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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: Bacterial vaginosis recurrence is common, and although easily treated, it can quickly recur. This review details
aerobic vaginitis some of the identified biologic mechanisms that result in recurrence or treatment failure and also discusses
African American women
other types of vaginitis that can co-occur, mimic bacterial vaginosis, or both, and advises the clinician on
bacterial vaginosis
recurrent vaginitis
diagnosis and treatment. Bacterial vaginosis increases the risk for acquiring sexually transmitted infections,
HIV 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.

white women. However, an in-depth discussion of these disparities


American Association of Nurse Practitioners (AANP) mem-
is outside of the scope of this report.
bers 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 Diagnosis
evaluation at aanp.inreachce.com.
BV results from an alteration of the vaginal flora. A number of
etiologic organisms have been identified, including Gardnerella
Introduction vaginalis, Atopobium vaginae, Megasphaera phylotype 1 and 2,
Leptotrichia aminionii, Mobiluncus spp, Prevotella spp, Mycoplasma
Bacterial vaginosis (BV) is a common vaginal infection affecting hominis, Bacteroides spp, Sneathia, and BV-associated bacteria
approximately 30% of women of childbearing age in the United (BVAB)1, 2, and 3.4 Risk factors for developing BV include sexual
States and represents the most common vaginal infection in activity, particularly unprotected intercourse, an increased num-
women between the ages of 15 and 44 years.1 BV has been asso- ber of sexual partners, and women who have sex with women.
ciated with an increased risk of acquiring sexually transmitted in- Being of African or African American descent, douching, and
fections (STIs), including human immunodeficiency virus (HIV), having an intrauterine uterine device also increases the risk for
gonorrhea, chlamydia, and herpes simplex virus. BV can also lead to developing BV.5
pelvic inflammatory disease, preterm birth, and posthysterectomy Although there are ample data that detail the risk factors asso-
and postpartum vaginal infections.2 ciated with BV infection, research to date has not been able to
In addition to the physical risks, qualitative studies have shown identify the exact causative mechanism that leads to this dysbiosis.
that women who suffer from BV, particularly recurrent BV, expe- It is known that in BV the typical predominance of hydrogen
rience a decrease in their quality of life (QOL).3 Reported disrup- peroxide and lactic acide producing Lactobacillus, which helps to
tions in QOL range from embarrassment about any perceived odor, keep the vaginal pH < 4.5 is disrupted, allowing for the growth and
decrease in self-esteem, interruption of intimate relationships, so- proliferation of the anaerobic microbes mentioned above. This shift
cial isolation, and decrease in work productivity.3 BV is more in flora results in bacterial overgrowth leading to the common
common in African American women, who are more than 3-times symptoms of vaginal discharge and vaginal odor experienced by
as likely to experience BV compared with white women.4 patients.6
Despite the prevalence of BV and availability of treatment, The first bacterium identified to represent BV infection was G.
recurrence and treatment failure are common. This review explores vaginalis, and it is still considered the primary pathogen associated
the diagnosis and treatment of acute and recurrent BV, reports the with this diagnosis. In 1983, Amsel7 proposed clinical diagnostic
mechanisms by which recurrence and treatment failure occur, and criteria for BV that was previously known as nonspecific vaginitis as
highlights the disparities noted between African American and identified by Gardner and Dukes in 1955.4

https://doi.org/10.1016/j.nurpra.2019.03.010
1555-4155/© 2019 Elsevier Inc. All rights reserved.
