This document provides an overview of oropharyngeal candidiasis including its etiology, epidemiology, clinical manifestations, diagnosis, and treatment. Key points include: Candida albicans is the most common cause, infecting 45-65% of children and 52% of adults. Risk factors include diabetes, immunosuppression, antibiotics, and xerostomia. Clinical presentations include pseudomembranous, erythematous, and hyperplastic lesions. Diagnosis involves microscopy, culture, and histology. Treatment involves topical or systemic antifungals like nystatin, fluconazole, or echinocandins depending on severity. Prevention emphasizes managing predisposing factors and good oral

1. Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the
Infectious Diseases Society of America
Peter G. Pappas,1 Carol A. Kauffman,
Clinical Infectious Diseases 2009; 48:503–35
Oropharyngeal Candidiasis: Etiology, Epidemiology, Clinical Manifestations, Diagnosis,
and Treatment
Crest Oral-B at dentalcare.com Continuing Education Course, February 3, 2011

2.  Synonyms- candidosis, moniliasis, thrush
 Kolnick (1980) stated that it is a dimorphic yeastlike fungus candida
albicans commonly occuring in oral cavity.
 Bredicevsky et al (1984) reported from a study of 140 healthy children
that 45% of 3- 5.5 yrs age and 65% of 6- 12 yrs of age were candida
carriers.
 In earlier study 52% of normal adults were carriers.
 This review provides a comprehensive overview of the etiology, clinical
presentations, diagnosis, and management strategies of oral candidosis
commonly encountered in dental practice.
Wood & Goaz 3rd Edi

3. More than 95% of Candida‐associated infections are
caused by five major species: C. albicans, Candida
glabrata, Candida parapsilosis, Candida tropicalis etc
 Candida parapsilosis occurs with high frequency in
premature neonates and in patients with vascular
catheters.
 Candida glabrata infections are common in the elderly.
 Candida tropicalis plays an important role as a cause of
invasive diseases in patients with haematological
malignancy.
Marr K, Seidel K, White T, Bowden R. Candidemia in allogeneic blood and marrow transplant recipients:
evolution of risk factors after the adoption of prophylactic fluconazole. J Inf Dis2000;181:309–16.

4. some changes must takes place in the local environment to produce conditions
favourable to its relative overgrowth and tissue invasion. Following changes have
been identified-
 A proportional change in compititive flora will predispose a person to candidiasis.
 A drastic reduction in the resistence of the tissues also favors the infection.
 In recent years, the number of immunocompromised individuals increased due
to various factors including increasing incidence like Diabetes, Prolonged average
life expectancies, Broadspectrum antibiotics, Immuno suppressive agents,
Invasive surgical procedures such as solid organ or bone marrow transplantation,
HIV infection etc
B.G. Tarcın, Oral Candidosis: Aetiology, Clinical Manifestations,
Diagnosis and Management, J Mar Uni I of H Sci Vol: 1,2, 2011;141-150

5. SYSTEMIC FACTORS LOCAL FACTORS
Physiological factors
Infancy, old age
Endocrine disorders
Diabetes mellitus, hypothyroidism
Nutritional factors
Iron, folic acid,
vitamin B12 deficiency
Blood dyscrasias and malignancies
Acute leukemia, agranulocytosis
Immune defects,
immunosuppression
AIDS, thymic aplasia
Xerostomia
Sjogren’s syndrome,
radiotherapy,
medications
Medications
Broad spectrum antibiotics,
corticosteroids
High-carbohydrate diet
Dentures
Smoking
B.G. Tarcın, Oral Candidosis: Aetiology, Clinical Manifestations,
Diagnosis and Management, J Mar Uni I of H Sci Vol: 1,2, 2011;141-150

6. Xerostomia:
 Saliva contains IgA which inhibits binding of Candida albicans to mucosal
surfaces. It also provides a flushing action which removes Candida albicans
from oral cavity.
 In case of xerostomia both these actions are absent because of lack of saliva
production, so chances of candidiasis is more in oral cavity.
 Xerostomia is also seen in case of anticancer treatment and irradiation
which increases the proliferation of candidal cells and resistance of Candida
cells to antifungal drugs.
 Xerostomia is also seen in case of Sjogren’s syndrome because of
lymphocytic infiltration and destruction of salivary glands.

