Vulvovaginal Candidiasis, Causes, Symptoms, Treatment

Vulvovaginal candidiasis

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Vulvovaginal candidiasis is defined as symptomatic vaginitis (inflammation of the vagina), which often involves the vulva (erythema and swelling), caused by infection with a Candida yeast. The predominant symptom is vulvar itching. Abnormal vaginal discharge (which may be minimal — a ‘cheese-like’ material or a watery secretion) may also be present. Vulvar burning, soreness, and irritation are also common symptoms, and these may be accompanied by dysuria or dyspareunia, which worsen during the week prior to menses. Differentiation from other forms of vaginitis requires the presence of yeast on microscopy of vaginal fluid.

Candidiasis

Anothers Name of Candidiasis

Synonyms of Candidiasis

  • Candidosis
  • Moniliasis

Subdivisions of Candidiasis

  • Candida Granuloma
  • Candida Infection around the Nails
  • Candida Paronichia
  • Candidiasis of the Skin
  • Cutaneous Candidiasis
  • Cutaneous Moniliasis
  • Mucocutaneous Candidiasis, Chronic
  • Oral Candidiasis
  • Penis, infected by Candida
  • Systemic Candidiasis
  • Thrush
  • Vaginitis, Caused by Candida
  • Vulvovaginitis, Caused by Candida
  • Yeast Infection, Systemic

Types/Classification of Candidiasis

Thrush

Candidiasis may be divided into these types

Mucosal candidiasis

  • Oral candidiasis (thrush, oropharyngeal candidiasis)[rx][rx]
      • Pseudomembranous candidiasis[rx]
      • Erythematous candidiasis[rx][rx]
      • Hyperplastic candidiasis[rx]
      • Denture-related stomatitis[rx][rx] — Candida organisms are involved in about 90% of cases
      • Angular cheilitis[rx][rx] — Candida species are responsible for about 20% of cases, mixed infection of C. albicans and Staphylococcus aureus for about 60% of cases.
      • Median rhomboid glossitis[rx]
  • Candidal vulvovaginitis (vaginal yeast infection)[rx][rx]
  • Candidal balanitis — infection of the glans penis,[rx] almost exclusively occurring in uncircumcised males[rx]
  • Esophageal candidiasis (candidal esophagitis)[rx][rx]
  • Gastrointestinal candidiasis[rx][rx][rx]
  • Respiratory candidiasis[rx][rx]

Cutaneous candidiasis

  • Candidial folliculitis[rx]
  • Candidal intertrigo[rx]
  • Candidal paronychia[rx]
  • Perianal candidiasis, may present as pruritus ani[rx]
  • Candidid
  • Chronic mucocutaneous candidiasis[rx]
  • Congenital cutaneous candidiasis[rx]
  • Diaper candidiasis: an infection of a child’s diaper area[rx]
  • Erosio interdigitalis blastomycetica
  • +
  • Candidial onychomycosis (nail infection) caused by Candida[rx][rx]

Systemic The term is Candidiasis or Thrush. T

  • Candidemia, a form of fungemia which may lead to sepsis[rx]
  • Invasive candidiasis (disseminated candidiasis) — organ infection by Candida[rx]
  • Chronic systemic candidiasis (hepatosplenic candidiasis) — sometimes arises during recovery from neutropenia[rx][rx]

Antibiotic candidiasis (iatrogenic candidiasis)

Proposed revised classification of Oral Candidosis Primary oral candidosis (Group I)

Acute

  • Pseudomembranous
  • Erythematous

Chronic

  • Erythematous
  • Pseudomembranous
  • Hyperplastic
  • Nodular
  • Plaque-like

Candida-associated lesions

  • Angular cheilitis
  • Denture stomatitis
  • Median rhomboid glossitis

Keratinized primary lesions superinfected with Candida

  • Leukoplakia
  • Lichen planus
  • Lupus erythematosus.

Secondary oral candidoses (Group II)

  • Oral manifestations of Systemic mucocutaneous.
  • Candidosis (due to diseases such as thymic aplasia and candidosis endocrinopathy syndrome).

