Sensitivity Testing With Trimethoprim/Sulphamethoxazole

In practice, TMP/SMX should be regarded as a single drug; its two components ultimately have the same effect on bacteria, that is, to deprive an organism of its folate co-enzymes. Synergy occurs over a wide range of ratios, and attainment of optimum proportions assumes importance only when minimum concentrations are present. Sensitivity testing presents no problem provided a small inoculum is used, and the medium contains < 0.01 μg of thymidine/ml. Although thymidine interferes with the in-vitro activity of TMP/SMX, it is not present in animals in sufficiently high concentrations to affect the in-vivo activity. Sulphonamides enhance the sensitivity of sulphonamide-resistant strains to TMP because, in spite of apparent resistance, the sulphonamides depress the store of folates in these organisms. Synergy can only be excluded by performing complicated two-dimensional titration tests. In practice, inhibition zones of 14 mm indicate that the infection will respond to treatment with TMP/SMX. The effect of sulphonamides in delaying the emergence of TMP resistance is inversely proportional to the degree of sulphonamide resistance. The majority of TMP-resistant variants, at least of the Enterobacteriaceas family, are probably avirulent. More significant is the detection of R factors conferring a high degree of TMP resistance; however, so far the transference rates are low, suggesting that the likelihood of the spread of these factors is not high.