Kathmandu University

School of Sciences

Candidiasis

Pharmacotherapeutics II
School of Sciences
Kathmandu University, Dhulikhel, Nepal
Kathmandu University

School of Sciences

Overview
• Introduction
• Pathophysiology
• Classification
• Diagnosis
• Treatment
• References

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Introduction
• Candidiasis ( Moniliasis) is a fungal infection caused by yeasts
which is belong to genus Candida.

• There are more than 20 different species of candida that can

cause infection but the most common one is Candida albicans.

• These organisms typically infect the skin, nails, mucous

membrane , gastrointestinal tract, urinary and respiratory tracts
and they may also cause systemic disease.

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Candida albicans
• Candida is yeast, a type of fungus. It is the most common
fungal human pathogen causing diseases ranging from
superficial mucosal to life-threatening systemic infections.

• It is found in human microflora that asymptomatically

colonizes many areas of the human body that is on skin,
mouth, throat, gut, and vagina where its proliferation is
controlled by the host immune system. Healthy bacteria in
body control the balance of Candida.

• When Candida is off-balance, the yeast overgrows and causes

infection (candidiasis).
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RISK FACTORS
• Burns
• Granulocytopenia
• Prolonged hospitalization
• Bone marrow transplantation
• Recent bacterial infection
• Solid organ transplantation
• Recent surgery
(liver, kidney) • Gastrointestinal tract surgery
• Hematologic malignancies
• Central intravascular access
• Foley catheters
devices
• Solid neoplasms
• Premature birth
• Recent chemotherapy or • Haemodialysis
radiation therapy • Acute and chronic renal failure
• Corticosteroids
• Mechanical ventilation for longer
• Broad-spectrum antibiotics
than 3 days

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Pathophysiology
• Candida species are yeast like fungi that can form true hyphae
and pseudohyphae.

• Candida species are confined to human and animal reservoirs;

however

• Candida species contain their own set of well-recognized but

not well-characterized virulence factors that may contribute to
their ability to cause infection.

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The main virulence factors include the following:

• Surface molecules that permit adherence of the organism to

other structures (eg, human cells, extracellular matrix,
prosthetic devices)

• Acid proteases and phospholipases that involve penetration

and damage of cell envelopes

• Ability to convert to a hyphal form (phenotypic switching).

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As with most fungal infections, host defects also play a significant role
in the development of candidal infections. Host defence mechanisms
against Candida infection and their associated defects that allow
infection are as follows:
• Intact mucocutaneous barriers - Wounds, intravenous catheters,
burns, ulcerations
• Phagocytic cells -Granulocytopenia
• Polymorphonuclear leukocytes - Chronic granulomatous disease
• Monocytic cells -Myeloperoxidase deficiency
• Complement -Hypocomplementemia
• Immunoglobulins -Hypogammaglobulinemia
• Cell-mediated immunity - Chronic mucocutaneous candidiasis,
diabetes mellitus, cyclosporin A, corticosteroids, HIV infection
• Mucocutaneous protective bacterial flora - Broad-spectrum
antibiotics

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• The first step in the development of a candidal infection is

colonization of the mucocutaneous surfaces.
• All of the factors outlined are associated with increased
colonization rates.
• The routes of candidal invasion include:

– disruption of a colonized surface (skin or mucosa),

allowing the organisms access to the bloodstream, and
– persorption via the gastrointestinal wall, which may occur
following massive colonization with large numbers of
organisms that pass directly into the bloodstream.

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Classification
Candidiasis

Mucocutaneous Cutaneous Systemic

 Oropharengeal  Endocarditis
 Intertrigo
candidiasis  Paroncychia and  candidemia
 Angular candidiasis  Meningitis
onychomycosis
 Oesophagitis  Diaper dermatitis  Disseminated candidiasis
 Vulvovaginitis  Candidial granuloma  Endopthalmitis
 Chronic mucocutaneous
candidiasis
 Ocular candidiasis

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Mucocutaneous Candidiasis
Oropharyngeal candidiasis
• Candidiasis in the mouth and throat is also called oropharyngeal
candidiasis.
• The patient has a history of HIV infection, wears dentures, has diabetes
mellitus, or has been exposed to broad-spectrum antibiotics or inhaled
steroids. Patients are frequently asymptomatic. However, some of the
symptoms may include the following:
– Sore and painful mouth
– Burning mouth or tongue
– Dysphagia
– Whitish thick patches on the oral mucosa
• Physical examination reveals a diffuse erythema and white patches that
appear on the surfaces of the buccal mucosa, throat, tongue, and gums.

