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SUMMARY
Bacterial vaginosis (BV) is the most common vaginal syndrome afflicting fertile, premenopausal and pregnant women.
BV is associated with important adverse health conditions and infectious complications. Therapy with oral or local
recommended antibiotics is often associated with failure and high rates of recurrences. 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. This review investigated the evidence for the use of a single
strain or cocktail of probiotics, administered orally or intravaginally, either alone or in conjunction with antibiotics
for the treatment of BV. Lactobacilli 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 suggesting that, beside strain characteristics, the amount of exogenously applied lactobacilli could
have a role in the effectiveness of the product. However, substantial heterogeneity in products, trial methodologies and
outcome measures do not provide sufficient evidence for or against recommending probiotics for the treatment of BV.
KEY WORDS: Bacterial vaginosis, Probiotics, Lactobacilli, Controlled clinical trials.
Received May 12, 2013
INTRODUCTION
The female lower genital tract, consisting of vagina and ectocervix, is an ecological niche where
several aerobe and anaerobe microorganisms coexist in a dynamic balance. The homeostasis of
the vaginal ecosystem results from complex interactions and synergies among the host and different microorganisms that colonize the vaginal
mucosa (Mrdh, 1991; Sobel, 1997). This ecosystem is dynamic with changes in structure and
composition being influenced by age, menarche,
time in menstrual cycle, pregnancy, infections,
methods of birth control, sexual activity, use of
Corresponding author
Paola Mastromarino
Department of Public Health and Infectious Diseases
Section of Microbiology
Universit Sapienza
Piazzale Aldo Moro, 5 - 00185 Roma, Italy
E-mail: paola.mastromarino@uniroma1.it
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BACTERIAL VAGINOSIS
Bacterial vaginosis (BV) represents the most common vaginal syndrome afflicting fertile, premenopausal and pregnant women, with an incidence rate ranging from 5% to 50% (Sobel, 1997).
BV is a complex, polymicrobial disorder characterized by an overgrowth of strict or facultative
anaerobic bacteria (Gardnerella vaginalis,
Atopobium vaginae, Prevotella spp., Mobiluncus
spp., Mycoplasma hominis) and a reduction of
lactobacilli particularly those producing hydrogen peroxide (Fredricks et al., 2005; Lamont et
al., 2011). women with BV typically complain of
vaginal discomfort and homogeneous malodorous vaginal discharge, which is more noticeable
after unprotected intercourse, although a substantial fraction of women are asymptomatic
(Klebanoff et al., 2004). The overgrowth of vaginal anaerobes determines an increased production of amines (putrescine, cadaverine and
trimethylamine) that become volatile at alkaline
pH, i.e. after sexual intercourse and during the
menstrual cycle, and contribute to the typical
malodor of the vaginal discharge (Chen et al.,
1979). BV is frequently disregarded since the
symptoms are often insignificant, however the
clinical consequences could be important. In fact,
the alterations in the vaginal microbiota have
been associated with ascending infections and
obstetric complications (Koumans et al., 2002),
as well as with urinary tract infections (Harmanli
et al., 2000). In women undergoing in vitro fertil-
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CLINICAL TRIALS
Studies have been carried out to assess the efficacy of a single strain or cocktail of probiotics
administered orally or intravaginally in the treatment of BV (Falagas et al., 2007). Two types of
experimental approaches have been used in clinical trials using probiotics for treatment of BV.
In the first, BV therapy was carried out using on-
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TABLE 1 - Clinical trials on probiotics use for treatment of bacterial vaginosis (BV).
Authors
Size
Type of study/
duration
Intervention
BV cure rate
Anukam et al.,
2006b
40
R, oB, AC
30 days
Mastromarino et al.,
2009
34
R, DB, PC
3 week
50% compared to 6%
control
(P = 0.017)
Parent et al.,
1996
32
R, PC
4 week
Halln et al.,
1992
57
R, DB, PC
20-40 days
21% compared to 0%
control
(P = NS)
R = randomized; DB = double blind; PC = placebo controlled; oB = observer blind. AC = active controlled. CFU = colony forming units.
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TABLE 2 - Clinical trials on probiotics use combined with antibiotic treatment for BV.
Authors
Size
Type of study
duration
Intervention
BV cure rate
Anukam
et al., 2006a
125
R, DB, PC
30 days
Petricevic
and witt,
2008
190
R, oB, PC
4 weeks
Larsson
et al., 2008
100
R, DB, PC
6 menstrual
periods
Eriksson
et al., 2005
187
R, DB, PC
2 menstrual
periods
Bradshaw
et al., 2012
268
R, DB, PC
6 months
R = randomized; DB = double blind; PC = placebo controlled; oB = observer blind. CFU = colony forming units.
234
cacy of vaginal probiotic capsules for BV prophylaxis in healthy women with a history of recurrent BV (Ya et al., 2010). one hundred and
twenty healthy Chinese women with a history of
recurrent BV (2 BV episodes in the previous
year) were assigned randomly to daily vaginal
prophylaxis with 1 capsule that containing 8109
CFU of L. rhamnosus (6.8109 CFU), L. acidophilus (0.4109 CFU) and Streptococcus thermophilus (0.4109 CFU) or 1 placebo capsule for
7 days on, 7 days off, and 7 days on. Probiotic
prophylaxis resulted in lower recurrence rates for
BV (15.8% vs 45.0%; P<0.001) through 2 months
as assessed according to Amsel criteria. Between
the 2 and 11-month follow-up period, women
who received probiotics reported a lower incidence of BV (10.6% vs 27.7%; P=0.04). However
a limitation of this study was that 11-month outcomes were collected by telephone follow-up interview.
DISCUSSION
In recent years several clinical trials have been
performed to investigate whether specific strains
of lactobacilli, administered either orally or intra-vaginally, in combination with antibiotics or
not, could be effective in the treatment or prevention of vaginal infections. The studies using
lactobacilli to treat BV, albeit small in size,
showed the potential of probiotics to cure BV.
Although the species used in the various trials differed, three out of four studies reported a significant cure rate (Parent et al., 1996; Anukam et al.,
2006b; Mastromarino et al., 2009). when probiotics were used following antibiotic treatment,
the BV cure rate was increased and recurrence
rates were reduced in three out of five studies
(Anukam et al., 2006a; Petricevic and witt, 2008;
Larsson et al., 2008).
An important issue concerns the prevention of
BV recurrence in healthy women with a history
of recurrent BV. Despite the important adverse
health conditions associated with abnormal vaginal flora, no preventive treatments are available.
The positive results obtained in the only clinical
trial using lactobacilli in healthy Chinese women
(Ya et al., 2010) suggest the potential of probiotics for BV prophylaxis. It is noteworthy that,
unlike antibiotics, lactobacilli probiotics can be
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could act as confounding factors hindering a real comparison among the trials and also may account for the different effectiveness of the treatments.
Larger, well-designed randomized controlled trials with standardized methodologies are needed
to confirm the benefits of probiotics in the treatment of BV.
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