Causes of Vulvovaginal Candidiasis

  • Antibiotic use Yeast infections are common in women who take antibiotics. Broad-spectrum antibiotics, which kill a range of bacteria, also kill healthy bacteria in your vagina, leading to overgrowth of yeast.
  • Increased estrogen levels Yeast infections are more common in women with higher estrogen levels — such as pregnant women or women taking high-dose estrogen birth control pills or estrogen hormone therapy.
  • Uncontrolled diabetes – Women with poorly controlled blood sugar are at greater risk of yeast infections than women with well-controlled blood sugar.
  • Impaired immune systemWomen with lowered immunity — such as from corticosteroid therapy or HIV infection — are more likely to get yeast infections.
Candidiasis
Oral thrush. Close-up of the mouth of an 82-year-old woman with a candidiasis infection (white areas). Candidiasis, known as thrush, is an infection by the fungus Candida albicans.

Symptoms of Candidiasis

Candidiasis in the mouth and throat can have many different symptoms, including:

  • White patches on the inner cheeks, tongue, roof of the mouth, and throat (photo showing candidiasis in the mouth)
  • Redness or soreness
  • Cotton-like feeling in the mouth
  • Loss of taste
  • Pain while eating or swallowing
  • Cracking and redness at the corners of the mouth
  • White or yellow patches on the tongue, lips, gums, roof of mouth, and inner cheeks
  • Redness or soreness in the mouth and throat
  • Cracking at the corners of the mouth
  • Pain when swallowing, if it spreads to the throat

Symptoms of candidiasis in the esophagus usually include pain when swallowing and difficulty swallowing.

In case of Genital Candidiasis

The symptoms include

  • Extreme itchiness in the vagina
  • Redness and swelling of the vagina and vulva (the outer part of the female genitals)
  • Pain and burning when you pee
  • Discomfort during sex
  • Vaginal pain and soreness
  • Vaginal rash
  • Thick, white, odor-free vaginal discharge with a cottage cheese appearance
  • Watery vaginal discharge
  • A thick, white “cottage cheese” discharge from the vagina
  • Itching, burning, or irritation of the vagina or vulva, which is the tissue surrounding the vagina
  • Pain or soreness in the vagina or the vaginal opening
  • Vaginal burning with intercourse or urination
  • A thick, white, odorless discharge that resembles cottage cheese, or a watery discharge

A man with a yeast infection may have an itchy rash on his penis.

Diagnosis of Vulvovaginal Candidiasis

Specimen collection

The specimen should be collected from an active lesion; old ‘burned out’ lesions often do not contain viable organisms.

  • Collect the specimen under aseptic conditions.
  • Collect sufficient specimen.

Use sterile collection devices and containers

  • Label the specimen appropriately; all clinical specimens should be considered as potential biohazards and should be handled with care using universal precautions.
  • The specimen should be kept moist or in a transport medium and stored in a refrigerator at 4ºC. Due to variety of clinical forms of oral candidiasis, a number of different types of specimens may be submitted to the laboratory.[]

Smear

  • Smears are taken from the infected oral mucosa, rhagades and the fitting side of the denture, preferably with wooden spatulas. Smears were fixed immediately in ether/alcohol 1:1 or with spray fix. Dry preparations may be examined by Gram stain method and periodic acid Schiff (PAS) method.[]

Swabs

  • Swabs are seeded on Sabouraud’s agar (25ºC or room temperature), on blood agar (35ºC), on Pagano-Levin medium (35ºC) or on Littmann’s substrate (25ºC). Incubation at 25ºC is done to ensure recovery of species growing badly at 35ºC. Sabouraud’s dextrose agar is frequently used as a primary culture medium. Since mixed yeast infections are seen in the oral cavity more frequently than previously thought, particularly in immunocompromised or debilitated patients, Pagano-Levin agar or Littmann’s substrate, are useful supplements, because they enable distinction of yeasts on the basis of difference in colony color.[]

Biopsy

  • Biopsy specimen should in addition be sent for histopathological examination when chronic hyperplastic candidosis is suspected.[]

Imprint culture technique

  • Sterile, square (2.2 × 2.5 cm), plastic foam pads are dipped in peptone water and placed on the restricted area under study for 30-60 seconds. Thereafter the pad is placed directly on Pagano-Levin or Sabouraud’s agar, left in situ for the first 8 hours of 48 hours incubation at 37ºC. Then, the candidal density at each site is determined by a Gallenkamp colony counter and expressed as colony forming units per mm2 (CFU mm-2).[,] Thus, it yields yeasts per unit mucosal surface. It is useful for quantitative assessment of yeast growth in different areas of the oral mucosa and is thus useful in localizing the site of infection and estimating the candidal load on a specific area (Budtz-Jorgensen, 1978, Olsen and Stenderup A, 1990).[,]