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 Oral candidiasis ( Thrush)

• Oral candidiasis is an infection of the oral cavity or mucus

membrane lining by Candida albicans.
• Candida is part of the normal oral microflora of immunocompetent
individuals.
• Most of these species live in the oral cavity as a commensal
population rather than a pathological one.
• The condition is generally obtained secondary to immune
suppression, including extremes of age (newborns and
elderly), immunocompromising diseases such as HIV/AIDS, and
chronic systemic steroid and antibiotic use.

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• A common sign of thrush is

presence of creamy white,
slightly raised lesions in mouth
usually on tongue.

• The lesions can be painful and

may bleeds slightly when scrape
them or brush teeth

• In severe cases the lesions may

spread into esophagus, or
swallowing tube causing pain or
difficulty swallowing.

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 Angular Cheilitis
• Angular cheilitis is a candidal infection of the corners
of the mouth, with crusted red raw fissures that are
sore and easily bleed when the mouth is opened
wide

• A moist environment due to the accumulation of

saliva in the corners of the mouth
favors Candida growth. Wearing dentures, licking the
lips and facial wrinkling at the commissures and
along the nasolabial fold contribute to the
accumulation of saliva; hence, chronically moist
commissures and angular cheilitis.

• Other factors linked to the etiology of angular

cheilitis include iron, folic acid, thiamine, riboflavin,
and vitamin B12 deficiencies.
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 Chronic atrophic candidiasis (denture stomatitis): This is the

most common forms of the disease. The presenting signs and
symptoms include chronic erythema and edema of the portion of the
palate that comes into contact with dentures.

 Erythematous candidiasis: This is associated with an erythematous

patch on the hard and soft palates.
• The most common location is on the dorsal surface of the tongue,
where there are patchy depapillated areas with minimal
pseudomembrane formation.
• There is both an asymptomatic and symptomatic variant, the later of
is characterized by burning or pain.

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denture stomatitis Erythematous candidiasis

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Esophagitis
• Candidiasis in the esophagus (the tube
that connects the throat to the stomach)
is called esophageal candidiasis or
Candida esophagitis.

• Esophageal candidiasis is one of the

most common infections in people
living with HIV/AIDS.

• It is an inflammation of the esophagus.

Esophagitis can cause painful, difficult
swallowing.

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• Patients may be asymptomatic or may have one or more of the

following symptoms:

– Normal oral mucosa (>50% of patients)

– Dysphagia
– Odynophagia
– Retrosternal pain
– Epigastric pain
– Nausea and vomiting

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Vulvovaginitis
• Vulvovaginitis, or inflammation of the vulva and
vagina caused by inflammatory changes in the
vaginal and vulvar epithelium secondary to
infection with Candida species, most
commonly Candida albicans.

• Candida is part of the normal flora in many

women and is often asymptomatic.

• Therefore, candidal vulvovaginitis requires both

the presence of candida in the vagina/vulva as
well as the symptoms of irritation, itching,
dysuria, or inflammation.

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Candida balanitis
• Patients report penile pruritus along with whitish patches on the
penis.
• Candida balanitis is acquired through direct sexual contact with a
partner who has VVC.
• Physical examination initially reveals vesicles on the penis that later
develop into patches of whitish exudate.
• The rash occasionally spreads to the thighs, gluteal folds, buttocks,
and scrotum.

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Candida cystitis:
• Many patients are asymptomatic. However, bladder invasion
may result in frequency, urgency, dysuria, hematuria, and
suprapubic pain.

• Candida cystitis may or may not be associated with the use of

a Foley catheter. Physical examination may reveal suprapubic
pain; other findings are unremarkable.

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Urinary tract candidiasis

• The urinary bladder may also be infected by Candida spp.
• Normally the urinary bladder is sterile, thus, the presence of
Candida spp. may lead to Candida cystitis, which is known as a
symptomatic lower UTI.
• Sometimes, Candida cystitis may lead to symptomatic
candiduria (Yeasts can be detected in urine )

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Chronic mucocutaneous candidiasis (CMCC) is a

heterogeneous group of syndromes with the
common features of chronic
noninvasive Candida infections of the skin, nails,
and mucous membranes.
• Chronic mucocutaneous candidiasis is frequently
associated with endocrinopathies, such as the
following:
• Hypoparathyroidism, Addison disease,
Hypothyroidism, Diabetes mellitus, Autoimmune
antibodies to adrenal, thyroid, and gastric tissues
(approximately 50%), Thymomas, Dental
dysplasia, Polyglandular autoimmune disease,
Antibodies to melanin-producing cells.

