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emedicine.medscape.com

Candidiasis
Updated: Jan 17, 2020
Author: Jose A Hidalgo, MD; Chief Editor: Michael Stuart Bronze, MD

Overview

Practice Essentials
Candidiasis (see the image below) is a fungal infection caused by yeasts from the genus Candida. Candida albicans is the
predominant cause of the disease.

Soreness and cracks at the lateral angles of the mouth (angular cheilitis) are a frequent expression of candidiasis in
elderly individuals. Courtesy of Matthew C. Lambiase, DO.

Signs and symptoms

Chronic mucocutaneous candidiasis

Findings reveal disfiguring lesions of the face, scalp, hands, and nails. Chronic mucocutaneous candidiasis is occasionally
associated with oral thrush and vitiligo.

Oropharyngeal candidiasis

Individuals with oropharyngeal candidiasis (OPC) usually have a history of HIV infection, wear dentures, have diabetes
mellitus, or have been exposed to broad-spectrum antibiotics or inhaled steroids. Although patients are frequently
asymptomatic, when symptoms do occur, they can include the following:

Sore and painful mouth

Burning mouth or tongue

Dysphagia
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Thick, whitish 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.

The following are the 5 types of OPC:

Membranous candidiasis - One of the most common types; characterized by creamy-white, curdlike patches on the
mucosal surfaces

Chronic atrophic candidiasis (denture stomatitis) - Also thought to be one of the most common forms of the disease;
presenting signs and symptoms include chronic erythema and edema of the portion of the palate that comes into
contact with dentures

Erythematous candidiasis - Associated with an erythematous patch on the hard and soft palates

Angular cheilitis - Inflammatory reaction characterized by soreness, erythema, and fissuring at the corners of the
mouth

Mixed - A combination of any of the above types is possible

Esophageal candidiasis

Patients with esophageal candidiasis may be asymptomatic or may have 1 or more of the following symptoms:

Normal oral mucosa (>50% of patients)

Dysphagia

Odynophagia

Retrosternal pain

Epigastric pain

Nausea and vomiting

Physical examination almost always reveals oral candidiasis.

Nonesophageal gastrointestinal candidiasis

The following symptoms may be present:

Epigastric pain

Nausea and vomiting

Abdominal pain

Fever and chills

Abdominal mass (in some cases)

Genitourinary tract candidiasis

The types of genitourinary tract candidiasis are as follows:

Vulvovaginal candidiasis (VVC) - Erythematous vagina and labia; a thick, curdlike discharge; and a normal cervix
upon speculum examination[1]

Candida balanitis - Penile pruritus and whitish patches on the penis

Candida cystitis - Many patients are asymptomatic, but bladder invasion may result in frequency, urgency, dysuria,
hematuria, and suprapubic pain

Asymptomatic candiduria - Most catheterized patients with persistent candiduria are asymptomatic

Ascending pyelonephritis - Flank pain, abdominal cramps, nausea, vomiting, fever, chills and hematuria

Fungal balls - Intermittent urinary tract obstruction with subsequent anuria and ensuing renal insufficiency

See Clinical Presentation for more detail.

Diagnosis
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Diagnostic tests for candidiasis include the following:

Mucocutaneous candidiasis - For a wet mount, scrapings or smears obtained from skin, nails, or oral or vaginal
mucosa are examined under the microscope; a potassium hydroxide smear, Gram stain, or methylene blue is useful
for direct demonstration of fungal cells

Cutaneous candidiasis - Using a wet mount, scrapings or smears obtained from skin or nails can be examined under
the microscope; potassium hydroxide smears are also useful

Genitourinary candidiasis - A urinalysis should be performed; evidence of white blood cells (WBCs), red blood cells
(RBCs), protein, and yeast cells is common; urine fungal cultures are useful

Gastrointestinal candidiasis - Endoscopy with or without biopsy

See Workup for more detail.

Management

See the list below:

Cutaneous candidiasis - Most localized cutaneous candidiasis infections can be treated with any number of topical
antifungal agents (eg, clotrimazole, econazole, ciclopirox, miconazole, ketoconazole, nystatin)

Chronic mucocutaneous candidiasis - This condition is generally treated with oral azoles

Oropharyngeal candidiasis - This can be treated with either topical antifungal agents or systemic oral azoles

Esophageal candidiasis - Treatment requires systemic therapy with fluconazole

VVC - Topical antifungal agents or oral fluconazole can be used[2]

Candida cystitis - In noncatheterized patients, Candida cystitis should be treated with fluconazole; in catheterized
patients, the Foley catheter should be removed or replaced; if the candiduria persists after the catheter change, then
patients can be treated with fluconazole

See Treatment and Medication for more detail.

Background
Candidiasis is caused by infection with species of the genus Candida, predominantly with Candida albicans.Candida
species are ubiquitous fungi that represent the most common fungal pathogens that affect humans. The growing problem of
mucosal and systemic candidiasis reflects the enormous increase in the number of patients at risk and the increased
opportunity that exists for Candida species to invade tissues normally resistant to invasion. Candida species are true
opportunistic pathogens that exploit recent technological advances to gain access to the circulation and deep tissues.

The increased prevalence of local and systemic disease caused by Candida species has resulted in numerous new clinical
syndromes, the expression of which depends primarily on the immune status of the host. Candida species produce a wide
spectrum of diseases, ranging from superficial mucocutaneous disease to invasive illnesses, such as hepatosplenic
candidiasis, Candida peritonitis, and systemic candidiasis. The management of serious and life-threatening invasive
candidiasis remains severely hampered by delays in diagnosis and the lack of reliable diagnostic methods that allow
detection of both fungemia and tissue invasion by Candida species.

Advances in medical technology, chemotherapeutics, cancer therapy, and organ transplantation have greatly reduced the
morbidity and mortality of life-threatening disease. Patients who are critically ill and in medical and surgical ICUs have been
the prime targets for opportunistic nosocomial fungal infections, primarily due to Candida species. Studies suggest that the
problem is not under control and, in fact, show it is worsening. On a daily basis, virtually all physicians are confronted with a
positive Candida isolate obtained from one or more various anatomical sites. High-risk areas for Candida infection include
neonatal, pediatric, and adult ICUs, both medical and surgical.[3] Candida infections can involve any anatomical structure.

Pathophysiology

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Candida species are yeastlike fungi that can form true hyphae and pseudohyphae. For the most part, Candida species are
confined to human and animal reservoirs; however, they are frequently recovered from the hospital environment, including
on foods, countertops, air-conditioning vents, floors, respirators, and medical personnel. They are also normal commensals
of diseased skin and mucosal membranes of the gastrointestinal, genitourinary, and respiratory tracts.

Candida species also contain their own set of well-recognized but not well-characterized virulence factors that may
contribute to their ability to cause infection.[4] 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)

As with most fungal infections, host defects also play a significant role in the development of candidal infections. Host
defense 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

Risk factors associated with invasive or systemic candidiasis include the following[5] :

Granulocytopenia

Bone marrow transplantation

Solid organ transplantation (liver, kidney)

Parenteral hyperalimentation

Hematologic malignancies

Foley catheters

Solid neoplasms

Recent chemotherapy or radiation therapy

Corticosteroids

Broad-spectrum antibiotics

Burns

Prolonged hospitalization

Severe trauma

Recent bacterial infection

Recent surgery

Gastrointestinal tract surgery

Central intravascular access devices

Premature birth

Hemodialysis

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Acute and chronic renal failure

Mechanical ventilation for longer than 3 days

The first step in the development of a candidal infection is colonization of the mucocutaneous surfaces. All of the factors
outlined above are associated with increased colonization rates. The routes of candidal invasion include (1) disruption of a
colonized surface (skin or mucosa), allowing the organisms access to the bloodstream, and (2) persorption via the
gastrointestinal wall, which may occur following massive colonization with large numbers of organisms that pass directly into
the bloodstream.

Frequency
United States

Candida species are the most common cause of fungal infection in immunocompromised persons. Oropharyngeal
colonization is found in 30%-55% of healthy young adults, and Candida species may be detected in 40%-65% of normal
fecal flora.

Three of every 4 women experience at least one bout of vulvovaginal candidiasis (VVC) during their lifetime.

More than 90% of persons infected with HIV who are not receiving highly active antiretroviral therapy (HAART) eventually
develop oropharyngeal candidiasis (OPC), and 10% eventually develop at least one episode of esophageal candidiasis.[6]

In persons with systemic infections, Candida species are now the fourth most commonly isolated pathogens from blood
cultures.[7]

Clinical and autopsy studies have confirmed the marked increase in the incidence of disseminated candidiasis, reflecting a
parallel increase in the frequency of candidemia. This increase is multifactorial in origin and reflects increased recognition of
the fungus, a growing population of patients at risk (eg, patients undergoing complex surgical procedures, patients with
indwelling vascular devices), and the improved survival rates among patients with underlying neoplasms or collagen-
vascular disease and patients who are immunosuppressed.

International

Similar rates of mucocutaneous and systemic candidiasis/candidemia have been observed worldwide.[8, 9] In fact,
throughout the world, Candida species have replaced Cryptococcus species as the most common fungal pathogens
affecting immunocompromised hosts.

Mortality/Morbidity
Mucocutaneous candidiasis: Most candidal infections are mucocutaneous and, as such, do not cause mortality. However, in
patients with advanced immunodeficiency due to HIV infection, these mucosal infections can become refractory to antifungal
therapy and may lead to severe oropharyngeal and esophageal candidiasis that initiates a vicious cycle of poor oral intake,
malnutrition, wasting, and early death.