Impression culture technique

  • Taking maxillary and mandibular alginate impressions, transporting them to the laboratory and casting in 6% fortified agar with incorporated Sabouraud’s dextrose broth. The agar models are then incubated in a wide necked, sterile, screw-topped jar for 48-72 hours at 37ºC and the CFU of yeasts estimated.[]

Saliva

  • This simple technique involves requesting the patient to expectorate 2 ml of mixed unstimulated saliva into a sterile, universal container, which is then vibrated for 30 seconds on a bench vibrator for optimal disaggregation. The number of Candida expressed as CFU/ml of saliva is estimated by counting the resultant growth on Sabouraud’s agar using either the spiral plating or Miles and Misra surface viable counting technique. Patients who display clinical signs of oral candidiasis usually have more than 400 CFU/mL.[]

Oral rinse technique

  • It was first described by Mckendrik, Wilson and Main (1967) and later modified by Samaranayake et al. (1968).[]

Paper Points

  • An absorbable sterile point is inserted to the depth of the pocket and kept there for 10 sec and then the points are transferred to a 2 ml vial containing Moller’s VMGA III transport medium, (which also facilitates survival of facultative and anaerobic bacteria).[]

Commercial identification kits

  • The Microstix-candida (MC) system consists of a plastic strip to which is affixed a dry culture area (10 mm × 10 mm) of modified Nickerson medium (Nickerson, 1953) and a plastic pouch for incubation. The O Yeast-I dent system is based on the use of chromogenic substances to measure enzyme activities. Ricult-N dip slide technique is similar to, but of higher sensitivity than MC system.[]

Histological identification

  • Demonstration of fungi in biopsy specimens may require several serial sections to be cut.[] Fungi can be easily demonstrated and studied in tissue sections with special stains. The routinely used Hematoxylin and Eosin stain poorly stains Candida species. The specific fungal stains such as PAS stain, Grocott-Gomori’s methenamine silver (GMS) and Gridley stains are widely used for demonstrating fungi in the tissues, which are colored intensely with these stains.[]
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Physiological tests

  • The main physiological tests used in definitive identification of Candida species involve determination of their ability to assimilate and ferment individual carbon and nitrogen sources.[,]

Phenotypic methods

Serotyping

  • Serotyping is limited to the two serotypes (A and B), a fact that makes it inadequate as an epidemiologic tool. It has recently been shown that there can be wide discrepancies in the results obtained with different methods of serotyping,[,]

Resistogram typing

  • Resistograms do not correlate with pathogenic potential and even though improvements have been made in the method growth end-points often present problems because of inoculum size, interpretation and reproducibility.

Yeast ‘Killer Toxin’ typing

  • These authors initially used nine killer strains, developing a triplet code to distinguish between 100 strains of C. albicans and found 25 killer- sensitive types. This method was expanded by using 30 killer strains and three antifungal agents, which appeared to discriminate between sufficient numbers of strains of C. albicans.

Morphotyping

  • This method has been used in a study of the morphotypes of 446 strains of C. albicansisolated from various clinical specimens.

Biotyping

  • Williamson (1987) has proposed a simpler method. This system comprised three tests, the APIZYM system, the API 20C system and a plate test for resistance to boric acid. This system was found to distinguish a possible 234 biotypes, of which 33 were found among the 1430 isolates of C. albicanstaken from oral, genital and skin sites.

Protein typing

  • Non-lethal mutations of proteins during the yeast cell cycle yield proteins of differing physical properties between strains, which may be distinguishable by one or two dimensional gel electrophoresis. These methods have been used to separate C. albicans at the subspecies level.

