Introduction
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.1 Candida infections can involve any anatomical structure.
Pathophysiology
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.2 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 florae - Broad-spectrum antibiotics
Risk factors associated with invasive or systemic candidiasis include the following:3
- 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
- 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 florae.
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.4
In persons with systemic infections, Candida species are now the fourth most commonly isolated pathogens from blood cultures.5
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.6,7 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 Candida esophagitis, 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 are at high risk for blood culture–proven late-onset candidiasis (defined as sepsis that develops after age 72 h).8
Clinical
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.
- 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.
- Candida folliculitis: 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.
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 and vitiligo.
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
- 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.
- Mixed: A combination of any of the above types is possible.
- 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:
- 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.
- 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:
- Nonesophageal gastrointestinal candidiasis
- 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.9
- 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.
- 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.10
- 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 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. The patient's history commonly reveals the following:
- Several days of fever that is unresponsive to broad-spectrum antimicrobials; frequently the only marker of infection
- Prolonged intravenous catheterization
- 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. Candida species, primarily C albicans and Candida parapsilosis (>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 fever unresponsive to antimicrobials, hypotension, shock, new or changing murmurs, and large septic emboli to major organs, a characteristic of fungal endocarditis.
- Candida species are currently the fourth most commonly isolated organism in blood cultures, and Candida infection is generally considered a nosocomial infection. The patient's history commonly reveals the following:
- 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.
- Candida endophthalmitis: 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.11 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.
- 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.
- The patient's history reveals a broad range of manifestations, including the following.
- 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 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.
- 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:
- 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 peritonitis12
- 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
- Candida splenic 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:13
- C albicans, the most common species identified (50-60%)
- 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
- 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.14
- 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.
More on Candidiasis |
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References
Pappas PG, Rex JH, Lee J, et al. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis. Sep 1 2003;37(5):634-43. [Medline].
Yang YL. Virulence factors of Candida species. J Microbiol Immunol Infect. Dec 2003;36(4):223-8. [Medline].
Pappas PG. Invasive candidiasis. Infect Dis Clin North Am. Sep 2006;20(3):485-506. [Medline].
de Repentigny L, Lewandowski D, Jolicoeur P. Immunopathogenesis of oropharyngeal candidiasis in human immunodeficiency virus infection. Clin Microbiol Rev. Oct 2004;17(4):729-59, table of contents. [Medline].
Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. Jan 2007;20(1):133-63. [Medline].
Morgan J. Global trends in candidemia: review of reports from 1995-2005. Curr Infect Dis Rep. Nov 2005;7(6):429-39. [Medline].
Colombo AL, Nucci M, Park BJ, et al. Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers. J Clin Microbiol. Aug 2006;44(8):2816-23. [Medline].
Maródi L, Johnston RB Jr. Invasive Candida species disease in infants and children: occurrence, risk factors, management, and innate host defense mechanisms. Curr Opin Pediatr. Dec 2007;19(6):693-7. [Medline].
Sobel JD. Vulvovaginal candidosis. Lancet. Jun 9 2007;369(9577):1961-71. [Medline].
Malani AN, Kauffman CA. Candida urinary tract infections: treatment options. Expert Rev Anti Infect Ther. Apr 2007;5(2):277-84. [Medline].
Shah CP, McKey J, Spirn MJ, et al. Ocular candidiasis: a review. Br J Ophthalmol. Apr 2008;92(4):466-8. [Medline].
Blot SI, Vandewoude KH, De Waele JJ. Candida peritonitis. Curr Opin Crit Care. Apr 2007;13(2):195-9. [Medline].
Vazquez JA, Sobel JD. Candidiasis. In: Clinical Mycology, Dismukes WE, Pappas PG, and Sobel JD, eds. Oxford Univers. 2003:143-87.
Eiland EH, Hassoun A, English T. Points of concern related to the micafungin versus caspofungin trial. Clin Infect Dis. Feb 15 2008;46(4):640-1; author reply 641. [Medline].
Alexander BD, Pfaller MA. Contemporary tools for the diagnosis and management of invasive mycoses. Clin Infect Dis. 2006;43:S15-S27.
Odabasi Z, Mattiuzzi G, Estey E, et al. Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis. Jul 15 2004;39(2):199-205. [Medline].
Shepard JR, Addison RM, Alexander BD, et al. Multicenter evaluation of the Candida albicans/Candida glabrata peptide nucleic acid fluorescent in situ hybridization method for simultaneous dual-color identification of C. albicans and C. glabrata directly from blood culture bottles. J Clin Microbiol. Jan 2008;46(1):50-5. [Medline].
Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis. Jan 15 2004;38(2):161-89. [Medline].
Chandrasekar PH, Sobel JD. Micafungin: a new echinocandin. Clin Infect Dis. Apr 15 2006;42(8):1171-8. [Medline].
Vazquez JA, Sobel JD. Anidulafungin: a novel echinocandin. Clin Infect Dis. Jul 15 2006;43(2):215-22. [Medline].
[Best Evidence] Nurbhai M, Grimshaw J, Watson M, et al. Oral versus intra-vaginal imidazole and triazole anti-fungal treatment of uncomplicated vulvovaginal candidiasis (thrush). Cochrane Database Syst Rev. Oct 17 2007;CD002845. [Medline].
Charlier C, Hart E, Lefort A, et al. Fluconazole for the management of invasive candidiasis: where do we stand after 15 years?. J Antimicrob Chemother. Mar 2006;57(3):384-410. [Medline].
Sobel JD, Revankar SG. Echinocandins--first-choice or first-line therapy for invasive candidiasis?. N Engl J Med. Jun 14 2007;356(24):2525-6. [Medline].