A. Jones / The Journal for Nurse Practitioners 15 (2019) 420e423 421

The diagnosis of BV can be made clinically if the patient meets 3 associated with BV, is now known to adhere to the vaginal
of the 4 following criteria: (1) presence of a homogenous, thin, epithelium, which creates a sticky biofilm on the vaginal wall. It is
grayish-white discharge; (2) vaginal pH  4.5; (3) positive whiff thought that this film may limit penetration of the antibiotics
test (amine odor with application of 10% potassium hydroxide to intended to eradicate bacterial growth. The film may also serve as a
sample); and (4) clue cells (vaginal epithelial cells with a speckled support scaffolding that allows adherence of other organisms to the
appearance due to being coated with bacteria) on visualization biofilm, enhancing colonization of the vagina with various bacterial
using wet mount microscopy.8 species.2 Although BV is considered a polymicrobial condition, G
Nugent scoring is also a reliable method of diagnosis commonly vaginalis is the most prominent organism. It is the focus of ongoing
used in research studies but is not often seen in clinical practice microbiological studies because of its unique qualities that can
because it requires Gram staining of the sample. The Nugent score affect virulence and resistance.
assesses the quantity of the expected Lactobacillus organisms usu- One of the areas of current interest regarding G vaginalis is
ally present in the vaginal flora in relation to the quantity of other which genotypes of G vaginalis produce sialidase and which do not.
organisms, such as G vaginalis and Mobiluncus spp, that are asso- It is believed that sialidase-producing genotypes are more likely to
ciated with BV. The sample is scored on a 0 to 10 scale. Scores that be associated with biofilm development and subsequently may
fall in the normal range (0-3) indicate there is an adequate presence increase the risk of resistant and recurrent infections.10
of Lactobacillus with the absence of G vaginalis and Mobiluncus spp In 2016, Schuyler et al published a study that helped broaden
morphotypes. The intermediate range (4-6) represents a decrease our understanding of G vaginalis resistance to metronidazole.11
in Lactobacillus concentrations but also with the presence of G Four previously identified findings revealed that 2 of the 4 known G
vaginalis and Mobiluncus spp. Scores in the highest range (7-10) vaginalis clades were metronidazole resistant. The 2 remaining
demonstrate the absence of Lactobacillus and the presence of large clades, which showed less resistance, were more closely related in
amounts of G vaginalis and Mobiluncus.4 phylogenetic characteristics. The authors proposed that women
In clinical settings in which microscopy is not available, detec- with BV may be colonized with multiple G vaginalis clades and that
tion of G vaginalis DNA using the Affirm VPIII test (Becton, Dick- this inherent sensitivity or resistance to metronidazole may impact
inson and Company, Franklin Lakes, NJ) can be used to help support treatment outcomes and the likelihood of recurrence. It has been
a diagnosis of BV, particularly in patients with odorous vaginal recommended that further research in this area be undertaken to
discharge and an elevated vaginal pH.4 The OSOM BVBlue (Sekisui translate this finding into the clinical setting and provide clinicians
Diagnostics, LLC, Lexington, MA) can also be used as a point-of-care with tests to distinguish between BV clades that are more likely to
test for BV diagnosis because results are available within 10 mi- fail treatment due to innate resistance.11
nutes. This test detects the presence of increased sialidase enzyme
activity. Sialidase is an enzyme that is frequently produced by BV- Treatment of Recurrence
associated bacteria that enhances the pathogenicity of organisms
by allowing for easier invasion and destruction of tissues. Its The recommended treatment for recurrent BV is metronidazole,
presence indicates the existence of a BV-related bacteria.4 0.75% gel twice weekly for 4 to 6 months, after appropriate treat-
Vaginal culture is not useful for diagnosing BV, because many of ment of the initial episode of BV with metronidazole or clinda-
the microorganisms associated with the condition are not mycin. This method has been shown to reduce the rates of BV
amenable to culture and because colonization of the vagina with recurrence by more than 50%.9 Some data support the use of boric
various organisms may make culture results difficult to interpret.9 acid intravaginally to reacidify the vagina and help create an
It is important to note that although G vaginalis is the primary environment that encourages Lactobacillus and a healthy flora,
bacteria associated with BV, its presence does not always indicate resulting in a decrease of BV recurrence. With this regimen,
an infection, because this bacterium has also been found in the metronidazole is prescribed for the usual 7-day course along with
vaginal flora of healthy individuals without BV and may be present vaginal boric acid, 600 mg once daily at bedtime for 21 days. The
in as many as 55% women who do not have BV.2,4 patient is seen immediately after completion of this regimen and
reassessed. If in remission, the patient begins a twice-weekly
