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Updates and Controversies in
the Management of Common
Vulvovaginal Infections
January 13, 2009
Eaton Hotel
Hongkong
Ditas D. Decena, MD, FPOGS, MPH
PHYSIOLOGICAL and THERAPEUTIC
APROACH TO VAGINAL INFECTIONS
UPDATES AND CONTROVERSIES
Ditas D. Decena, MD, FPOGS, MPH
• Professor in the Royal and Pontifical University,Faculty of Medicine & Surgery,
University of Santo Tomas, Manila Philippines
• Masters in Public Health, University of the Philippines
• Trained in Endoscopic Surgery in India and Maternal Nutrition at the University of
California, Davis
• Member, Committee on Residency Training Program, University of Santo Tomas
Hospital Inc. Department of Obstetrics and Gynecology
• Author of the study “Metronidazole with Lactacyd vaginal gel in Bacterial Vaginosis”
published in the Journal of Obstetrics and Gyecology Research 2006
Points of Discussion


Determinants of infectious disease
Common vaginal infections




Bacterial vaginosis
Trichomoniasis
Candidiasis
Treatment modalities


Specific pharmacotherapy
Lactic acid, lactoserum wash, douche and gel
Infectious Disease

Result of interactions of microorganisms
with host
Disease =
(number of organism X virulence of organism )
host defenses
Smith
Determinants of Infectious
Disease
1.
Host’s defenses
2.
Properties of microorganisms
1. Categories of Host Defenses
Anatomical barriers
 Nonspecific cellular and humoral
defenses
 Immunologically specific cellular and
humoral defenses
 Local immunity

Larsen B. Microbiology 2nd ed CREOG 1998
Anatomical Barriers
Performed by intact tissues (skin and
mucosa)
 Normal vaginal flora
 Endocervical mucus (biochemical
impediment)

Larsen B. Microbiology 2nd ed CREOG 1998
Skin Barrier Homeostasis
Acid mantle (ph 4.5 – 5.9)
Lactic acid and amino acid (sweat)
 Free fatty acids (sebum)
 Carboxylic and urocranic acid

Rippke F. et al. Stratum Corneum pH in Atopic Dermatitis. Am
J. Clin Dermatol 2004; 5 (4): 217-223
Skin pH (4.5 – 5.9)
Varies in different body areas
 Depends on skin moisture content
(higher moisture; higher pH)
 Changes in pH → “contact & atopic
dermatitis”

Rippke F. et al. Stratum Corneum pH in Atopic Dermatitis. Am
J. Clin Dermatol 2004; 5 (4): 217-223
Vulvar Skin

Stratified squamous epithelium
Contains hair follicles, sebaceous, sweat
and apocrine glands
 Has a high moisture content

Subject to both primary and
secondary infections
 Sensitive to hormonal, metabolic and
allergic influences

Vaginal Ecosystem
estrogen
glycogen
Promotes growth of
lactobacilli, inhibits
growth of pathogenic
bacteria
lactobacilli
lactic acid
pH 3.8 – 4.5
Endogenous vaginal flora of
asymptomatic healthy women
 Lactobacillus sp.
 Klebsiella pneumoniae
 Corynebacterium
 Proteus vulgaris
 Diphtheroids
 Prevotella bivia
 Streptococcus sp.
 P. melaninogenica
 Staphylococcus
epidermidis
 Bacteroides fragilis
 Enterococcus faecalis
 Escherichia coli
 Fusobacterium nucleatum
 Fusobacterium
necrophorum
Hillier SL. Normal vaginal flora. In: Holmes KK et al., eds. Sexually Transmitted Diseases.
1999:191-204.
HEALTHY VAGINAL ECOSYSTEM
Dominated by certain species of Lactobacillus that
control and suppress the growth of other
endogenous bacteria through different
mechanisms:
- Lactic acid
- Hydrogen peroxide (H2O2)
- Bacteriocins
2. Properties of Microorganisms

