Proposed BV Treatment options [[My personal notes are in double brackets]]
Efficacy of Vitamin C Vaginal Tablets as Prophylaxis for Recurrent Bacterial Vaginosis: A Randomised, Double-Blind, Placebo-Controlled Clinical Trial; Vladislav N. Krasnopolskya, Vera N. Prilepskayab, Franco Polattic, Nina V. Zarochentsevaa, Guldana R. Bayramovab, Maurizio Caserinid, Renata Palmierid, e
-Treatment overview during trials: Within 24 hours of cure from a recent episode of BV by metronidazole or clindamycin, implement vitamin C for six consecutive monthly cycles. Each cycle consists of inserting one vaginal tablet for 6 consecutive days during each month following menses [[Use with tampon to keep the vitamin C inside]].
-Tablets are 250mg ascorbic acid [[though many women on various forums have claimed to use 500 mg with success]] in a silicone carrier that ensures prolonged action [[find one without added sugars, such as Twinlab C-500 Caps, Crystalline Vitamin C capsules]].
-No statistical significance was noted within the 3-month period, only becoming apparent during month 5. Conclusion was that the regular use of the tablets for the suggested duration following the success of metronidazole treatment reduces the reoccurrence rate from 32.4\\% to 16.2\\%.
“A therapeutic approach in the treatment of BV relapse is to re-establish and maintain the physiological acidity of the vagina, as the growth of anaerobes and other faecal bacteria is inhibited by low pH. Attempts to achieve this via re-colonisation with exogenous lactobacilli have not been successful. Another, more accepted approach is to reduce vaginal pH, in order to create a negative environment for pathogen growth and to achieve long-lasting normalisation of vaginal flora using intravaginal ascorbic acid (vitamin C). The use of antibiotics may induce resistance in the pool of bacteria recognised to cause BV and, conversely, could affect the normal flora of lactobacilli , favouring recurrence within a few weeks in over 70\\% of women taking antibiotics for bacterial vaginosis . Ascorbic acid [[250 mg, in a silicone carrier that ensures prolonged action]] plays a vital role in maintaining low vaginal pH values and enhances healing processes in the vaginal ecosystem - recolonisation with lactic acid bacteria. The mechanism of action is simple: through the lowering of vaginal pH to the physiological level of 3.8 - 4.5, anaerobic overgrowth is inhibited and the conditions for the re-growth of physiological lactobacilli flora are re-established. “
“The results of the present study show that 250 mg ascorbic acid vaginal tablets taken 6 days per month safely halves the risk of BV recurrence from 32.4\\% to 16.2\\% during a 6-month prophylactic treatment. The O.R. confirms that subjects treated with placebo had a doubled risk of BV recurrence compared with the group of subjects treated with vitamin C. Considering the time to the first BV relapse, treatment of at least five cycles is necessary in order to reduce, at a significant level, the risk of BV recurrence. As this was a prophylaxis study, in women who at the screening visit were healthy and who terminated the study in case of relapse, a between-treatment difference in clinical parameters was not expected. At the same time, differences in pH were not expected but conversely, a reduction in pH was noted for 3-month and 6-month treatment. “
In conclusion, regular use of silicon-coated vitamin C (250 mg) tablets, after the standard antibiotic treatment for BV, protects women by reducing the risk of recurrence probably by re-establishing the normal lactobacilli flora that is able to maintain vaginal pH.”
Bacterial Vaginosis Biofilms: Challenges to Current Therapies and Emerging Solutions; Daniela Machado, Joana Castro, Ana Palmeira-de-Oliveira, José Martinez-de-Oliveira, and Nuno Cerca.
“Being polymicrobial in nature, BV etiology remains unclear. However, it is certain that BV involves the presence of a thick vaginal multi-species biofilm, where G. vaginalis is the predominant species. Similar to what happens in many other biofilm-related infections, standard antibiotics, like metronidazole, are unable to fully eradicate the vaginal biofilm, which can explain the high recurrence rates of BV. Furthermore, antibiotic therapy can also cause a negative impact on the healthy vaginal microflora. These issues sparked the interest in developing alternative therapeutic strategies. This review provides a quick synopsis of the currently approved and available antibiotics for BV treatment while presenting an overview of novel strategies that are being explored for the treatment of this disorder, with special focus on natural compounds that are able to overcome biofilm-associated antibiotic resistance.”
Current available treatments
Metronidazole and clindamycin are shown to be effective against anaerobic microorganisms, though tinidazole was the most recently approved antimicrobial agent for BV treatment, and is considered an alternative antimicrobial agent, particularly whenever metronidazole and clindamycin are unavailable or not tolerated. Being a second generation nitroimidazole with a longer half-life than metronidazole, it requires lower dosages, to be taken less frequently than metronidazole.
Although antibiotics are effective against anaerobic microorganisms, the have an inability to completely eradicate the densely-structured polymicrobial BV biofilms-associated bacteria G. Vaginalis.
