The Antimicrobial Implications of the Pharmacokinetics of Cotrimoxazole in CAPO Patients
Cotrimoxazole (TMP/SMX) has been used to treat continuous ambulatory peritoneal dialysis (CAPD) associated peritonitis. It is considered bactericidal for some species. The most common single organism responsible for this type of peritonitis is Staph. epidermidis (SE). When the drug is given orally, the typical ratio of TMP to SMX achieved in the peritoneal fluid is 1:5, which is different from the optimal combination for antimicrobial synergy of 1:19. This study investigated the antimicrobial activity of TMP alone and TMP/SMX by agar dilution at ratios of 1:19, 1:10 and 1:5 against 99 strains of Staphylococcus epidermis (SE). The majority of strains were susceptible to TMP and to all ratios of TMP/SMX by the routine agar dilution methods. We studied the bactericidal activity of TMP/SMX against one strain each of SE and of Staph. aureus (SA) in pooled uninfected spent dialysate by killing curve experiments. TMP at concentrations of 0.5 to 2.0 μg/ml was bacteriostatic. TMP/SMX became slowly bactericidal when 5 % lysed horse blood, a source of thymidine phosphorylase, was added to the dialysate. It is concluded that susceptibility tests of inhibition do not predict bactericidal activity of TMP/SMX in recovered dialysate. Inhibition of TMP/ SMX is most likely due to thymidine present in dialysate. TMP alone was as effective against SE as TMP/ SMX. Until it is shown that bactericidal activity is not required for cure of CAPD-related peritonitis, cotrimoxazole should not be used routinely for its treatment.