Gribble M J, Puterman M L
Department of Medicine, University Hospital, Vancouver, British Columbia, Canada.
Am J Med. 1993 Aug;95(2):141-52. doi: 10.1016/0002-9343(93)90254-m.
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.
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.
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.
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.
确定在间歇性导尿的前4个月中，复方新诺明（TMP-SMX）对近期脊髓损伤患者预防尿路感染的疗效。
129例近期急性脊髓损伤的成年人（112例男性，17例女性）参与了一项随机、双盲、安慰剂对照试验，研究时间长达16周。每天给予低剂量复方新诺明（TMP 40mg，SMX 200mg）或安慰剂。每周进行临床观察、尿培养以及直肠和尿道拭子培养。出现突破性菌尿的受试者接受常规抗菌治疗，并继续进行预防。
66例接受复方新诺明治疗的受试者（57例男性，9例女性）和60例接受安慰剂治疗的受试者（52例男性，8例女性）可进行疗效评估。在男性受试者中，30%接受复方新诺明治疗的受试者和56%接受安慰剂治疗的受试者在50%或更多的研究周内出现菌尿（p = 0.003）。复方新诺明治疗组受试者出现菌尿的时间间隔延长（p < 0.0001）。在任何给定周内无菌尿的复方新诺明治疗组受试者下一周出现菌尿的概率（0.26）低于安慰剂治疗组受试者（0.49）（p < 0.0001）。在57例接受复方新诺明治疗的男性中，有4例至少发生1次明确的症状性菌尿（菌尿、发热以及至少1种尿路感染的典型表现），而在52例接受安慰剂治疗的男性中，有18例发生（p < 0.0003）。在女性中我们观察到了类似趋势，但差异未达到统计学显著性，可能是因为女性数量较少。在近期严重损伤的这群患者中，疑似由药物引起的不良事件很常见，导致复方新诺明组10%的患者和安慰剂组8%的患者停止研究。不良事件包括中性粒细胞减少（复方新诺明组：2例；安慰剂组：3例）、假膜性结肠炎（复方新诺明组：1例）、严重皮疹（复方新诺明组：2例；安慰剂组：1例）以及药物热（复方新诺明组：1例）。安慰剂组中由对复方新诺明耐药的微生物引起的所有菌尿发作比例意外地高（51%），并且根据研究入组年份逐渐增加。到第3年，安慰剂组的所有受试者至少有1次对复方新诺明耐药的菌尿发作。在两个研究组中，相似比例的受试者从直肠拭子（复方新诺明组49%，安慰剂组42%）和尿道拭子（复方新诺明组33%，安慰剂组26%）中分离出对复方新诺明耐药的革兰氏阴性肠道杆菌。
在使用间歇性导尿进行膀胱再训练期间，复方新诺明预防可显著降低近期急性脊髓损伤患者的菌尿和症状性尿路感染。然而，在这群患者中，复方新诺明引起的不良反应很常见。对复方新诺明耐药的微生物的定植和突破性菌尿很频繁，可能会严重限制这种策略的有效性，尤其是在医疗机构环境中。