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Cutaneous Candidiasis
• This is an unusual form of cutaneous candidiasis that
manifests as a diffuse eruption over the trunk, thorax, and
extremities.

• Physical examination reveals a widespread rash that begins as

individual vesicles that spread into large confluent areas.

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Candidal intertrigo
• Candidal intertrigo refers to superficial skin-
fold infection caused by the yeast, candida.
• The patient has a history of intertrigo
affecting any site in which skin surfaces are
in close proximity, providing a warm and
moist environment.
• Physical examination reveals a rash that
begins with vesiculopustules that enlarge
and rupture, causing maceration and
fissuring. The area involved has a scalloped
border with a white rim consisting of
necrotic epidermis that surrounds the
erythematous macerated base. Satellite
lesions are commonly found and may
coalesce and extend into larger lesions.
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Paronychia and onychomycosis

• A paronychia is an infection around the
nail, caused by the yeast-like organism
Candida.

• Paronychia and onychomycosis are

frequently associated with immersion of the
hands in water and with diabetes mellitus.

• Physical examination reveals an area of

inflammation that becomes warm,
glistening, tense, and erythematous and may
extend extensively under the nail. It is
associated with secondary nail thickening,
ridging, discoloration, and occasional nail
loss.

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• Diaper dermatitis is inflammation of the

skin under a diaper.

• Candida granuloma is a variant of

chronic mucocutaneous candidiasis
associated with chronic infection mainly by
Candida albicans in which the skin lesions
are rather granulomatous and
hyperkeratotic

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Systemic Candidiasis
• Systemic candidiasis can be divided into 2 primary syndromes:
candidemia and disseminated candidiasis (organ infection by
Candida species).
• Deep organ infections due to Candida species are generally
observed as part of the disseminated candidiasis syndromes and
may involve one or more organs.

Candidemia
• Candida species are currently the fourth most commonly isolated
organism in blood cultures, and Candida infection is generally
considered a nosocomial infection.

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• The patient's history commonly reveals the following:

– Several days of fever that is unresponsive to broad-spectrum
antimicrobials; frequently the only marker of infection
– Prolonged intravenous catheterization
– Possibly associated with multiorgan infection
• Physical examination results may include the following:
– Fever
– Macronodular skin lesions (approximately 10%)
– Candidal endophthalmitis (approximately 10%-28%)
– Occasionally, septic shock (hypotension, tachycardia,
tachypnea)

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Macronodular skin lesions

Candidal endophthalmitis

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Disseminated candidiasis
• Disseminated candidiasis, also known as Candida septicemia,
is a systemic infection of Candida species that can present in
the debilitated or immunocompromised patient.

• Risk factors include prolonged systemic steroids or antibiotic

administration, immunosuppressive medications in association
with organ transplantation, (HIV) /(AIDS), neoplastic disease,
chemotherapy, hemodialysis, Foley or other catheterization,
recent gastrointestinal surgery, or parenteral hyperalimentation
as well as injection drug use.

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Endocarditis
• Candida species, primarily C albicans and Candidaparapsilosis
(>60% of cases), are the most common cause of fungal endocarditis.

• The aortic and mitral valves are most commonly involved. The
endocarditis may be exogenous (due to direct inoculation during
surgery) or endogenous (due to hematogenous dissemination during
bloodstream invasion.

• Candida endocarditis is associated with 4 main risk factors,

including intravenous heroin use (frequently associated with C
parapsilosis infection), chemotherapy, prosthetic valves
(approximately 50%), and prolonged use of central venous catheters.

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CNS infections due to Candida species

• CNS infections due to Candida species are rare and difficult to
diagnose.
• The two primary forms of infection include the exogenous infection
and the endogenous infection. The exogenous infection results from
postoperative infection, trauma, lumbar puncture, or shunt placement.
• The endogenous infection results from hematogenous dissemination
and thus involves the brain parenchyma and is associated with multiple
small abscesses.
• The spectrum of this disease includes the following:
Meningitis, Granulomatous vasculitis, Diffuse cerebritis with
microabscesses, Mycotic aneurysms, Fever unresponsive to broad-
spectrum antimicrobials, Mental status changes.