Treatment and Recurrence metronidazole regimen for 4 to 6 months.9
Probiotics have been evaluated as an adjunct treatment of acute
The recommended treatments for BV, according to the 2015 BV infection and to deter recurrence. Although individual studies
Centers for Disease Control and Prevention Sexually Transmitted have reported positive outcomes with the use of probiotics, evi-
Disease guidelines, are: (1) oral metronidazole, 500 mg twice dence to support the use of probiotics for treatment or prevention
daily for 7 days; (2) metronidazole, 0.75% gel intravaginally at of this condition is not yet available.12 There has also been research
bedtime for 5 days; or (3) clindamycin cream, 2% intravaginally at evaluating the use of presumptive treatment for BV at monthly
bedtime for 7 days. Alternative regimens include tinidazole, 2 g intervals to reduce BV recurrences, the results of which have
daily for 2 days; tinidazole, 1 g daily for 5 days; clindamycin, 300 demonstrated some success.13
mg twice daily for 7 days; or clindamycin ovules, 100 mg intra- A more novel treatment approach is the use of thermoplastic
vaginally at bedtime for 3 days.9 polyurethane-based intravaginal rings, similar in concept to the
Reported cure rates for an episode of acute BV vary but have NuvaRing (Merck, Kenilworth, NJ) which is being investigated as a
been estimated to be between 70% and 80%. Unfortunately, more potential method of delivering antimicrobials and lactic acid to the
than 50% of BV cases will recur at least once within the following 12 vaginal flora for prevention of recurrent BV. There is, however,
months.3 Because the etiology of BV is still not entirely understood, some discussion that intravaginal rings can be prone to biofilm
identifying the cause of recurrent cases is challenging. formation and colonization by bacteria, which would be a potential
Reinfection may play a role in explaining recurrent BV, but limitation of this type of treatment, and further studies are needed
treatment failure is a more likely contributor. There are several to evaluate the feasibility of this modality. If mechanical properties
theories that try to explain recurrence and persistent symptoms. related to drug release and delivery can be optimized and there is
The existence of a biofilm in the vagina is one such theory and is the an adequate method to address the possibility of biofilm formation,
subject of ongoing research. Biofilms occur when microorganisms intravaginal rings could become a convenient treatment option for
adhere to surfaces. G vaginalis, one of the primary organisms BV.14
422 A. Jones / The Journal for Nurse Practitioners 15 (2019) 420e423

Prior research has also demonstrated an association between low As such, treatment for DIV is recommended to continue daily for
serum vitamin D levels and an increased prevalence of BV. Unfortu- 4 to 6 weeks, which differs from the recommended 7-day
nately, subsequent investigations have not shown a decrease in BV treatment for AV.21
recurrence with high-dose vitamin D supplementation.15 Diagnosis of AV and DIV has been limited in the US due to a need
for specialized expertise with microscopy, particularly phase
Behavioral Interventions contrast microscopy, to confirm this diagnosis. With an initial
estimated prevalence of between 7% and 12%, there is a missed
Sexual activity has been identified as a risk factor for BV, but opportunity for adequate treatment of women who are suffering
there is not yet sufficient evidence to determine whether it is from BV or AV.19 Whether racial and ethnic disparities exist in these
sexually transmitted. BV-associated bacteria have been found in the situations is not known.
male genitalia, although there is no identified male equivalent of BV
that results from this colonization.3 Studies have evaluated the
Discussion of Racial Disparities
benefit of concurrent treatment of male sexual partners of women
with BV and have not been able to demonstrate benefit to support
Although G vaginalis is the most common and primary organism
partner treatment.3 Prior studies have demonstrated that having
associated with BV, research has demonstrated that the bacterial
multiple sexual partners, having a new sexual partner, having a
composition in the vagina is very diverse. The National Institutes of
female sexual partner, and unprotected intercourse are behavioral
Health sponsored the Human Microbiome Project (2017), which
risk factors for BV.16 Limited data suggest that reducing the number
had the task of determining the genetic sequencing of the micro-
of sexual partners, using condoms during intercourse, and
organisms that are usually present on the skin, mouth, nose,
adequate cleaning of shared sexual accessories by women who
digestive tract, and vagina, in an effort to further characterize what
have sex with women may help to prevent BV recurrence.17 Given
is usually found in healthy populations compared with those with
that the risk for BV is enhanced by sexual activity, abstinence has
disease.22 There is evidence that the composition of the micro-
been proposed as a method to prevent recurrence because BV is
biome (the aggregate of microorganisms that live in and on the
rarely seen in women who have never been sexually active.
human body) can vary by ethnicity.
