Invasive candidiasis is an infection (

candidiasis Candidiasis is a fungal infection due to any type of '' Candida'' (a type of yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth ...

) that can be caused by various species of ''Candida'' yeast. Unlike ''Candida'' infections of the mouth and throat (

oral candidiasis Oral candidiasis, also known as oral thrush among other names, is candidiasis that occurs in the mouth. That is, oral candidiasis is a mycosis (yeast/fungal infection) of ''Candida'' species on the mucous membranes of the mouth. ''Candida albica ...

) or vagina ( ''Candidal'' vulvovaginitis), invasive candidiasis is a serious, progressive, and potentially fatal infection that can affect the blood (

fungemia Fungemia is the presence of fungi or yeasts in the blood. The most common type, also known as candidemia, candedemia, or systemic candidiasis, is caused by '' Candida'' species; candidemia is also among the most common bloodstream infections of a ...

), heart, brain, eyes, bones, and other parts of the body.

Signs and symptoms

Symptoms of invasive candidiasis can be confused with other medical conditions, however, the most common symptoms are fever and chills that do not improve with antibiotic treatment. Other symptoms develop as the infection spreads, depending on which parts of the body are involved.

Presentation

Invasive candidiasis can manifest as serious diseases including as

endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...

endophthalmitis Endophthalmitis is inflammation of the interior cavity of the eye, usually caused by infection. It is a possible complication of all intraocular surgeries, particularly cataract surgery, and can result in loss of vision or loss of the eye itself ...

osteomyelitis Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...

, and central nervous system infections.

Cause

Invasive candidiasis is caused by 15 of the more than 150 known species of ''Candida''. These species, all confirmed by isolation from patients, are: C. albicans, ''C. glabrata'', ''C. tropicalis'', ''C. parapsilosis'', ''C. krusei'', ''C. guilliermondii'', ''C. lusitaniae'', ''C. dubliniensis'', ''C. pelliculosa'', ''C. kefyr'', ''C. lipolytica'', C. famata, ''C. inconspicua'', ''C. rugosa'', and ''C. norvegensis''. Over the last 20–30 years, ''C. albicans'' has been responsible for 95% of infections, with, ''C. glabrata'', ''C. parapsilosis'', ''C. tropicalis'', and ''C. krusei'' causing the majority of the remaining cases. Recently, ''C. auris'', a species first reported in 2009, has been found to cause invasive candidiasis. ''C. auris'' has attracted attention because it can be resistant to the

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as crypto ...

medications used to treat candidiasis.

Resistance

Resistance to antifungal treatment can arise from species with intrinsic resistance that experience selection pressure or spontaneous induction of resistance in isolates from normally susceptible species. For ''Candida'', the most common is the former, as seen by the emergence of resistant ''C. glabrata'' following the introduction of

fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prevent ...

and of ''C. parapsilosis'' where there was increased use of

echinocandin Echinocandins are a class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been termed the " penicillin of antifungals," along ...

s. Insufficient dosing of azoles has also led to the emergence of resistance. Observed rates of echinocandin resistance for ''C. glabrata'' are between 2 and 12%. Acquired echinocandin resistance has also been reported for ''C. albicans'', ''C. tropicalis'', ''C. krusei'', ''C. kefyr'', ''C. lusitaniae'', and ''C. dubliniensis''.

Emergent species

Candida auris ''Candida auris'' is a species of fungus that grows as yeast. It is one of the few species of the genus '' Candida'' which cause candidiasis in humans. Often, candidiasis is acquired in hospitals by patients with weakened immune systems. ''C. ...

'' is an emerging

multidrug-resistant Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are c ...

yeast that can cause invasive candidiasis and is associated with high mortality. It was first described in 2009. Since then, ''C. auris'' infections, specifically fungemia, have been reported from South Korea, India, South Africa, Kuwait, Colombia, Venezuela, Pakistan, the United Kingdom and the United States. The strains isolated in each region are genetically distinct, indicating that this species is emerging in different locations. The reason for this pattern is unknown.

