Noninvasive oral and vaginal candidiasis

Question 1

Vaginal Physiology: What is normal?

Answer 1

● Healthy vagina is host to a number of microorganisms
○ live in balance without adverse effects
● Harmony disrupted:
○ overproduction of host organisms or colonization can occur
● Some vaginal discharge is normal
○ most prominent mid-cycle around time of ovulation
● Normal discharge is scant, odorless and clear or whitish in colour
● Vaginal pH normally 3.5-5.5

Question 2

Common causes of vaginal infections characterized by
discharge & vulvovaginitis

Answer 2

1. Bacterial vaginosis (BV)
2. Trichomoniasis
3. Vulvovaginal candidiasis (VVC) * “Yeast Infection”

Question 3

Differential Diagnosis

Answer 3

q

Question 4

VVC - Vulvovaginal Candidiasis

Answer 4

● Usually caused by overgrowth of Candida albicans (80 – 92%), but other
species may be responsible
● Approximately 75% of persons with vaginas will experience at least one
episode of VVC during their lifetime
● Other species are more resistant to imidazole antifungals
● Not usually considered sexually transmitted, although sexual factors can be
important. There is a dramatic increase in the frequency of VVC once one becomes sexually active. In addition, oral-genital contact can increase the risk

Question 5

Classification of VVC

Answer 5

Uncomplicated VVC (all of the following):
● sporadic or infrequent
● mild-to-moderate symptoms or findings
● Candida albicans infection (suspected or proven)
● non-immunocompromised
Complicated VVC (any of the following):
● recurrent (4 or more episodes/12 months)
● severe symptoms or findings
● non-albicans Candida
● Those with diabetes, immunocompromising conditions, or immunosuppressive therapy

Question 6

Predisposing Factors for VVC

Answer 6

● Pregnancy
● Medications (antibiotics, corticosteroids, chemotherapy, hormone therapy,
oral contraceptives, levonorgestrel intrauterine systems, tamoxifen),
contraceptive agents (spermicide, sponge, diaphragm)
● Diabetes mellitus
● Immunocompromised conditions
● Diet (excess refined carbohydrates)
● Chemical irritants (antiseptics, deodorants, sprays, soaps), douching
● Stress
● Menses
● Synthetic undergarments
● Tight-fitting clothing

Question 7

Which patients may need referral for further evaluation?

Answer 7

● Pregnant individuals
● Prepubertal (VVC not common)
● Presents with vaginal symptoms for 1st time
● Recurrence of VVC within 2 months of last episode
● Immunosuppressed
● Underlying illness such as diabetes
● Risk of STI (e.g., history of unprotected intercourse, multiple
partners, casual sexual encounters

Question 8

CPS Algorithm

Answer 8

q

Question 9

Goals of Treatment VVC

Answer 9

● Relieve symptoms
● Cure the infection
● Prevent recurrence
● Prevent misdiagnosis and delayed treatment

Question 10

Non Pharmacological Measures

Answer 10

● Although there is no specific nonpharmacologic therapy for
vulvovaginal candidiasis, preventive measures are suggested for
those wishing to avoid recurrences.
● Good hygiene
● Avoid vaginal deodorants, douches, harsh soaps and perfumed
products
● Avoid tight clothing and synthetic underwear
● ?Dietary modifications (ie. yogurt with lactobacillus - inconsistent
results in studies, yeast or sugar free diets - no data)

Question 11

Uncomplicated VVC Treatment

Answer 11

May be safely and effectively treated with non-prescription
antifungal agents
80-95% cure rate in healthy individuals with topical or oral azoles
Asymptomatic treatment is unnecessary
Selection based on patient preferences/experiences

Question 12

TOPICAL VS ORAL TREATMENT????

