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Artículo Infecciones ginecologicas

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The Journal for Nurse Practitioners 15 (2019) 420e423
Contents lists available at ScienceDirect
The Journal for Nurse Practitioners
journal homepage: www.npjournal.org
Bacterial Vaginosis: A Review of Treatment, Recurrence, and
Disparities
Ashley Jones, MS, FNP-BC
a b s t r a c t
Keywords:
aerobic vaginitis
African American women
bacterial vaginosis
recurrent vaginitis
HIV
Bacterial vaginosis recurrence is common, and although easily treated, it can quickly recur. This review details
some of the identified biologic mechanisms that result in recurrence or treatment failure and also discusses
other types of vaginitis that can co-occur, mimic bacterial vaginosis, or both, and advises the clinician on
diagnosis and treatment. Bacterial vaginosis increases the risk for acquiring sexually transmitted infections,
including human immunodeficiency virus, which is important to note because there are still significant racial
disparities in the rates of new human immunodeficiency virus diagnosis between African American and
white women. Adequately treating bacterial vaginosis may help to narrow this gap.
© 2019 Elsevier Inc. All rights reserved.
American Association of Nurse Practitioners (AANP) members may receive 1.0 continuing education contact hours,
including 0.75 pharmacology credit, approved by AANP, by
reading this article and completing the online posttest and
evaluation at aanp.inreachce.com.
Introduction
Bacterial vaginosis (BV) is a common vaginal infection affecting
approximately 30% of women of childbearing age in the United
States and represents the most common vaginal infection in
women between the ages of 15 and 44 years.1 BV has been associated with an increased risk of acquiring sexually transmitted infections (STIs), including human immunodeficiency virus (HIV),
gonorrhea, chlamydia, and herpes simplex virus. BV can also lead to
pelvic inflammatory disease, preterm birth, and posthysterectomy
and postpartum vaginal infections.2
In addition to the physical risks, qualitative studies have shown
that women who suffer from BV, particularly recurrent BV, experience a decrease in their quality of life (QOL).3 Reported disruptions in QOL range from embarrassment about any perceived odor,
decrease in self-esteem, interruption of intimate relationships, social isolation, and decrease in work productivity.3 BV is more
common in African American women, who are more than 3-times
as likely to experience BV compared with white women.4
Despite the prevalence of BV and availability of treatment,
recurrence and treatment failure are common. This review explores
the diagnosis and treatment of acute and recurrent BV, reports the
mechanisms by which recurrence and treatment failure occur, and
highlights the disparities noted between African American and
https://doi.org/10.1016/j.nurpra.2019.03.010
1555-4155/© 2019 Elsevier Inc. All rights reserved.
white women. However, an in-depth discussion of these disparities
is outside of the scope of this report.
Diagnosis
BV results from an alteration of the vaginal flora. A number of
etiologic organisms have been identified, including Gardnerella
vaginalis, Atopobium vaginae, Megasphaera phylotype 1 and 2,
Leptotrichia aminionii, Mobiluncus spp, Prevotella spp, Mycoplasma
hominis, Bacteroides spp, Sneathia, and BV-associated bacteria
(BVAB)1, 2, and 3.4 Risk factors for developing BV include sexual
activity, particularly unprotected intercourse, an increased number of sexual partners, and women who have sex with women.
Being of African or African American descent, douching, and
having an intrauterine uterine device also increases the risk for
developing BV.5
Although there are ample data that detail the risk factors associated with BV infection, research to date has not been able to
identify the exact causative mechanism that leads to this dysbiosis.
It is known that in BV the typical predominance of hydrogen
peroxide and lactic acide producing Lactobacillus, which helps to
keep the vaginal pH < 4.5 is disrupted, allowing for the growth and
proliferation of the anaerobic microbes mentioned above. This shift
in flora results in bacterial overgrowth leading to the common
symptoms of vaginal discharge and vaginal odor experienced by
patients.6
The first bacterium identified to represent BV infection was G.