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Diagnosis
• Specimen depend on site of infection: e.g. UTI Urine, meningitis. CSF etc.,
Swabs, Urine, Blood, Respiratory specimens, CSF, vitreous sample, vaginal
swabs.
METHOD Description
Direct Microscopy • Stain: Gram stain, KOH, Giemsa,
GMS , or PAS stained smears.
• Budding yeast cells and
pseudohyphae will be seen in
stained smear or KOH.
Culture • Media: SDA & Blood agar at 37oC,
• Creamy moist colonies in 24 - 48
hours.

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METHOD DESCRIPTION
Blood Culture (If patient is febrile and you • Uses:
suspect septicemia) • Detection of circulating
microorganisms in septicemia
• Description :
Different types of blood culture bottles
and blood volumes
required:
■ Pediatric aerobic (0.5–4 mL blood)
■ Adult aerobic (5–10 mL blood)
■ Anaerobic (5–10 mL blood)
• Two sets of cultures before starting
antibiotics is ideal
Serology Patient serum ○ Test for Antigen , e.g.
Mannan antigen using ELISA ○ Test for
Antibodies e.g. Anti-mannan antibodies
PCR • For detection of nucleic acid.

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• Because C. albicans is the most common species to cause infection The

following tests are used to identify C. albicans:

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• If these 3 are positive this yeast is C.albicans, If negative, then

it could be any other yeast, we can do:
• Carbohydrate assimilations and fermentation.
• Commercial kits available for this like: API 20C, API 32C
• Culture on Chromogenic Media (CHROMagarTM Candida)

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Management
• The treatments used to manage Candida infections vary substantially and
are based on the anatomic location of the infection, the patients' underlying
disease and immune status, the patients' risk factors for infection, the
specific species of Candida responsible for infection, and, in some cases,
the susceptibility of the Candida species to specific antifungal drugs.

Cutaneous candidiasis
• Most localized cutaneous candidiasis infections may be treated with any
number of topical antifungal agents (eg, clotrimazole, econazole,
ciclopirox, miconazole, ketoconazole, nystatin).
• If the infection is a paronychia, the most important aspect of therapy is
drainage of the abscess, followed by oral antifungal therapy with either
fluconazole or itraconazole.

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ANTIFUNGAL DRUGS

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• In cases of extensive cutaneous infections, infections in

immunocompromised patients, folliculitis, or onychomycosis, systemic
antifungal therapy is recommended.

• For Candida onychomycosis, oral itraconazole appears to be most

efficacious.

• Two treatment regimens are available: the daily dose of itraconazole taken
for 3-6 months or the pulsed-dose regimen that requires a slightly higher
daily dose for 7 days, followed by 3 weeks of no drug administration. The
cycle is repeated every month for 3-6 months.

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Oropharyngeal candidiasis
• Oropharyngeal candidiasis OPC can be treated with either topical
antifungal agents (eg, nystatin, clotrimazole, amphotericin B oral
suspension) or systemic oral azoles (fluconazole, itraconazole, or
posaconazole).

• Infections in HIV-positive patients tend to respond more slowly and, in

approximately 60% of patients, recur within 6 months of the initial
episode.

• In these situations, in addition to attempting correction of the immune

dysfunction with HAART, higher doses of fluconazole (up to 800 mg/d) or
itraconazole (up to 600 mg/d) can be attempted. Posaconazole suspension
at 400 mg orally twice per day has also yielded excellent results in such
patients. Additionally, caspofungin 50 mg/d IV and anidulafungin 100
mg/d IV have also yielded excellent efficacy in such patents.
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Candida esophagitis
• Candida esophagitis requires systemic therapy with fluconazole for 14-21
days.

• Parenteral therapy with fluconazole may be required initially if the patient

is unable to take oral medications.

• Daily suppressive antifungal therapy with fluconazole 100-200 mg/d is

effective for preventing recurrent episodes, but it should be used only if the
recurrences become frequent or are associated with malnutrition due to
poor oral intake and wasting syndrome.

• Recommended alternatives for fluconazole-refractory disease include

itraconazole, voriconazole, caspofungin, micafungin, anidulafungin, and
amphotericin B.