Virulence





Adhesiveness
Invasiveness
Adaptation
Proliferation
 Growth inhibited at acid pH of 5
 Maximal growth at neutral pH
Optimum pH (3.8 – 4.5) growth of
Lactobacilli
Staphylococcus
Larsen B. Microbiology 2nd ed CREOG 1998
Rippke F. et al. Stratum Corneum pH in Atopic Dermatitis. Am J. Clin Dermatol
2004; 5 (4): 217-223
LACTOBACILLUS
Lactic Acid
As lactobacilli grow, the production of lactic
acid increases (~2.5 mg/mL)
The production of lactic acid maintains the vaginal pH < 4.5
(creating an inhospitable environment for the growth of
most endogenous pathogenic bacteria)
Low pH is a primary mechanism for maintaining the
equilibrium of a healthy vaginal ecosystem: as the pH of the
vagina increases, bacteriocin loses its effectiveness, hydrogen
peroxide is degraded, and lactobacilli cannot compete with the
other bacteria
Vulvar vs. Vaginal Infection

Anatomic distribution of symptoms
occasionally creates a semantic
misinterpretation of the clinical reality
First symptom: vulvar pruritus
First sign: erythema and edema of
vulvar skin
Semantic Compromise
Excessive vaginal fluid is not
appreciated until fluid flows from
vagina to vulva
Vaginal infections
Vulvovaginitis
Common Vaginal Infections
Candidiasis
Trichomoniasis
BV
Predominant symptom
pruritus
Profuse
discharge
Foul odor
Characteristic discharge
Curd like
Frothy
Thin grayish
white
4
5
6
Gram stain
Pseudo hyphae
(-)
Gram (-) rods
NSS mount
Pseudo hyphae
Flagellated
protozoa
Clue cells
10% KOH
Hyphae on
microscopy
(-)
+ amine odor
pH
Trichomonas Vaginalis
Bubbly discharge
Pap’s smear showing
resemblance of WBCs to
nonmotile parasites
Vulvovaginal Candidiasis
Bacterial Vaginosis
Characteristic milky
vaginal discharge of BV
Clue cells consistent with BV
Therapeutic Approach to Vaginal
Infections
Standard Treatment of BV



Metronidazole 500 mg twice daily for 7 days
Metronidazole gel 0.75%, 5 g intravaginally once daily
for 5 days
Clindamycin cream 5%, 5 g intravaginally hs for 7 days
Alternative Regimen
Clindamycin 300 mg twice daily for 7 days
 Clindamycin ovules 100 g intravaginally hs for 3 days
Candidiasis Treatment
Uncomplicated

Oral: Fluconazole 150 mg p. o. single dose
Intravaginal


Butoconazole 2% cream 5g intravaginal X 3 days
Butoconazole 2% cream 5g (sustained release)
single intravaginal application
CDC 2006
Candidiasis Treatment
Intravaginal






Clotrimazole 1% cream 5 g intravaginal X 7 – 14 days
Clotrimazole 100 mg tablet X 7 days
Clotrimazole 100 mg tablet – 2 tablets X 3 days
Clotrimazole 500 mg vaginal tablet – 1 tablet in a single
application
Miconazole 2% cream 5 g intravaginal X 7 days
Miconazole 100 mg vaginal suppository X 7 days
CDC 2006
Candidiasis Treatment




Miconazole 200 mg vaginal suppository – 1
supp. X 3 days
Nystatin 100,000 units vaginal tablet – 1 tablet X
14 days
Terconazole 0.4% cream 5 g intavaginal X 7
days
Terconazole 80 mg vaginal suppository X 3 days
CDC 2006
Trichomonas Treatment