Genetic methods

  • The earliest molecular methods used for fingerprinting C. albicans strains were karyotyping, restriction endonuclease analysis (REA) and restriction fragment length polymorphism (RFLP). In arbitrarily primed polymerase chain reaction (AP-PCR) analysis (synonym: randomly amplified polymorphic DNA (RAPD) analysis), the genomic DNA is used as a template and amplified at a low annealing temperature with use of a single short primer (9 to 10 bases) of an arbitrary sequence.[]

Serological tests

Serological tests for invasive candidiasis

  • Detection of antibodies

  • Slide agglutination

  • Immunodiffusion

  • Phytohemagglutination

  • Coelectosynersis

  • Immunoprecipitation

  • A and B immunofluorescence

  • Nonspecific Candida Antigens

  • Latex agglutination

  • Immunobloting

  • Cell Wall Components

  • Cell Wall Mannoprotein (CWMP)

  • b-(1,3)-D-glucan

  • Candida Enolase Antigen testing.[]

Immunodiagnosis

The use of specific antibodies labeled with fluorescent stain permits causative organisms to be diagnosed accurately within minutes. However, the preparation of specific antisera and purified polyclonal or monoclonal antibodies entails a much more extensive technical outlay, so the application of these reagents need only be considered when a very precise diagnosis is of therapeutic consequence (Olsen and Stenderup, 1990). The usefulness of antibody testing in the diagnosis of oral candidosis when other simpler, sensitive and reliable techniques are available is questionable (Silverman et al., 1990).[]

Invasive fungal infections; pathogens and characteristics of disease.

OPPORTUNISTIC PATHOGENS
Disease typeCausative agentClinical signs and symptoms
CandidiasisCandida sppAcute disseminated: fever, chills, polymyalgia, polyarthralgia, not tender pinkish skin lesions, retinal exudates.
Chronic: complaints of the organ involved.
AspergillosisAspergillus sppUnremitting fever and pulmonary infiltrates during antibiotic therapy. Chest pain, pleural rub, pleural effusion, hemoptysis. Halo and air crescent sign on chest radiograph and CT scan.
Clinical and radiologic sinusitis.
CryptococcosisCryptococcus neoformansFlu-like symptoms; skin lesions, headache without meningismus.
ZygomycosisRhizopus spp
Absidia spp
Mucor spp
Like aspergillosis, more outspoken rhino-cerebral form with serosanguinous nasal discharge.
OthersMalassezia furfurOften catheter-associated; pneumonia
TrichosporonsppSkin and lung lesions
Fusarium spp
Pseudallescheria boydiiOften positive bloodcultures. Skin lesions, severe myalgia. Abscess formation with symptoms depending on organ involved.
ScedosporiumsppLike aspergillosis; wound infections.
Alternaria spp
ENDEMIC PATHOGENS
Disease typeCausative agentClinical signs and symptoms
BlastomyscosisBlastomyces dermatitidisUlcerative lesions; skin, urogenital tract
Central nervous system
HistoplasmosisHistoplasma capsulatumPulmonary infiltrates; mucocutaneous ulcers
Hepatosplenomegaly
CoccidioidomycosisCoccidioidis immitisPulmonary infection. Dissemination with osteomyelitis, arthritis, meningitis.
Para-coccidioidomycosisParacoccidioidis brasiliensisPulmonary infection. Dissemination to skin, mucosa and lymphnodes.
PenicilliosisPenicillium marneffeiSkin and subcutaneous laesions, lung, lymphadenitis, splenomegaly.

 

Treatment of Vulvovaginal Candidiasis

Treatment of candidiasis varies, depending on the area affected:

  • Thrush – Doctors treat thrush with topical, antifungal medications such as nystatin (Mycostatin and others) and clotrimazole. For mild cases, a liquid version of nystatin can be swished in the mouth and swallowed, or a clotrimazole lozenge can be dissolved in the mouth. For more severe cases, an antifungal drug such as fluconazole (Diflucan) can be taken once a day by mouth.
  • Esophagitis – Candida esophagitis is treated with an oral antifungal drug such as fluconazole.
  • Cutaneous candidiasis – This skin infection can be effectively treated with a variety of antifungal powders and creams. The affected area must be kept clean and dry and protected from chafing.
  • Vaginal yeast infections  – Vaginal yeast infections can be treated with antifungal medications that are applied directly into the vagina as tablets, creams, ointments or suppositories. These include butoconazole (Femstat), clotrimazole (Gyne-Lotrimin), miconazole (Monistat, Vagistat and others), nystatin (Mycostatin and others), and tioconazole (Monistat-1, Vagistat-1). A single dose of oral fluconazole can be used. Sex partners usually do not need to be treated.
  • Deep candidiasis – This infection usually starts with an intravenous anti-fungal drug, such as voriconazole or fluconazole. People with very low white blood cell counts may need an alternative intravenous antifungal drug, such as caspofungin or micafungin.

