Invasive candidiasis is an infection (

candidiasis Candidiasis is a fungal infection due to any species of the genus '' Candida'' (a 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 ...

) that can be caused by various species of ''Candida'' yeast. Unlike ''Candida'' infections of the mouth and throat ( oral candidiasis) or vagina ( ''Candidal'' vulvovaginitis), invasive candidiasis is a serious, progressive, and potentially fatal infection that can affect the blood ( fungemia), 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 fungemia,

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, o ...

, endophthalmitis,

osteomyelitis Osteomyelitis (OM) is the infectious inflammation of bone marrow. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The feet, spine, and hips are the most commonly involved bones in adults. The cause is ...

, 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 ...

medications used to treat candidiasis.

Resistance

Resistance to

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. These include candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to pr ...

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 dubbed the "penicillin of antifungals," along w ...

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'' is an emerging multidrug-resistant 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 * Long-term

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 intensive care medicine. An inten ...

stay * Abdominal surgery (aggravated by anastomotic leakage or repeat laparotomies) * Immunosuppressive diseases * Acute necrotizing pancreatitis * Malignant hematologic disease * Solid-organ transplantation *

Hematopoietic stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce ...

* Solid- organ tumors *

Neonates In common terminology, a baby is the very young offspring of adult human beings, while infant (from the Latin word ''infans'', meaning 'baby' or 'child') is a formal or specialised synonym. The terms may also be used to refer to Juvenile (orga ...

(especially low birth weight and preterm infants) *

Broad-spectrum antibiotic A broad-antimicrobial spectrum, spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are ...

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 centr ...

* Internal prosthetic device *

Total parenteral nutrition Parenteral nutrition (PN), or intravenous feeding, is the feeding of nutritional products to a person intravenously, bypassing the usual process of eating and digestion. The products are made by pharmaceutical compounding entities or standard pha ...

Hemodialysis Hemodialysis, American and British English spelling differences#ae and oe, also spelled haemodialysis, or simply ''"'dialysis'"'', is a process of filtering the blood of a person whose kidneys are not working normally. This type of Kidney dialys ...

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 vertebra ...

use *

Chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

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

Transmission

Invasive candidiasis is a nosocomial infection with the majority of cases associated with hospital stays.

Diagnosis

Because many ''Candida'' species are part of the

human microbiota Human microbiota are microorganisms (bacteria, viruses, fungi and archaea) found in a specific environment. They can be found in the stomach, intestines, skin, genitals and other parts of the body. Various body parts have diverse microorganisms. S ...

, 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 Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...

pericardium The pericardium (: pericardia), 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 inelastic connective tissue (fibrous pericardium), ...

pericardial fluid Pericardial fluid is the serous fluid secreted by the Serous membrane, serous layer of the pericardium into the pericardial cavity. The pericardium consists of two layers, an outer fibrous layer and the inner serous layer. This serous layer has t ...

, 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 fungemia, 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 language, Greek words: 'tissue', 'suffering', and ''-logy, -logia'' 'study of') is the light microscope, microscopic examination of Tissue (biology), tissue in order to study the manifestations of dis ...

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 o ...

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 institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...

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 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, hence th ...

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 perforation Gastrointestinal perforation, also known as gastrointestinal rupture, is a hole in the wall of the gastrointestinal tract. The gastrointestinal tract is composed of hollow digestive organs leading from the mouth to the anus. Symptoms of gastroi ...

s 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 that can lead to the emergence of resistance.

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. It is a member of a class of antifungals termed the echinocandins. It works by inhibiting the enzyme (1→3)-β-D-glucan synthase and thereby di ...

, micafungin, or anidulafungin) given intravenously.

Fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. These include candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to pr ...

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 cryptococ ...

, 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

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

s) 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

{{Medical resources , ICD10 = {{ICD10, B37 , ICD9 = , ICDO = , OMIM = , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet =
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