Conquering Resistant Vulvovaginitis

Conquering Resistant
Vulvovaginitis
Hope K. Haefner, M.D.
The University of Michigan
Center for Vulvar Diseases
Disclosures
Hope Haefner, MD has no relevant financial
relationships with any commercial interest
Learning Objectives
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At the end of this presentation, the participant
will:
Understand “itis” versus “osis”
Understand the various forms of vaginitis
Be comfortable diagnosing and treating
recurrent/resistant bacterial vaginosis and
trichomonas
Understand the various forms of candida
vulvovaginitis
Be comfortable diagnosing and treating
recurrent/resistant candida vulvovaginitis
Causes for Elevated Vaginal pH
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Menses
Heavy cervical mucus
Semen
Ruptured membranes
Hypoestrogenism
Desquamative vaginitis
• Trichomoniasis
• Bacterial vaginosis
• Foreign body with
infection
• Streptococcal
vaginitis (group A)
CDC STD TREATMENT GUIDELINES
http://www.cdc.gov/std/treatment/2010/defa
ult.htm
The 2010 Treatment Guidelines are now online
Resistant/Recurrent disease focus
BV Diagnosis
Clinical diagnosis (Amsel’s criteria)
-Thin gray-white discharge
-“Clue cells”
-Vaginal pH > 4.5
-Positive “whiff” test
-3 of 4 present = sensitivity 92% and specificity
77% (vs. gram stain using Nugent’s criteria)
Point of care tests for pH and amines, and
proline iminopeptidase are commercially
available
Clue Cells with Coccobaccilli
Absence of lactobacilli
Loss of WBC (hence vaginosis, not vaginitis)
Bacteria between cells
Sensitivity of Microscopy vs. Culture
• Bacterial vaginosis 92%
(Amsel’s)
• Trichomonas
60-70%
• Yeast
22 -50%
New Thoughts
Diagnosis
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•
•
•
•
Pap smear not helpful (low sensitivity)
QuickVue Advance for G. vaginalis
Proline amino peptidase (Pip Activity)
DNA probe for G. vaginalis (Affirm)
BV-Blue OSOM (detects vaginal fluid
sialidase from anaerobes)
• pH tests
? New Thoughts
STD
• 1975 round table discussion, Dr. Josey
stated “In my opinion, H.v. vaginitis is a
form of venereal disease.
• 2009 Editorial commentary Dr.
Schwebke…It is time to accept (again) that
BV is sexually transmitted
Complications with BV
• Preterm delivery
• Increased risk of pelvic inflammatory
disease (PID) and infertility
• Increased susceptibility to HIV
acquisition/transmission
2010 CDC Current Recommendations for
Bacterial Vaginosis
Recommended regimens
Metronidazole 500 mg orally twice a day for 7
days
OR
Metronidazole gel, 0.75%, one full applicator (5
g) intravaginally, once a day for 5 days
OR
Clindamycin cream, 2%, one full applicator (5 g)
intravaginally at bedtime for 7 days
2010 CDC Current Recommendations for
Bacterial Vaginosis Alternative Regimens
Tinidazole 2 g orally once daily for 2 days
OR
Tinidazole 1 g orally once daily for 5 days
OR
Clindamycin 300 mg orally twice daily for 7 days
OR
Clindamycin ovules 100 mg intravaginally once at
bedtime for 3 days
Metronidazole 750 mg ER
• The FDA has approved metronidazole
750 mg extended release tablets once
daily for 7 days
Bacterial Vaginosis
• 30% - 80% of patients have BV
recurrence within 3 months to 9
months
• No uniform definition (3 or more
confirmed attacks per year)
• Make sure diagnosis is correct
Recurrent Bacterial Vaginosis

Long term metronidazole

Considerable relapse after cessation
of suppressive therapy
 Metronidazole
gel 0.75% twice weekly
for 6 months after completion of a
recommended regimen
 Effective in maintaining a clinical cure
for 6 months
Resistant Bacterial Vaginosis
(cont.)