7. Diabetes Mellitus:
Growth of Candida albicans thrives on increased levels of glucose in saliva
which increases the ability of Candida albicans to adhere to oral mucous
membranes.
Medicines:
Prolonged use of antibiotics depletes normal oral flora and enables
proliferation of Candida albicans in the oral cavity. In asthmatic patients due to
use of steroid inhalers. Steroid aerosols interfere with the normal balance of
microflora and favor the proliferation of candida albicans. Whereas systemic
steroids cause suppression of the immune system.

9. 3 Basic Types-
 1. pseudomembranous
 2. chronic hyperplastic
 3. atrophic red lesions

10. PRIMARY
 Acute forms
Pseudomembranous
Erythematous
 Chronic forms
Pseudomembranous
Erythematous
Hyperplastic (nodular or plaque-like)
 Candida-associated lesions
Denture stomatitis
Median rhomboid glossitis
Angular cheilitis
 Keratinized primary lesions superinfected with Candida
Leukoplakia
Lichen planus
Lupus erythematosus
SECONDARY
Oral manifestations of systemic ds
Pseudomembranous mucocutaneous candidosis

11. Type Site C / f Image
Pseudo
membranous
("thrush")
Buccal mucosa,
tongue, palate,
uvula
White thick plaques that, when
removed, leave an erythematous
bleeding surface
Varies according to the extent and
severity but includes burning,
pain, and taste changes
Erythematous
or atrophic
Palate, tongue Diffuse erythema Soreness
Angular
cheilitis
Angles of mouth Cracking and inflammation of the
corner of the mouth Pain,
soreness, and/or burning
Chronic
hyperplastic
candidiasis /
candidal
leukoplakia
Lip commisures,
cheeks, palate,
and tongue, skin,
nails
chronic form of oral
Candidiasis, firm white
Nonscrappable leathery plaque

12. Type Site C/F Image
Median Rhomboid
Glossitis
(hyperplastic)
located in the central
area of the dorsum of
the tongue
Erythematous patches of
atrophic papillae, chronic
atrophic candidiasis,
nodular,
Chronic Multifocal
Candidiasis
Dorsum of tongue &
midline of the hard
palate (kissing
lesions),
multiple areas of chronic
atrophic wartlike growths.
Asso with dentures, ortho
appliances etc
Immunocompromis
ed (HIV)- associated
Candidiasis
Gingiva, dorsum of
tongue
Asso with ANUG

13. Candidiasis is also a common manifestation of a variety of other
immunodeficiencies, including
 Severe combined immunodeficiency syndrome,
 DiGeorge syndrome,
 Hereditary myeloperoxidase deficiency
 Chediak-Higashi syndrome.
Farah CS, Ashman RB, Challacombe SJ. Oral candidosis. Clin Dermatol. 2000;18: 553-562.

14. D/D C/F Candidiasis
Chemical burn h/o medicament application, non
scrappable
scrappable
Superficial bacterial infection h/o other ds, medication,
bacterial colonies
Fungal
colonies
Traumatic ulcer h/o trauma No
Necrotic ulcer of systemic
diseases
Associated with Systemic ds like
leukemia, sickle cell anemia,
uremia.
Sec- inf to
systemic ds
Mucous patch of syphillis Descrete, small, white necrotic
lesion
Diffuse
Gangrenous stomatitis Flat, Green slough, noma, foul
odour, painful
Raised, white
Differential Diagnosis By Wood & Goaz 3rd Edi

15.  Samples
 Whitish patches from mucous membrane of mouth
 Sputum
Samples
• Whitish patches from mucous
membrane of mouth
• Sputum
Method of collection
• Sterile swabs

16. Direct examination (Microscopy)
A smear taken from the lesion is fixed on to
microscope slides and then stained either
by the gram stain or by the periodic acid
Schiff (PAS) technique. Using these
methods, candidal hyphae and yeasts
appear either dark blue(Gram-stain) or
red/purple (PAS)

17. Germ tube test (Reynold’s-Braude
Phenomenon)
• Culture of candida treated with sheep/normal
human serum is incubated at 37 C for 2-4 hours
• No constriction seen at the point of attachment
to the yeast cell
• Appear in 2 hours for C.albicans
Chlamydospore formation
• Suspected strain of Candida isolates gron on
CMA or rice starch agar and incubated at 25 C
• Formation of large, highly refractile, thick walled,
terminal chlamydospores in 2-3 days of
incubation

