小児科領域におけるSulfamethoxazole-Trimethoprim合剤の基礎的ならびに臨床的検討

抄録

Experimental and clinical studies of sulfamethoxazole (SMX) -trimethoprim (TMP) combination product have revealed the following results :
The assessment of bacterial sensitivity to SMX-TMP combination was made according to agar plate dilution method employing MUELLER-HINTON agar (pH 7.4) added with 7. 5% hemolyzed horse blood. The sensitivity of most of coagulase-positive Staphylococcal strains was 400 mcg/ml or more. Twenty-six out of 36 strains demonstrated minimum inhibitory concentrations (MICs) in exess of 200 mcg/ml of SMX. The peak distribution of TMP sensitivity ranged in the area of 0.2 mcg/ml. Twenty of 23 Escherichia coli strains demonstrated MICs higher than 400 mcg/m1 of SMX but the growth of all strains was inhibited by TMP concentrations less than 0.78 mcg/ml. The peak MIC distribution of SMX was found at 0. 1 mcg/ml. The activity of SMX-TMP combination against Staphylococci was enhanced as the ratio of TMP content within the combination increase. For SMX-sensitive Staphylococci the activity of SMX was potentiated by 2³-2⁴ times by combination with TMP in a ratio of 20 : 1. The growth of SMX-resistant Staphylococci were also inhibited by potentiation by the combination in the order of 2⁶-2⁷ times. The activity of TMP in the combination was reduced by 2^1/4-2^1/5 times in comparison with that of TMP when employed alone. The activities against Escherichia coli strains are subject to greater fluctuations than those seen with Staphylococci. The combination of SMX-TMP demonstrated potentiated activities against SMX-sensitive Escherichia coli greater by 2³-2₄ times than those of SMX alone. The activity against SMX-resistant strains was also strengthened by an average of 2¹⁰ times, while the activity of TMP in the combination was reduced by 2^1/3-2^1/4 times than that of TMP alone.
A clinical trial of SMX-TMP combination product in 17 pediatric patients with bacterial infection (ages ranging from 8 months to 10 years and 2 months) revealed 11 effective and 6 ineffective cases, an effective rate of 64.7%. The correlation between in vitro sensitivity of clinically isolated strains and therapeutic response was studied in 11 instances. All 3 patients from whom SMX-sensitive Staphylococcus aureus had been isolated responded to the combination. Two cases infected with SMX-resistant Staphylococci strains were classified as non-responders. Two strains of β-hemolytic Streptococci were snesitive to SMX and 1 of them was a responder and the other a nonresponder. SMX-TMP combination product was effective in all 4 patients with Streptococcus viridans infection, only one of which was sensitive and the other 3 were resistant to SMX. No untoward reactions were recorded.