Risk factors

Patients with the following conditions, treatments or situations are at increased risk for invasive candidiasis. *

Critical illness Intensive care medicine, also called critical care medicine, is a medical specialty that deals with seriously or critically ill patients who have, are at risk of, or are recovering from conditions that may be life-threatening. It includes pro ...

* Long-term

intensive care unit 220px, Intensive care unit An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensiv ...

stay * Abdominal surgery (aggravated by

anastomotic An anastomosis (, plural anastomoses) is a connection or opening between two things (especially cavities or passages) that are normally diverging or branching, such as between blood vessels, leaf veins, or streams. Such a connection may be normal ...

leakage or repeat laparotomies) * Immunosuppressive diseases * Acute necrotizing pancreatitis * Malignant hematologic disease * Solid-organ transplantation * Hematopoietic stem cell transplantation * Solid- organ tumors * Neonates (especially low birth weight and preterm infants) * Broad-spectrum antibiotic treatment *

Central venous catheter A central venous catheter (CVC), also known as a central line(c-line), central venous line, or central venous access catheter, is a catheter placed into a large vein. It is a form of venous access. Placement of larger catheters in more central ...

* Internal prosthetic device * Total parenteral nutrition * Hemodialysis *

Glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...

use *

Chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

* Noninvasive ''Candida'' colonization (particularly if multifocal)

Transmission

Invasive candidiasis is a

nosocomial A hospital-acquired infection, also known as a nosocomial infection (from the Greek , meaning "hospital"), is an infection that is acquired in a hospital or other health care facility. To emphasize both hospital and nonhospital settings, it is ...

infection with the majority of cases associated with hospital stays.

Diagnosis

Because many ''Candida'' species are part of the human microbiota, their presence in the mouth, the vagina, sputum, urine, stool, or skin is not definitive evidence for invasive candidiasis. Positive culture of ''Candida'' species from normally sterile sites, such as blood,

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...

pericardium The pericardium, also called pericardial sac, is a double-walled sac containing the heart and the roots of the great vessels. It has two layers, an outer layer made of strong connective tissue (fibrous pericardium), and an inner layer made of ...

, pericardial fluid, or biopsied tissue, is definitive evidence of invasive candidiasis. Diagnosis by culturing allows subsequent susceptibility testing of causative species. Sensitivity of blood culture is far from ideal, with a sensitivity reported to be between 21 and 71%. Additionally, whereas blood culture can establish a diagnosis during

, the blood may test negative for deep-seated infections because candida may have been successfully cleared from the blood. Diagnosis of invasive candidiasis is supported by

histopathologic Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...

evidence (for example, yeast cells or

hypha A hypha (; ) is a long, branching, filamentous structure of a fungus, oomycete, or actinobacterium. In most fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium. Structure A hypha consists of one or ...

e) observed in specimens of affected tissues. Additionally, elevated serum β-glucan can demonstrate invasive candidiasis while a negative test suggests a low likelihood of systemic infection. The emergence of multidrug-resistant ''C. auris'' as a cause of invasive candidiasis has necessitated additional testing in some settings. ''C. auris''-caused invasive candidiasis is associated with high mortality. Many ''C. auris'' isolates have been found to be resistant to one or more of the three major antifungal classes (azoles, echinocandins, and polyenes) with some resistant to all three classes – severely limiting treatment options. Biochemical-based tests currently used in many laboratories to identify fungi, includin
API 20C AUX and VITEK-2
cannot differentiate ''C. auris'' from related species (for example, ''C. auris'' can be identified as ''C. haemulonii''). Therefore, the

Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...

recommends using a diagnostic method based on matrix-assisted laser desorption/ionization-time of flight mass spectrometry or a molecular method based on sequencing the D1-D2 region of the

28s rDNA 28S ribosomal RNA is the structural ribosomal RNA (rRNA) for the LSU rRNA, large subunit (LSU) of eukaryotic cytoplasmic ribosomes, and thus one of the basic components of all eukaryotic cells. It has a size of 25S in plants and 28S in mammals, ...

to identify ''C. auris'' in settings where it may be present.

