title: Efficacy of oral metronidazole with vaginal clindamycin or vaginal probiotic for bacterial vaginosis: randomised placebo-controlled double-blind trial.
abstract: BACKGROUND
  To determine if oral metronidazole (MTZ-400 mg bid) with 2% vaginal clindamycin-cream (Clind) or a Lactobacillus acidophilus vaginal-probiotic containing oestriol (Prob) reduces 6-month bacterial vaginosis (BV) recurrence.
  
  
  METHODS
  Double-blind placebo-controlled parallel-group single-site study with balanced randomization (1:1:1) conducted at Melbourne Sexual Health Centre, Australia. Participants with symptomatic BV [Nugent Score (NS) = 7-10 or ≥3 Amsel's criteria and NS = 4-10], were randomly allocated to MTZ-Clind, MTZ-Prob or MTZ-Placebo and assessed at 1,2,3 and 6 months. MTZ and Clind were administered for 7 days and Prob and Placebo for 12 days. Primary outcome was BV recurrence (NS of 7-10) on self-collected vaginal-swabs over 6-months. Cumulative BV recurrence rates were compared between groups by Chi-squared statistics. Kaplan-Meier, log rank and Cox regression analyses were used to compare time until and risk of BV recurrence between groups.
  
  
  RESULTS
  450 18-50 year old females were randomized and 408 (91%), equally distributed between groups, provided ≥1 NS post-randomization and were included in analyses; 42 (9%) participants with no post-randomization data were excluded. Six-month retention rates were 78% (n = 351). One-month BV recurrence (NS 7-10) rates were 3.6% (5/140), 6.8% (9/133) and 9.6% (13/135) in the MTZ-Clind, MTZ-Prob and MTZ-Placebo groups respectively, p = 0.13. Hazard ratios (HR) for BV recurrence at one-month, adjusted for adherence to vaginal therapy, were 0.43 (95%CI 0.15-1.22) and 0.75 (95% CI 0.32-1.76) in the MTZ-Clind and MTZ-Prob groups compared to MTZ-Plac respectively. Cumulative 6-month BV recurrence was 28.2%; (95%CI 24.0-32.7%) with no difference between groups, p = 0.82; HRs for 6-month BV recurrence for MTZ-Clind and MTZ-Prob compared to MTZ-Plac, adjusted for adherence to vaginal therapy were 1.09(95% CI = 0.70-1.70) and 1.03(95% CI = 0.65-1.63), respectively. No serious adverse events occurred.
  
  
  CONCLUSIONS
  Combining the recommended first line therapies of oral metronidazole and vaginal clindamycin, or oral metronidazole with an extended-course of a commercially available vaginal-L.acidophilus probiotic, does not reduce BV recurrence.
  
  
  BACKGROUND
  ANZCTR.org.au ACTRN12607000350426.
authors.affiliation: Melbourne School of Population Health, University of Melbourne, Melbourne, Australia. cbradshaw@mshc.org.au
authors.forename: Catriona S
authors.initials: CS
authors.lastname: Bradshaw
authors.forename: Marie
authors.initials: M
authors.lastname: Pirotta
authors.forename: Deborah
authors.initials: D
authors.lastname: De Guingand
authors.forename: Jane S
authors.initials: JS
authors.lastname: Hocking
authors.forename: Anna N
authors.initials: AN
authors.lastname: Morton
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
authors.forename: Glenda
authors.initials: G
authors.lastname: Fehler
authors.forename: Andrea
authors.initials: A
authors.lastname: Morrow
authors.forename: Sandra
authors.initials: S
authors.lastname: Walker
authors.forename: Lenka A
authors.initials: LA
authors.lastname: Vodstrcil
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Fairley
mesh_terms: D000282:Administration, Intravaginal; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002981:Clindamycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008795:Metronidazole / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D019936:Probiotics / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D057566:Self Report; D013997:Time Factors; D016896:Treatment Outcome; D014622:Vaginal Creams, Foams, and Jellies; D016585:Vaginosis, Bacterial / Q000178:diet therapy / Q000188:drug therapy*; D055815:Young Adult; D016903:Drug Monitoring
chemical_list: D000900:Anti-Bacterial Agents; D010919:Placebos; D014622:Vaginal Creams, Foams, and Jellies; D008795:Metronidazole; D002981:Clindamycin