Treatment for Recommendations

  • An echinocandin (caspofungin: loading dose 70 mg, then 50 mg daily; micafungin: 100 mg daily; anidulafungin: loading dose 200 mg, then 100 mg daily) is recommended as initial therapy (strong recommendation; high-quality evidence).
  • Fluconazole, intravenous or oral, 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily is an acceptable alternative to an echinocandin as initial therapy in selected patients, including those who are not critically ill and who are considered unlikely to have a fluconazole-resistant Candida species (strong recommendation; high-quality evidence).
  • Testing for azole susceptibility is recommended for all bloodstream and other clinically relevant Candida isolates. Testing for echinocandin susceptibility should be considered in patients who have had prior treatment with an echinocandin and among those who have infection with C. glabrata or C. parapsilosis (strong recommendation; low-quality evidence).
  • Transition from an echinocandin to fluconazole (usually within 5–7 days) is recommended for patients who are clinically stable, have isolates that are susceptible to fluconazole (eg, C. albicans), and have negative repeat blood cultures following initiation of antifungal therapy (strong recommendation; moderate-quality evidence).
  • For infection due to C. glabrata, transition to higher-dose fluconazole 800 mg (12 mg/kg) daily or voriconazole 200–300 (3–4 mg/kg) twice daily should only be considered among patients with fluconazole-susceptible or voriconazole-susceptible isolates (strong recommendation; low-quality evidence).
  • Lipid formulation amphotericin B (AmB) (3–5 mg/kg daily) is a reasonable alternative if there is intolerance, limited availability, or resistance to other antifungal agents (strong recommendation; high-quality evidence).
  • Transition from AmB to fluconazole is recommended after 5–7 days among patients who have isolates that are susceptible to fluconazole, who are clinically stable, and in whom repeat cultures on antifungal therapy are negative (strong recommendation; high-quality evidence).
  • Among patients with suspected azole- and echinocandin-resistant Candidainfections, lipid formulation AmB (3–5 mg/kg daily) is recommended (strong recommendation; low-quality evidence).
  • Voriconazole 400 mg (6 mg/kg) twice daily for 2 doses, then 200 mg (3 mg/kg) twice daily is effective for candidemia, but offers little advantage over fluconazole as initial therapy (strong recommendation; moderate-quality evidence).Voriconazole is recommended as step-down oral therapy for selected cases of candidemia due to C. krusei (strong recommendation; low-quality evidence).
  • All nonneutropenic patients with candidemia should have a dilated ophthalmological examination, preferably performed by an ophthalmologist, within the first week after diagnosis (strong recommendation; low-quality evidence).
  • Follow-up blood cultures should be performed every day or every other day to establish the time point at which candidemia has been cleared (strong recommendation; low-quality evidence).
  • Recommended duration of therapy for candidemia without obvious metastatic complications is for 2 weeks after documented clearance of Candida species from the bloodstream and resolution of symptoms attributable to candidemia (strong recommendation; moderate-quality evidence).

II. Should Central Venous Catheters Be Removed in Nonneutropenic Patients With Candidemia?

Recommendation

  • Central venous catheters (CVCs) should be removed as early as possible in the course of candidemia when the source is presumed to be the CVC and the catheter can be removed safely; this decision should be individualized for each patient (strong recommendation; moderate-quality evidence).