vaginalis, and it is still considered the primary pathogen associated
with this diagnosis. In 1983, Amsel7 proposed clinical diagnostic
criteria for BV that was previously known as nonspecific vaginitis as
identified by Gardner and Dukes in 1955.4
A. Jones / The Journal for Nurse Practitioners 15 (2019) 420e423
The diagnosis of BV can be made clinically if the patient meets 3
of the 4 following criteria: (1) presence of a homogenous, thin,
grayish-white discharge; (2) vaginal pH 4.5; (3) positive whiff
test (amine odor with application of 10% potassium hydroxide to
sample); and (4) clue cells (vaginal epithelial cells with a speckled
appearance due to being coated with bacteria) on visualization
using wet mount microscopy.8
Nugent scoring is also a reliable method of diagnosis commonly
used in research studies but is not often seen in clinical practice
because it requires Gram staining of the sample. The Nugent score
assesses the quantity of the expected Lactobacillus organisms usually present in the vaginal flora in relation to the quantity of other
organisms, such as G vaginalis and Mobiluncus spp, that are associated with BV. The sample is scored on a 0 to 10 scale. Scores that
fall in the normal range (0-3) indicate there is an adequate presence
of Lactobacillus with the absence of G vaginalis and Mobiluncus spp
morphotypes. The intermediate range (4-6) represents a decrease
in Lactobacillus concentrations but also with the presence of G
vaginalis and Mobiluncus spp. Scores in the highest range (7-10)
demonstrate the absence of Lactobacillus and the presence of large
amounts of G vaginalis and Mobiluncus.4
In clinical settings in which microscopy is not available, detection of G vaginalis DNA using the Affirm VPIII test (Becton, Dickinson and Company, Franklin Lakes, NJ) can be used to help support
a diagnosis of BV, particularly in patients with odorous vaginal
discharge and an elevated vaginal pH.4 The OSOM BVBlue (Sekisui
Diagnostics, LLC, Lexington, MA) can also be used as a point-of-care
test for BV diagnosis because results are available within 10 minutes. This test detects the presence of increased sialidase enzyme
activity. Sialidase is an enzyme that is frequently produced by BVassociated bacteria that enhances the pathogenicity of organisms
by allowing for easier invasion and destruction of tissues. Its
presence indicates the existence of a BV-related bacteria.4
Vaginal culture is not useful for diagnosing BV, because many of
the microorganisms associated with the condition are not
amenable to culture and because colonization of the vagina with
various organisms may make culture results difficult to interpret.9
It is important to note that although G vaginalis is the primary
bacteria associated with BV, its presence does not always indicate
an infection, because this bacterium has also been found in the
vaginal flora of healthy individuals without BV and may be present
in as many as 55% women who do not have BV.2,4
Treatment and Recurrence
The recommended treatments for BV, according to the 2015
Centers for Disease Control and Prevention Sexually Transmitted
Disease guidelines, are: (1) oral metronidazole, 500 mg twice
daily for 7 days; (2) metronidazole, 0.75% gel intravaginally at
bedtime for 5 days; or (3) clindamycin cream, 2% intravaginally at
bedtime for 7 days. Alternative regimens include tinidazole, 2 g
daily for 2 days; tinidazole, 1 g daily for 5 days; clindamycin, 300
mg twice daily for 7 days; or clindamycin ovules, 100 mg intravaginally at bedtime for 3 days.9
Reported cure rates for an episode of acute BV vary but have
been estimated to be between 70% and 80%. Unfortunately, more
than 50% of BV cases will recur at least once within the following 12
months.3 Because the etiology of BV is still not entirely understood,
identifying the cause of recurrent cases is challenging.
Reinfection may play a role in explaining recurrent BV, but
treatment failure is a more likely contributor. There are several
theories that try to explain recurrence and persistent symptoms.
The existence of a biofilm in the vagina is one such theory and is the
subject of ongoing research. Biofilms occur when microorganisms
adhere to surfaces. G vaginalis, one of the primary organisms
421
associated with BV, is now known to adhere to the vaginal
epithelium, which creates a sticky biofilm on the vaginal wall. It is
thought that this film may limit penetration of the antibiotics
intended to eradicate bacterial growth. The film may also serve as a
support scaffolding that allows adherence of other organisms to the
biofilm, enhancing colonization of the vagina with various bacterial
species.2 Although BV is considered a polymicrobial condition, G
vaginalis is the most prominent organism. It is the focus of ongoing
microbiological studies because of its unique qualities that can
affect virulence and resistance.
One of the areas of current interest regarding G vaginalis is
which genotypes of G vaginalis produce sialidase and which do not.
