SMZ/ml. In contrast, all 38 isolates of Mycobacterium chelonei were resistant to 32 micrograms of SMZ/ml. All species were highly resistant to TMP, with minimal inhibitory concentrations (MICs) of greater than or equal to 64 micrograms/ml. The MICs of TMP-SMZ for these organisms were similar to the MICs of SMZ alone. These results support the use of sulfonamides for treatment of infections due to M. fortuitum and M. marinum and suggest the need for further clinical and laboratory studies of the activity of these drugs against several additional mycobacterial species. TMP-SMZ appears to offer no advantage (in vitro) over SMZ alone against any of these organisms.

Use of trimethoprim-sulfamethoxazole for treatment of infections due to Nocardia.

Trimethoprim-sulfamethoxazole (TMP-SMZ) was used for treatment of 34 patients with pulmonary or cutaneous nocardiosis. Of nine patients with primary cutaneous disease, eight had rapid resolution of their infection after short-term therapy and none have relapsed after a follow-up of more than six months. The 25 patients with pulmonary nocardiosis had a good clinical response, but three of five (60%) who completed less than three months of therapy relapsed within four weeks. Of the 10 patients who completed four to six months of therapy, only one (10%) relapsed and this relapse was due to drug resistance. By the method of serial dilution in agar, 96% of 59 isolates of Nocardia had MICs of SMZ of less than 25 micrograms/ml. Fewer than 20% were susceptible to 2.5 micrograms of TMP/ml. Synergy between TMP and SMZ was usually present with ratios of TMP to SMZ of 1:5, 1:1, or 5:1, but was less common at a ratio of 1:20. Disk susceptibility testing was easy to perform and readily separated sensitive from resistant strains. TMP-SMZ is highly effective for the treatment of nocardiosis, but the question of whether it is more effective clinically than a sulfonamide alone remains unanswered.