Avoidance of vaginal hygiene practices, such as douching, have also
As it relates to this review, such variance has been demonstrated
been recommended to prevent recurrent BV.18
with respect to the vaginal flora. Evaluation of the microbiome of
African American women has found that instead of the expected
Aerobic Vaginitis
dominance of the protective Lactobacillus spp, G vaginalis, BVAB1,
and other anaerobes predominate. When Lactobacillus was present,
Although reinfection, resistance, and treatment failure can
it was the species that was the least protective against BV. These
make achieving long-term remission of BV challenging, diffi-
findings were in direct contrast to white women, who were colo-
culty in achieving adequate remission of BV symptoms could
nized with various protective Lactobacillus spp, including L crisp-
also be due to diagnostic error. A newly identified clinical con-
atus, L jensenii, and L gasseri.23 The fact that African American
dition referred to as aerobic vaginitis (AV) was described by
women are less likely to have protective Lactobacillus strains and
Donders et al in 2017 and shares common characteristics with
more likely to be colonized with L iners (which produces less lactic
the clinical presentation of BV.19 AV can present with yellow
acid) may account for the higher average pH in the vaginal secre-
vaginal discharge, labial or vaginal erythema, dyspareunia, and
tions of African American women and suggest why they are more
vulvar pain, including burning or stinging. To diagnose AV, wet
susceptible to BV.8,23
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 HIV Disparities
have had treatment failure of BV could have had misdiagnosed
AV in some cases.20 Although having BV is distressing enough, the more significant
Some consider AV to be the aerobic equivalent to BV and may health concerns are the conditions that are more likely to develop
be caused by gastrointestinal flora such as Escherichia coli, as a result of BV. Acquisition of sexually transmitted infections, in
Staphylococcus aureus, Streptococcus agalactiae, and Enterococcus particular, HIV, is more likely to occur in women with BV. Atashili et
faecalis, because they can co-occur with BV and other forms of al conducted a meta-analysis of studies in 2008 and found that BV
vaginitis. This distinction is important because it explains substantially increased the risk of HIV acquisition by 60%. There are
treatment failure if this diagnosis was missed and treated solely several proposed mechanisms by which this may occur. One theory
with metronidazole.19 is that the hydrogen peroxide byproduct of Lactobacillus meta-
Severe AV can progress to a condition that is better described bolism inactivates the HIV virus. Women with a noted absence of
in the US literature as desquamative inflammatory vaginitis Lactobacillus would not benefit from this protection.24
(DIV). There is a bit of controversy regarding the language and Another proposed mechanism is that an inflammatory state
fundamental differences in the conceptualization of this disease created by the interaction between certain interleukins and Toll-
progression. In the US, DIV is considered fundamentally an in- like receptors causes an increase in the recruitment of target cell
flammatory response secondarily resulting in dysbiosis rather populations. There is also evidence suggesting that BV can enhance
than a primarily infectious state.21 The signs, symptoms, and HIV replication and increase vaginal shedding of HIV.23
microscopic examination findings are similar to those reported Sub-Saharan Africa has high rates of BV and the highest preva-
in AV. Although opinions differ about the etiology of AV and BV, lence of HIV in the world. In the US, African American women share
treatment with clindamycin 2% cream is recommended for both. a disproportionate burden of HIV/AIDS diagnosis, with infection
Given that a component of inflammation is hallmark leading to rates 20-times higher than the rate of white women, and account
the diagnosis of AV and BV, consideration of topical corticoste- for nearly two-thirds of all new infections among women.23 This
roids may be useful as well, such as compounded hydrocortisone continues to be a significant public health issue, and a better un-
10% cream. Where their treatment strategies differ is that DIV is derstanding of BV may help to positively impact the HIV/AIDs
considered to be a chronic condition with potential for relapse. epidemic, especially as it relates to African American women.