Answer 12

● No statistical difference for clinical cure rate shown between oral and
intra-vaginal antifungal treatment
● Some patients may prefer oral therapy because of its convenience

Difference amongst topical agents?
● There are no significant differences in in vitro activity or clinical efficacy among
the topical azole agents
● The selection of a topical azole antimycotic agent should be based primarily on an
the individual’s preference as to product formulation.
○ Consider: cost, convenience, adherence, portability and history of response
or side effects to prior treatments

Question 13

Treatment Overview

Answer 13

● Self-treatment recommended for patients who have been previously
diagnosed with a yeast infection
● 2 imidazoles are available as non-prescription treatment in Canada
○ Clotrimazole
○ Miconazole
● Topical prescription product
○ Terconazole (0.4% vaginal cream)
● Non-prescription oral option: Fluconazole (Diflucan One, CanesOral,
generics)

Question 14

Treatment: Topical and Intravaginal

Answer 14

clotrimazole
miconazole

Question 15

Adverse Effects: Topical

Answer 15

Common = burning, redness, irritation, stinging and itching
Switching brands may alleviate this side effect
Note: Terconazole - Health Canada safety warning: Anaphylaxis and
toxic epidermal necrolysis (TEN) have been reported during
terconazole therapy. Therapy should be discontinued if anaphylaxis
or TEN develops

Question 16

Topical Azoles

Answer 16

Interactions:
● Possible interaction of miconazole with warfarin
○ May increase INR (monitor for bleeding or switch to
clotrimazole)
● Topical Imidazoles may diminish effects of vaginal progesterone -
avoid concomitant use
● Ovules diminish effectiveness of condoms & diaphragms

Question 17

Information for the Patient: Topical

Answer 17

● Must be used for the specified number of days, consecutively
● Should recommend using during any part of the menstrual
cycle, even during menstruation
● Should not use tampons with topical treatment
○ Potentially absorbs medication
○ Provides a hospitable environmental medium for fungus to grow on
● Applicator for intravaginal creams/tabs/ovules
● If vulvar symptoms significant – topical can be used externally
to vulva and/or perineum
● Applied at bedtime to increase contact time with vaginal
tissues

Question 18

Treatment Oral

Answer 18

fluconazole

Question 19

Fluconazole in pregnancy

SOGC Statement on the Use of Fluconazole during
Pregnancy (2018)
A recent CMAJ publication by Bérard et al.1 has again
highlighted that clinicians must exert caution and carefully
consider alternative antifungal preparations prior to
prescribing or recommending Fluconazole during pregnancy. q

Answer 19

Recent analysis of Quebec pregnancy cohort (1998-2015) compared women*
exposed to low dose (≤ 150 mg) and high dose ≥ 150mg fluconazole (Berard et al.
CMAJ 2019;191:E179-87)
Use of fluconazole associated with increased risk of spontaneous abortion compared with no
exposure (OR 2.23, 95% CI 1.96-2.54)
Exposure to high dose fluconazole during first trimester associated with increase risk of cardiac septal
closure anomalies (OR 1.81; 95% CI 1.04-3.14)
Systematic review (Zhang et al. BJOG 2019;126:1546-52)
Oral fluconazole use during first trimester marginally increased risk of congenital malformations (OR
1.09;95% CI 0.99-1.2; p=0.088); high-dose users OR 1.19; 95% CI 1.01-1.4; p=0.039)
Significantly increased risk of spontaneous abortion (OR 1.99; 95% CI 1.38-2.88; p< 0.001)

Question 20

Severe - may require further assessment

Answer 20

Extensive vulvar erythema, edema, excoriation of fissure
formation
Fluconazole 150mg PO q72hr x 2 doses
Intravaginal azole (same as uncomplicated) x 10-14 days

Question 21

Time to symptomatic relief and follow up

Answer 21

If no relief after 1 week, REFER
Increased irritation or symptoms (may indicate adverse reaction
to product or inappropriate therapy), REFER

Question 22

Complications VVC - Recurrent

Answer 22

● For patients prone to recurrent VVC who require antibiotics,
prophylactic topical or oral azoles, such as fluconazole 150mg po can
be initiated
● Non-albicans Candida species are found in 10-20% of patients
○ Conventional antifungal therapy is not as effective

Question 23

Recurrent VVC - Induction Treatment

Answer 23

Fluconazole or intravaginal azole + boric acid
● Fluconazole 150 mg po once every 72 hours x 3 doses
○ Efficacy 92%
○ Should be avoided in pregnancy where possible
OR
● Topic azole x 10-14 days
○ Ex - clotrimazole × 7–14 days to achieve mycologic remission

Boric acid 300-600 mg gelatin capsule intravaginally once daily
for 14 days.
● Contraindicated in pregnancy
● Efficacy 80%
● Local irritation, vaginal burning; more pronounced with
higher dose.
Compounded product - boric acid in gelatin capsule

