The <i>in vitro</i> Demonstration of the Efficacy of Trimethoprim as an Antibacterial Agent in a Comparative Bacteriological Study on the Effects of Trimethoprim, Sulfamethoxazole and the Combination Trimethoprim/Sulfamethoxazole

Abstract

The minimal inhibitory concentrations of trimethoprim (TMP), sulfamethoxazole (SMZ) and the combination trimethoprim/sulfamethoxazole (TMP/SMZ) in a ratio of 1:20 have been determined for 97 bacterial strains (66 Escherichia coli, 13 Proteus mirabilis, 22 Enterococcus, 12 Staphylococcus, 4 Klebsiella and Enterobacter and 4 others) using the agar-dilution technique. The same strains and an additional 31 strains were tested for sensitivity to TMP/SMZ and SMZ by the agar-diffusion test. 48 of them were also examined for TMP sensitivity by this method. All strains had been isolated from urine of patients suffering from acute urinary tract infections. 43% of these strains were sensitive to SMZ, 90% were sensitive to TMP and 95% to TMP/SMZ. The potentiation of TMP by combination with SMZ was more than 5-fold in 97% of the sulfonamide-sensitive strains and in 54.8% of the sulfonamide-resistant strains. The in vitro results seem to indicate that TMP is almost as useful a bacteriostatic chemotherapeutic as its combination with SMZ. The enhancement of its activity by sulfonamides in man cannot yet be evaluated, because only insufficient experience exists in the treatment with TMP alone. TMP and TMP/SMZ were also tested for bactericidal activities on 5 strains. Against 3 of these strains TMP as well as TMP/SMZ showed only bacteriostatic activities. With the other 2 strains slight bactericidal activities of TMP and TMP/SMZ could be demonstrated within 18 h of incubation. There was no major difference between TMP and TMP/SMZ as far as bactericidal activities were concerned. For sensitivity testing the agar-diffusion technique using two discs that contain the single components or one disc containing 1.25 μg TMP is recommended, since it could be shown that the potentiation of TMP by SMZ cannot sufficiently be demonstrated by the agar-diffusion technique using one disc containing both substances.

Preventive Effects of Trimethoprim, Sulphamethoxazole and the Combination Trimethoprim/Sulphamethoxazole on Experimental Staphylococcic Pyelonephritis in Rats

“…This finding is in contradiction to the former ones. Since we were in agreement with KOchler's and K o ch's [5] point of view about the insufficiency of detailed clinical and experimental trials to eluci date the superiority of the TMP/SMZ combination on the sole use of TMP, the present investigation was carried out. In this study, preventive effects of TMP and sulphamethoxazole (SMZ) alone and combined on the development of experimental hematogenous pyelonephritis in rats were investigated.…”

“…Bacteri cidal action of this combination is due to the blockade of folate synthesis in bacteria concomitantly during two successive phases [1,2]. Although the synergy of the two components is reflected in an often appreciable de crease in the level of minimum inhibitory doses and bactericidal doses in in vivo and in vitro experiments [3,4], K uchler and K och [5] have re cently reported that according to the results of their experiments in vivo the inhibitory effect of trimethoprim (TMP) alone equaled to the effect of the combination. This finding is in contradiction to the former ones.…”

Efficacy of Trimethoprim, Sulfamethoxazole and the Combination of Both in Acute Urinary Tract Infection

“…The bacterial count was determined semiquantitatively by spreading 0.01 ml urine evenly on a sheep-blood agar plate and by counting the colonies after 18 h of incubation at 37 °C [28].…”

“…In a previous paper [28] we reported on comparative studies on the antibacterial action of trimethoprim (TMP), sulfamethoxazole (SMZ), and their combination (TMP/SMZ) in vitro. We concluded that TMP alone is often as effective as its combination with SMZ.…”