Table 2.
Emerging (2013–2015) therapeutic strategies against BV-related vaginal biofilms.
| Agent | Application/Tested in (n = population size, in in vivo studies) | Main results | References |
|---|---|---|---|
| PLANTS AND PLANTS EXTRACTS | |||
| In vivo | |||
| Extract of the Brazilian pepper tree | Evaluate the effect of gel containing 7.4% extract of the Brazilian pepper tree (1 D × 1 W); n = 137 BV women | Low cure rate (13.9%). Side effects including abdominal pain; heat; burning; rash | Leite et al., 2011 |
| Garlic tablet | Analyze the effect of oral garlic (2 × D for 1 W); n = 60 BV women | Moderate cure rate (63.3%). Side effects (15%) | Mohammadzadeh et al., 2014 |
| Zataria multiflora | Analyze the efficiency of 5 g of intravaginal cream of 0.1% Zataria multiflora (for 7 D) n = 70 BV women | High cure rate (92.9%). Alleviation of BV-symptoms | Abdali et al., 2015 |
| In vitro | |||
| 19 plant extracts tested | Test the antimicrobial activity of extracts in G. vaginalis | 7 plant extracts showed antimicrobial activity | Naidoo et al., 2013 |
| Seaweed extracts | Screening involving 44 species of seaweed extract with potential anti-G. vaginalis activity | Extracts of the seaweed Ulva pertusa displayed a strongest activities against G. vaginalis | Ha et al., 2014 |
| PROBIOTICS | |||
| In vivo | |||
| L. crispatus DM8909 | Evaluate the efficacy of intravaginal capsule of probiotics (1 × D for 10 D) n = 25 BV women | High cure rate (96%) 30 D after beginning the BV treatment | Ling et al., 2013 |
| L. fermentum LF15 and L. plantarum LP01 | Evaluate the efficacy of probiotics to improve the Nugent score n = 24 BV women | Lactobacilli significantly reduced the Nugent score below the threshold of 7 after 28 D | Vicariotto et al., 2014 |
| L. rhamnosus GR-1 and L. reuteri RC-14 | Evaluate the effect of oral capsules of probiotics (1 × D for 6 W) n = 395 BV women | Normal vaginal microbiota were present in more than half of patients (51.1%). Undisclosed side effects reported | Vujic et al., 2013 |
| VSL3® | Evaluate the efficacy of oral probiotic (2 × D for 5 D, followed by 1 × D for 10 D) n = 20 pregnant women with BV | Absent of vaginal discharge; reduction of the itching and leukorrhea; improvement of constipation occurs | Facchinetti et al., 2013 |
| In vitro | |||
| L. fermentum LF15 | Analyze the inhibitory activity of the neutralized supernatants of probiotic against G. vaginalis | Reduced the Nugent score below the threshold of 7. L. fermentum LF15 showed an inhibitory activity against G. vaginalis | Vicariotto et al., 2014 |
| L. fermentum L23 | Analyze the colonization ability and curative effect of probiotic in female BALB/c mice infected with G. vaginalis. | L. fermentum L23 inhibited the growth of G. vaginalis | Daniele et al., 2014 |
| L. fermentum SK5 | Analyze the effect of probiotic in adhesion of E. coli and G. vaginalis to intestinal and vaginal cells, respectively | L. fermentum SK5 inhibit pathogenic microorganisms by production antimicrobial substance (bacteriocin-like and hydrogen peroxide) | Kaewnopparat et al., 2013 |
| ANTIMICROBIAL PEPTIDES | |||
| In vitro | |||
| Fermenticin HV6b | Evaluate the antimicrobial activity of bacteriocin in G. vaginalis | Inhibition of G. vaginalis; immobilization and spermicidal activity; induce apoptosis in cancerous cells | Kaur et al., 2013 |
| Retrocyclin | Test the effect of retrocyclin in BV-associated bacteria | Pathogenic vaginal bacteria were inhibited by retrocyclin. Retrocyclin was well-tolerated by host tissues and by commensal vaginal bacteria | Eade et al., 2013 |
| ADJUVANTS OF ANTIBIOTIC THERAPHY | |||
| In vivo | |||
