Clinical details are presented of 16 patients from whom thymine-requiring (thy−) mutants of pathogenic organisms were isolated; all had been treated with co-trimoxazole. The urine of six patients infected with thy− mutants contained levels of a thymine-like compound sufficient to support their growth. This might be the result either of the breakdown of pus cells or of thymine production by living bacteria that persist in stones or scar tissue, a suggestion supported by the observation of mutant growth “in satellitism” in vitro. Since 1975 we have isolated mutants from patients who have had short courses of co-trimoxazole, in contrast to those we reported upon previously, all except one of whom had had long courses. We are now isolating thy− mutants more frequently than hitherto. Secondary mutations to a low thymine requirement may now be occurring more rapidly, thereby allowing more mutant organisms to survive. The clinical significance of infection with thy− mutants is not yet clear, but evidence is accumulating that they are pathogenic. Alternative chemotherapy is suggested for patients from whom such mutants have been isolated.
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