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• Vulvovaginal candidiasis (VVC) can be managed with either

topical antifungal agents or a single dose of oral fluconazole.
• A single dose of oral fluconazole (150 mg) in acute episodes of
VVC has been shown to yield clinical and microbiological efficacy
as good as or better than topical antifungal agents.
• A small percentage (< 5%) of women experience chronic recurrent
VVC infections, which often require long-term or prophylactic oral
azole therapy for control.
• In such patients, the recommended regimen includes fluconazole
150 mg every other day for 3 doses, followed by weekly fluconazole
150-200 mg for 6 months. This regimen prevents further recurrence
in more than 80% of women.

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• For asymptomatic candiduria, therapy generally depends on the

presence or absence of an indwelling Foley catheter.

• Candiduria frequently resolves by simply changing the Foley

catheter (20%-25% of patients). Thus, most experts agree that
asymptomatic candiduria associated with a Foley catheter does not
require treatment in most cases. However, eradicating candiduria
prior to any form of instrumentation or urological manipulation is
prudent.

• Candida cystitis in noncatheterized patients should be treated with

fluconazole at 200 mg/d orally for at least 10-14 days.

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Candidemia and disseminated candidiasis

• In patients without neutropenia, fluconazole is the drug of choice in
most cases of candidemia and disseminated candidiasis, fluconazole
at a dose of 400 mg/d is as efficacious as amphotericin B.

• An echinocandin is recommended for candidemia in most patients

with neutropenia. Fluconazole is an alternative in patients who are
less critically ill and who have no recent azole exposure.
Voriconazole can be used when additional mold coverage is desired.

• The standard recommended dose for fluconazole is 800 mg as the

loading dose, followed by fluconazole at a dose of 400 mg/d for at
least 2 weeks of therapy after a demonstrated negative blood culture
result or clinical signs of improvement.

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• Available echinocandins for candidemia include the following:

• Caspofungin can be initiated as a 70-mg loading dose, followed by
50 mg/d intravenously to complete a minimum of 2 weeks of
antifungals after improvement and after blood cultures have cleared.

• Anidulafungin can be initiated as a 200-mg loading dose, followed

by 100 mg intravenously to complete a minimum of 2 weeks of
antifungals after improvement and after blood cultures have cleared.

• Micafungin can be administered at 100 mg/d intravenously to

complete a minimum of 2 weeks of antifungals after improvement
and after blood cultures have cleared.

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• Additional options for candidemia include the following:

• Voriconazole can be initiated at 6 mg/kg intravenously or

orally twice per day, followed by 3 mg/kg orally twice per day
or 200 mg orally twice per day.

• Amphotericin B deoxycholate can be administered at 0.7

mg/kg/d intravenously for a total dose of 1-2 g over a 4- to 6-
week period.

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Chronic mucocutaneous candidiasis

• This condition is generally treated with oral azoles, such as
fluconazole at a dose of 100-400 mg/d or itraconazole at a
dose of 200-600 mg/d until the patient improves.

Alternative antifungal regimens

• Alternative regimens may be considered in patients who are
intolerant to the treatment regimens or when the infection is
refractory to the antifungal regimen. The combination of
amphotericin B and flucytosine has been recommended in
several special situations.

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Surgical Care
• Major organ infections associated with candidal abscess formation
may require surgical drainage procedures along with the appropriate
antifungal therapy.
• Prosthetic joint infection with Candida species requires the removal
of the prosthesis.
• Surgical debridement is generally necessary for sternal infections
and frequently for vertebral osteomyelitis.
• Splenic abscesses occasionally require splenectomy.
• Valve replacement surgery is always indicated to treat endocarditis.
• In addition to medical management, vitrectomy is a therapeutic
option in fungal endophthalmitis.

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References
• https://emedicine.medscape.com/article/213853-overview
• R AN, Rafiq NB. Candidiasis. [Updated 2022 Aug 7]. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available
from: https://www.ncbi.nlm.nih.gov/books/NBK560624/
• https://www.slideshare.net/bishnukoirala2/candidiasis-causes-and-their-tr
eatment
• https://www.slideshare.net/r-selime/candidiasis-60718391
• Bouopda Tamo SP. Candida Infections: Clinical Features, Diagnosis and
Treatment. Infect Dis Clin Microbiol 2020; 2: 91-102.
• http://ksumsc.com/download_center/Archive/2nd/438/3-%20Endocrine
%20block/Teamwork/Microbiology/L1-Candidiasis%20.pdf

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