18. Fungal culture
• Sabouraud Dextrose Agar + Antibiotics ( Cream, Pasty,
Smooth colonies in 3-4 days of incubation at 37 C)
• Cornmeal Agar (Characteristic terminal chlamydospores,
yeast cells and pseudohyphae in clusters at 25 C)
• CHROM agar (light green to bluish green colonies)
Biochemical tests
• Sugar assimilation and fermentation tests are used
for identification of species.
• C. albicans ferment Glucose and Maltose with acid
and gas production, but not sucrose and lactose.
• Pale pink coloration in Tetrazolium reduction
medium

19. Sabourauds dextrose agar
 Swabs streaked onto Sabourauds dextrose agar.
 Incubated at 37 degree Celcius for 3 days.
 Creamy moist colonies
 Microscopically : Yeast cells, Pseudohyphae and
Blastoconidia
 Sputum cultures have NO VALUE.
 ALL depends on the OVERGROWTH OF Candida yeast.

20. Typing of Candida strains
• Serotyping
• Isoenzyme profiling
• Morphotyping
• Resistence pattern
Immunodiagnosis
• PCR based tests for candida-DNA
detection
• Detection of Candida albicans- derived
molecules
• ELISA, RIA, CIE, PHA and LPA

21. Detection of metabolites
• Detection of D-mannose and D-arabinitol in
sera by gas liquid chromatography
• G-test for detection of glucan
Skin tests
• It is not useful for diagnosis but is used to
evaluate cell mediated immunity.
Animal Pathogenicity
• Tests on rabbits and mice for susceptibility to
different candidia species
Clinical microbiology, 2nd edition, B.S.Nagoba, Asha Pichare

23.  Topical therapy used for milder forms.
 Extensive disease in patients with immunosuppression (most notably,
disease in HIV/AIDS patients), and disease in which there are symptoms
that suggest esophageal involvement (e.g., pain on swallowing) are best
treated with systemic therapy.
 Prolonged suppressive therapy may be required if the immunosuppressive
condition does not remit.

24. Antifungal Chemotherapy: Mild
 Nystatin Oral Suspension
 Nystatin is a polyene antifungal agent. It binds to ergosterol in
fungal plasma membrane and through pore-forming mechanisms
increase membrane permeability, effects leakage of essential
cellular components, and promotes cell death.

25.  To reduce the risk of relapse, treatment should be continued
for at least 48 hours after the elimination of all signs and
symptoms associated with the infection. The oral suspension
may also be used as holding solution for prostheses when they
are removed from the oral cavity.
 Common adverse effects of nystatin include contact mucositis
and Stevens-Johnson syndrome.

26.  Clotrimazole Troches
 Clotrimazole is an azole antifungal agent. It blocks 14α-sterol
demethylase, a fungus specific cytochrome enzyme that
initiates the conversion of lanosterol to ergosterol. This leads
to structural and functional plasma membrane damage and cell
death.
 Clotrimazole troches may be effective in the treatment of
mild oropharyngeal candidiasis refractory to nystatin.
However, since clotrimazole troches contain sucrose, their
long-term use may be a problem in caries-prone patients.
Common adverse effects include pruritus and a burning
sensation.

27. Fluconazole
 Fluconazole is an azole antifungal agent.
 It blocks 14α-sterol demethylase (the enzyme responsible for the
demethylation of lanosterol to egrosterol); and promotes structural
and functional plasma membrane damage, and cell death.
 Its clinical activity is well established against most candida species.
 Following oral administration fluconazole is well absorbed (100%
bioavailability) and diffuses freely into saliva.
 Common adverse effects- nausea, vomiting, diarrhea, abdominal
pain.
 Hepatotoxicity is a rare serious adverse effect.

28.  It is a polyene obtained from Strptomyces nodosus.
 It is active against a wide range of yeast and fungi.
 Dose orally 50- 100 mg qid
 Fungizone , candid B
 Adverse effects- High toxicity, chills, fever,nausea,
vomiting, dyspnoea

29. Itraconazole, Posaconazole, and Voriconazole
 These azole antifungal agents have a broader spectrum of
activity than fluconazole.
 Fluconazole- refractory infections should be treated initially
with itraconazole solution or posaconazole suspension.
 Voriconazole is recommended when treatment with other azole
antifungal agents has failed.

