Xie Huan Yu, Feng Dan, Wei Dong Mei, Mei Ling, Chen Hui, Wang Xun, Fang Fang
Department of Obstetrics and Gynecology, People's Hospital of Deyang City, No. 173, Tai Shan North Road, Deyang, Sichuan, China, 618000.
Cochrane Database Syst Rev. 2017 Nov 23;11(11):CD010496. doi: 10.1002/14651858.CD010496.pub2.
Vulvovaginal candidiasis (VVC) is estimated to be the second most common form of infection after bacterial vaginosis. The ability of probiotics in maintaining and recovering the normal vaginal microbiota, and their potential ability to resist Candidas give rise to the concept of using probiotics for the treatment of VVC.
To assess the effectiveness and safety of probiotics for the treatment of vulvovaginal candidiasis in non-pregnant women.
We searched the following databases to October 2017: Sexually Transmitted Infections Cochrane Review Group's Specialized Register, CENTRAL, MEDLINE, Embase and eight other databases. We searched in following international resources: World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, Web of Science and OpenGrey. We checked specialty journals, reference lists of published articles and conference proceedings. We collected information from pharmaceutical companies and experts in the field.
Randomized controlled trials (RCT) using probiotics, alone or as adjuvants to conventional antifungal drugs, to treat VVC in non-pregnant women. Trials recruiting women with recurrent VVC, coinfection with other vulvovaginal infections, diabetes mellitus, immunosuppressive disorders or taking immunosuppressant medication were ineligible for inclusion. Probiotics were included if they were made from single or multiple species and in any preparation type/dosage/route of administration.
Two review authors independently assessed trials for eligibility and quality and extracted data. We resolved any disagreements through consensus. The quality of the evidence was assessed using the GRADE approach.
Ten RCTs (1656 participants) met our inclusion criteria, and pharmaceutical industry funded none of these trials. All trials used probiotics as adjuvant therapy to antifungal drugs. Probiotics increased the rate of short-term clinical cure (risk ratio (RR) 1.14, 95% confidence interval (CI) 1.05 to 1.24, 695 participants, 5 studies, low quality evidence) and mycological cure (RR 1.06, 95% CI 1.02 to 1.10, 969 participants, 7 studies, low quality evidence) and decreased relapse rate at one month (RR 0.34, 95% CI 0.17 to 0.68, 388 participants, 3 studies, very low quality evidence). However, this effect did not translate into a higher frequency of long-term clinical cure (one month after treatment: RR 1.07, 95% CI 0.86 to 1.33, 172 participants, 1 study, very low quality evidence; three months after treatment: RR 1.30, 95% CI 1.00 to 1.70, 172 participants, one study, very low quality evidence) or mycological cure (one month after treatment: RR 1.26, 95% CI 0.93 to 1.71, 627 participants, 3 studies, very low quality evidence; three months after treatment: RR 1.16, 95% CI 1.00 to 1.35, 172 participants, one study, very low quality evidence). Probiotics use did not increase the frequency of serious (RR 0.80, 95% CI 0.22 to 2.94; 440 participants, 2 studies, low quality evidence). We found no eligible RCTs for outcomes as time to first relapse, need for additional treatment at the end of therapy, patient satisfaction and cost effectiveness.
AUTHORS' CONCLUSIONS: Low and very low quality evidence shows that, compared with conventional treatment, the use of probiotics as an adjuvant therapy could increases the rate of short-term clinical and mycological cure and decrease the relapse rate at one month but this did not translate into a higher frequency of long-term clinical or mycological cure. Probiotics use does not seem to increase the frequency of serious or non-serious adverse events. There is a need for well-designed RCTs with standardized methodologies, longer follow-up and larger sample size.
据估计,外阴阴道念珠菌病(VVC)是仅次于细菌性阴道病的第二常见感染形式。益生菌维持和恢复正常阴道微生物群的能力及其抵抗念珠菌的潜在能力引发了使用益生菌治疗VVC的概念。
评估益生菌治疗非妊娠女性外阴阴道念珠菌病的有效性和安全性。
我们检索了以下数据库至2017年10月:性传播感染Cochrane综述小组专业注册库、CENTRAL、MEDLINE、Embase和其他八个数据库。我们检索了以下国际资源:世界卫生组织国际临床试验注册平台、ClinicalTrials.gov、科学网和OpenGrey。我们查阅了专业期刊、已发表文章的参考文献列表和会议论文集。我们从制药公司和该领域专家处收集信息。
使用益生菌单独或作为传统抗真菌药物的辅助剂治疗非妊娠女性VVC的随机对照试验(RCT)。招募复发性VVC、合并其他外阴阴道感染、糖尿病、免疫抑制性疾病或正在服用免疫抑制剂的女性的试验不符合纳入标准。如果益生菌由单一或多种菌株制成,且为任何制剂类型/剂量/给药途径,则纳入研究。
两位综述作者独立评估试验的纳入资格和质量并提取数据。我们通过共识解决任何分歧。使用GRADE方法评估证据质量。
十项RCT(1656名参与者)符合我们的纳入标准,且这些试验均无制药行业资助。所有试验均使用益生菌作为抗真菌药物的辅助治疗。益生菌提高了短期临床治愈率(风险比(RR)1.14,95%置信区间(CI)1.05至1.24,695名参与者,5项研究,低质量证据)和真菌学治愈率(RR 1.06,95%CI 1.02至1.10,969名参与者,7项研究,低质量证据),并降低了一个月时的复发率(RR 0.34,95%CI 0.17至0.68,388名参与者,3项研究,极低质量证据)。然而,这种效果并未转化为更高频率的长期临床治愈(治疗后一个月:RR 1.07,95%CI 0.86至1.33,172名参与者,1项研究,极低质量证据;治疗后三个月:RR 1.30,95%CI 1.00至1.70,172名参与者,1项研究,极低质量证据)或真菌学治愈(治疗后一个月:RR 1.26,95%CI 0.93至1.71,627名参与者,3项研究,极低质量证据;治疗后三个月:RR 1.16,95%CI 1.00至1.35,172名参与者,1项研究,极低质量证据)。使用益生菌并未增加严重不良事件的发生率(RR 0.80,95%CI 0.22至2.94;440名参与者,2项研究,低质量证据)。我们未找到关于首次复发时间、治疗结束时额外治疗需求、患者满意度和成本效益等结局的符合纳入标准的RCT。
低质量和极低质量证据表明,与传统治疗相比,使用益生菌作为辅助治疗可提高短期临床和真菌学治愈率,并降低一个月时的复发率,但这并未转化为更高频率的长期临床或真菌学治愈。使用益生菌似乎并未增加严重或非严重不良事件的发生率。需要设计良好、方法标准化、随访时间更长且样本量更大的RCT。