• Treat for longer periods (10 – 14 days) with same
agent
• Switch Agent
• ? Suppression
• ? Condom use
• Acidification of vagina has not been helpful
• Exogenous Lactobacillus recolonization using
suppositories and other alternative rx?
• Emergence of clindamycin-resistant anaerobic
gram-neg rods
Tinidazole vs. Metronidazole: Chemical Structure
Addition of an ethyl- sulfonyl group to the N-1 position on the
tinidazole molecule increases the ease of electron transfer
CH2 CH2 SO2 CH2 CH3
O2N
N
CH3
CH2 CH2 OH
O2N
N
N
N
Tinidazole
CH3
Metronidazole
Tinidazole Use in BV
• Numerous published studies demonstrating
efficacy
• Varying doses (overall trend lower dose)
– Tinidazole 500 mg po bid x 2 weeks for
resistant BV
– Single 2g dose of tinidazole more effective than
single 2g dose of metronidazole
– Tinidazole 2g/day x 2d more effective than
tinidazole single 2g dose
– Tinidazole 500mg BID x 5 days highly effective
New Treatment Thoughts
Hydrogen peroxide 3% vaginal irrigations
(30 ml qhs x 1 week per vagina)
Cardone A et al. Minerva Ginecol 2003;55:483-92
New Treatment Thoughts
Boric acid per vagina for
bacterial vaginosis
Reichman, Akins and Sobel used
600 mg per vagina x 21 days for
recurrent BV.
No randomized placebo controlled studies
Tea Tree Oil
Multiple methods. One is to use a 5-day course of pessaries,
each with 200mg Tea Tree oil in a vegetable Oil base.
New Treatment Thoughts
Decrease dietary fat intake
Neggers YH. et al. Dietary intake
of selected nutrients affects bacterial vaginosis
in women. Journal of Nutrition. 2007;137(9):2128-33
Hormonal contraception decreases the risk of BV
Rifkin SB et al. Hormonal contraception and risk of
bacterial vaginosis diagnosis in an observational study
of women attending STD clinics in Baltimore, MD.
Contraception. 2009;80:63-7.
Probiotics for Bacterial Vaginosis
AKA
To lactobacilli or not
lactobacilli…
that is the question
Lactobacillus
• Recent systematic review of 25 studies
found lactobacilli were beneficial for BV
but not for candida (Abad CL, Safdar N.
Journal of Chemotherapy
2009;21:243,252)
• Double-blind placebo-controlled trial found
intravaginal lactobacilli useful in treating
BV. (Mastromarino P, et al. Clinical
Microbiology & Infection 2009;15:67-74)
OBGYN Management
December 2010;22(12)50.
• Probiotic blend containing 8 billion colonyforming units of various lactobacilli po bid
- Dr. Firestone Aventura, Florida
- Ya W, Reifer C, Miller LE. Efficacy of
vaginal probiotic capsules for recurrent
bacterial vaginosis: a double-blind,
randomized, placebo-controlled study. Am
J Obstet Gynecol 2010;203:120-1.
Bacterial Vaginosis
Management of Sex Partners
Response to therapy and the
likelihood of relapse or recurrence are
not affected by treatment of her sex
partner(s). Therefore, routine
treatment of sex partners is not
recommended
2010 CDC STD Treatment Guidelines
Trichomonas
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170 million cases worldwide
 North America, more than 8 million new cases
annually
Anaerobic protozoan found only in lower
genitourinary tract of humans
Transmitted by sexual contact
High rate of infectivity
 80% of women with affected partner become
infected
Trichomoniasis Diagnostic Methods Women
Test
Sensitivity
Specificity
Cost
Ease of Use Time to Results
Wet Mount
60-70%
>90%
low
Culture
75-95%
>95%
medium
easy
long
In-Pouch™ culture
80-95%
>95%
low
easy
medium
Pap smear
50-98%
90-96%
low
easy
easy
PCR
88-97%
98-99%
high
difficult
OSOM® TV test
83%
>97%
low
easy
short
long
long
short (10 min)
2010 CDC Current
Recommendations
for Trichomoniasis
Recommended Regimens
Metronidazole 2 g orally in a single dose
OR
Tinidazole 2 g orally in a single dose
Alternative Regimen
Metronidazole 500 mg orally twice a day for 7
days
Trichomoniasis
95% cure
Metronidazole = CH6H9N303
We will be discussing the 5% of the
population that fails the usual
treatment
Trichomoniasis Treatment Failure
• If treatment failure occurs with
metronidazole 2 g single dose and
reinfection is excluded, the patient can
be treated with metronidazole 500 mg
orally twice daily for 7 days
• For patients failing this regimen,
treatment with tinidazole or
metronidazole at 2 g orally for 5 days
should be considered
2010 CDC STD Treatment Guidelines
Trichomoniasis Treatment Failure
• If these therapies are not effective,
further management should be
discussed with a specialist
• The consultation should ideally include
determination of the susceptibility of T.