Metronidazole 2g p o single dose
Tinidazole 2g p o single dose
Alternative
 Metronidazole 500mg BID X 7 days
CDC 2006
Physiological Approaches to
Infections
 Feminine
wash
 Douche
 Vaginal
gel
Why prescribe feminine wash?
1.
Hygiene
2.
Relieve vulvar irritation
3.
4.
Postpartum care: cleaning
episiotomy wound
Prevention and /or treatment of
vulvovaginitis
Acidic Wash vs. Soap
Cross-over
Cross-over
10.00
5.50
9.75
5.25
9.50
9.25
5.00
9.00
8.75
pH
Propionibacteria/cm2 (log)
10.25
8.50
4.75
8.25
4.50
8.00
7.75
4.25
7.50
7.25
4.00
123
10
17
24
31
38
45
52
59
1 23
10
17
Days
24
31
38
45
52
59
Days
Soap
Acid wash
Evolution of the propiobacterium counts per square centimeters (1), and of the mean pH value
(2) on the subjects foreheads during repeat applications of alkaline soap and acidic syndet in
the frame of a comparative crossover trial - = soap first 4 weeks, then syndet for 4 weeks - =
syndet first 4 weeks, the soap 4 for weeks.
Koring et al.1995
Lactic acid for external hygiene



Provides relief of itching and reduces
inflammation
Reacidifies the environment alkalinized by
pathogens
Fights infections
Lactoserum and Lactic Acid on External
Genitalia in Thai Women
Number and percentage of women on rating the product according to the evaluation criteria
Number and percentage of
satisfaction
Evaluation criteria
Total
number
Fragrance
free (%)
N = 100
Sweet
flora (%)
N = 100
Spring
fresh (%)
N = 100
Pvalue
99 (99)
99 (99)
1.000
1.
Ease of use
300
100 (100)
2.
Ability to refresh
300
99 (99)
3.
Scent
300
93 (93)
4.
Cleansing ability
300
98 (98)
5.
Overall assessment
300
100 (100) 100 (100)
97 (97)
96 (96)
1.000
0.482
100 (100) 100 (100)
0.331
100 (100) 100 (100) 100 (100)
1.000
High percentage of satisfaction and tolerability 2005
Tansupasiri et. Al.
2005
Assessment of the effectiveness and
tolerability of Lactacyd FH when
used as adjunctive external vaginal
wash to standard treatment of
Bacterial vaginosis
Nguyen Thi Ngoc Phuong et al.
Vietnam Gyne-OB Association Journal, 2005
The improvement of functional
symptoms
Experience of malodor relief
77.1 *
65
82.1 *
84.2
88
*
*
71
69.8
59.7
28.9
*
63.5
40.2
N=96
8
n=103
18.6
4.8
D1
(*) p< 0.05
D2
D3
D4
Lactacyd FH use (n=96)
D5
D6
D7
Non-Lactacyd FH use (n=103)
Nguyen Thi Ngoc Phuong et al. Vietnam OB Gyne Association 2005
The improvement of functional
symptoms
Experience of pruritus relief
*
90.3
91.7
98.6 *
98.6 *
98.6 *
89.7
89.7
91.2
D4
D5
D6
100 *
88.2
89.7
66.7
75.0
57.4
D1
D2
(*) p < 0.05
D3
Lactacyd FH use (n=96)
Nguyen Thi Ngoc Phuong et al. Vietnam OB Gyne Association 2005
D7
Non-Lactacyd FH use (n=103)
Conclusion

Adding Lactacyd FH as external vaginal
wash to standard regimen
(Metronidazole) in Bacterial vaginosis is
useful in relieving symptoms.
Nguyen Thi Ngoc Phuong et al. Vietnam OB Gyne Association 2005
Types of Douching Solution
Plain water
 Water with acetic acid (acidic solution)
 Betel
 Povidone iodine
 Lactic acid; lactoserum

Meta-analysis of studies on vaginal douching and risk of
pelvic inflammatory disease
Wolner-Hanssen Internal
Control

