Study Objective: To compare single-dose and 10-day treatment regimens of trimethoprim-sulfamethoxazole in women with acute dysuria, urgency, or urinary frequency.
Design: Double-blind, randomized, placebo-controlled trial.
Setting: Student health center at a major university.
Patients: Consecutive sample of 255 young women including 216 with a bacteriologically documented urinary tract infection.
Intervention: Single-dose treatment (trimethoprim, 320 mg and sulfamethoxazole, 1600 mg) given to 116 women and 10-day treatment (trimethoprim, 160 mg and sulfamethoxazole, 800 mg, twice daily) given to 125 women. Women with a history of sulfonamide allergy were given trimethoprim alone: 10 received single-dose treatment (200 mg) and 5 received 10-day treatment (100 mg, twice daily).
Measurements and Main Results: The rates for resolution of symptoms at 3 days, 13 days, and 6 weeks after entry into the study were not significantly different between treatment groups. Among women with urinary tract infections, cumulative crude rates of recurrence in the single-dose and 10-day treatment groups, respectively, were 24% compared with 5% at 13 days after entry (P = 0.0002; 95% confidence interval [Cl] for difference in proportions, 10%, 28%) and 32% compared with 21% at 6 weeks after entry (P = 0.07; 95% Cl, -2%, 24%). Factors independently associated with lower cure rates were a history of a urinary tract infection within the previous 6 weeks (adjusted odds ratio [OR], 3.8; 95% Cl, 1.4 to 10.6) and presence of 105 bacteria/mL or greater in an initial midstream culture (adjusted OR, 2.9; 95% Cl, 1.2 to 7.0). After controlling for these factors, the risk of failure after single-dose treatment was not statistically significantly different from 10-day treatment at 6 weeks (adjusted OR, 1.6; 95% Cl, 0.8 to 3.2; P = 0.21). Compared to 10-day treatment, single-dose treatment less effectively eradicated Escherichia coli from the vaginal flora (P < 0.001) and led more often to early same-strain recurrences (P = 0.003). Meaningful adverse effects occurred in 12% of women given single-dose treatment compared with 25% of women receiving 10-day treatment (P = 0.009).
Conclusions: Compared with single-dose treatment, 10-day treatment yields a superior cure rate at 2 weeks after the start of treatment, but by 6 weeks the advantage of longer treatment no longer exists. This effect may be explained by the lesser effectiveness of single-dose treatment in eradicating vaginal E. coli, resulting in more frequent same-strain recurrences within 2 weeks of treatment. Adverse effects occur nearly twice as often among patients receiving 10-day treatment. An intermediate duration of treatment, for example, 3 days, may be optimal and should be tested in future studies.