Candidemia and disseminated candidiasis: Mortality rates associated with these infections have not improved markedly over
the past few years and remain in the range of 30%-40%. Systemic candidiasis causes more case fatalities than any other
systemic mycosis. More than a decade ago, investigators reported the enormous economic impact of systemic candidiasis
in hospitalized patients. Candidemia is associated with considerable prolongation in hospital stays (70 d vs 40 d in
comparable patients without fungemia). Although mucocutaneous fungal infections, such as oral thrush and
Candidaesophagitis, are extremely common in patients with AIDS, candidemia and disseminated candidiasis are
uncommon.

Sex

Neither sex is predisposed to candidal colonization; however, VVC is the second most common cause of vaginitis in women.

Age

Persons at the extremes of age (neonates and adults >65 y) are most susceptible to candidal colonization. Mucocutaneous
candidiasis is also more prevalent in neonates and older adults. Very-low-birth-weight and extremely-low-birth-weight infants
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are at high risk for blood culture–proven late-onset candidiasis (defined as sepsis that develops after age 72 h).[10]

Presentation

History
Candidiasis can cause a wide spectrum of clinical syndromes, as described below. The clinical presentation can vary
depending on the type of infection and the degree of immunosuppression.

Cutaneous candidiasis syndromes

Generalized cutaneous candidiasis: This is an unusual form of cutaneous candidiasis that manifests as a diffuse eruption
over the trunk, thorax, and extremities. The patient has a history of generalized pruritus, with increased severity in the
genitocrural folds, anal region, axillae, hands, and feet. Physical examination reveals a widespread rash that begins as
individual vesicles that spread into large confluent areas.

Intertrigo: The patient has a history of intertrigo affecting any site in which skin surfaces are in close proximity, providing a
warm and moist environment. A pruritic red rash develops. 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 (see image below).

Erythema, maceration, and satellite pustules in the axilla, accompanied by soreness and pruritus, result in a form of
intertrigo. Courtesy of Matthew C. Lambiase, DO.

Metastatic skin lesions: Characteristic skin lesions occur in approximately 10% of patients with disseminated candidiasis
and candidemia. The lesions may be numerous or few and are generally described as erythematous, firm, nontender
macronodular lesions with discrete borders. Biopsy specimens of these lesions demonstrate yeast cells, hyphae, or
pseudohyphae, and cultures are positive for Candida species in approximately 50% of cases.

Candidafolliculitis: The infection is found predominantly in the hair follicles and, rarely, can become extensive.

Paronychia and onychomycosis: Paronychia and onychomycosis are frequently associated with immersion of the hands in
water and with diabetes mellitus. The patient has a history of a painful and erythematous area around and underneath the
nail and nail bed. 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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Chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis describes a group of Candida infections of the skin, hair, nails, and mucous
membranes that tends to have a protracted and persistent course.

History: Most infections begin in infancy or during the first 2 decades of life; onset in people older than 30 years is rare.

Most patients survive for prolonged periods and rarely experience disseminated fungal infections. The most common cause
of death is bacterial sepsis.

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

Physical examination: Findings reveal disfiguring lesions of the face, scalp, hands, and nails. This is occasionally associated
with oral thrush (see image below) and vitiligo.

White plaques are present on the buccal mucosa and the undersurface of the tongue and represent thrush. When wiped
off, the plaques leave red erosive areas. Courtesy of Matthew C. Lambiase, DO.

Gastrointestinal tract candidiasis

Oropharyngeal candidiasis

The patient usually 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

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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. The following are the 5 types of oropharyngeal candidiasis (OPC):

Membranous candidiasis: This is one of the most common types and is characterized by creamy-white curdlike
patches on the mucosal surfaces.

Erythematous candidiasis: This is associated with an erythematous patch on the hard and soft palates.

Chronic atrophic candidiasis (denture stomatitis): This type is also thought to be one of 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.

Angular cheilitis: An inflammatory reaction, this type is characterized by soreness, erythema, and fissuring at the
corners of the mouth (see image below).

Soreness and cracks at the lateral angles of the mouth (angular cheilitis) are a frequent expression of candidiasis
in elderly individuals. Courtesy of Matthew C. Lambiase, DO.

Mixed: A combination of any of the above types is possible.

Esophageal candidiasis

The patient's history usually includes chemotherapy, the use of broad-spectrum antibiotics or inhaled steroids, the presence
of HIV infection or hematologic or solid-organ malignancy. 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

Physical examination almost always reveals oral candidiasis.

Nonesophageal gastrointestinal candidiasis

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The patient usually has a history of neoplastic disease of the gastrointestinal tract. The esophagus is the most commonly
infected site, followed by the stomach. Less commonly, patients have chronic gastric ulcerations, gastric perforations, or
malignant gastric ulcers with concomitant candidal infection. The small bowel is the third most common site of infection
(20%). The frequency of candidal infection in the small bowel is the same as in the large bowel. Approximately 15% of
patients develop systemic candidiasis.

Physical examination findings vary depending on the site of infection. The diagnosis, however, cannot be made solely on
culture results because approximately 20%-25% of the population is colonized by Candida. The following symptoms may be
present:

Epigastric pain

Nausea and vomiting

Abdominal pain

Fever and chills

Abdominal mass (in some cases)

Respiratory tract candidiasis

The respiratory tract is frequently colonized with Candida species, especially in hospitalized patients. Approximately
20%-25% of ambulatory patients are colonized with Candida species.

Laryngeal candidiasis: This is an uncommon form of invasive candidiasis that sometimes results in disseminated infection. It
is primarily seen in patients with underlying hematologic or oncologic malignancies. The patient may present with a sore
throat and hoarseness. The physical examination findings are generally unremarkable, and the diagnosis is frequently made
with direct or indirect laryngoscopy.

Candida tracheobronchitis: This is also an uncommon form of invasive candidiasis. Most patients with Candida
tracheobronchitis are HIV-positive or are severely immunocompromised. Most patients with Candida tracheobronchitis
report fever, productive cough, and shortness of breath. Physical examination reveals dyspnea and scattered rhonchi. The
diagnosis is generally made with bronchoscopy.

Candida pneumonia: This rarely develops alone and is associated with disseminated candidiasis in rare cases. The most
common form of infection is multiple lung abscesses due to the hematogenous dissemination of Candida species. The high
degree of Candida colonization in the respiratory tract greatly complicates the diagnosis of Candida pneumonia. The history
reveals risk factors similar to those of disseminated candidiasis, along with reports of shortness of breath, cough, and
respiratory distress. Physical examination reveals fever, dyspnea, and variable breath sounds, ranging from clear to rhonchi
or scattered rales.

Genitourinary tract candidiasis

Vulvovaginal candidiasis (VVC): This is the second most common cause of vaginitis. The patient's history includes vulvar
pruritus, vaginal discharge, dysuria, and dyspareunia. Approximately 10% of women experience repeated attacks of VVC
without precipitating risk factors. Physical examination findings include a vagina and labia that are usually erythematous, a
thick curdlike discharge, and a normal cervix upon speculum examination.[1]

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 (see image below).

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Dry, red, superficially scaly, pruritic macules and patches on the penis represent candidal balanitis. Courtesy of Matthew
C. Lambiase, DO.

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.

Asymptomatic candiduria: Most catheterized patients with persistent candiduria are asymptomatic, similar to
noncatheterized patients. Most patients with candiduria have easily identifiable risk factors for Candida colonization. Thus,
invasive disease is difficult to differentiate from colonization based solely on culture results because approximately 5%-10%
of all urine cultures are positive for Candida.[11]

Ascending pyelonephritis: The use of stents and indwelling devices, along with the presence of diabetes, is the major
predisposing risk factor in ascending infection. Most patient report flank pain, abdominal cramps, nausea, vomiting, fever,
chills and hematuria. Physical examination reveals abdominal pain, costovertebral-angle tenderness, and fever.

Fungal balls: This is due to the accumulation of fungal material in the renal pelvis. The condition may produce intermittent
urinary tract obstruction with subsequent anuria and ensuing renal insufficiency.

Hepatosplenic candidiasis (chronic systemic candidiasis)

Hepatosplenic candidiasis is a form of systemic candidiasis in patients with an underlying hematologic malignancy and
neutropenia and develops during the recovery phase of a neutropenic episode. The patient's history includes the following:

Fever unresponsive to broad-spectrum antimicrobials

Right upper quadrant pain

Abdominal pain and distension

Jaundice (rare)

Physical examination findings include right upper quadrant tenderness and hepatosplenomegaly (< 40%).

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.[12, 13] The patient's history commonly reveals the following:

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Several days of fever that is unresponsive to broad-spectrum antimicrobials; frequently the only marker of infection

Prolonged intravenous catheterization

A history of several key risk factors (see Pathophysiology)

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)

Other causes of candidemia without invasive disease include the following:

Intravascular catheter-related candidiasis: This entity usually responds promptly to catheter removal and antifungal
treatment.

Suppurative thrombophlebitis: This is associated with prolonged central venous catheterization. Suppurative
thrombophlebitis manifests as fever and persistent candidemia despite appropriate antifungal therapy and catheter
removal. Sepsis and septic shock may develop.

Endocarditis: The frequency of endocarditis has recently increased.[14] 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. The physical
examination reveals a broad range of manifestations, including feverunresponsive to antimicrobials, hypotension,
shock, new or changing murmurs, and large septic emboli to major organs, a characteristic of fungal endocarditis.

Disseminated candidiasis

This is frequently associated with multiple deep organ infections or may involve single organ infection. Unfortunately, blood
cultures are negative in up to 40%-60% of patients with disseminated candidiasis. The history of a patient with presumptive
disseminated candidiasis reveals a fever unresponsive to broad-spectrum antimicrobials and negative results from blood
culture. Physical examination reveals fever (may be the only symptom) with an unknown source and associated sepsis and
septic shock.

