Invasive candidiasis

Last updated
Invasive candidiasis
Specialty Infectious disease
Symptoms fever and chills

Invasive candidiasis is an infection (candidiasis) 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. [1] [2]

Contents

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. [3] [2]

Presentation

Invasive candidiasis can manifest as serious diseases including as fungemia, endocarditis, endophthalmitis, osteomyelitis, and central nervous system infections. [4]

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. [4] 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. [4] 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 medications used to treat candidiasis. [5]

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 and of C. parapsilosis where there was increased use of echinocandins. 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.[ citation needed ]

Emergent species

Candida auris is an emerging multidrug-resistant yeast that can cause invasive candidiasis and is associated with high mortality. [6] It was first described in 2009. [6] 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. [6] The strains isolated in each region are genetically distinct, indicating that this species is emerging in different locations. [6] The reason for this pattern is unknown. [6]

Risk factors

Patients with the following conditions, treatments or situations are at increased risk for invasive candidiasis. [4] [2] [7]

Transmission

Invasive candidiasis is a nosocomial  infection with the majority of cases associated with hospital stays. [4]

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. [2]

Positive culture of Candida species from normally sterile sites, such as blood, cerebrospinal fluid, pericardium, pericardial fluid, or biopsied tissue, is definitive evidence of invasive candidiasis. [2] Diagnosis by culturing allows subsequent susceptibility testing of causative species. [8] [7] Sensitivity of blood culture is far from ideal, with a sensitivity reported to be between 21 and 71%. [7] 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. [7]

Diagnosis of invasive candidiasis is supported by histopathologic evidence (for example, yeast cells or hyphae) observed in specimens of affected tissues. [2]

Additionally, elevated serum β-glucan can demonstrate invasive candidiasis while a negative test suggests a low likelihood of systemic infection. [9] [2]

The emergence of multidrug-resistant C. auris as a cause of invasive candidiasis has necessitated additional testing in some settings. [6] C. auris-caused invasive candidiasis is associated with high mortality. [6] 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. [6] Biochemical-based tests currently used in many laboratories to identify fungi, including API 20C AUX and VITEK-2, cannot differentiate C. auris from related species (for example, C. auris can be identified as C. haemulonii). [6] Therefore, the Centers for Disease Control and Prevention 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 to identify C. auris in settings where it may be present. [6]

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. [7] For example, one group would be patients recovering from abdominal surgery that may have gastrointestinal perforations or anastomotic leakage. [7] Antifungal prophylaxis can reduce the incidence of fungemia by approximately 50%, but has not been shown to improve survival. [7] 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. [7]

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 echinocandin class antifungal (caspofungin, micafungin, or anidulafungin) given intravenously. Fluconazole, amphotericin B, and other antifungals may also be used. [10] 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. [10] Retrospective observational studies suggest that prompt presumptive antifungal therapy (based on symptoms or biomarkers) is effective and can reduce mortality. [7]

Epidemiology

Invasive candidiasis is estimated to affect more than 250,000 people and cause more than 50,000 deaths worldwide every year. [7] The CDC estimates that approximately 46,000 cases of healthcare-associated invasive candidiasis occur each year in the US. [11]  The estimated mortality attributable to fungemia is 19-40%. [7] [11] 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. [11] Fungemia is one of the most common bloodstream infections in the United States. [11] In general, observed incidence rates have been stable or trending higher but declining rates have been achieved with improvements in hygiene and disease management. [7]

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. [7]

The distribution of Candida species causing invasive candidiasis has changed over the past decades. [7] C. albicans had been the dominant pathogen but now accounts for just half of the isolates. [7] 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. [7] Regional species distribution guides treatment recommendations since the species exhibit different susceptibilities to azole and echinocandin classes of antifungals. [7]

The virulence of Candida species differs considerably, with C. parapsilosis and C. krusei being less virulent than C. albicans, C. tropicalis, and C. glabrata. [7] This variation is reflected in mortality rates. [7]

Related Research Articles

<span class="mw-page-title-main">Candidiasis</span> Fungal infection due to any type of Candida

Candidiasis is a fungal infection due to any type of Candida. 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 and throat. Other symptoms may include soreness and problems swallowing. When it affects the vagina, it may be referred to as a yeast infection or thrush. Signs and symptoms include genital itching, burning, and sometimes a white "cottage cheese-like" discharge from the vagina. Yeast infections of the penis are less common and typically present with an itchy rash. Very rarely, yeast infections may become invasive, spreading to other parts of the body. This may result in fevers along with other symptoms depending on the parts involved.