vaginalis to metronidazole and
tinidazole. Consultation and T. vaginalis
susceptibility testing is available from
CDC (telephone: 404-718-4141;
website: http://www.cdc.gov/std
2010 CDC STD Treatment Guidelines
Trichomoniasis
Treatment Failure
Other Suggestions
• Once reinfection excluded, retreat with
metronidazole 1.0 gm po bid x 14 days or
• Tinidazole 1.0 gm po bid x 14 days or
• Retreat with tinidazole orally (28 g) as
above plus tinidazole vaginally 500 mg per
vagina bid (7-14 grams)
Trichomoniasis
? Allergic to Metronidazole
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Betadine intravaginally
Paromomycin
Intravaginal clotrimazole
DESENSITIZATION
Trichomoniasis
Management of Sex Partners
• Sex partners of patients with T. vaginalis should
be treated
• Patients should be instructed to avoid sex until
they and their sex partners are cured (i.e., when
therapy has been completed and patient and
partner(s) are asymptomatic)
2010 CDC STD Treatment Guidelines
Vulvovaginal Candidiasis (VVC)
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13 million cases annually in the United
States
75% of all women will have at least 1
episode of VVC (40-45% of these will have
at least 2 or more episodes in lifetime)
10-20% of women with VVC will have
complicated VVC
Sensitivity of Microscopy vs. Culture
• Bacterial vaginosis 92%
(Amsel’s)
• Trichomonas
60-70%
• Yeast
22 -50%
Recurrent VVC
• Four or more symptomatic
episodes/year
• Vaginal culture should be obtained to
confirm diagnosis and identify
species
2010 CDC STD Treatment Guidelines
Recurrent VVC
• To maintain clinical and mycologic
control, a longer duration of initial
therapy (e.g., 7–14 days of topical
therapy or a 100-mg, 150-mg, or 200mg oral dose of fluconazole every
third day for a total of 3 doses [day 1,
4, and 7 ]) then 100-mg, 150-mg, or
200-mg dose weekly for 6 months
2010 CDC STD Treatment Guidelines
Recurrent Vulvovaginal
Candidiasis
• If this regimen is not feasible, some
specialists recommend topical clotrimazole
200 mg twice a week, clotrimazole (500mg dose vaginal suppositories once
weekly), or other topical treatments used
intermittently
Recurrent Vulvovaginal
Candidiasis
2010
• Suppressive maintenance antifungal
therapies are effective in reducing RVVC
• 30%–50% of women will have recurrent
disease after maintenance therapy is
discontinued
Fluconazole
Adverse Effects
 Nausea and vomiting in 3-4% (long term
therapy)
 Liver effects
 Chronic therapy
 AIDS patients
Resistance on the rise
Fluconazole Resistance
• C. glabrata
• C. krusei
• Rare cases of fluconazole resistance in C. albicans
Torulopsis (Candida) glabrata
on Cornmeal-Tween 80 agar:
Small, compacted blastoconidia
with no pseudohyphae formed
Candida albicans KOH
Microbiology of
Vulvovaginal Candidiasis 429 pts
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C. albicans
70.8 %
C. glabrata
18.9 %
C. parapsilosis
5.0 %
C. krusei
2.0 %
S. cerevisiae
1.5 %
C. tropicalis
1.4 %
C. lusitaniae
0.2 %
Trichosporon sp. 0.2 %
Richter SS, et al. J Clin Micro 2005;43:2155-62
Antifungal Susceptibilities of Candida
Species Causing Vulvovaginitis
and Epidemiology of Recurrent Cases
Sandra S. Richter, Rudolph P. Galask, Shawn A.