Candidaendophthalmitis

The two primary forms of Candida endophthalmitis are the exogenous form and the endogenous form. Exogenous
endophthalmitis is associated with either accidental or iatrogenic (postoperative) injury of the eye and inoculation of the
organism from the environment. Endogenous endophthalmitis results from hematogenous seeding of the eye. It has been
found in 10%-28% of patients with documented candidemia. Recently, newer studies have shown a decreasing incidence of
Candida endophthalmitis, possibly due to an increased awareness of this complication and the initiation of early or empirical
antifungal therapy.[15] It is important to note that hematogenous candidal endophthalmitis is a marker of disseminated
candidiasis.

The patient's history reveals a broad range of manifestations, including the following.

Eye injury

Ophthalmic surgery

Underlying risk factors for candidemia

Asymptomatic and detected upon physical examination

Ocular pain

Photophobia

Scotomas

Floaters

Physical examination reveals fever.

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Funduscopic examination reveals early pinhead-sized off-white lesions in the posterior vitreous with distinct margins and
minimal vitreous haze. Classic lesions are large and off-white, similar to a cotton-ball, with indistinct borders covered by an
underlying haze. Lesions are 3-dimensional and extend into the vitreous off the chorioretinal surface. They may be single or
multiple.

Renal candidiasis

This is frequently a consequence of candidemia or disseminated candidiasis. The patient’s history includes fever that is
unresponsive to broad-spectrum antimicrobials. Frequently, patients are asymptomatic and lack symptoms referable to the
kidney.

Physical examination findings are generally unremarkable, and the diagnosis is made with a urinalysis and with a renal
biopsy. Otherwise, this condition is commonly diagnosed at autopsy.

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 (eg, disseminated candidiasis).

As with other organ infections due to Candida species, patients usually have underlying risk factors for disseminated
candidiasis. CNS infections due to Candida species are frequently found in patients hospitalized for long periods in ICUs.
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

Physical examination reveals the following:

Fever

Nuchal rigidity

Confusion

Coma

Candida arthritis, osteomyelitis, costochondritis, and myositis

Candidal musculoskeletal infections were once uncommon; recently, they have become much more common, possibly due
to the increased frequency of candidemia and disseminated candidiasis. The most common sites of involvement continue to
be the knee and the vertebral column. The pattern of involvement is similar to the pattern observed in bacterial infections.
The infection may be divided into exogenous or endogenous forms. The exogenous infection is due to the direct inoculation
of the organisms, such as postoperative infection or trauma. Affected sites include the following:

Ribs and leg bones (patients < 20 y)

Vertebral column and paraspinal abscess (adulthood)

Flat bones (any age group)

Sternum - Generally observed postoperatively after cardiac surgery

The patient is frequently asymptomatic, and the history reveals risk factors typical of disseminated candidiasis, as well as
pain localized over the affected site. The physical examination findings are frequently unremarkable but may reveal
tenderness over the involved area, erythema, and bone deformity, occasionally in association with a draining fistulous tract.

Arthritis: Candida arthritis is generally a complication of disseminated candidiasis but may be caused by trauma or direct
inoculation due to surgery or steroid injections. Most cases are acute and begin as a suppurative synovitis. A high
percentage of cases progress to osteomyelitis. In addition, Candida arthritis after joint replacement is not uncommon.

Osteomyelitis: Candida osteomyelitis originates either exogenously or endogenously. The exogenous infection is due to
direct inoculation of the organisms via routes such as postoperative infection, trauma, or steroid injections. The endogenous

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form is a complication of candidemia or disseminated candidiasis. In most cases due to hematogenous seeding, the
vertebral disks are involved and frequently progress to discitis with contiguous extension into the vertebrae body. Other
bones affected include the wrist, femur, scapula, and proximal humerus.

Costochondritis: This is an uncommon form of infection and also has two modes of infection. Candida costochondritis is
usually due to hematogenous infection spread or direct inoculation during surgery (median sternotomy). Costochondritis is
frequently associated with pain localized over the involved area.

Myositis: Candida myositis is uncommon but is frequently associated with disseminated candidiasis. Most patients are
neutropenic and report muscular pain.

Myocarditis-pericarditis

This infection is usually due to direct hematogenous spread in association with candidemia and is rarely due to the direct
extension from the sternum or the esophagus. Myocarditis-pericarditis occurs as diffuse abscesses scattered throughout the
myocardium surrounded by normal cardiac tissue. In patients with disseminated candidiasis, the rate of Candida
myocarditis-pericarditis has been documented as high as 50%. The patient history reveals serious complications in 10-20%
of cases without valvular disease. Physical examination reveals fever, hypotension, shock, tachycardia, and new murmurs
or rubs (or recent changes in previously detected murmurs).

Candida peritonitis[16]

The patient history frequently reveals an association with gastrointestinal tract surgery, viscous perforation, or peritoneal
dialysis. Candida peritonitis tends to remain localized, disseminating into the bloodstream in only 15% of cases. The range
of manifestations is broad and includes fever and chills, abdominal pain and cramping, nausea, vomiting, and constipation.
The isolation of Candida species from the peritoneal fluid in surgical patients needs to be carefully evaluated.

Physical examination may reveal the following:

Fever

Abdominal distention

Abdominal pain

Absent bowel sounds

Rebound tenderness

Localized mass

Candidasplenic abscess and hypersplenism

Both are manifestations of disseminated candidiasis and are usually simultaneously associated with liver involvement.
Manifestations of hypersplenism are common (see Hepatosplenic candidiasis).

Candida cholecystitis

This is uncommon and is generally associated with bacterial cholangitis and ascending cholangitis. In general, Candida
cholecystitis is diagnosed at the time of surgery when a culture is obtained.

Physical
See History for physical examination findings paired with clinical syndromes.

Causes
Over 200 species of Candida exist in nature; thus far, only a few species have been associated with disease in humans.

The medically significant Candida species include the following[17] :

C albicans, the most common species identified (50%-60%)

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Candida glabrata (previously known as Torulopsis glabrata) (15%-20%)

C parapsilosis (10%-20%)

Candida tropicalis (6%-12%)

Candida krusei (1%-3%)

Candida kefyr (< 5%)

Candida guilliermondi (< 5%)

Candida lusitaniae (< 5%)

Candida dubliniensis, primarily recovered from patients infected with HIV

Candida auris

C glabrata and C albicans account for approximately 70%-80% of Candida species recovered from patients with candidemia
or invasive candidiasis. C glabrata has recently become very important because of its increasing incidence worldwide, its
association with fluconazole resistance in up to 20% of clinical specimens, and its overall decreased susceptibility to other
azoles and polyenes.

C krusei is important because of its intrinsic resistance to ketoconazole and fluconazole (Diflucan); it is also less susceptible
to all other antifungals, including itraconazole (Sporanox) and amphotericin B.

Another important Candida species is C lusitaniae; although not as common as other Candida species, C lusitaniae is of
clinical significance because it may be intrinsically resistant to amphotericin B, although it remains susceptible to azoles and
echinocandins.

C parapsilosis is also an important species to consider in hospitalized patients. It is especially common in infections
associated with vascular catheters prosthetic devices. Additionally, in vitro analyses have shown that echinocandins have a
higher minimum inhibitory concentration (MIC) against C parapsilosis than other Candida species. The clinical relevance of
this in vitro finding has yet to be determined.[18]

C tropicalis has frequently been considered an important cause of candidemia in patients with cancer (leukemia) and in
those who have undergone bone marrow transplantation.

C auris is a globally emerging invasive Candida species that is associated with a high mortality rate and that is often
resistant to multiple antifungal drugs. The CDC has issued a global clinical alert for this fungus and has asked laboratories
to report C auris cases and to send isolates to state and local health departments and to the CDC. As of February 28, 2019,
587 cases of C auris infection had been reported in the United States, mostly in New York, Illinois, and New Jersey among
residents of nursing homes.[19]

A 2020 report from the US Centers for Disease Control and Prevention described three chronically ill people in New York
who were identified as having pan-resistant C auris infection. The report stated that the pan-resistant C auris infection
developed after the patients had received antifungal medications, including echinocandins, a class of drugs that targets the
fungal cell wall.[20]

DDx

Diagnostic Considerations
See the list below:

Cutaneous candidiasis - Dermatitis (contact, allergic), folliculitis

Gastrointestinal tract candidiasis - Esophagitis due to herpes simplex virus, herpes zoster, induced by radiation,
gastroesophageal reflux disease

Respiratory candidiasis - Bacterial pneumonia, viral pneumonia, tracheitis, Aspergillus pneumonia

Genitourinary tract candidiasis - Bacterial cystitis or pyelonephritis

Candidemia - Bacterial sepsis, bacterial endocarditis

Disseminated candidiasis - Bacterial meningitis, bacterial sepsis, bacterial endocarditis, tuberculosis

Chronic mucocutaneous candidiasis - HIV-seropositive state, chronic granulomatous disease

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Hepatosplenic candidiasis - Hepatic abscess, cholelithiasis, cholecystitis, acalculous cholecystitis, ascending

cholangitis, graft versus host disease, granulomatous hepatitis, relapsed malignancy

Differential Diagnoses
Abdominal Abscess

Aspergillosis

Bacterial Sepsis

Cryptococcosis

Septic Shock

Workup

Workup

Laboratory Studies
Unfortunately, results from the routine laboratory studies are often nonspecific and not very helpful. Clinicians are required
to act definitively and early based on a high index of suspicion. In the past, many patients with life-threatening candidiasis
died without receiving antifungal therapy. Systemic candidiasis should be suspected in patients with persistent leukocytosis
and either persistent neutropenia or other risk factors and who remain febrile despite broad-spectrum antibiotic therapy. To
be effective, antifungal therapy should be provided early and empirically in such high-risk patients. Cultures of nonsterile
sites, although not useful for establishing a diagnosis, may demonstrate high degrees of candidal colonization. Always
consider positive culture results from sterile sites to be significant and evidence of infection.