Recent Douching



Random
Control

1-2 times/month
1-2 times/month

≥ 3 times/month
Scholes
Recent Douching

 3 times/month


≥ 4 times/month

Recent Douching
Pooled RR
0.2
0.4
0.6
1.0
2
ODDS RATIO
3
4
5 6
7
8 9
Zhang et. Al
1997
Possible factors for douching
and PID



Pressure douching
Timing of douching during menstrual
cycle
Frequency
Zhang, Thomas 1997
Meta-analysis of studies on vaginal douching and risk of
ectopic pregnancy

Chow
Occasional
Weekly
Overall
Daling
Once every few months


1/month

Weekly
Chow




Ever douched
Current douching
Zhang et. Al
1997

Phillips Current douching

Kendrick Current douching

> 10 years

Pooled RR Current douching
0.2
0.4
0.6
1.0
2
ODDS RATIO
3
4
5 6
7
8 9
Metronidazole
with Lactacyd
Vaginal gel in
BV
Open-labeled,
randomized, 3-arm
comparative study
Effect of Treatment on Lactobacilli Colony Count*
*Repeated Measures ANOVA: p<0.001 across visits; p=0.0045 at day 8 between lactic acid gel group and metronidazole
group; p=0.0002 at day 14 between combination arm and metronidazole arm and between LVG arm and metronidazole arm.
Decena, Sison, Manalastas, Padolina, Palaypayon, Co, Dancel, Lelis,
J.Obstet.Gynaecol.Res Vol 32, No. 2:243-251, April, 2006
Effect of Treatment on Vaginal pH*
Figure 2: Frequency of patients with Vaginal pH <4.7 across time
% of patients with pH < 4.7 .
80
60
Lactacyd vaginal gel
metronidazole
40
metronidazole +
Lactacyd vaginal gel
20
0
Baseline
Day 3
Day 8
Day 14
*Cochran’s Q test: p <0.001 across visits; 2 test: p>0.05 across treatment groups
Decena, Sison, Manalastas, Padolina, Palaypayon, Co, Dancel, Lelis,
J.Obstet.Gynaecol.Res Vol 32, No. 2:243-251, April, 2006
Recurrence of Foul-Smelling Vaginal
Discharge at Day 56
Frequency of Recurrent* Foul-smelling Vaginal Discharge
No. of Patients
5
4/28
(14.3%)
4
3
2
Decena et. Al
2005
2/30
(6.7%)
1/28
(3.6%)
1
0
Lactacyd vaginal gel
metronidazole
metronidazole+Lactacyd
vaginal gel
*Fisher’s exact test: p=0.4965 across treatment groups.
Study Conclusion



Lactacyd vaginal gel (LVG) is safe and as efficacious
as metronidazole in the treatment of bacterial
vaginosis.
There is evidence that Lactacyd vaginal gel (LVG),
when combined with metronidazole, is superior to
metronidazole alone in promoting lactobacilli
colonization
Lactacyd vaginal gel (LVG) as an adjunct to
metronidazole appears to result to a better longterm treatment effect on BV.
Lactic acid for internal hygiene


Adjunct treatment in bacterial
vaginosis
Promotes the growth of Lactobacilli
Physiological Therapeutic Approaches
in Vaginal Infections
Summary
 Anatomical barriers as the acid mantle in the skin
and normal vaginal flora are important host’s
defenses
 Lactic acid wash in combination with standard
regimen is effective in relieving symptoms of
Bacterial vaginosis
 Lactic acid vaginal gel (LVG) is safe and as
efficacious as metronidazole in the treatment of
bacterial vaginosis.
 Specific pharmacotherapy for vaginal infections is
still the mainstay of treatment
Take home messages
The vaginal microflora does not consist of a static
population but, rather, a dynamic one (types and
concentrations continuously fluctuate in accordance
with the changing environment).
Lactic acid wash and gel has been shown to be
tolerated and efficacious in prevention and treatment
of vulvovaginal infections.
Thank you!