Toh Swee-Ling, Boswell-Ruys Claire L, Lee Bon San B, Simpson Judy M, Clezy Kate R
Spinal Medicine Department, Prince of Wales Hospital, Level 2, High Street Entrance, Randwick, NSW, Australia, 2031.
Cochrane Database Syst Rev. 2017 Sep 8;9(9):CD010723. doi: 10.1002/14651858.CD010723.pub2.
Neuropathic or neurogenic bladder describes a process of dysfunctional voiding as the result of injury in the brain, spinal cord or nerves innervating the bladder. People with neuropathic bladder, such as from spinal cord injury (SCI), are at significant risk of morbidity from urinary tract infections (UTI). Effective methods to prevent UTI in people with SCI have been sought for many years. Probiotics (micro-organisms that exert beneficial health effects in the host) have been recommended for bacterial interference of the urological tract to reduce colonisation by uropathogen and to manage the dual problems of infection and antibiotic resistance.
This review looked at the benefits and harms of probiotics in preventing symptomatic UTI in people with neuropathic bladder compared with placebo, no therapy, or non-antibiotic prophylaxis (cranberry juice, methenamine hippurate, topical oestrogen).
We searched the Cochrane Kidney and Transplant Specialised Register up to 10 March 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.
All randomised controlled trials (RCTs), quasi-RCTs and cross-over RCTs looking at the use of probiotics for the prophylaxis of UTI in people with neuropathic bladders was considered for inclusion. Men, women and children of all ages with neuropathic bladders from neurological injury such as suprapontine, supra sacral and sacral aetiologies was included. All bladder management types, including reflex voiding, time voiding, indwelling and intermittent catheterization were eligible for this review.Studies comparing probiotics to placebo, no treatment or other non-antibiotic prophylaxis was included. Studies comparing probiotics with antibiotics or in combination with antibiotics were excluded.
Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI were planned for continuous outcomes.
This review includes a total of three studies (one cross-over and two parallel RCTs) which involved 110 participants. All three studies looked at intravesical instillation of a low virulent Escherichia coli (E. coli) strain in reducing the risk of symptomatic UTI in participants with neuropathic bladder, predominantly from SCI. Two studies used the E. coli 83972 strain and one study used the E. coli HU2117 strain.We did not find any RCTs involving other probiotics or other routes of administration for preventing UTI in people with neuropathic bladder.There was consistency in definition of symptomatic UTI in all three studies. Symptoms that all studies considered were relevant to diagnose UTI were adequately defined. All three studies defined microbiological diagnosis of symptomatic UTI.Asymptomatic bacteriuria was not considered an outcome measure in any of the included studies; however it was defined in two studies to establish successful inoculation.It is uncertain if the risk of symptomatic UTI is reduced with bladder inoculation using E. coli because the certainty of the evidence is very low (3 studies, 110 participants: RR 0.32, 95% CI 0.08 to 1.19; I = 82%).Two studies reported adverse events. One study reported one episode of autonomic dysreflexia. One study reported three symptomatic UTI occurring in two patients, and two studies mentioned the absence of septicaemia and pyelonephritis. Intravesical instillation was reported as "generally safe". One study reported high attrition rates in participants due to the need to adhere to strict instillation protocols.The overall quality of the studies was poor. All three studies had high risk of attrition bias due to failure of an intention-to-treat analysis which undermines the randomisation process and weakened the results of the studies. All three studies also had high risk of reporting bias.
AUTHORS' CONCLUSIONS: In this review, there were no studies identified addressing oral probiotics in preventing UTI in people with neuropathic bladder. It is uncertain if the risk of symptomatic UTI is reduced in people with neuropathic bladders via intravesical instillation of non-pathogenic E. coli as data were derived from small studies with high risk of bias.Although very minimal levels of harm was reported with this procedure, due to variable success rates, the need for strict adherence to instillation protocols together with high attrition rates in these studies, it is doubtful bladder instillation will be a widely accepted intervention in its current form.It is recommended that further appropriately powered RCTs with more robust methodological reporting be carried out.