In September 2014, the FDA gave marketing approval for the T2Candida Panel and T2Dx Instrument (T2Candida), the first
direct blood test for detecting five Candida species that cause bloodstream infections (C albicans and/or C tropicalis, C
parapsilosis, C glabrata and/or C krusei).[21, 22] T2Candida can use single blood sample to identify these five yeasts within
3-5 hours, whereas traditional testing methods can take up to 6 days to detect, and even longer to identify, Candida species.
Therefore, this test potentially allows earlier administration of appropriate antifungal therapy and may reduce disease
severity and/or the mortality risk from sepsis.[21, 22] However, blood cultures should be used to confirm T2Candida results
owing to the potential for false-positive results.

Approval was based on a study of 1500 patients, in which T2Candida correctly categorized almost 100% of negative
specimens as negative for the presence of Candida, and another study of 300 blood samples with specific concentrations of
yeast, in which the test correctly identified the organism in 84%-96% of positive samples.[21, 22]

Mucocutaneous candidiasis

For a wet mount, scrapings or smears obtained from skin, nails, or oral or vaginal mucosa are examined under the
microscope for hyphae, pseudohyphae, or budding yeast cells.

A potassium hydroxide smear, Gram stain, or methylene blue is useful for direct demonstration of fungal cells.

Cultures from affected nails may help identify the etiologic agent responsible for onychomycosis versus other noninfectious
causes.

Candidemia and disseminated candidiasis[23]

Blood cultures are helpful but yield positive results in only 50%-60% of cases of disseminated infection.

Urinalysis may be helpful and may show either colonization or renal candidiasis.

The serum (1,3)β-D-glucan detection assay (Glucatell, Fungitell) is a nonculture assay that was approved for use in the
United States in May 2004. This assay measures the level of β-glucan (a fungal cell wall component). In a large multicenter
study, the assay yielded a high specificity and positive predictive value with highly reproducible results.[24]

Cultures of nonsterile sites, although not useful for establishing a diagnosis, may be useful for initiating antifungal therapy in
patients with fever that is unresponsive to broad-spectrum antimicrobials. Therefore, appropriate interpretation is required.
Positive results from blood cultures and cultures from other sterile sites always imply the presence of invasive disease.
Positive results from sterile sites should always be taken as significant and should always prompt treatment.

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Gastrointestinal, respiratory, and urinary tract cultures that are positive for Candida may not always represent invasive
disease. However, these should be considered sites of colonization.

Cutaneous candidiasis: Using a wet mount, scrapings or smears obtained from skin or nails can be examined under
microscopy for hyphae, pseudohyphae, or budding yeast cells. Potassium hydroxide smears are also useful.

Genitourinary candidiasis: A urinalysis should be performed. Evidence of WBCs, RBCs, protein, and yeast cells is common.
Additionally, urine fungal cultures are useful.

Respiratory tract candidiasis

Sputum Gram stain may demonstrate WBCs and yeast cells.

Sputum cultures may demonstrate Candida species.

Lung biopsy is mandatory to definitively establish the diagnosis of respiratory tract candidiasis because of the high
frequency of yeast colonization of the respiratory tract.

Gastrointestinal candidiasis

Endoscopy with or without biopsy is necessary to establish the diagnosis.

Focal hepatosplenic candidiasis

Serum alkaline phosphatase levels are commonly elevated.

Species identification

C albicans, C dubliniensis, and Candida stellatoidea can be identified morphologically via germ-tube formation (hyphae are
produced from yeast cells after 2-3 h of incubation) or biochemical assays.

CHROMagar Candida allows for the presumptive identification of several Candida species by using color reactions in
specialized media that demonstrate different colony colors depending on the species of Candida.

API20C and API32C are biochemical assays that allow for the identification of the different Candida species with more
precision. These assays evaluate the assimilation of numerous carbon substrates and generate profiles used in the
identification of different fungal species.

The C albicans peptide nucleic acid (PNA) fluorescence in situ hybridization (FISH) test can be used to identify C albicans in
24-48 hours when the probe is added to smears that are made directly from the blood culture bottle and followed by
hybridization. A newer version of this test now allows for the simultaneous identification of either C albicans or C glabrata.
[25]

Antifungal susceptibility testing

In vitro susceptibility testing for Candida species is now standardized using the Clinical Laboratory Standards Institute
(CLSI) microbroth dilution (CLSI M27-A2, 2002) or the disk diffusion (CLSI M44-P, 2003) methodology. This was formerly
known as the National Committee for Clinical Laboratory Standards (NCCLS) microbroth dilution.

These methods may be helpful in guiding difficult therapeutic decisions. Most of the difficult decisions involve antifungal-
refractory oral or esophageal candidiasis in patients with advanced HIV disease.

Nonculture Candida detection assays

The Candida mannan assay yields a sensitivity of 31%-90% (less for non-albicans Candida species).

The Candida heat labile antigen assay yields a sensitivity of 10%-71%.

The D-arabinitol assay yields a sensitivity of 50% but is not useful for infection with C krusei or C glabrata.

The enolase assay yields a sensitivity of 55%-75%, which improves with serial testing.

The (1,3)β-D-glucan assay is an amebocyte lysis assay with a sensitivity of 75-100% and a specificity of 88%-100%. It is a
broad-spectrum assay that detects Aspergillus, Candida, Fusarium, Acremonium, and Saccharomyces species. β-D-glucan
is a cell wall component in a wide variety of fungi and can be detected based on its ability to activate factor G of the
horseshoe crab coagulation cascade. The Fungitell assay may be used in the evaluation of invasive fungal infections
caused by the fungi mentioned above. The assay does not detect infections caused by Cryptococcus neoformans or
Zygomycetes.

Molecular assays such as the polymerase chain reaction (PCR) assay and DNA probes are still under development and in
the early investigational phases, but they appear promising.

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A new, rapid test for Candida infections of the bloodstream may cut patient mortality from 40% to 11% by diagnosing
candidemia 25 times faster than blood culture can and quickly identifying the Candida species that is causing the infection.
The new test, T2Candida, uses polymerase chain reaction (PCR) assay to amplify Candida DNA in blood, with the genetic
material hybridizing to superparamagnetic nanoparticles coated with complementary DNA. The nanoparticles aggregate into
"microclusters," which greatly alter a T2 magnetic resonance (T2MR) signal.[26, 27]

Imaging Studies
Imaging studies are not required or useful in the diagnosis of cutaneous candidiasis, oropharyngeal candidiasis (OPC), or
vulvovaginal candidiasis (VVC).

Chest radiography may be useful in differentiating a bacterial pneumonia as the cause of fever in patients who are
hospitalized. Patients with bronchopneumonia due to hematogenous candidiasis usually have multilobar involvement.

Esophagography/upper gastrointestinal studies may be useful for detecting abnormalities in the esophagus and stomach.
Unfortunately, these studies are not helpful in determining the microbiologic etiology of the infection.

Ultrasonography may be useful for diagnosing hepatosplenic abscess. The classic bull's eye or target lesions are observed
in the liver and spleen.

Echogenic foci with degrees of shadowing

Intra-abdominal abscess formation

Cholelithiasis

Renal abscess

Renal fungus balls

CT scanning with contrast enhancement may be useful for diagnosing the following:

Hepatosplenic candidiasis

Intra-abdominal abscess or peritonitis

Renal abscess

Pyelonephritis

Echocardiography may be useful for excluding or including Candida endocarditis as a possible diagnosis. It is extremely
useful because fungal endocarditis is frequently associated with large vegetations that are easily observed on standard
echocardiograms.

Procedures
In patients with candidemia or disseminated candidiasis, obtaining a tissue biopsy of the involved areas is frequently helpful
in establishing the presence of Candida infection and invasion.

Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy provide adequate tissue for diagnosis of pulmonary
candidiasis.

Endoscopy provides direct examination of the esophagus and stomach, one of the organ systems most commonly infected
with Candida species. It is also necessary for excluding other causes of esophagitis.

Echocardiography may be useful for excluding or including Candida species as a cause of endocarditis. It is extremely
useful because fungal endocarditis is frequently associated with large vegetations that are easily observed using standard
echocardiography.

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Histologic Findings
Fixed tissues can be stained with hematoxylin and eosin. In addition, fungal hyphae may be demonstrated with Grocott
silver-methenamine, methylene blue, or periodic acid-Schiff staining. The classic appearance demonstrates the Candida
species as either round or ovoid yeast cells, hyphae, or pseudohyphae.

Treatment

Medical Care
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.

There have been significant changes in the management of candidiasis in the last few years, particularly related to the
appropriate use of echinocandins and expanded-spectrum azoles for candidemia, other forms of invasive candidiasis, and
mucosal candidiasis. Updated guidelines were published in 2016 by the Infectious Disease Society of America (IDSA),[28]
replacing previous versions from 2009[29] and 2004.[30] These latest recommendations include the echinocandins
caspofungin, micafungin, and anidulafungin, along with fluconazole, as well as lipid formulations of amphotericin B in
various situations.