<i>Candida albicans</i> Species of fungus

Candida albicans is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usually a commensal organism, but it can become pathogenic in immunocompromised individuals under a variety of conditions. It is one of the few species of the genus Candida that cause the human infection candidiasis, which results from an overgrowth of the fungus. Candidiasis is, for example, often observed in HIV-infected patients. C. albicans is the most common fungal species isolated from biofilms either formed on (permanent) implanted medical devices or on human tissue. C. albicans, C. tropicalis, C. parapsilosis, and C. glabrata are together responsible for 50–90% of all cases of candidiasis in humans. A mortality rate of 40% has been reported for patients with systemic candidiasis due to C. albicans. By one estimate, invasive candidiasis contracted in a hospital causes 2,800 to 11,200 deaths yearly in the US. Nevertheless, these numbers may not truly reflect the true extent of damage this organism causes, given new studies indicating that C. albicans can cross the blood–brain barrier in mice.

<span class="mw-page-title-main">Antifungal</span> Pharmaceutical fungicide or fungistatic used to treat and prevent mycosis

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 cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.

<i>Candida</i> (fungus) Genus of ascomycete fungi

Candida is a genus of yeasts and is the most common cause of fungal infections worldwide. In fact, it is the largest genus of medically important yeasts.

<span class="mw-page-title-main">Fluconazole</span> Antifungal medication

Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts. It is given either by mouth or by injection into a vein.

<span class="mw-page-title-main">Oral candidiasis</span> Fungal infection

Oral candidiasis, also known as oral thrush among other names, is candidiasis that occurs in the mouth. That is, oral candidiasis is a mycosis of Candida species on the mucous membranes of the mouth.

<span class="mw-page-title-main">Fungal infection</span> Disease caused by fungi to animals or humans

Fungal infection, also known as mycosis, is a disease caused by fungi. Different types are traditionally divided according to the part of the body affected; superficial, subcutaneous, and systemic. Superficial fungal infections include common tinea of the skin, such as tinea of the body, groin, hands, feet and beard, and yeast infections such as pityriasis versicolor. Subcutaneous types include eumycetoma and chromoblastomycosis, which generally affect tissues in and beneath the skin. Systemic fungal infections are more serious and include cryptococcosis, histoplasmosis, pneumocystis pneumonia, aspergillosis and mucormycosis. Signs and symptoms range widely. There is usually a rash with superficial infection. Fungal infection within the skin or under the skin may present with a lump and skin changes. Pneumonia-like symptoms or meningitis may occur with a deeper or systemic infection.

<span class="mw-page-title-main">Caspofungin</span> Antifungal medication

Caspofungin 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 works by inhibiting the enzyme (1→3)-β-D-glucan synthase and thereby disturbing the integrity of the fungal cell wall. Caspofungin was the first inhibitor of fungal (1→3)-β-D-glucan synthesis to be approved by the United States Food and Drug Administration. Caspofungin is administered intravenously.

<span class="mw-page-title-main">Fungal pneumonia</span> Infection of the lungs by fungi

Fungal pneumonia is an infection of the lungs by fungi. It can be caused by either endemic or opportunistic fungi or a combination of both. Case mortality in fungal pneumonias can be as high as 90% in immunocompromised patients, though immunocompetent patients generally respond well to anti-fungal therapy.