Question 24

Recurrent VVC - Maintenance Treatment

Answer 24

● Fluconazole 150 mg po once weekly. Recurrence occurred in 10%
while receiving therapy.
● Clotrimazole 500 mg intravaginally once a month.
● Boric acid 300 mg capsule intravaginally for 5 days each month; start
1st day of cycle. Recurrence 30%
Maintenance therapy duration: minimum 6 months

Question 25

Transmission to Partners

Answer 25

Sexual partners unlikely to acquire the yeast infection (more frequently
in uncircumcised individuals)
● Balanitis, characterized by erythematous areas on the glans of the
penis in conjunction with pruritus or irritation
● Usually does not require treatment
○ Topical azole if treatment required (1-2x/daily x 7 Days) or oral
fluconazole 150 mg PO single dose
Consider treatment of partners in patients with recurrent infections

Question 26

Probiotics

Answer 26

● Overall quality of evidence is low or very low
● Systematic review found compared with conventional antifungal
drugs used alone, probiotics as adjuvant therapy could enhance
their effect of short term clinical cure and relapse
● Does not seem to influence rate of long-term clinical cure
● If the patient wishes to use such a bacterial replacement while
taking antibiotics, it will not interfere with therapy but the
combination will likely not reduce the occurrence of vulvovaginal
candidiasis

Question 27

Oral candidiasis
Pathophysiology

Answer 27

● 25-75% of healthy immunocompetent adults carry Candida as
part of their normal oral flora
● When normal flora compromised, Candida overgrowth may
occur
● Oral candidiasis – mucocutaneous opportunistic infection
caused by Candida species
● Most common fungal infection in both immunocompetent and
immunocompromised individuals

Question 28

Sciences Risk Factors

Answer 28

disease states

medications

other

Question 29

Goals of Therapy

Answer 29

● Resolve infection or reduce acute candida overgrowth to a level
that can be controlled by the host’s defences and thereby prevent
complications (e.g., progression to esophageal candidiasis)
● Prevent recurrences by managing any underlying risk factors
(e.g., use of inhaled corticosteroids, poor dental hygiene,
uncontrolled diabetes mellitus) and instituting antifungal
prophylaxis if warranted (e.g., in high-risk patients - HIV/AIDS or
advanced cancer)

Question 30

Clinical Presentation

Answer 30

● Classic presentation – white plaque on tongue,
buccal mucosa, hard palate, soft palate and
oropharynx
● Typically asymptomatic
● Symptomatic patients may have burning sensation
or changes in taste
● Classic marker – easy to wipe off plaques leaving
behind erythematous surface

Question 31

Pharmacological Treatment

Answer 31

Topical nystatin oral suspension
○ Adults: 400 000-600 000 (~4-6 mL of 100,000 unit suspension) units 4 times daily
(swish and swallow) x 7-14 days
○ Infant thrush: 100 000 units (1mL) in each side of mouth QID x 7–14 days
■ In breastfeeding infant, consider topical treatment of nipple (clotrimazole,
nystatin, miconazole - but lacks safety data. Refer for assessment of latching
and possible dual therapy.
○ Used commonly for initial episodes and mild cases
○ Well tolerated, no clinically significant interactions (minimal absorption from GI tract)

● Fluconazole 100-200 mg PO daily x 7-14 days
○ 2nd line due to azole-resistant Candida strains
○ For moderate to severe disease
○ Preventive therapy for recurrent infections.
■ 100mg 3x/wk PO * HIV-infected patients
■ 100mg daily or 3x/weekly PO (Drug of choice)

Question 32

Counselling Points for Nystatin Suspension

Answer 32

● Shake the bottle well before you measure each dose.
● Swish nystatin around your mouth and then swallow the
liquid. Retain in mouth for as long as possible (ie. several
minutes if possible)
● Do not eat or drink anything for 5-10+ minutes after each
dose.
● Try to brush your teeth 20 to 30 minutes after taking
nystatin, as it contains sugar. Brush your teeth at least
twice a day, especially before going to bed.
● Avoid concomitant topical use with chlorhexidine (ex
denture wearers) as will negate effect

Question 33

Monitoring and Follow-up

Answer 33

● Improvement in signs and symptoms within 48-72 hours
● Monitor patients at risk of recurrence (e.g., antibiotic use, etc)
● Once antifungal treatment is initiated, advise the patient to
monitor symptoms on a daily basis during treatment and for
up to 2 weeks after clearing of symptoms to ensure the
infection has completely resolved.