Fluconazole is still considered a first-line agent in nonneutropenic patients with candidemia or suspected invasive
candidiasis. However, a post-hoc analysis of clinical trial data comparing anidulafungin with fluconazole for treatment of
invasive candidiasis found that anidulafungin was more effective in treating severely ill patients.[31] A revision of data
outcomes on treatment of invasive candidiasis in clinical trials appears to favor use of echinocandins in terms of increased
rate of survival. This type of finding may have an impact on future treatment recommendations and strategies of drug use for
invasive candidiasis in different groups of patients.[32, 33]

In August 2013, the FDA announced that clinicians should no longer prescribe ketoconazole (Nizoral, Janssen
Pharmaceuticals) tablets as a first-line therapy for any fungal infection, including Candida and dermatophyte infections,
because of the risk for severe liver injury, adrenal insufficiency, and adverse drug interactions.[34, 35] The FDA also
cautioned that ketoconazole tablets should not be prescribed for any patient with underlying liver disease. The labeling
changes do not apply to topical formulations of ketoconazole in creams, shampoos, foams, and gels. Oral ketoconazole is
now indicated only for endemic mycoses in patients who fail to respond to or cannot tolerate other treatments.

Ketoconazole tablets were also withdrawn from the market in the European Union in July 2013.[34, 35]

The therapeutic options available for the management of invasive candidiasis and candidemia have continued to increase
with the addition of newer echinocandins[36, 37] and triazoles.

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. In
cases of extensive cutaneous infections, infections in immunocompromised patients, folliculitis, or onychomycosis, systemic
antifungal therapy is recommended. For Candida onychomycosis, oral itraconazole (Sporanox) 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.

Gastrointestinal candidiasis

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. Approximately 3%-5% of patients with advanced HIV infection (CD4 cell counts < 50/µL) may develop
refractory OPC. 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. Amphotericin B is rarely necessary to treat

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such cases, but, when used, low doses of amphotericin B can be used (0.3-0.7 mg/kg) and have been shown to be
effective.

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.

Genitourinary tract candidiasis

Vulvovaginal candidiasis (VVC) can be managed with either topical antifungal agents or a single dose of oral fluconazole.[2]
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.[1] This regimen prevents further recurrence in more than 80% of women. In pregnant women, just one or
two oral doses of fluconazole for vaginal candidiasis during pregnancy was not associated with significantly increased risks
of stillbirth or neonatal death, according to a 2018 Scandinavian cohort study.[38]

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.

For Candida cystitis in catheterized patients, the first step is always to remove the nidus of infection. Thus, the Foley
catheter should be removed or replaced prior to initiating antifungal therapy. If the candiduria persists after the catheter
change, then patients can be treated with 200 mg/d of fluconazole orally for 14 days. Alternative therapy includes
amphotericin B bladder irrigation. However, its use for the treatment of funguria is significantly limited, primarily because of
the required maintenance of a urinary catheter; lack of adequate studies to define the dose, duration, and method of
administration; restriction of its use to uncomplicated lower urinary tract infections; and the availability of more convenient
treatment options (eg, oral fluconazole therapy). The use of amphotericin B bladder irrigation is rarely needed. Administering
intravenous amphotericin B to treat candiduria is rarely necessary.

Renal candidiasis

Regardless of whether the infection involves hematogenous dissemination to the kidney or ascending infection
(pyelonephritis), systemic antifungal therapy is required. The most recent comparative studies indicate that fluconazole at
400 mg/d intravenously or orally for a minimum of 2 weeks is as effective as amphotericin B without the toxicities normally
associated with amphotericin B. For amphotericin B, the daily dose is 0.5-0.7 mg/kg intravenously for a total dose of 1-2 g
administered over a 4- to 6-week period.

Candidemia

This requires treatment in all patient populations. Current recommendations depend on the presence or absence of
neutropenia.[29]

In patients without neutropenia, fluconazole is the drug of choice in most cases of candidemia and disseminated
candidiasis. Studies conducted by the MSG have demonstrated that fluconazole at a dose of 400 mg/d is as efficacious as
amphotericin B. In addition, fluconazole has several advantages, including lower nephrotoxicity rates (< 2%) and ease of
use because of the high degree of bioavailability and the long half-life of the drug.[39] Thus, once the gastrointestinal tract is
functional, the parenteral antifungal may be switched to the oral formulation with the same efficacy. Alternative options listed
below need to be considered depending on history of previous exposure to antifungals, the probability of fluconazole
resistance according to the species of Candida recovered, the presence of comorbid conditions, and the clinical status of
the patient.[40]

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. This
treatment regimen can be used for infections due to C albicans, C tropicalis, C parapsilosis, C kefyr, C dubliniensis, C
lusitaniae, and C guilliermondi.

A critical component in the management of candidemia and disseminated candidiasis is the removal of the focus of
infection, such as intravenous and Foley catheters.
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Available echinocandins for candidemia include the following:

Caspofungin (Cancidas) 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. Caspofungin is a broad-
spectrum semisynthetic echinocandin. It is an effective alternative for severe mucosal infections and systemic
infections due to Candida, especially those due to non-albicans Candida species such as C glabrata.

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. Anidulafungin is a broad-
spectrum echinocandin. It is an effective alternative for severe mucosal infections and systemic infections due to
Candida, especially those due to non-albicans Candida species such as C glabrata.[41]

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. Micafungin is a broad-spectrum echinocandin. It has been
shown to be an effective alternative for severe mucosal infections and systemic infections due to Candida, especially
those due to non-albicans Candida species such as C glabrata.[42]

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. Based on the findings from a global multicenter clinical trial, voriconazole has
also been approved for use in candidemia in patients who are not neutropenic.[43]

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.

Liposomal preparations of amphotericin B have comparable efficacy to conventional amphotericin B, but renal toxicity
is considerably less common with the former.

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. The initial therapy for acute infection is always followed by maintenance therapy
with the same azole for life.

Hepatosplenic candidiasis

Induction therapy is initially started with amphotericin B deoxycholate for at least 2 weeks, followed by consolidation therapy
with fluconazole at a dose of 400 mg/d for an additional 4-12 weeks depending on the response.

Respiratory tract candidiasis

If the diagnosis is established based on biopsy findings, then the infection is treated as disseminated candidiasis.

Invasive candidiasis

Empirical treatment options for suspected invasive candidiasis include the following:

Empirical antifungal therapy should be considered for critically ill patients with risk factors for invasive candidiasis and
no other cause of fever, and it should be based on clinical assessment of risk factors, serologic markers for invasive
candidiasis, and/or culture data from nonsterile sites. (Its benefits have not been clearly determined.)[44]

This continues to be a problematic decision since criteria for starting empirical antifungal therapy remain poorly
defined. Empirical therapy in persistently febrile and neutropenic patients should cover infections caused by yeasts
and molds.

The choice of drugs in nonneutropenic patients is similar to that for proven candidiasis. Recommended agents
include fluconazole or an echinocandin.

In neutropenic patients, a lipid formulation of amphotericin B, caspofungin, or voriconazole is recommended. Azoles

should not be used for empirical therapy in individuals who have received an azole for prophylaxis.

Disseminated candidiasis with end organ infection

Disseminated candidiasis with end organ involvement requires an individualized approach. Thus, the manifestation of
invasive candidiasis involving localized structures, such as in Candida osteomyelitis, arthritis, endocarditis, pericarditis, and
meningitis, requires prolonged antifungal therapy for at least 4-6 weeks. The optimum dosage and duration of therapy for
various types of deep candidal infection have not been definitively determined.

The standard recommended dose for most Candida infections is fluconazole at 800 mg as the loading dose, followed by
fluconazole at a dose of 400 mg/d either intravenously or orally for at least 2 weeks of therapy after a demonstrated
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negative blood culture result or clinical signs of improvement.

The echinocandins have become first-line therapy for this type of infection in many situations because of their efficacy and
low incidence of adverse events and drug interactions.

Caspofungin (Cancidas)[45] 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. Caspofungin is a broad-
spectrum semisynthetic echinocandin. It is an effective alternative for severe mucosal infections and systemic infections due
to Candida, especially those due to non-albicans Candida species such as C glabrata.

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. Anidulafungin is a broad-spectrum
echinocandin. It is an effective alternative for severe mucosal infections and systemic infections due to Candida, especially
those due to non-albicans Candida species such as C glabrata.[41]

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. Micafungin is a broad-spectrum echinocandin. It has been shown to be
an effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to non-
albicans Candida species such as C glabrata.[42]

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. Based on the findings from a global multicenter clinical trial, voriconazole has also been
approved for use in candidemia in patients who are not neutropenic.[43]

Amphotericin B deoxycholate has been an alternative to fluconazole for many years. However, with the advent of the newer
azoles and the echinocandins, its role as a primary or secondary option needs to be reconsidered. The dose for
amphotericin B deoxycholate is 0.5-0.7 mg/kg/d intravenously to achieve a minimum of 1- to 2-g total dose. For the
treatment of invasive candidiasis caused by less-susceptible species, such as C glabrata and C krusei, higher doses (up to
1 mg/kg/d) should be considered.

Liposomal preparations of amphotericin B are recommended at doses between 3 and 5 mg/kg/d when used for invasive
candidiasis.

Special situations involving antifungal resistance

Several of the Candida species require special mention because of their known intrinsic resistance to antifungals.

Because C glabrata is known to be resistant to fluconazole in 15%-25% of cases and has decreased susceptibility to most
antifungals, C glabrata infections require a change in conventional antifungal therapy. The drugs of choice for such
infections are the echinocandins: caspofungin 70 mg intravenously as a loading dose, followed by 50 mg/d; anidulafungin
200-mg loading dose, followed by 100 mg/d; or micafungin 100 mg/day intravenously. An alternative is voriconazole at 6
mg/kg administered twice on the first day, followed by 3 mg/kg twice per day or 200 mg twice per day orally; other options
include amphotericin B deoxycholate (1 mg/kg/d), or lipid preparations of amphotericin B at 3-5 mg/kg/d.