[Best Evidence] Reboli AC, Rotstein C, Pappas PG, et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. Jun 14 2007;356(24):2472-82. [Medline].
Kuse ER, Chetchotisakd P, da Cunha CA, et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet. May 5 2007;369(9572):1519-27. [Medline].
[Best Evidence] Kullberg BJ, Sobel JD, Ruhnke M, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet. Oct 22-28 2005;366(9495):1435-42. [Medline].
Pachl J, Svoboda P, Jacobs F, et al. A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clin Infect Dis. May 15 2006;42(10):1404-13. [Medline].
Khan FA, Slain D, Khakoo RA. Candida endophthalmitis: focus on current and future antifungal treatment options. Pharmacotherapy. Dec 2007;27(12):1711-21. [Medline].
Ostrosky-Zeichner L, Oude Lashof AM, Kullberg BJ, et al. Voriconazole salvage treatment of invasive candidiasis. Eur J Clin Microbiol Infect Dis. Nov 2003;22(11):651-5. [Medline].
Skiest DJ, Vazquez JA, Anstead GM, et al. Posaconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection. Clin Infect Dis. Feb 15 2007;44(4):607-14. [Medline].
van Burik JA, Ratanatharathorn V, Stepan DE, et al. Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis. Nov 15 2004;39(10):1407-16. [Medline].
Husain S, Paterson DL, Studer S, et al. Voriconazole prophylaxis in lung transplant recipients. Am J Transplant. Dec 2006;6(12):3008-16. [Medline].
Ullmann AJ, Cornely OA. Antifungal prophylaxis for invasive mycoses in high risk patients. Curr Opin Infect Dis. Dec 2006;19(6):571-6. [Medline].
Pfaller MA, Pappas PG, Wingard JR. Invasive fungal pathogens: current epidemiological trends. Clin Infect Dis. 2006;43:S3-S14.
Pfaller MA, Pappas PG, Wingard JR. Invasive fungal pathogens: current epidemiological trends. Clin Infect Dis. Aug 1 2006;43 (Suppl 1):S3-S14. [Full Text].
Leleu G, Aegerter P, Guidet B. Systemic candidiasis in intensive care units: a multicenter, matched-cohort study. J Crit Care. Sep 2002;17(3):168-75. [Medline].
Zaoutis TE, Heydon K, Localio R, et al. Outcomes attributable to neonatal candidiasis. Clin Infect Dis. May 1 2007;44(9):1187-93. [Medline].
Cornely OA, Lasso M, Betts R, et al. Caspofungin for the treatment of less common forms of invasive candidiasis. J Antimicrob Chemother. Aug 2007;60(2):363-9. [Medline].
Kauffman CA. Clinical efficacy of new antifungal agents. Curr Opin Microbiol. Oct 2006;9(5):483-8. [Medline].
Powderly WG, Gallant JE, Ghannoum MA, et al. Oropharyngeal candidiasis in patients with HIV: suggested guidelines for therapy. AIDS Res Hum Retroviruses. Dec 10 1999;15(18):1619-23. [Medline].
Sable CA, Strohmaier KM, Chodakewitz JA. Advances in antifungal therapy. Annu Rev Med. 2008;59:361-79. [Medline].
Viscoli C, Girmenia C, Marinus A, et al. Candidemia in cancer patients: a prospective, multicenter surveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC). Clin Infect Dis. May 1999;28(5):1071-9. [Medline].
Further Reading
Bodey GP (Ed). Candidiasis. Pathogenesis, diagnosis and treatment. 2nd ed. New York, NY; Raven Press; 1993.
Calderone RA (Ed). Candida and candidiasis. Washington, DC; ASM Press; 2002.
NCCLS. Method for Antifungal Disk Diffusion Susceptibility Testing of Yeasts; Proposed Guideline. NCCLS document M44-P [ISBN 1-56238-488-0]. NCCLS, Pennsylvania, USA 2003
NCCLS. Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard-Second Edition. NCCLS document M27-A2 [ISBN 1-56238-469-4]. NCCLS, Pennsylvania, USA 2002.
Keywords
candidiasis, Candida albicans, C albicans, fungal infection, candidal infection, candidosis, fungus infection, Candida, mucocutaneous candidiasis, candidemia, disseminated candidiasis, candidal colonization, candidiasis syndromes, intertrigo, paronychia, onychomycosis, oral thrush, mucosal candidiasis, systemic candidiasis, hepatosplenic candidiasis, fungemia, granulocytopenia, oropharyngeal candidiasis, OPC esophageal candidiasis, vulvovaginal candidiasis, VVC, cutaneous candidiasis syndromes, chronic mucocutaneous candidiasis
Addison disease, membranous candidiasis, erythematous candidiasis, chronic atrophic candidiasis, nonesophageal gastrointestinal candidiasis, respiratory tract candidiasis, laryngeal candidiasis, genitourinary tract candidiasis, candidal endophthalmitis, intravascular catheter-related candidiasis, fungal endocarditis, renal candidiasis, Candida peritonitis, Candida esophagitis, Candida folliculitis, Candida balanitis, Candida cystitis, Candida tracheobronchitis, Candida pneumonia, Candida splenic abscess, Candida hypersplenism
Candida cholecystitis, Candida arthritis, Candida osteomyelitis, Candida costochondritis, Candida myositis, Candida myocarditis-pericarditis, Candida endocarditis fungal meningitis, Candida parapsilosis , C parapsilosis, Candida glabrata , C glabrata, Candida tropicalis , C tropicalis
Candida krusei , C krusei, Candida kefyr, C kefyr, Candida dubliniensis , C dubliniensis, Candida guilliermondi , C guilliermondi, Candida lusitaniae , C lusitaniae