A. Jones / The Journal for Nurse Practitioners 15 (2019) 420e423 423

Conclusion 10. Hardy L, Jespers V, Van den Bulck M, et al. The presence of the putative
Gardnerella vaginalis sialidase A gene in vaginal specimens is associated with
bacterial vaginosis biofilm. PloS One. 2017;12(2):e0172522. https://doi.org/
Although BV is the most common vaginal infection in women of 10.1371/journal.pone.0172522.
childbearing age, it is still not fully understood. Treatment with 11. Schuyler JA, Mordechai E, Adelson ME, Sobel JD, Gygax SE, Hilbert DW. Iden-
metronidazole is helpful for some patients. However, recent tification of intrinsically metronidazole-resistant clades of Gardnerella vagi-
nalis. Diagn Microbiol Infect Dis. 2016;84:1-3.
research has identified various sources for treatment failure and 12. Hanson L, Vandevusse L, Jerme  M, Abad C, Safdar N. Probiotics for treatment
recurrence, including G vaginalis clades with inherent metronida- and prevention of urogenital infections in women: a systematic review.
zole resistance, biofilm formation that prevents penetration of J Midwifery Womens Health. 2016;61(3):339-355.
13. Balkus J, Srinivasan S, Anzala O, et al. Impact of periodic presumptive treat-
antibiotics, and similar but distinct forms of vaginitis that mimic ment for bacterial vaginosis on the vaginal microbiome among women
some of the symptoms of BV but require a different treatment. The participating in the preventing vaginal infections trial. J Infect Dis. 2017;215:
incidence of AV and DIV are likely underreported, particularly in 723-731.
14. Verstraete G, Vandenbussche L, Kasmi S, et al. Thermoplastic polyurethane-
primary care settings where the use of microscopy has waned over based intravaginal rings for prophylaxis and treatment of (recurrent) bacte-
the years in favor of DNA-based methods for the diagnosis of rial vaginosis. Int J Pharm. 2017;529:218-226.
vaginal infections. 15. Turner A, Reese P, Chen P, et al. Serum vitamin D status and bacterial vaginosis
prevalence and incidence in Zimbabwean women. Am J Obstet Gynecol.
BV increases the risk of acquiring HIV and other STIs and in- 2016;215(3):332.e1-332.e10.
creases the risk for preterm births. In addition, recurrent BV has 16. Bautista C, Wurapa E, Sateren W, Morris S, Hollingsworth B, Sanchez J. Bac-
been shown to decrease QOL. The burden of this illness has terial vaginosis: a synthesis of the literature on etiology, prevalence, risk
factors, and relationship with chlamydia and gonorrhea infections. Mil Med
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Res. 2016;3(1):4.
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research to continue in this area. %20treatment&source¼search_result&selectedT itle¼1~81&usage_
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obic vaginitis: no longer a stranger. Res Microbiol. 2017;168(9-10):
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2018;6:78.
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landscape. uptodate.com/contents/desquamative-inflammatory-vaginitis?search¼
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Nonspecific vaginitis: diagnostic criteria and microbial and epidemiological
associations. Am J Med. 1983;74(1):14-22. Ashley Jones, MS, FNP-BC, works as a nurse practitioner at The Ohio State University,
8. Van der Veer C, van Houdt R, van Dam A, de Vries H, Bruisten S. Accuracy of a Wexner Medical Center, OSU Family Practice, Gahanna, Ohio. She is available at
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9. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, In compliance with national ethical guidelines, the author reports no relationships
2015. MMWR Recomm Rep Morb Mortal Wkly Rep Recomm Rep. 2015;64(RR-03):1. with business or industry that would pose a conflict of interest.

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