If in vitro susceptibility assays are available, it may be worthwhile to establish the in vitro susceptibility of the C glabrata
strain to fluconazole. If the MIC is less than 8 μg/mL, then fluconazole can be used at 400 mg/d intravenously or orally.

C krusei infections necessitate the use of an agent other than fluconazole, because this organism is intrinsically resistant to
fluconazole and has a decreased susceptibility to itraconazole, ketoconazole, and amphotericin B. Thus, the preferred
regimen includes echinocandins (caspofungin, anidulafungin, or micafungin) voriconazole, or amphotericin B at 1 mg/kg/d.
Infections due to C lusitaniae or C guilliermondi necessitate the use of fluconazole, voriconazole, or the echinocandins
because these isolates are frequently intrinsically resistant to amphotericin B or develop resistance to amphotericin B while
the patient is on therapy.

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. For instance, this combination has been used in immunocompromised patients with endophthalmitis,
meningitis, or osteomyelitis. Flucytosine appears to interact synergistically with amphotericin B in animal models.

The role of other combinations of antifungals to treat complicated Candida infections needs to be evaluated. A human
recombinant monoclonal antibody against heat shock protein 90 was recently reported to significantly improve outcomes in
patients treated with lipid-associated amphotericin B for confirmed invasive candidiasis.[46] However, larger randomized
trials need to be performed before this drug can be used clinically.

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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.[47]

Consultations
In some forms of candidiasis, involving physicians of different specialties for some of the specific infections may be
necessary. Some examples of these situations include endocarditis, endophthalmitis, peritonitis, osteomyelitis, and other
forms of invasive candidiasis that may require surgical drainage and debridement.

Ophthalmologist

General surgeon

Cardiothoracic surgeon

Gastroenterologist

Infectious disease specialist

Orthopedic surgeon

Guidelines

Infectious Diseases Society of America Guidelines

Guidelines on the treatment of candidiasis by the Infectious Diseases Society of America are as follows:[28]

The IDSA recommends an echinocandin as first-line treatment for candidemia (caspofungin: loading dose 70 mg,
then 50 mg daily; micafungin: 100 mg daily; anidulafungin: loading dose 200 mg, then 100 mg daily), rather than
fluconazole, as echinocandins kill, rather than inhibit, these pathogens.
Fluconazole, intravenous or oral, 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily is an acceptable
alternative to an echinocandin as initial therapy in selected patients, including those who are not critically ill and who
are considered unlikely to have a fluconazole-resistant Candida species.
In neutropenic patients, lipid formulation amphotericin B, 3-5 mg/kg daily, is an effective but less attractive alternative
because of the potential for toxicity.
Fluconazole could be used in high-risk patients in adult ICUs with a high rate (>5%) of invasive candidiasis.
Daily bathing of ICU patients with chlorhexidine, which has been shown to decrease the incidence of bloodstream
infections including candidemia, could be considered.
The updated guidelines also advocate consultation with infectious disease specialists for the early identification of
different Candida strains, optimal antifungal treatment, and better patient outcomes.
The guidelines advocate testing for azole susceptibility in clinically relevant Candida isolates. Testing for
echinocandin susceptibility should be considered in patients who have undergone prior treatment with an
echinocandin and in those with C glabrata or C parapsilosis infection.
Candidiasis should be considered in patients who deteriorate with no obvious cause, have unexplained fever, have
an elevated white blood cell count, have recently undergone abdominal surgery, or have a central venous catheter.
Remove a catheter as early as possible in patients with candidemia if the catheter is the presumed source and can
be safely removed. Other intravascular devices should also be removed.
For neonatal candidiasis, amphotericin B deoxycholate 1 mg/kg daily is recommended for neonates with
disseminated candidiasis.
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Lumbar puncture and dilated retinal examination are recommended in neonates with serum or urine cultures that are
positive for Candida species .
Empiric antifungal therapy should be considered in patients with clinical evidence of intra-abdominal infection and
significant risk factors for candidiasis, including recent abdominal surgery, anastomotic leaks, or necrotizing
pancreatitis.

Medication

Medication Summary
Successful therapy for serious systemic Candida infections requires initiation of antifungal therapy as early as possible, as
soon as adequate culture results are obtained.

Different classes of antifungals are now available to manage any type of candidal infection. Azoles, fluconazole in particular,
[39] have become the mainstay of therapy over the past few years. These include topical and systemic agents.
Posaconazole is the most recent addition to this group of antifungals. Polyenes include amphotericin B, liposomal
amphotericin B formulations, and topical nystatin. Allylamines include terbinafine, which is formulated in a topical
preparation and an oral tablet. The newest group of antifungals is echinocandins, including caspofungin, micafungin, and
anidulafungin. These drugs have shown excellent clinical efficacy, a low incidence of adverse events, a good safety profile,
and ease of use.[48, 49]

Azole Antifungals

Class Summary
These agents are synthetic compounds that include 2 groups, imidazoles and triazoles. Triazoles have 3 atoms of nitrogen
in the azole ring. Imidazoles have only two. The primary mechanism of action is inhibition of lanosterol 14-alpha-
demethylase, an enzyme required for the synthesis of ergosterol, the main component of fungal cell membranes. Imidazole
agents include miconazole, ketoconazole, and clotrimazole.

In August 2013, the FDA announced that clinicians should no longer prescribe ketoconazole (Nizoral, Janssen
Pharmaceuticals) tablets as a first-line therapy for any fungal infection, including Candida and dermatophyte infections,
because of the risk for severe liver injury, adrenal insufficiency, and adverse drug interactions.[34, 35] The FDA also
cautioned that ketoconazole tablets should not be prescribed for any patient with underlying liver disease. The labeling
changes do not apply to topical formulations of ketoconazole in creams, shampoos, foams, and gels. Oral ketoconazole is
now indicated only for endemic mycoses in patients who fail to respond to or cannot tolerate other treatments.

Ketoconazole tablets were also withdrawn from the market in the European Union in July 2013.[34, 35]

Triazole agents, which are now the most commonly used azoles, include fluconazole, itraconazole, econazole, terconazole,
butoconazole, and tioconazole. Newer triazoles (ie, voriconazole, posaconazole, ravuconazole) are active against
fluconazole-resistant strains of Candida. Voriconazole and posaconazole have shown high efficacy against candidiasis in
recent clinical trials.[43, 50, 51]

Topical agents are frequently used as front-line agents to manage localized or superficial forms of candidiasis such as
cutaneous candidiasis, oropharyngeal candidiasis (OPC), and vulvovaginal candidiasis (VVC). These preparations are
available as a cream for topical use, as troches for OPC, and as a vaginal suppositories or tablets for vaginitis.

Fluconazole (Diflucan)
Triazole with less effect on human sterol metabolism. Does not decrease cortisol and testosterone levels, as occurs with
ketoconazole. Has fewer adverse effects and better tissue distribution than older systemic imidazoles. Available PO/IV and
has demonstrated efficacy in topical and invasive forms of candidiasis. Available in 50-, 100-, 150-, and 200-mg tabs.

Daily dose varies with indication.

Itraconazole (Sporanox)

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Has fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P450-
dependent synthesis of ergosterol, a vital component of fungal cell membranes. Effective against broad range of fungi,
including Candida species, and is indicated for treatment of cutaneous, oral, esophageal, and disseminated candidiasis.

Available IV, 100-mg caps, and oral solution at 10 mg/mL.

Caps require gastric acidity for absorption and should be taken with food to increase absorption. Liquid formulation
increases bioavailability and decreases need for acidity for proper absorption.

Use of solution has been recommended in mucosal and invasive candidiasis, while caps can be used in onychomycosis and
dermatophyte infections.

Voriconazole (Vfend)
Available as tablet, suspension and parenteral preparations. Effective as fluconazole against esophageal candidiasis, and
as effective as amphotericin B deoxycholate in treatment of candidemia and invasive candidiasis. In Europe, it has been
approved for "treatment of fluconazole-resistant serious invasive Candida infections (including C krusei)." Additionally,
associated with fewer breakthrough fungal infections when used as empiric therapy in febrile neutropenic patients. FDA
approved for esophageal candidiasis and candidemia.

Posaconazole (Noxafil)
Novel triazole antifungal agent. Blocks ergosterol synthesis of cell membrane by inhibiting enzyme lanosterol 14-alpha-
demethylase and sterol precursor accumulation. Action results in cell membrane disruption. Available as oral susp (200
mg/5 mL). Approved for treatment of OPC, including OPC refractory to itraconazole and/or fluconazole and for prophylaxis
of infections due to Candida and Aspergillus in patients who are at high risk, such as those undergoing stem cell transplants
with graft versus host disease or with prolonged neutropenia due to a hematologic malignancy or its treatment.

Glucan synthesis inhibitors (echinocandins)

Class Summary
These agents inhibit the formation of fungal cell wall. The antifungal class has expanded with the approvals of caspofungin,
micafungin, and anidulafungin. Indications are evolving but have been approved for complicated forms of invasive
candidiasis, candidemia, disease refractory to other systemic antifungals, and intolerance to amphotericin B. They are broad
spectrum and fungicidal against most Candida species, except C parapsilosis and C guilliermondii.

Caspofungin (Cancidas)
FDA approved to treat candidemia, invasive candidiasis, and esophageal candidiasis. Initially approved to treat refractory
invasive aspergillosis. Also approved as empiric therapy for presumed fungal infections in febrile neutropenic patients. First
of a new class of antifungal drugs (glucan synthesis inhibitors). Inhibits synthesis of (1,3) β -D-glucan, an essential
component of fungal cell wall. This component is not found in mammalian cell walls.