神经源性膀胱描述了因大脑、脊髓或支配膀胱的神经损伤而导致排尿功能障碍的过程。患有神经源性膀胱的人,如脊髓损伤(SCI)患者,面临着因尿路感染(UTI)而发病的重大风险。多年来一直在寻找预防SCI患者发生UTI的有效方法。益生菌(在宿主体内发挥有益健康作用的微生物)已被推荐用于泌尿系统的细菌干扰,以减少尿路病原体的定植,并处理感染和抗生素耐药性这两个双重问题。
本综述旨在探讨与安慰剂、无治疗或非抗生素预防措施(蔓越莓汁、马尿酸乌洛托品、局部雌激素)相比,益生菌在预防神经源性膀胱患者发生有症状UTI方面的益处和危害。
我们通过与信息专家联系,使用与本综述相关的检索词,检索了截至2017年3月10日的Cochrane肾脏与移植专业注册库。专业注册库中的研究是通过检索CENTRAL、MEDLINE、EMBASE、会议论文集、国际临床试验注册平台(ICTRP)检索门户和ClinicalTrials.gov识别出来的。
所有探讨使用益生菌预防神经源性膀胱患者UTI的随机对照试验(RCT)、半随机对照试验和交叉RCT均被考虑纳入。纳入所有因神经损伤(如脑桥上、骶上和骶部病因)导致神经源性膀胱的各年龄段男性、女性和儿童。所有膀胱管理类型,包括反射性排尿、定时排尿、留置导尿和间歇性导尿,均符合本综述的条件。纳入比较益生菌与安慰剂、无治疗或其他非抗生素预防措施的研究。排除比较益生菌与抗生素或与抗生素联合使用的研究。
使用随机效应模型获得效应的汇总估计值,结果以二分类结局的风险比(RR)及其95%置信区间(CI)表示,对于连续性结局计划采用均值差(MD)或标准化均值差(SMD)及95%CI。
本综述共纳入三项研究(一项交叉研究和两项平行RCT),涉及110名参与者。所有三项研究均观察了膀胱内灌注低毒力大肠杆菌菌株以降低神经源性膀胱患者(主要是SCI患者)发生有症状UTI的风险。两项研究使用大肠杆菌83972菌株,一项研究使用大肠杆菌HU2117菌株。我们未发现任何涉及其他益生菌或其他给药途径预防神经源性膀胱患者UTI的RCT。所有三项研究中对有症状UTI的定义一致。所有研究认为与UTI诊断相关的症状均有充分定义。所有三项研究均对有症状UTI进行了微生物学诊断。在任何纳入研究中,无症状菌尿均未被视为结局指标;然而,在两项研究中对其进行了定义以确定成功接种。尚不确定通过膀胱灌注大肠杆菌是否能降低神经源性膀胱患者发生有症状UTI的风险,因为证据的确定性非常低(3项研究,110名参与者:RR 0.32,95%CI 0.08至1.19;I² = 82%)。两项研究报告了不良事件。一项研究报告了一例自主神经反射异常。一项研究报告两名患者发生了三例有症状UTI,两项研究提到未发生败血症和肾盂肾炎。膀胱内灌注被报告为“总体安全”。一项研究报告由于需要遵守严格的灌注方案,参与者的脱落率很高。研究的总体质量较差。所有三项研究因未进行意向性分析而存在较高的脱落偏倚风险,这破坏了随机化过程并削弱了研究结果。所有三项研究还存在较高的报告偏倚风险。
在本综述中,未发现探讨口服益生菌预防神经源性膀胱患者UTI的研究。由于数据来自存在高偏倚风险的小型研究,尚不确定通过膀胱内灌注非致病性大肠杆菌是否能降低神经源性膀胱患者发生有症状UTI的风险。尽管该操作报告的危害程度非常低,但由于成功率可变、需要严格遵守灌注方案以及这些研究中的高脱落率,目前形式的膀胱灌注是否会成为一种被广泛接受的干预措施值得怀疑。建议开展进一步的、样本量足够且方法报告更严谨的RCT。