Co-trimoxazole in prevention of bacteriuria after prostatectomy.

In a prospective, double-blind trial prophylactic cotrimoxazole produced a highly significant reduction in the incidence of bacteriuria after prostatectomy. Only two out of 38 patients who received the drug developed bacteriuria compared with 19 out of 36 patients on placebo. Klebsiella-Enterobacter spp and coagulase-negative staphylococci were responsible for most infections. Although co-trimoxazole prophylaxis is obviously effective, widespread use might increase the incidence of bacterial resistance.     

Co-trimoxazole and Azathioprine: A Safe Combination

Ninety-four patients receiving immunosuppressive therapy with azathioprine and prednisone after human cadaver kidney transplantation developed urinary tract infections and were treated with co-trimoxazole or another antibiotic in a controlled randomized prospective trial. The incidence of leucopenia in the group treated with co-trimoxazole (10·6%) was not significantly different from that in the group treated with other antibiotics (23·6%). Leucopenia when it occurred did so soon after transplantation at a time when the function of the renal transplant was poor in relation to the dosage of azathioprine given. In all cases the temporary withdrawal of azathioprine relieved the leucopenia despite continuation of the co-trimoxazole treatment. This study did not provide any evidence that co-trimoxazole plus azathioprine was a more potent cause of leucopenia than azathioprine alone.     

Suppression of Thymidine Uptake of Human Lymphocytes by Co-trimoxazole

Co-trimoxazole (trimethoprim-sulphamethoxazole) causes a decrease in the uptake of labelled thymidine in lymphocytes cultured in the presence of phytohaemagglutinin. This phenomenon was observed in 60% of 25 subjects. In cultures affected by the drug the mean suppression was 84%. A small decrease in thymidine uptake was noted with trimethoprim and sulphamethoxazole separately, but the effect was much more pronounced with the combination of the two drugs. The mechanism responsible for this phenomenon is discussed. The action is probably not due to the ability of these drugs to interfere with folic acid metabolism and it is likely that there is no direct effect on DNA synthesis.The suppression of thymidine uptake by lymphocytes in vitro in the presence of co-trimoxazole may not have any obvious clinical significance. However, in view of a report of an immunosuppressive action of trimethoprim in mice, it is possible that the leucopenia observed in some patients treated with this drug may have been caused by a similar mechanism.These experiments show that lymphocytes in vitro are suppressed by co-trimoxazole in concentrations comparable to, or smaller than, those found in vivo under normal therapeutic conditions. They are therefore likely to be clinically relevant.     

Co-trimoxazole effect on human alveolar macrophages of AIDS patients

Compelling evidence suggests that co-trimoxazole prophylaxis reduces mortality in HIV-infected patients, although it is unclear whether these effects are directly related to antimicrobial activities. We evaluated in vitro phagocytosis and killing of Staphylococcus aureus in alveolar macrophages (AM) obtained from AIDS patients who smoke, treated (n=19) or not treated (n=13) with co-trimoxazole, as compared to non-HIV-infected healthy smokers (n=15). Phagocytosis and killing of Staphylococcus aureus by AM obtained from non-co-trimoxazole treated AIDS patients were significantly lower compared to non-HIV-infected healthy smokers. In contrast, AIDS patients treated with co-trimoxazole prophylaxis showed phagocytosis and killing levels similar to those of healthy controls. These results might help to clarify the observed positive effect of co-trimoxazole on survival in HIV-infected patients.     

Comparative trial of Co-trimoxazole and Chloramphenicol in Typhoid Fever

A comparative trial of co-trimoxazole and chloramphenicol was conducted in two groups of 50 patients each to try to resolve conflicting opinions on the relative merits of the two drugs in the treatment of typhoid fever. We conclude that in our part of India co-trimoxazole is superior to chloramphenicol and that differences in our findings to those of others may perhaps be accounted for by differences in strains of Salmonella typhi, ethnic differences, and possibly differences in herd immunity to typhoid.     

Clinical Evaluation of Co-trimoxazole and Furazolidone in Treatment of Shigellosis in Children

Co-trimoxazole (trimethoprim—sulphamethoxazole) was compared with furazolidone in the treatment of shigellosis in two groups of 33 and 30 patients respectively. Those treated with co-trimoxazole recovered more quickly; none had shigellae in the faeces four days after the start of treatment, whereas in the group given furazolidone eight still had positive stool cultures seven days after treatment.The susceptibility of 104 shigella strains to seven antimicrobial agents was studied by plate dilution technique. All agents but tetracycline and chloramphenicol were found highly effective against most of the strains tested. All shigella isolates were resistant to sulphamethoxazole, and 63% were sensitive to trimethoprim. Potentiation of trimethoprim by sulphamethoxazole was shown in that all strains tested became sensitive to the combination of trimethoprim and sulphamethoxazole in a ratio of 1:20.