Micafungin (Mycamine)
A member of a new class of antifungal agents, echinocandins, that inhibit cell wall synthesis. Echinocandins inhibit the
synthesis of (1,3)-β -D-glucan, an essential component of the fungal cell wall, not present in mammalian cells. Indications
include prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation, treatment of
esophageal candidiasis, candidemia, and invasive candidiasis.

Anidulafungin (Eraxis)
One of the newer antifungal agents belonging to the echinocandin class. Also inhibits synthesis of (1,3)-β -D-glucan, an
essential component of fungal cell walls. Indicated for treatment of esophageal candidiasis, candidemia, and other forms of
candidal infections (eg, intra-abdominal abscesses, peritonitis).

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Polyenes

Class Summary
These are broad-spectrum fungicidal agents. Mechanism of action is by insertion into fungal cytoplasmic membrane,
causing increases in permeability. Membrane channel activity is increased at lower doses, and pores are formed at higher
concentrations.

Amphotericin B (Fungizone, Amphocin)

One of the oldest antifungals, in use for more than 40 y, and the criterion standard of antifungal therapy.

In recent years, lipid formulations have been developed. Total dose must be adjusted depending on type of candidal
infection being treated. Most patients receive total dose of 0.5-1.5 g.

Amphotericin B, lipid formulations (Amphotec, Abelcet, AmBisome)

Novel lipid formulations of amphotericin B that deliver higher concentrations of drug with a theoretical increase in therapeutic
potential and decreased nephrotoxicity.

Formulation types include amphotericin B lipid complex (ABLC, Abelcet), amphotericin B colloidal dispersion (ABCD,
Amphotec), and liposomal amphotericin B (L-AMB, AmBisome).

ABLC and ABCD approved for treating adults and children intolerant of conventional amphotericin B or with fungal infections
refractory to conventional amphotericin B. L-AMB is approved for aspergillosis, candidiasis, cryptococcosis, and neutropenic
patients with persistent fever on broad-spectrum antibiotics.

Nystatin (Mycostatin)
Fungicidal and fungistatic antibiotic obtained from Streptomyces noursei. Effective against various yeasts and yeastlike
fungi. Changes permeability of fungal cell membrane after binding to cell membrane sterols, causing cellular contents to
leak. Membrane channel activity is increased at lower doses, and pores are formed at higher concentrations.

Antimetabolite

Class Summary
Flucytosine is an antimetabolite originally developed for the treatment of leukemia.

Flucytosine (Ancobon)
It is deaminated to 5-fluorouracil in the fungal cell by an enzyme not present in mammalian cells, and inhibits RNA and
protein synthesis. Active against Candida and Cryptococcus species and generally used in combination with amphotericin
B. It has been used in studies in invasive candidiasis. Avoid use as single agent because of ability to quickly develop
resistance in vivo.

Topical azoles

Class Summary
These agents are used extensively to treat common mucocutaneous uncomplicated forms of candidiasis.

Clotrimazole (Mycelex, Femizole-7)

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Broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal
cells.

Butoconazole (Femstat-3, Gynazole-1)

Broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal
cells.

Use 2% vaginal cream. Available OTC.

Miconazole vaginal (Monistat, Micatin)

Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol. Membrane permeability is increased, causing
nutrients to leak out, resulting in fungal cell death. Lotion preferred in intertriginous areas. If cream is used, apply sparingly
to avoid maceration effects.

Tioconazole (Vagistat-1)
Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol. Membrane permeability is increased, causing
nutrients to leak out, resulting in fungal cell death.

Terconazole vaginal (Terazol-7, Terazol-3)

Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol. Membrane permeability is increased, causing
nutrients to leak out, resulting in fungal cell death.

Allylamines

Class Summary
These agents cause a deficiency of ergosterol within the fungal cell wall, causing fungal cell death.

Terbinafine (Daskil, Lamisil)

For treatment of paronychia; allylamine antifungal, which inhibits squalene epoxidase and decreases ergosterol synthesis,
causing fungal-cell death.

Use medication until symptoms significantly improve.

Duration of treatment should be >1 wk but not >4 wk. May not be as effective for candidal infections as azole antifungals.

Follow-up

Further Outpatient Care

Mucocutaneous candidiasis

Patients treated in the outpatient area may be discharged home with medications. Instruct patients to follow up if the
symptoms persist or worsen.

If the infections are recurrent, perform an HIV antibody test and rule out conditions that produce immune suppression, such
as hematologic malignancies, solid organ malignancy, and diabetes mellitus. If no etiology is established, refer the patients
for consultation with an infectious disease specialist to rule out an underlying immune deficiency.

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Candidemia and disseminated candidiasis

Because of the severity of the infections, some patients may remain hospitalized for a prolonged period.

Patients on outpatient amphotericin B must be monitored 2-3 times weekly because of its high incidence of adverse effects.
The parameters that need to be monitored include CBC count with differentials; electrolyte evaluations; and serum
magnesium, BUN, and serum creatinine levels.

Further Inpatient Care

Inpatient care is frequently prolonged because of the severe nature of the disseminated infections. Antifungal therapy may
be necessary for a prolonged period, either parenterally or orally.

(1,3)β-D-glucan assay is a useful nonculture method for diagnosis of invasive candidiasis. A decrease in levels during
therapy has been associated with treatment success in patients on echinocandin therapy with proven invasive candidiasis.
Consecutive serum measurements may be useful as prognostic markers of response.[52]

Inpatient & Outpatient Medications

With newer treatment modalities that have been recently instituted, de-escalation of antifungal therapy or the rapid switch
from intravenous to oral administration is encouraged. Recent clinical studies suggest that patients who are clinically stable
and have a functional gastrointestinal tract on day 4-5 of parenteral intravenous antifungal administration should be
switched from intravenous to oral therapy with either fluconazole or voriconazole.

Although relatively uncommon, patients may be discharged home on parenteral antifungal therapy or oral azole therapy with
close monitoring for toxicity.

Transfer
Transfer patients to the service that can care for the specific candidal infections (eg, general surgery, ICU).

Transfer patients with sepsis or altered mental status to an appropriate critical care unit.

Deterrence/Prevention
Antifungal prophylaxis of invasive candidiasis in high-risk patients is currently recommended for the following[29, 53] :

Stem cell transplant recipients, primarily those with allogeneic transplants, are recommended to receive fluconazole
initiated 1 day prior to neutropenia and continued until neutropenia resolves. Micafungin and posaconazole are also
recommended for this indication.[54]

Solid organ transplant recipients may be considered for antifungal prophylaxis with fluconazole or liposomal
amphotericin B for the prevention of candidiasis. This is recommended for postoperative antifungal prophylaxis in
liver, pancreas, and small bowel transplant recipients at high risk of candidiasis. Additional indications are being
investigated.[55]

For patients with chemotherapy-induced neutropenia, fluconazole, posaconazole, or caspofungin is recommended

during induction chemotherapy for the duration of neutropenia.

Most recent candidiasis treatment guidelines recommend prophylaxis in high-risk ICU patients in adult units that have
high incidence of invasive candidiasis.[28] Oral nystatin prophylaxis has been shown to decrease colonization in ICU
patients and needs to be investigated as a potential strategy to control candida-related infection in appropriately
selected patients in this setting.[56]
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Currently, no strong indications exist for primary or secondary prevention of oropharyngeal candidiasis (OPC) or vaginal
candidiasis in patients infected with HIV. However, concern does exist about the potential development of resistance or
colonization by resistant species or strains of Candida. Prophylaxis may be indicated in a select group of patients with
recurrent symptomatic candidiasis.

Control the blood glucose level in patients with diabetes mellitus.

Eliminate or decrease risk factors such as steroids, cyclosporin, and tacrolimus.

Nosocomial candidemia prevention should be based on hand hygiene, optimal catheter care, and prudent antimicrobial use.
[57]

Complications
If left untreated, candidemia can lead to metastatic foci of infection in the eyes, vertebral column, liver, spleen, CNS, and
kidneys. Initiate prompt treatment to prevent foci of infection, abscess formation, and death.

Prognosis
Prognosis depends on several factors, such as the site of infection, the degree and type of immunosuppression, and the
rapidity of diagnosis and treatment.

Mucocutaneous candidiasis carries an excellent prognosis, with no mortality and only minimal morbidity.

Systemic candidiasis carries a mortality rate of 30-40% and is generally correlated with the degree of immunosuppression
and the underlying disease. In certain groups of patients, the presentation of Candida infection increases the likelihood of
death, lengthens hospital stays, and increases hospitalization costs.[58, 59]

The longer the delay to initiate antifungal therapy, the higher the morbidity and mortality associated with candidemia and
disseminated candidiasis.

Patient Education
Inform patients and their families about the risk factors associated with mucosal and systemic candidiasis. In addition,
inform them that the systemic form of the disease is extremely serious and is associated with high morbidity and mortality
rates unless aggressive action is undertaken.

For patient education resources, see Infections Center, Children's Health Center, and Skin Conditions & Beauty Center, as
well as Candidiasis (Yeast Infection), Yeast Infection Diaper Rash, and Yeast Infection Skin Rash.

Questions & Answers

Overview

What is candidiasis?

What are the signs and symptoms of chronic mucocutaneous candidiasis?

What are the signs and symptoms of oropharyngeal candidiasis (OPC)?

Which physical findings suggest oropharyngeal candidiasis (OPC)?

What are the types of oropharyngeal candidiasis (OPC)?

What are the symptoms of esophageal candidiasis?

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What are symptoms of nonesophageal GI candidiasis?

What are the types of genitourinary tract candidiasis?

Which tests are performed in the workup of candidiasis?

