Efficiency of oral versus vaginal probiotic Lactobacillusrhamnosus GR-1 and Lactobacillus reuteri RC-14m in the treatment of bacterial vaginosis among non pregnant women

Abstract

Urogenital infections are one of the most common causes for a woman to visit a gynecologist or a urologist. Carter and colleagues estimated that one billion women around the world suffer from infections such as non-sexually transmitted urogenital infections, which include BV, UTI, and yeast vaginitis (Carter et al., 1999). The annual cost of healthcare services is staggering, reaching $2 billion in the United States alone and over $6 billion worldwide (Waigankar and Patel, 2011). Worldwide, BV is common among women of reproductive age, with variations according to the population studied (Kenyon et al., 2013). It is present in about 27-31% of general population. However, more than 50 % of cases of BV are asymptomatic (Jenifer et al., 2007). A higher prevalence (55.5%) of BV among non pregnant females attending the out patient clinics of Ain Shams University Maternity Hospital (Marwa et al., 2005). BV is an imbalance in the ecology of the normal vaginal flora that is characterized by the depletion of lactobacilli andassociated with a group of pathogenic anaerobic microorganisms including G. vaginalis, M.hominis, Prevotella, and Peptostreptococcus rather than a specific pathogen. However the exact causative pathogen has not been figured out. It is characterized by a malodorous vaginal discharge, high vaginal pH. (Kumar et al., 2011).And associated with important adverse health conditions and infectious complications. (Mastromarino et al., 2013) A lot of antimicrobial agents (e.g., metronidazole, tinidazole and clindamycin) have been used in the treatment of bacterial vaginosis (Spiegel et al., 1991). Therapy with oral or local recommended antibiotics are quite effective, but it is often associated with failure and high rates of recurrences (Mastromarino et al., 2013). The dominance of lactobacilli in healthy vaginal microbiota and its depletion in BV has given rise to the concept of oral or vaginal use of probiotic Lactobacillus strains for treatment and prevention of BV (Mastromarino et al., 2013). Lactobacilli play an important role in the inhibition of growth, adhesion, and spread of pathogenic microbes (Lepargneur et al., 2002). Its use in BV is supported by positive results obtained in some clinical trials. The majority of clinical trials yielding positive results have been performed using probiotic preparations containing high doses of lactobacilli (around 109 CFU) suggesting that, beside strain characteristics, the amount of exogenously applied lactobacilli could have a role in the effectiveness of the product (Mastromarino et al., 2013). Moreover, observational data using prolonged repetitive courses of Lactobacillus-containing probiotics appear to be more promising than short courses. It is noteworthy that, unlike antibiotics, lactobacilli probiotics can be used over a long period without adverse effects (Bradshaw et al., 2012). The use of probiotics for the treatment of BV provided a ray of hope by natural and nontoxic treatment modality (Dover et al., 2008). This pilot study was conducted to compare the efficiency of orally versus vaginal route of proboitic L. rhamnosus GR-1 and L. reuteri RC-14 in treatment of symptomatic BV among non pregnant women. This was based on the presence of two types of treatment methodologies for the treatment of BV using probiotics, the first is oral administration of the Lactobacillus, whereas the second is local administration of the same in the vagina of the patient. Fifty women with BV were selected for this work from those attending the gynecology outpatient clinic at Ain Shams University Maternity Hospital throughout the period starting from august 2010 to november 2011. The inclusion criteria were: • Age 20-40 years. • Diagnosis of BV was based on Amsel’s criteria, defined as the presence of three out of the following four criteria:- (Amsel et al., 1983) - Thin, gray and homogeneous vaginal discharge. - Unpleasant fishy odor before or after addition of 10% KOH to a drop of vaginal discharge (Whiff test). - Vaginal pH>4.5. - The presence of clue cells (vaginal epithelial cells heavily coated with bacteria) in saline wet mount or gram stained smear. Those who fulfilled the inclusion criteria (N=50) were interviewed to explain the study and its benefits for them and an informed consent were obtained from each participant before starting of treatment protocol, full medical history taking, medically examined and vaginal swab was taken. The fifty participant randomly received oral capsules twice daily for 14 days and vaginal capsules twice daily for 5 days as supplied by the candidate. Oral capsules were 2 capsules containing L. rhamnosus GR-1 and L. reuteri RC-14(109 each organism/capsule) (Fem-Dophilus™ capsules, by Jarrow Formulas, USA) versus placebo and vaginal capsules were containing L. rhamnosus GR-1 and L. reuteri RC-14(109 each organism/capsule) (Fem-Dophilus™ capsules, by Jarrow Formulas, USA) versus placebo guided that no patient received combined therapy. All participant were evaluated at 2 week and 4 weeks after the beginning of therapy, follow up based on clinical improvement and laboratory investigations including vaginal pH and vaginal smear (absence of clue cells in vaginal smears, pH, whiff test and Nugent scoring). Patients records for side effects and use of antimicrobial agents occurred during the study were collected. At the end of the study, all data were gathered and patients were tabulated into two groups, group II(N=25) received oral capsules contain L.rhamnosus GR-1 and L. reuteri RC-14(109 each organism/capsule) (Fem-Dophilus™ capsules, by Jarrow Formulas, USA) twice daily for 14 days and placebo vaginal capsules twice daily for 5 days and group II(N=25) received oral placebo tablets twice daily for 14 days and vaginal capsules contain L. rhamnosus GR-1and L. reuteri RC-14 (109 each organism/capsule) (Fem-Dophilus™ capsules, by Jarrow Formulas, USA) twice daily for 5 days. Data were statistically described in terms of mean, standard deviation ( SD), or frequencies (number of cases) and percentages when appropriate. Collected data were compared before, after 2 week and 4 weeks of treatment. Comparison of numerical variables between the study groups was done using Student t test for independent samples (pH). For comparing categorical data (Whiff test, discharge, clue cells, Nugent score), Chi square (2) test was performed. p values less than 0.05 was considered statistically significant. Follow up of our patients revealed that cure rate was higher in group I (58.3%) than in group II (53%), although no significant difference was found between the groups. Improvement rate was higher in group II (9 cases accounting for 37.5%) than in group I (7 cases accounting for 29.2%) this difference was statistically insignificant. Resistance was higher in group I (3cases accounting for 12.5%) than group II (2 cases accounting for 8.3%) this difference was statistically insignificant. Relapse was higher in group I (1 cases accounting for 4.5%) while there was no relapse in group II (0%) this difference was statistically insignificant.