It is believed that sialidase-producing genotypes are more likely to
be associated with biofilm development and subsequently may
increase the risk of resistant and recurrent infections.10
In 2016, Schuyler et al published a study that helped broaden
our understanding of G vaginalis resistance to metronidazole.11
Four previously identified findings revealed that 2 of the 4 known G
vaginalis clades were metronidazole resistant. The 2 remaining
clades, which showed less resistance, were more closely related in
phylogenetic characteristics. The authors proposed that women
with BV may be colonized with multiple G vaginalis clades and that
this inherent sensitivity or resistance to metronidazole may impact
treatment outcomes and the likelihood of recurrence. It has been
recommended that further research in this area be undertaken to
translate this finding into the clinical setting and provide clinicians
with tests to distinguish between BV clades that are more likely to
fail treatment due to innate resistance.11
Treatment of Recurrence
The recommended treatment for recurrent BV is metronidazole,
0.75% gel twice weekly for 4 to 6 months, after appropriate treatment of the initial episode of BV with metronidazole or clindamycin. This method has been shown to reduce the rates of BV
recurrence by more than 50%.9 Some data support the use of boric
acid intravaginally to reacidify the vagina and help create an
environment that encourages Lactobacillus and a healthy flora,
resulting in a decrease of BV recurrence. With this regimen,
metronidazole is prescribed for the usual 7-day course along with
vaginal boric acid, 600 mg once daily at bedtime for 21 days. The
patient is seen immediately after completion of this regimen and
reassessed. If in remission, the patient begins a twice-weekly
metronidazole regimen for 4 to 6 months.9
Probiotics have been evaluated as an adjunct treatment of acute
BV infection and to deter recurrence. Although individual studies
have reported positive outcomes with the use of probiotics, evidence to support the use of probiotics for treatment or prevention
of this condition is not yet available.12 There has also been research
evaluating the use of presumptive treatment for BV at monthly
intervals to reduce BV recurrences, the results of which have
demonstrated some success.13
A more novel treatment approach is the use of thermoplastic
polyurethane-based intravaginal rings, similar in concept to the
NuvaRing (Merck, Kenilworth, NJ) which is being investigated as a
potential method of delivering antimicrobials and lactic acid to the
vaginal flora for prevention of recurrent BV. There is, however,
some discussion that intravaginal rings can be prone to biofilm
formation and colonization by bacteria, which would be a potential
limitation of this type of treatment, and further studies are needed
to evaluate the feasibility of this modality. If mechanical properties
related to drug release and delivery can be optimized and there is
an adequate method to address the possibility of biofilm formation,
intravaginal rings could become a convenient treatment option for
BV.14
422
A. Jones / The Journal for Nurse Practitioners 15 (2019) 420e423
Prior research has also demonstrated an association between low
serum vitamin D levels and an increased prevalence of BV. Unfortunately, subsequent investigations have not shown a decrease in BV
recurrence with high-dose vitamin D supplementation.15
Behavioral Interventions
Sexual activity has been identified as a risk factor for BV, but
there is not yet sufficient evidence to determine whether it is
sexually transmitted. BV-associated bacteria have been found in the
male genitalia, although there is no identified male equivalent of BV
that results from this colonization.3 Studies have evaluated the
benefit of concurrent treatment of male sexual partners of women
with BV and have not been able to demonstrate benefit to support
partner treatment.3 Prior studies have demonstrated that having
multiple sexual partners, having a new sexual partner, having a
female sexual partner, and unprotected intercourse are behavioral
risk factors for BV.16 Limited data suggest that reducing the number
of sexual partners, using condoms during intercourse, and
adequate cleaning of shared sexual accessories by women who
have sex with women may help to prevent BV recurrence.17 Given
that the risk for BV is enhanced by sexual activity, abstinence has
been proposed as a method to prevent recurrence because BV is
rarely seen in women who have never been sexually active.
Avoidance of vaginal hygiene practices, such as douching, have also
been recommended to prevent recurrent BV.18
Aerobic Vaginitis
Although reinfection, resistance, and treatment failure can
make achieving long-term remission of BV challenging, difficulty in achieving adequate remission of BV symptoms could
also be due to diagnostic error. A newly identified clinical condition referred to as aerobic vaginitis (AV) was described by
Donders et al in 2017 and shares common characteristics with
the clinical presentation of BV.19 AV can present with yellow
vaginal discharge, labial or vaginal erythema, dyspareunia, and
vulvar pain, including burning or stinging. To diagnose AV, wet
mount microscopy is performed with evaluation for pH > 4.5,
epithelial inflammation, the presence of leukocytes, and absence
of lactobacilli. It is plausible that women who were believed to
have had treatment failure of BV could have had misdiagnosed
AV in some cases.20
Some consider AV to be the aerobic equivalent to BV and may
be caused by gastrointestinal flora such as Escherichia coli,
Staphylococcus aureus, Streptococcus agalactiae, and Enterococcus
faecalis, because they can co-occur with BV and other forms of
vaginitis. This distinction is important because it explains
treatment failure if this diagnosis was missed and treated solely
with metronidazole.19
Severe AV can progress to a condition that is better described
in the US literature as desquamative inflammatory vaginitis
(DIV). There is a bit of controversy regarding the language and
fundamental differences in the conceptualization of this disease
progression. In the US, DIV is considered fundamentally an inflammatory response secondarily resulting in dysbiosis rather
than a primarily infectious state.21 The signs, symptoms, and
microscopic examination findings are similar to those reported
in AV. Although opinions differ about the etiology of AV and BV,
treatment with clindamycin 2% cream is recommended for both.
Given that a component of inflammation is hallmark leading to
the diagnosis of AV and BV, consideration of topical corticosteroids may be useful as well, such as compounded hydrocortisone
10% cream. Where their treatment strategies differ is that DIV is
considered to be a chronic condition with potential for relapse.