| EcoVag® with clindamycin or metronidazole | Analyze the efficiency of 2% clindamycin cream (1 × D for 1 W), 300 mg of oral clindamycin (for 1W) and oral probiotic capsules (for 5D). After the next menstruation was applied 0.75% of metronidazole gel (5D) and probiotic capsules (for 5D) n = 10 BV women | Treatment with antibiotics in combination with EcoVag® provide long-term cure against BV | Pendharkar et al., 2015 |
| L. acidophilus and L. bifidus with metronidazole | Analyze the efficiency of 500 mg of oral metronidazole (2 × D for 1 W), metronidazole cream (for 5 D) and oral probiotic capsules (2 × D for 10 D) n = 173 BV women | Low recurrence rate (15%) after 3 M post-BV treatment. Undisclosed side effects reported | Bodean et al., 2013 |
| L. acidophilus and L. rhamnosus with tinidazole and metronidazole | Analyze the efficiency of 2 g of tinidazole (for 2 D), vaginal suppositories of 1 g of metronidazole (D1 and D3) and topical vaginal probiotics (from the 5 D of the treatment) n = 297 BV women | Reduction of BV recurrence. Recolonization of the vagina with lactobacilli | Kovachev and Vatcheva-Dobrevski, 2013 |
| L. casei var rhamnosus - Lcr 35 with metronidazole | Evaluate the efficiency of 500 mg of metronidazole (2 × D for 5 D), local application of 1 g of metronidazole ovules (D1 and D3) and vaginal ovules of probiotic (2 × D for 7 D) n = 30 BV women | Increased the clinical and microbiological efficacy of the antibiotic therapy and restore the microbial balance in the vaginal ecosystem | Kovachev and Dobrevski-Vacheva, 2013 |
| L. rhamnosus BMX 54 with metronidazole | Evaluate the efficiency of 500 mg of oral metronidazole and probiotic (2 × D for 1 W) n = 125 BV women | Significant replace of the BV-associated flora by a health vaginal flora and re-establishment of the physiological acid vaginal after 2 M of treatment | Recine et al., 2016 |
| L. rhamnosus, L. acidophilus, S. thermophilus and L. bulgaricus with metronidazole | Evaluate the efficiency of 500 mg of oral metronidazole (2 × D for 7 D), topical metronidazole cream (for 5 D) and vaginal ovules of probiotics (1 × D for 6 D) n = 173 BV women | Recurrence rate was 30%. Undisclosed side effects reported | Bodean et al., 2013 |
| Miconazole with metronidazole | Evaluate the efficiency of 750 mg of vaginal suppositories of metronidazole and 200 mg of miconazole (5 consecutive D for each M for 12 M) n = 116 BV women | Monthly treatment with intravaginal metronidazole plus miconazole reduced the proportion of visits with BV during 12 M of follow-up | McClelland et al., 2015 |
| Vitamin C with metronidazole or clindamycin | Evaluate the efficiency of 250 mg of vitamin C as prophylaxis (6 D each M for 6 M) after episode of BV treated either metronidazole or clindamycin n = 74 BV women | Reduction of BV recurrence (32.4% to 16.2%). Side effects including burning, itching, skin irritation, candidiasis and bronchitis | Krasnopolsky et al., 2013 |
| Vitamin D with metronidazole | Evaluate the efficiency of 500 mg of oral metronidazole (2 × D for 7 D) and 9 doses of vitamin D (for 24 W) n = 59 women | BV recurrence was not reduced by vitamin D supplementation | Turner et al., 2014 |
| In vitro | |||
| Lauramide arginine ethyl ester with clindamycin | Evaluate the impact of this therapy in bacterial biofilms of Lactobacillus spp., G. vaginalis and other BV-associated bacteria | LAE synergized with clindamycin against biofilms of G. vaginalis but not biofilm-associated vaginal lactobacilli | Algburi et al., 2015 |
| Lauramide arginine ethyl ester with metronidazole | Evaluate the impact of this therapy in bacterial biofilms of Lactobacillus spp., G. vaginalis and other BV-associated bacteria | LAE synergized with metronidazole against biofilms of G. vaginalis but not biofilm-associated vaginal lactobacilli | Algburi et al., 2015 |