Probiotics have been shown to modulate vaginal microbiota:
“In the human vagina, certain Lactobacillus strains can act as probiotics, preventing the growth of BV-associated bacteria through two main mechanisms: the inhibition of pathogens adhesion to vaginal epithelium (Machado et al., 2013); and the production of antimicrobial compounds like hydrogen peroxide (Mastromarino et al., 2002), lactic acid (Boskey et al., 2001) and bacteriocins (Aroutcheva et al., 2001b). Diverse pharmaceutical formulations containing probiotic lactobacilli strains have reduced BV symptoms, improved the vaginal microflora profile, being usually well-tolerated (Rossi et al., 2010;Hantoushzadeh et al., 2012; Facchinetti et al., 2013; Vujic et al., 2013; Vicariotto et al., 2014). “
“In contrast, despite their therapeutic potential, some clinical trials have not detected a significant improvement in BV management (Falagas et al., 2007). Alternatively, probiotics have been proposed as adjuvants to antibiotic therapy [[meaning, using probiotics following the use of antibiotics]]. Several combinations of metronidazole, clindamycin or tinidazole with lactobacilli probiotic preparations have displayed promising results in BV treatment since they have been associated with high cure rates, low recurrence or quick re-establishment of an healthy vaginal microflora (Marcone et al., 2010; Bodean et al., 2013; Recine et al., 2016).”
“Probiotics have also been used in an attempt to specifically deal with BV biofilms. Remarkably, in 2007, Saunders and colleagues showed that L. reuteri RC-14 was able to disruptin vitro G. vaginalis biofilms (Saunders et al., 2007). Later, McMillan and colleagues demonstrated that probiotic L. reuteri RC-14 and L. rhamnosus GR-1 were able to incorporate themselves into BV-biofilm, composed by G. vaginalis and A. vaginae, causing both the disruption of the biofilm structure and bacterial cell death (McMillan et al., 2011). These findings provide some evidence of how lactobacilli probiotics might interfere with an abnormal vaginal microflora, reinforcing the hypothesis that probiotics could eradicate vaginal pathogenic biofilms and restore the normal microflora in in vivo situations.”
“It has also been proposed that prebiotics [[such as the product Multigyn FloraPlus]], nutritional substances that stimulate the growth of probiotics, could be used as alternative to treat BV (Roberfroid, 2007). Interestingly, Rousseau and colleagues demonstrated that prebiotic preparations containing oligosaccharides were able to promote the growth of beneficial lactobacilli strains but not of the pathogenic microorganisms often found in urogenital infections including G. vaginalis (Rousseau et al., 2005). “
“Later, Zeng and colleagues compared the efficacy of a prebiotic gel containing sucrose with 0.75\\% metronidazole vaginal gel to treat BV (Zeng et al., 2010). In that study, the prebiotic gel displayed a similar therapeutic cure rate to metronidazole, having a major advantage of quicker restoration of the normal vaginal microflora. Recently, Coste and colleagues evaluated the efficacy and safety of another prebiotic gel, applied as adjuvant therapy [[combined with antibiotic treatment]], in women treated for BV and showed an improved recovery of the normal vaginal flora, reducing the risk of recurrences (Coste et al., 2012).
“Surprisingly, up to now only one study evaluated the capability of plant-derived compound to eradicate BV biofilms. Interestingly, Braga and colleagues showed that thymol, a molecule present in thyme essential oil, had an inhibitory effect upon both newly formed and mature G. vaginalis biofilms, which supports the importance of exploring essential oils and their main constituents as therapeutic alternative to treat BV (Braga et al., 2010). Furthermore, the expectations on essential oils as effective agents against BV-biofilms can be inferred from studies in other related vaginal biofilms (Palmeira-de-Oliveira et al., 2012; Bogavac et al., 2015).” [[The suggested delivery was through douche]].
-“Recently, Bahamondes and colleagues verified that a soap containing lactic acid and lactoserum could be used for external intimate hygiene, reducing BV recurrence after treatment with oral metronidazole (Bahamondes et al., 2011). “
-“Interestingly, vitamin C, when coated with silicon, allowed the constant release of the active agent, resulting in a long-lasting vaginal low pH and prevention of vaginal irritation (Polatti et al., 2006). Other studies reported an effective and safe use of vaginal vitamin C tablets in BV treatment (Petersen et al., 2011), contributing to improve abnormal vaginal pH and microflora, especially in pregnant women (Zodzika et al., 2013). Additionally, the regular use of vitamin C during 6 days per month, for 6 months after successful BV treatment, was shown to decrease the risk of BV recurrence (Krasnopolsky et al., 2013).
-“Another alternative comes in the form of buffering agents. Polycarbophil [[like the product Replens]] is a weak poly-acid that it is able to adhere to vaginal epithelial cells, acting as a buffer in the vaginal secretions (Milani et al., 2000). “
-“Another agent that has been long used in the treatment of vaginal infections is boric acid (Van Slyke et al., 1981) [[This could be the 600 mg tablets from brands pH-D, BoriCap, Bona Dea, or Boric Balance as of a recent Google search]]. Recently, Reichman and colleagues reported that the use of boric acid in combination with a nitroimidazole reduce the BV recurrence (Reichman et al., 2009), suggesting a potential impact on BV biofilms. However, this need to be further studied and in vitro biofilm experiments will elucidate the role of boric acid in BV prevention.”
Conclusions and future directions:
BV current approved therapies are not sufficient to deal with this multi-species biofilm-related vaginal disorder. Future, research should address biofilm communities with a particular emphasis on multi-species biofilms, a topic that only recently emerged (Castro and Cerca, 2015). By properly addressing the complex interactions established in multi-species biofilms, novel strategies will hopefully overcome the high recurrence and relapse rates associated with BV.