Messer, Richard J. Hollis, Daniel J. Diekema, and
Michael A. Pfaller
Department of Pathology and Department of Obstetrics
and Gynecology University of Iowa Carver College of
Medicine, Iowa City, Iowa
Journal of Clinical Microbiology. 43(5):2155-62, 2005 May.
Recurrent yeast before
treatment
Other Antifungals
Boric Acid
OH
B
HO
OH
• Puratronic, 99.99995%
(metals basic)
• Formula
H3BO3
• Formula Weight
61.83
• Form
Crystalline Powder
• Melting Point
170.90
• Merck Number
11,1336
Boric Acid
• Fill 0-gel capsule halfway (600 mg)
– For treatment of acute infection; insert per
vagina qhs x 14 days
– For prevention of recurrence; insert per
vagina twice weekly
KEEP AWAY FROM CHILDREN
Butoconazole Nitrate 2%
Bioadhesive and sustained release
properties
Single dose
Efficacy rate equivalent to lengthier
treatments
5-Flucytosine
• Pyrimidine developed for cancer
therapy
• 500 mg / 5 grams compounded in
hydrophilic cream base
• Insert 5 gram per vagina qhs x 14
days
Nystatin
Can also be used for recurrent disease prevention
100,000 U per day per vagina for 3-6 months
Nystatin
Rachel Fuller Brown and Elizabeth Lee Hazen
developed the drug in the 1950s
Gentian Violet
• Gentian Violet
– 0.25 – 1% aqueous
solution of aniline dye
– Paint on mucous
membrane weekly
– Use 1% in office only
– May cause ulceration
– Safe in pregnancy
Saccharomyces cerevisiae
Erythematous / Irritated Vulva
• Rx with combination
topical antifungal and
steroid
(nystatin/triamcinolone
acetonide ointment)
Other treatments
• Amphotericin B vaginal suppositories
• Flucytosine
Alternative Treatments
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Lactobacillus
Garlic tampons
Teatree oil
Echinacea/Goldenseal
Yeast-gard Suppositories 15
– Pulsatilla (Homeopathically
prepared To 28X)
– Candida Parapsilosis
(Homeopathically prepared to
28X)
– Candida Albicans
(Homeopathically prepared to
28X)
Albaconazole
• New antifungal that will soon be tested in
the United States
• Triazole derivative with potent and broadspectrum antifungal activity and a
remarkably long half-life in dogs, monkeys,
and humans
Vulvovaginal Candidiasis
in Pregnancy
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VVC frequently occurs during pregnancy
Only topical azole therapies, applied for 7
days, are recommended for use among
pregnant women
Antibiotics and Yeast

Fluconazole 150 mg po at start of
antibiotics and once weekly throughout the
duration of antibiotics
Vulvovaginal Candidasis
Management of Sex Partners
VVC is not usually acquired through
sexual intercourse; no data support the
treatment of sex partners. A minority of
male sex partners might have balanitis,
which is characterized by erythematous
areas on the glans of the penis in
conjunction with pruritus or irritation.
These men benefit from treatment with
topical antifungal agents to relieve
symptoms.
2010 CDC STD Treatment Guidelines
? Glucose Tolerance Test
• In patients not known to have diabetes, it
is not necessary to perform a GTT in premenopausal, healthy females
• In post-menopausal females with RVVC, a
GTT should be obtained
Sobel JD. Management of Patients with recurrent
vulvovaginal candidiasis. Drugs 2003;63:1059-66