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 any kind. Infections by other fungi, including Saccharomyces, Aspergillus and Cryptococcus, are also called fungemia. It is most commonly seen in immunosuppressed or immunocompromised patients with severe neutropenia, cancer patients, or in patients with intravenous catheters. It has been suggested that otherwise immunocompetent patients taking infliximab may also be at a higher risk for fungemia.

<span class="mw-page-title-main">Anidulafungin</span> Antifungal medication

Anidulafungin (INN) is a semisynthetic echinocandin used as an antifungal drug. It was previously known as LY303366. It may also have application in treating invasive Aspergillus infection when used in combination with voriconazole. It is a member of the class of antifungal drugs known as the echinocandins; its mechanism of action is by inhibition of (1→3)-β-D-glucan synthase, an enzyme important to the synthesis of the fungal cell wall.

Candida parapsilosis is a fungal species of yeast that has become a significant cause of sepsis and of wound and tissue infections in immunocompromised people. Unlike Candida albicans and Candida tropicalis, C. parapsilosis is not an obligate human pathogen, having been isolated from nonhuman sources such as domestic animals, insects and soil. C. parapsilosis is also a normal human commensal and it is one of the fungi most frequently isolated from human hands. There are several risk factors that can contribute to C. parapsilosis colonization. Immunocompromised individuals and surgical patients, particularly those undergoing surgery of the gastrointestinal tract, are at high risk for infection with C. parapsilosis. There is currently no consensus on the treatment of invasive candidiasis caused by C. parapsilosis, although the therapeutic approach typically includes the removal of foreign bodies such as implanted prostheses and the administration of systemic antifungal therapy. Amphotericin B and Fluconazole are often used in the treatment of C. parapsilosis infection.

Candida krusei is a budding yeast involved in chocolate production. Candida krusei is an emerging fungal nosocomial pathogen primarily found in the immunocompromised and those with hematological malignancies. It has natural resistance to fluconazole, a standard antifungal agent. It is most often found in patients who have had prior fluconazole exposure, sparking debate and conflicting evidence as to whether fluconazole should be used prophylactically. Mortality due to C. krusei fungemia is much higher than the more common C. albicans. Other Candida species that also fit this profile are C. parapsilosis, C. glabrata, C. tropicalis, C. guillermondii and C. rugosa. Candida krusei is the anamorph name; the teleomorph name for the same organism is Pichia kudriavzevii. The International Commission on the Taxonomy of Fungi (ICTF) and the Nomenclature Committee for Fungi (NCF) have proposed revising the standard name to Pichia kudriavzevii in 2021.

<i>Candida glabrata</i> Species of fungus

Candida glabrata is a species of haploid yeast of the genus Candida, previously known as Torulopsis glabrata. Despite the fact that no sexual life cycle has been documented for this species, C. glabrata strains of both mating types are commonly found. C. glabrata is generally a commensal of human mucosal tissues, but in today's era of wider human immunodeficiency from various causes, C. glabrata is often the second or third most common cause of candidiasis as an opportunistic pathogen. Infections caused by C. glabrata can affect the urogenital tract or even cause systemic infections by entrance of the fungal cells in the bloodstream (Candidemia), especially prevalent in immunocompromised patients.

<span class="mw-page-title-main">Echinocandin</span> Group of chemical compounds

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 with the related papulacandins, as their mechanism of action resembles that of penicillin in bacteria. β-glucans are carbohydrate polymers that are cross-linked with other fungal cell wall components, the fungal equivalent to bacterial peptidoglycan. Caspofungin, micafungin, and anidulafungin are semisynthetic echinocandin derivatives with limited clinical use due to their solubility, antifungal spectrum, and pharmacokinetic properties.

Pathogenic fungi are fungi that cause disease in humans or other organisms. Although fungi are eukaryotic, many pathogenic fungi are microorganisms. Approximately 300 fungi are known to be pathogenic to humans; their study is called "medical mycology". Fungal infections kill more people than either tuberculosis or malaria—about 2 million people per year.

