The following conclusions could be drawn from experimental and clinical studies of sulfamethoxazole (SMX) -trimethoprim (TMP) combination product.
1. Antimicrobial activity :
Minimal inhibitory concentrations (MICs) of SMX alone against 5 standard strains of Staphylococcus aureus ranged from 0.8 to over 100 mcg/ml and those of TMP alone were 0.8 to 1.56 mcg/ml. In contrast, activities of the combination of SMX and TMP mixed in a ratio of 20 : 1 recorded MICs of 0.8-1.56 mcg/ml MICs of SMX alone, TMP alone and SMX-TMP combination (20 : 1) in 4 strains of Escherichia coli were greater than 100, 0.05-0.2 and 0.2-0.8 mcg/ml, respectively.
2. Sensitivities of 52 strains of Staphylococcus aureus isolated from clinical materials gave, in term of MIC, greater than 100 mcg/ml for SMX alone in all strains, 0.4-3.12 mcg/ml for TMP alone and 1.6-25 mcg/ml for SMX-TMP combination.
3. MIC's of 51 strains of clinically isolated Escherichia coli were greater than 100 mcg/ml for SMX, 0.2-6.25 mcg/ml for TMP and 1.6-50 mcg/ml for the combination.
4. Blood concentration and renal excretion :
Investigations in 3 adult male volunteers indicated that peak blood levels of TMP 1/2 to 6 hours following a dose of 2 tablets of SMX-TMP combination product (800 mg of SMX and 160 mg of TMP) to empty stomach reached 0.87-1.07 mcg/ml as assessed by a bioassay employing a culture medium containing PABA. Blood levels of TMP 12 hours after a single oral dose averaged 0.4 mcg/ml. Urinary concentrations reached peak values of 116-360 mcg/ml during the period of 2-6 hours post-dose and the recovery in the urine up to 12 hours ranged 36-68 % of the administered dose. Blood levels of SMX determined chemically indicated that the compound reached peak values of 30-40 mcg/ml of free-SMX in 2-4 hours; total SMX-TMP concentrations were higher by 2-5 mcg /ml than those of free-SMX.
5. Thirty-five patients with infections of surgical field were given a trial with SMX-TMP combination product. Effective response was recorded in 24 patients, no effect in 8 and undetermined effect in 3. No significant untoward reactions were observed except for mild epigastralgia in 1 patient.