What are the treatment options for candidiasis?

What is candidiasis and what is its prevalence?

What is the role of candidiasis in the incidence of nosocomial infections?

What are Candida and where are they found?

Which factors contribute to the virulence of Candida?

What are host defense mechanisms against Candida infection?

Which risk factors are associated with invasive or systemic candidiasis?

What is the prevalence of candidiasis in the US?

What is the global prevalence of candidiasis?

What is the mortality and morbidity of mucocutaneous candidiasis in patients with HIV infection?

What is the mortality and morbidity of candidemia and disseminated candidiasis?

How does the incidence of candidiasis vary between males and females?

How does the incidence of candidiasis vary among age groups?

Presentation

Which history and physical findings suggest Candida endophthalmitis?

What is the presentation of candidiasis?

What are the signs and symptoms of generalized cutaneous candidiasis?

What are the signs and symptoms of intertrigo caused by candidiasis?

What is the manifestation of metastatic skin lesions of disseminated candidiasis and candidemia?

What is the manifestation of candida folliculitis?

What is the manifestation of paronychia and onychomycosis caused by candidiasis?

What is chronic mucocutaneous candidiasis?

Which history is associated with chronic mucocutaneous candidiasis?

Which physical findings suggest chronic mucocutaneous candidiasis?

Which history is associated with oropharyngeal candidiasis (OPC)?

Which physical findings suggest oropharyngeal candidiasis (OPC), and what are the types of OPC?

Which history and physical findings suggest esophageal candidiasis?

Which history findings are associated with nonesophageal GI candidiasis?

Which physical findings suggest nonesophageal GI candidiasis?

What is the prevalence of respiratory tract candidiasis?

Which history and physical findings suggest laryngeal candidiasis?

Which history and physical findings suggest Candida tracheobronchitis?

Which history and physical findings suggest Candida pneumonia?

Which history and physical findings suggest vulvovaginal candidiasis (VVC)?

Which history and physical findings suggest Candida balanitis?

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Which history and physical findings suggest Candida cystitis?

Which history and physical findings suggest asymptomatic candiduria?

Which history and physical findings suggest ascending pyelonephritis caused by candidiasis?

What is the manifestation of fungal balls secondary to candidiasis?

Which history and physical findings suggest hepatosplenic candidiasis (chronic systemic candidiasis)?

What are the primary syndromes of systemic candidiasis?

Which history suggests candidemia?

Which physical findings suggest candidemia?

What are the causes of candidemia without invasive disease?

Which history and physical findings suggest disseminated candidiasis?

What are the forms of Candida endophthalmitis?

Which history and physical findings suggest renal candidiasis?

Which history suggests CNS infections due to Candida species?

Which physical findings suggest CNS infections due to Candida?

Which history and physical findings suggest candidal musculoskeletal infections?

Which history suggests Candida arthritis?

What is Candida osteomyelitis?

What is Candida costochondritis?

What is Candida myositis?

Which history and physical findings suggest Candida myocarditis-pericarditis?

Which history and physical findings suggest Candida peritonitis?

What are Candida splenic abscess and hypersplenism?

What is Candida cholecystitis?

Which Candida species cause diseases in humans?

DDX

What are the diagnostic considerations of candidiasis?

What are the differential diagnoses for Candidiasis?

Workup

What is the role of lab studies in the workup of candidiasis?

Which blood tests for detecting Candida have been approved by the FDA for the workup of candidiasis?

Which lab studies are performed in the workup of mucocutaneous candidiasis?

Which lab studies are performed in the workup of candidemia and disseminated candidiasis?

Which lab studies are performed in the workup of cutaneous candidiasis?

Which lab studies are performed in the workup of genitourinary candidiasis?

Which lab studies are performed in the workup of respiratory tract candidiasis?

Which procedures are performed in the workup of GI candidiasis?

Which lab studies are performed in the workup of focal hepatosplenic candidiasis?

How are Candida species identified in the workup of candidiasis?

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What is the role of antifungal susceptibility testing in the workup of candidiasis?

What is the role of nonculture Candida detection assays in the workup of candidiasis?

What is the efficacy of T2Candida in the diagnosis of candidiasis?

What is the role of imaging studies in the workup of candidiasis?

What is the role of chest radiography in the workup of candidiasis?

What is the role of esophagography or upper GI studies in the workup of candidiasis?

What is the role of ultrasonography in the workup of candidiasis?

What is the role of CT scanning in the workup of candidiasis?

What is the role of echocardiography in the workup of candidiasis?

Which procedure may be performed in the workup of candidemia or disseminated candidiasis?

What is the role of bronchoscopy in the workup of candidiasis?

What is the role of endoscopy in the workup of candidiasis?

What is the role of echocardiography in the workup of candidiasis?

What are the expected histologic findings in candidiasis?

Treatment

What are the treatment options for candidiasis?

What are the IDSA recommendations for the treatment of candidiasis?

What is the role of fluconazole in the treatment of candidiasis?

What is the role of ketoconazole in the treatment of candidiasis?

What are the treatment options for cutaneous candidiasis?

What are the treatment options for oropharyngeal candidiasis (OPC)?

What are the treatment options for candidiasis infections in HIV-positive patients?

What are the treatment options for Candida esophagitis?

What are the treatment options for vulvovaginal candidiasis (VVC)?

What are the treatment options for asymptomatic candiduria?

What are the treatment options for Candida cystitis?

What are the treatment options for renal candidiasis?

What are the treatment options for candidemia in patients without neutropenia?

What are the treatment options for candidemia in patients with neutropenia?

What is the standard regimen of fluconazole for the treatment of candidemia?

Which echinocandins are used for the treatment of candidemia?

Besides echinocandins, what are other drug options for the treatment of candidemia?

Which medications are used for treating disseminated candidiasis with end organ infection?

What are the treatment options for chronic mucocutaneous candidiasis?

What are the treatment options for hepatosplenic candidiasis?

What are the treatment options for respiratory tract candidiasis?

What are the empirical treatment options for suspected invasive candidiasis?

What are the treatment options for disseminated candidiasis with end organ infection?
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What is the first-line therapy for disseminated candidiasis with end organ infection?

What are the treatment options for antifungal resistant candidiasis?

What are the alternative antifungal regimens for candidiasis treatment?

What is the indication for surgical drainage procedures in candidiasis?

What is the treatment for prosthetic joints infected with Candida?

What is the treatment of sternal candida infections?

What is the treatment for splenic abscess in patients with candidiasis?

What is the treatment for endocarditis in patients with candidiasis?

What is the treatment for fungal endophthalmitis?

When is specialist consultation needed for the treatment of candidiasis?

Guidelines

What are the IDSA treatment guidelines for candidiasis?

Medications

When should antifungal therapy for systemic Candida infections be initiated?

Which classes of antifungals are used in the treatment of candidiasis?

Which medications in the drug class Allylamines are used in the treatment of Candidiasis?

Which medications in the drug class Topical azoles are used in the treatment of Candidiasis?

Which medications in the drug class Antimetabolite are used in the treatment of Candidiasis?

Which medications in the drug class Polyenes are used in the treatment of Candidiasis?

Which medications in the drug class Glucan synthesis inhibitors (echinocandins) are used in the treatment of Candidiasis?

Which medications in the drug class Azole Antifungals are used in the treatment of Candidiasis?

Follow-up

What follow-up outpatient care is needed for mucocutaneous candidiasis?

What monitoring is required for patients receiving amphotericin B for the treatment of candidemia and disseminated
candidiasis?

How is candidiasis treated in an inpatient setting?

Which medications are indicated for inpatient and outpatient treatment of candidiasis?

What are indications for transfer of patients with candidiasis?

When is antifungal prophylaxis of invasive candidiasis indicated?

What are the indications for primary or secondary prevention of oropharyngeal candidiasis (OPC) or vaginal candidiasis?

How is candidiasis prevented in patients with diabetes mellitus?

How is candidiasis prevented or deterred?

How is nosocomial candidemia prevented?

What are the possible complications of untreated candidiasis?

Which factors affect the prognosis of candidiasis?

What is the prognosis of mucocutaneous candidiasis?

What is the prognosis of systemic candidiasis?

Which factor improves the prognosis of candidemia and disseminated candidiasis?

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What education should be given to patients with candidiasis?

Contributor Information and Disclosures

Author

Jose A Hidalgo, MD Assistant Professor, Universidad Nacional Mayor de San Marcos; Attending Physician, Department of
Internal Medicine, Division of Infectious Diseases, Guillermo Almenara Hospital, Peru

Jose A Hidalgo, MD is a member of the following medical societies: HIV Medicine Association, Infectious Diseases Society
of America

Disclosure: Nothing to disclose.

Coauthor(s)

Jose A Vazquez, MD, FACP, FIDSA Chief, Division of Infectious Diseases, Professor, Department of Medicine, Medical
College of Georgia at Augusta University

Jose A Vazquez, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians,
American Society for Microbiology, HIV Medicine Association, Immunocompromised Host Society, Infectious Diseases
Society of America, International AIDS Society, International Immunocompromised Host Society, International Society for
Human and Animal Mycology, International Society for Infectious Diseases, Medical Mycological Society of the Americas,
Michigan Infectious Disease Society, Mycological Society of America, National Foundation for Infectious Diseases

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cidara; Amplyx;
F2G<br/>Serve(d) as a speaker or a member of a speakers bureau for: Allergan; Astellas.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of
Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed
Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American
College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of
Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America,
Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

David Hall Shepp, MD Program Director, Fellowship in Infectious Diseases, Department of Medicine, North Shore
University Hospital; Associate Professor, New York University School of Medicine

David Hall Shepp, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Received salary from Gilead Sciences for management position.

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