PROPHYLAXIS OF URINARY-TRACT INFECTION IN PERSONS WITH RECENT SPINAL-CORD INJURY - A PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF TRIMETHOPRIM-SULFAMETHOXAZOLE

PURPOSE: To determine the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) for prophylaxis of urinary tract infection in persons with recent spinal cord injury, during the first 4 months of intermittent catheterization. PATIENTS AND METHODS: One hundred twenty-nine adults (112 men, 17 women) with recent acute spinal cord injury participated in a randomized, double-blind, placebo-controlled trial, and were studied for up to 16 weeks. Low-dose TMP-SMX (TMP 40 mg, SMX 200 mg) or placebo was given once daily. Clinical observations, urine cultures, and cultures of rectal and urethral swabs were made weekly. Subjects who developed breakthrough bacteriuria received conventional antimicrobial therapy and prophylaxis was continued. RESULTS: Sixty-six TMP-SMX recipients (57 men, 9 women) and 60 placebo recipients (52 men, 8 women) are evaluable for efficacy. Among male subjects, bacteriuria was present during 50% or more of study weeks in 30% of (TMP-SMX recipients and in 56% of placebo recipients (p = 0.003). The interval to the onset of bacteriuria was prolonged in TMP-SMX recipients (p <0.0001). TMP-SMX recipients without bacteriuria in any given week had a lower probability of having bacteriuria the subsequent week (0.26) than did placebo recipients (0.49) (p < 0.0001). At least 1 episode of definite symptomatic bacteriuria (bacteriuria and fever and at least 1 classical manifestation of urinary infection) occurred in 4 of 57 TMP-SMX-treated men and in 18 of 52 placebo-treated men (p < 0.0003). We observed similar trends in women, but differences did not reach statistical significance, perhaps because the number of females was small. Adverse events suspected to be due to medications were frequent in this population of patients with recent severe injuries and led to discontinuation of the study in 10% of the TMP-SMX group and 8% of the placebo group. Adverse events included neutropenia (TMP-SMX: two; placebo. three), pseudomembranous colitis (TMP-SMX: one), severe skin rash (TMP-SMX: two; placebo. one), and drug fever (TMP-SMX: one). The proportion of all episodes of bacteriuria that were due to TMP-SMX-resistant organisms was unexpectedly high in the placebo group (51%), and increased progressively according to year of enrollment in the study. By Year 3, all subjects in the placebo group had at least one episode of TMP-SMX-resistant bacteriuria. Gram-negative enteric bacilli resistant to TMP-SMX were recovered from rectal swabs (TMP-SMX 49%, placebo 42%) and urethral swabs (TMP-SMX 33%, placebo 26%) in similar proportions of subjects in the two study groups. CONCLUSIONS: Prophylaxis with TMP-SMX significantly reduces bacteriuria and symptomatic urinary tract infection in persons with recent acute spinal cord injury during bladder retraining using intermittent catheterization. However, adverse reactions attributable to TMP-SMX are common in this population. Colonization and breakthrough bacteriuria with TMP-SMX-resistant organisms are frequent and may seriously limit the usefulness of this strategy, particularly in an institutional setting.