| Subtilosin with clindamycin | Evaluate the impact of this therapy in bacterial biofilms of Lactobacillus spp., G. vaginalis and other BV-associated bacteria | Subtilosin synergized with clindamycin against biofilms of G. vaginalis but not biofilm-associated vaginal lactobacilli | Algburi et al., 2015 |
| Subtilosin with clindamycin | Evaluate the synergistic potential of two-antimicrobial combinations against G. vaginalis and Lactobacillus spp. | Synergistic effect against G. vaginalis in terms of fractional inhibitory concentration index (FICI) | Cavera et al., 2015 |
| Subtilosin with metrodinazole | Evaluate the impact of this therapy in bacterial biofilms of Lactobacillus spp., G. vaginalis and other BV-associated bacteria | Subtilosin synergized with metronidazole against biofilms of G. vaginalis but not biofilm-associated vaginal lactobacilli | Algburi et al., 2015 |
| Subtilosin with metrodinazole | Evaluate the synergistic potential of two-antimicrobial combinations against G. vaginalis and Lactobacillus spp. | Synergistic effect against G. vaginalis in terms of fractional inhibitory concentration index (FICI) | Cavera et al., 2015 |
| OTHERS | |||
| In vivo | |||
| Vitamin C | Evaluate the efficiency of drops of 250 mg of vaginal tablets of vitamin C (1 × D for 6 D, followed by 1 × W for 12 W) n = 70 women with abnormal microflora which 16 women had BV | Vaginal ascorbic acid improves abnormal vaginal pH and microflora, especially in pregnant women, but is not well tolerated by all women | Zodzika et al., 2013 |
| Vitamin D | Evaluate the efficiency of drops of vitamin D (1 × D for 15W) n = 105 BV women | Moderate cure rate (63.5%). The administration of 2000 IU/day edible vitamin D was effective in eliminating asymptomatic BV | Taheri et al., 2015 |
| Octenidine dihydrochloride spray application | Evaluate the efficiency of octenidine (for 7 D) n = 24 women with recurrent BV | High initial cure rate (87.5%, after 10 D of treatment). Moderate cure rate after 12 M post-BV treatment (62.5%). A complete resistance to octenidine was verified in some of patients after 1 year of treatment (37.5%) | Swidsinski et al., 2015 |
| Estriol vaginal tablets and prebiotic lactoferrin (LF) | Evaluate the efficiency of 150 mg of estriol vaginal tablets and 700 mg LF (1 × D) n = 1 BV pregnant women | Recolonization of the vagina with lactobacilli was detected after 1 M to start the treatment. There were no findings of fetal disorders and placental abnormalities | Otsuki et al., 2014 |
| In vitro | |||
| Benzoyl Peroxide formulated Polycarbophil/Carbopol 934P Hydrogel | Evaluate the antimicrobial activity of benzoyl peroxide encapsulated in a hydrogel against G. vaginalis and Lactobacillus spp. | Inhibition the growth of G. vaginalis. Limited effect on healthy lactobacilli in the vaginal ecosystem | Xu et al., 2013 |
| DNAses | Evaluate the effect of DNAses in G. vaginalis biofilms and in a murine vaginal colonization model | 50% of biofilm inhibition at 100 μg/mL DNase and >10-fold inhibition of G. vaginalis colonization by DNase in a murine vaginal colonization model | Hymes et al., 2013 |
| Subtilosin within covalently cross-linked polyethylene glycol (PEG)-based hydrogels | Effect of subtilosin within covalently cross-linked polyethylene glycol (PEG)-based hydrogels on G. vaginalis and Lactobacillus spp. | The subtilosin-containing hydrogels inhibited the growth of G. vaginalis. The growth of vaginal lactobacilli was not significantly inhibited | Sundara Rajan et al., 2014 |
(D), Daily or day; (W), Weekly or Weeks; (M), Monthly or Months.