As such, treatment for DIV is recommended to continue daily for
4 to 6 weeks, which differs from the recommended 7-day
treatment for AV.21
Diagnosis of AV and DIV has been limited in the US due to a need
for specialized expertise with microscopy, particularly phase
contrast microscopy, to confirm this diagnosis. With an initial
estimated prevalence of between 7% and 12%, there is a missed
opportunity for adequate treatment of women who are suffering
from BV or AV.19 Whether racial and ethnic disparities exist in these
situations is not known.
Discussion of Racial Disparities
Although G vaginalis is the most common and primary organism
associated with BV, research has demonstrated that the bacterial
composition in the vagina is very diverse. The National Institutes of
Health sponsored the Human Microbiome Project (2017), which
had the task of determining the genetic sequencing of the microorganisms that are usually present on the skin, mouth, nose,
digestive tract, and vagina, in an effort to further characterize what
is usually found in healthy populations compared with those with
disease.22 There is evidence that the composition of the microbiome (the aggregate of microorganisms that live in and on the
human body) can vary by ethnicity.
As it relates to this review, such variance has been demonstrated
with respect to the vaginal flora. Evaluation of the microbiome of
African American women has found that instead of the expected
dominance of the protective Lactobacillus spp, G vaginalis, BVAB1,
and other anaerobes predominate. When Lactobacillus was present,
it was the species that was the least protective against BV. These
findings were in direct contrast to white women, who were colonized with various protective Lactobacillus spp, including L crispatus, L jensenii, and L gasseri.23 The fact that African American
women are less likely to have protective Lactobacillus strains and
more likely to be colonized with L iners (which produces less lactic
acid) may account for the higher average pH in the vaginal secretions of African American women and suggest why they are more
susceptible to BV.8,23
HIV Disparities
Although having BV is distressing enough, the more significant
health concerns are the conditions that are more likely to develop
as a result of BV. Acquisition of sexually transmitted infections, in
particular, HIV, is more likely to occur in women with BV. Atashili et
al conducted a meta-analysis of studies in 2008 and found that BV
substantially increased the risk of HIV acquisition by 60%. There are
several proposed mechanisms by which this may occur. One theory
is that the hydrogen peroxide byproduct of Lactobacillus metabolism inactivates the HIV virus. Women with a noted absence of
Lactobacillus would not benefit from this protection.24
Another proposed mechanism is that an inflammatory state
created by the interaction between certain interleukins and Tolllike receptors causes an increase in the recruitment of target cell
populations. There is also evidence suggesting that BV can enhance
HIV replication and increase vaginal shedding of HIV.23
Sub-Saharan Africa has high rates of BV and the highest prevalence of HIV in the world. In the US, African American women share
a disproportionate burden of HIV/AIDS diagnosis, with infection
rates 20-times higher than the rate of white women, and account
for nearly two-thirds of all new infections among women.23 This
continues to be a significant public health issue, and a better understanding of BV may help to positively impact the HIV/AIDs
epidemic, especially as it relates to African American women.
A. Jones / The Journal for Nurse Practitioners 15 (2019) 420e423
Conclusion
Although BV is the most common vaginal infection in women of
childbearing age, it is still not fully understood. Treatment with
metronidazole is helpful for some patients. However, recent
research has identified various sources for treatment failure and
recurrence, including G vaginalis clades with inherent metronidazole resistance, biofilm formation that prevents penetration of
antibiotics, and similar but distinct forms of vaginitis that mimic
some of the symptoms of BV but require a different treatment. The
incidence of AV and DIV are likely underreported, particularly in
primary care settings where the use of microscopy has waned over
the years in favor of DNA-based methods for the diagnosis of
vaginal infections.
BV increases the risk of acquiring HIV and other STIs and increases the risk for preterm births. In addition, recurrent BV has
been shown to decrease QOL. The burden of this illness has
disproportionately affected African American women, and the data
have clearly shown that BV is a larger public health issue than just
managing an inconvenient vaginitis. It is essential for ongoing
research to continue in this area.
Core nurse practitioner (NP) competencies include diagnosis
and treatment of illness.25 The NP should remain up to date with
the various methods for diagnosis and treatment of BV while also
maintaining awareness of similar conditions that can mimic or
overlap with this condition. Patients trust NPs to be knowledgeable,
use high-level diagnostic reasoning, and deliver exceptional patient
care. It is imperative to keep up with the ever-evolving clinical
landscape.
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Ashley Jones, MS, FNP-BC, works as a nurse practitioner at The Ohio State University,
Wexner Medical Center, OSU Family Practice, Gahanna, Ohio. She is available at
[email protected].
In compliance with national ethical guidelines, the author reports no relationships
with business or industry that would pose a conflict of interest.
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