Reversal of activity of trimethoprim against Gram-positive cocci by thymidine, thymine and ‘folates’

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Abstract
The reversal of the antibacterial activity of trimethoprim against different species of Gram-positive cocci (Staphylococcus aureus, Staph. epidermidis, Staph. saprophyticus, group B streptococci, Streptococcus faecalis and Str. faecium) by thymine, thymidine and various ‘folates’ (folate, folinate, dihydrofolate and tetrahydrofolate) was tested. Against group B streptococci and staphylococci only thymidine antagonized trimethoprim. However, for enterococci, thymine, thymidine, dihydrofolate, tetrahydrofolate and folinate all reversed the activity of trimethoprim, although by different amounts. Dihydrofolate was significantly more effective as a trimethoprim antagonist for Str. faecium than for Str. faecalis. While thymine and thymidine caused the MIC of trimethoprim against enterococci to increase more than 100-fold‘thereby rendering them resistant—the ‘folates’ brought about much smaller increases in trimethoprim MIC, in the order of ten-fold only. Thus, even in the presence of ‘folates’ enterococci remain sensitive in vitro to trimethoprim.

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