30. Caspofungin, Micafungin, and Anidulafungin
 Are echinocandins.
 They inhibit the synthesis of β (1, 3)-D-glucan, an essential
component of the fungal cell wall. The echinocandins are active
against most Candida spp., including those resistant to the azoles.
 Bioavailability- 100%
 Intravenous only
 Doses- caspofungin- CANCIDAS, starting dose of 70mg then
50mg/day
 Micafungin- , MICAMINE, 150mg od, prophylaxis 50mg/d
 Anidulafungin- ERAXIS- 100mg single loading dose on day 1 then
50mg/day for 14 days
 Adverse effects- impaire lever function, sensitivity reaction,
nausea, vomitting, headache, dyspnea, anemia
 Very expensive

31. Topical antifungal medications Brand name Indication
Miconazole cream 2% Angular cheilitis
Clotrimazole cream 1% Angular cheilitis
Ketoconazole cream 2% Angular cheilitis
Nystatin ointment 100,000 units/gram Mycostatin Angular cheilitis
Nystatin topical powder 100,000 units/gram Mycostatin Denture stomatitis
Nystatin oral suspension 100,000 units/gram Mycostatin Intraoral candidiasis
Betamethasone dipropionate clotrimazole
cream
Choloronic Angular
cheilitis
Clotrimazole troches 10 mg Mycelex Intraoral candidiasis
Amphotericin B 100 mg/ml Fungizone Intraoral candidiasis

32. Drug Dosage Brand name
Ketoconazole tablet 200 mg Nizoral,
Fluconazole tablet 100 mg Diflucan
Itraconazole tablet 100 mg Sporanox
caspofungin: 70 mg, then 50 mg Cancidas (MSD)
Casfung (Glenmark)
Caspogin (Cipla)
Casporan (Ranbaxy)
micafungin: 100 mg Micamine (Astellas )
anidulafungin: 200 mg Eraxis (MERK, pfizer)
Treatment Guidelines for Candidiasis • CID 2009:48

33. Appropriate medical treatment of the many predisposing systemic factors
and local measures such as meticulous oral hygiene, management of
xerostomia, and the maintenance of optimally functioning and clean
prostheses may prevent or minimize the incidence of clinical
oropharyngeal candidiasis.
These measures should include proper brushing of all oral tissues and all
surfaces of prostheses, removing prostheses at regular intervals to allow
for normal circulation in the supporting tissues, and periodic evaluation of
prostheses for proper tissue adaption.

34.  Chlorhexidine (CHX) mouthwash can help to
prevent oral candidiasis in people undergoing
CANCER TREATMENT.
 ASTHMATIC patients could REDUCE the
risk of oral thrush by washing mouth with
WATER after using INHALER.

36.  Shown in his study that 0.2% chlorhexidine gluconate mouth rinses have clinical
benefit in the treatment of oral candidiasis. However, there are reports of reduced
efficacy of Nystatin when used in combination with chlorhexidine gluconate, and
therefore it is often advised to delay Nystatin treatment for 30 min after the use
of chlorhexidine mouthwash
 Once-daily regimen of Fluconazole may be an excellent systemic therapeutic
choice with few side effects and drug interactions.
 Topical antifungal therapy may be continued as it reduces the dose and duration
of the systemic treatment required.

37. Erythematous candidiasis controlled after A 1-week course of fluconazole (100 mg/D).

38. Acutely painful pseudomembranous candidiasis of the palate. B, signs and
symptoms were controlled after 200 mg ketoconazole Daily for 3 days.

39. Painful candidiasis of tongue present for 3 weeks treated with clotrimazole (100 mg
troches) dissolved Orally twice daily for 1 week controlled the signs and symptoms.

41.  conducted a prospective observational study of 92 patients over 1 year,
including a nonblinded, randomized treatment trial of thrush with
clotrimazole troches or oral fluconazole.
 Clinical cure rates were similar with fluconazole (96%) and clotrimazole
(91%), but mycologic cure was better with fluconazole (49%) than
clotrimazole (27%).

42. Drug Dosage
Nystatin Pastilles or lozenges: 200,000U qid x 7-14 days
Suspension: 500,000 Units by swish & swallow qid x 7-14 days
Clotrimazole Suck on 1 troche 5x day x 7-14 days
Fluconazole 100 mg/d x 7-14 days
200mg for immunosuppressed patients and/or severe OPC
Itraconazole Suspension: 200 mg (20 ml) qid by swish & swallow without food x
7-14 days
Capsules: 200 mg/day (taken with food) x 2-4 weeks
Ketoconazole 200- 400 mg/day x 7-14 days
Capsofungin 70mg loading dose followed by 50mg/day
Amphotericin B 30-40mg/day for pts without neutropenia
40-50 mg/day for pts with neutropenia.