Prevention

Preventive antifungal treatment is supported by studies, but only for specific high-risk groups in intensive care units with conditions that put them at high risk for the disease. For example, one group would be patients recovering from abdominal surgery that may have gastrointestinal perforations or anastomotic leakage. Antifungal prophylaxis can reduce the incidence of fungemia by approximately 50%, but has not been shown to improve survival. A major challenge limiting the number of patients receiving prophylaxis to only those that can potentially benefit, thereby avoiding the creation of

selective pressure Any cause that reduces or increases reproductive success in a portion of a population potentially exerts evolutionary pressure, selective pressure or selection pressure, driving natural selection. It is a quantitative description of the amount of ...

that can lead to the emergence of

resistance Resistance may refer to: Arts, entertainment, and media Comics * Either of two similarly named but otherwise unrelated comic book series, both published by Wildstorm: ** ''Resistance'' (comics), based on the video game of the same title ** ''T ...

Treatment

Antifungals are used for treatment with the specific type and dose depending on the patient's age, immune status, and specifics of the infection. For most adults, the initial treatment is an

class antifungal (

caspofungin Caspofungin (INN) (brand name Cancidas) is a lipopeptide antifungal drug from Merck & Co., Inc. discovered by James Balkovec, Regina Black and Frances A. Bouffard. It is a member of a new class of antifungals termed the echinocandins. It wor ...

micafungin Micafungin, sold under the brand name Mycamine, is an echinochandin antifungal medication used to treat and prevent invasive fungal infections including candidemia, abscesses, and esophageal candidiasis. It inhibits the production of beta-1,3-g ...

, or

anidulafungin Anidulafungin (International nonproprietary name, INN) (trade names Eraxis, Ecalta) is a Semisynthesis, semisynthetic echinocandin used as an antifungal medication, antifungal drug. It was previously known as LY303366. It may also have applicatio ...

) given intravenously.

Fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prevent ...

amphotericin B Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis. Fo ...

, and other antifungals may also be used. Treatment normally continues for two weeks after resolution of signs and symptoms and ''Candida'' yeasts can no longer can be cultured from blood samples. Some forms of invasive candidiasis, such as infections in the bones, joints, heart, or central nervous system, usually need to be treated for a longer period. Retrospective observational studies suggest that prompt presumptive antifungal therapy (based on symptoms or biomarkers) is effective and can reduce mortality.

Epidemiology

Invasive candidiasis is estimated to affect more than 250,000 people and cause more than 50,000 deaths worldwide every year. The CDC estimates that approximately 46,000 cases of healthcare-associated invasive candidiasis occur each year in the US. The estimated mortality attributable to fungemia is 19-40%. However, because the majority of people who develop invasive candidiasis are already sick, it can be difficult to determine if the cause of death is directly attributable to the fungal infection. Fungemia is one of the most common bloodstream infections in the United States. In general, observed incidence rates have been stable or trending higher but declining rates have been achieved with improvements in hygiene and disease management. Deep-seated infections in bones, muscles, joints, eyes, or central nervous system can arise from a bloodstream infection or direct inoculation of ''Candida'' may occur, for example, during intestinal surgery. The distribution of ''Candida'' species causing invasive candidiasis has changed over the past decades. ''C. albicans'' had been the dominant pathogen but now accounts for just half of the isolates. Increasing dominance of ''C. glabrata'' in northern Europe, the United States, and Canada has been observed while ''C. parapsilosis'' has become more prominent in southern Europe, Asia, and South America. Regional species distribution guides treatment recommendations since the species exhibit different susceptibilities to azole and echinocandin classes of antifungals. The virulence of ''Candida'' species differs considerably, with ''C. parapsilosis'' and ''C. krusei'' being less virulent than ''C. albicans'', ''C. tropicalis'', and ''C. glabrata''. This variation is reflected in mortality rates.

References

External links

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Candidiasis (Invasive
in the MSD (Merck) Manual
Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America
Animal fungal diseases Sepsis