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.