Sulfamethoxazole-trimethoprim synergism for Neisseria gonorrhoeae

Abstract

Sulfamethoxazole and trimethoprim are synergistic against many bacteria in sulfamethoxazole/trimethoprim concentrations of 20:1, but single-dose therapy of gonorrhea with the combination is disappointing. We used agar dilution techniques to determine minimal inhibitory concentrations of sulfamethoxazole and trimethoprim for 168 gonococci isolated from men with acute urethritis in Atlanta, Ga. The geometric mean minimal inhibitory concentrations were 5.6 ,ug of sulfamethoxazole per ml and 24.3 ,tg of trimethoprim per ml, a ratio of 1:4. The concentration of sulfamethoxazole inhibiting 50% of gonococcal strains dropped only from 4.7 ,g/ml to 2.9 ,tg/ml with the addition of a 1/20 dilution of trimethoprim. We studied synergism with various ratios of sulfamethoxazole to trimethoprim against 20 random strains. A ratio of 1:1 was always synergistic and was the most synergistic ratio for 15 strains, whereas the 19:1 ratio was never the most synergistic. The 19:1 ratio failed to show synergism against seven strains, but showed antagonism at this ratio with five of these seven. The sulfamethoxazole/trimethoprim ratio of 19:1 usually achieved in serum after oral administration is minimally synergistic and is sometimes antagonistic for gonococci. Austin and colleagues tested 54 fresh isolates at two ratios of SMX/TMP and found that 1:3 was more synergistic than 20:1 (1). Stolz et al. found that a 1:1 ratio and a 1:20 ratio of SMX/TMP were more synergistic than the 20:1 ratio for 5 gonococcal isolates (23). Phillips and colleagues tested 30 strains and found that ratios of SMX/ TMP from 1:1 to 1:8 were generally more synergistic than ratios involving larger relative amounts of SMX (18). The ratio producing maximal synergy tended to be related to the ratio of the MICs of the individual drugs alone.We thought that the relatively low efficacy of single-dose SMX/TMP therapy for acute gonorrhea might result in part from a lack of synergism between the drugs. We determined the susceptibility to SMX and TMP of freshly isolated strains of N. gonorrhoeae and determined the synergistic effect of various combinations of the two drugs.

Influence of inoculum size on comparative susceptibilities of penicillinase-positive and -negative Neisseria gonorrhoeae to 31 antimicrobial agents

“…Against non-PPNG strains, the MIC was 4 to 8 ,ug/ml. Elsewhere, trimethoprim-sulfamethoxazole at a ratio of 1:19 was minimally synergistic against non-PPNG strains (16). In three recent studies, rosoxacin (a quinolone derivative) was effective in vitro against both PPNG and non-PPNG strains (10,11,18).…”