<span class="mw-page-title-main">Vaginal yeast infection</span> Medical condition

Vaginal yeast infection, also known as candidal vulvovaginitis and vaginal thrush, is excessive growth of yeast in the vagina that results in irritation. The most common symptom is vaginal itching, which may be severe. Other symptoms include burning with urination, a thick, white vaginal discharge that typically does not smell bad, pain during sex, and redness around the vagina. Symptoms often worsen just before a woman's period.

<i>Candida auris</i> Species of fungus

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. auris can cause invasive candidiasis (fungemia) in which the bloodstream, the central nervous system, and internal organs are infected. It has attracted widespread attention because of its multiple drug resistance. Treatment is also complicated because it is easily misidentified as other Candida species.

<i>Candida tropicalis</i> Species of fungus

Candida tropicalis is a species of yeast in the genus Candida. It is a common pathogen in neutropenic hosts, in whom it may spread through the bloodstream to peripheral organs. For invasive disease, treatments include amphotericin B, echinocandins, or extended-spectrum triazole antifungals.

<span class="mw-page-title-main">Ibrexafungerp</span> Medication

Ibrexafungerp, sold under the brand name Brexafemme, is an antifungal medication used to treat vulvovaginal candidiasis (VVC). It is taken orally. It is also currently undergoing clinical trials for other indications via an intravenous (IV) formulation. An estimated 75% of women will have at least one episode of VVC and 40 to 45% will have two or more episodes in their lifetime.

References

  1. ↑ "Invasive Candidiasis | Candidiasis | Types of Fungal Diseases | Fungal Diseases | CDC". www.cdc.gov. Retrieved 2017-04-02.
  2. 1 2 3 4 5 6 7 "Candidiasis (Invasive) – Infectious Diseases". MSD Manual Professional Edition. Retrieved 2017-04-06.
  3. ↑ "Symptoms | Invasive Candidiasis | Candidiasis | Types of Diseases | Fungal Diseases | CDC". www.cdc.gov. Retrieved 2017-04-03.
  4. 1 2 3 4 5 Yapar, Nur (2014-01-01). "Epidemiology and risk factors for invasive candidiasis". Therapeutics and Clinical Risk Management. 10: 95–105. doi: 10.2147/TCRM.S40160 . ISSN   1176-6336. PMC   3928396 . PMID   24611015.
  5. ↑ "Fatal Fungus Linked to 4 New Deaths – What You Need to Know". 2016-11-07. Retrieved 2017-04-04.
  6. 1 2 3 4 5 6 7 8 9 10 "Clinical Alert to U.S. Healthcare Facilities – Fungal Diseases | CDC". www.cdc.gov. June 2016. Retrieved 2017-04-06.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Kullberg, Bart Jan; Arendrup, Maiken C. (2015-10-08). "Invasive Candidiasis". The New England Journal of Medicine. 373 (15): 1445–1456. doi:10.1056/NEJMra1315399. hdl: 2066/152392 . ISSN   1533-4406. PMID   26444731. S2CID   43788.
  8. ↑ "Diagnosis and Testing | Invasive Candidiasis | Candidiasis | Types of Diseases | Fungal Diseases | CDC". www.cdc.gov. Retrieved 2017-04-03.
  9. ↑ Vincenzi, V.; Fioroni, E.; Benvegnù, B.; De Angelis, M.; Bartolucci, L.; Gradoli, C.; Valori, C. (1985-05-12). "[Effects of calcium antagonists on pancreatic endocrine secretion]". Minerva Medica. 76 (19–20): 919–921. ISSN   0026-4806. PMID   3889722.
  10. 1 2 "Treatment | Invasive Candidiasis | Candidiasis | Types of Diseases | Fungal Diseases | CDC". www.cdc.gov. Retrieved 2017-04-03.
  11. 1 2 3 4 "Statistics | Invasive Candidiasis | Candidiasis | Types of Diseases | Fungal Diseases | CDC". www.cdc.gov. Retrieved 2017-04-03.

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