III. What Is the Treatment for Candidemia in Neutropenic Patients?

Recommendations

  • An echinocandin (caspofungin: loading dose 70 mg, then 50 mg daily; micafungin: 100 mg daily; anidulafungin: loading dose 200 mg, then 100 mg daily) is recommended as initial therapy (strong recommendation; moderate-quality evidence).
  • Lipid formulation AmB, 3–5 mg/kg daily, is an effective but less attractive alternative because of the potential for toxicity (strong recommendation; moderate-quality evidence).
  • Fluconazole, 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily, is an alternative for patients who are not critically ill and have had no prior azole exposure (weak recommendation; low-quality evidence).
  • Fluconazole, 400 mg (6 mg/kg) daily, can be used for step-down therapy during persistent neutropenia in clinically stable patients who have susceptible isolates and documented bloodstream clearance (weak recommendation; low-quality evidence).
  • Voriconazole, 400 mg (6 mg/kg) twice daily for 2 doses, then 200–300 mg (3–4 mg/kg) twice daily, can be used in situations in which additional mold coverage is desired (weak recommendation; low-quality evidence). Voriconazole can also be used as step-down therapy during neutropenia in clinically stable patients who have had documented bloodstream clearance and isolates that are susceptible to voriconazole (weak recommendation; low-quality evidence).
  • For infections due to C. krusei, an echinocandin, lipid formulation AmB, or voriconazole is recommended (strong recommendation; low-quality evidence).
  • Recommended minimum duration of therapy for candidemia without metastatic complications is 2 weeks after documented clearance of Candida from the bloodstream, provided neutropenia and symptoms attributable to candidemia have resolved (strong recommendation; low-quality evidence).
  • Ophthalmological findings of choroidal and vitreal infection are minimal until recovery from neutropenia; therefore, dilated funduscopic examinations should be performed within the first week after recovery from neutropenia (strong recommendation; low-quality evidence).
  • In the neutropenic patient, sources of candidiasis other than a CVC (eg, gastrointestinal tract) predominate. Catheter removal should be considered on an individual basis (strong recommendation; low-quality evidence).
  • Granulocyte colony – stimulating factor (G-CSF)–mobilized granulocyte transfusions can be considered in cases of persistent candidemia with anticipated protracted neutropenia (weak recommendation; low-quality evidence).

IV. What Is the Treatment for Chronic Disseminated (Hepatosplenic) Candidiasis?

Recommendations

  • Initial therapy with lipid formulation AmB, 3–5 mg/kg daily OR an echinocandin (micafungin: 100 mg daily; caspofungin: 70-mg loading dose, then 50 mg daily; or anidulafungin: 200-mg loading dose, then 100 mg daily), for several weeks is recommended, followed by oral fluconazole, 400 mg (6 mg/kg) daily, for patients who are unlikely to have a fluconazole-resistant isolate (strong recommendation; low-quality evidence).
  • Therapy should continue until lesions resolve on repeat imaging, which is usually several months. Premature discontinuation of antifungal therapy can lead to relapse (strong recommendation; low-quality evidence).
  • If chemotherapy or hematopoietic cell transplantation is required, it should not be delayed because of the presence of chronic disseminated candidiasis, and antifungal therapy should be continued throughout the period of high risk to prevent relapse (strong recommendation; low-quality evidence).
  • For patients who have debilitating persistent fevers, short-term (1–2 weeks) treatment with nonsteroidal anti-inflammatory drugs or corticosteroids can be considered (weak recommendation; low-quality evidence).

V. What Is the Role of Empiric Treatment for Suspected Invasive Candidiasis in Nonneutropenic Patients in the Intensive Care Unit?

Recommendations

  • Empiric antifungal therapy should be considered in critically ill patients with risk factors for invasive candidiasis and no other known cause of fever and should be based on clinical assessment of risk factors, surrogate markers for invasive candidiasis, and/or culture data from nonsterile sites (strong recommendation; moderate-quality evidence). Empiric antifungal therapy should be started as soon as possible in patients who have the above risk factors and who have clinical signs of septic shock (strong recommendation; moderate-quality evidence).
  • Preferred empiric therapy for suspected candidiasis in nonneutropenic patients in the intensive care unit (ICU) is an echinocandin (caspofungin: loading dose of 70 mg, then 50 mg daily; micafungin: 100 mg daily; anidulafungin: loading dose of 200 mg, then 100 mg daily) (strong recommendation; moderate-quality evidence).
  • Fluconazole, 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily, is an acceptable alternative for patients who have had no recent azole exposure and are not colonized with azole-resistant Candida species (strong recommendation; moderate-quality evidence).
  • Lipid formulation AmB, 3–5 mg/kg daily, is an alternative if there is intolerance to other antifungal agents (strong recommendation; low-quality evidence).
  • Recommended duration of empiric therapy for suspected invasive candidiasis in those patients who improve is 2 weeks, the same as for treatment of documented candidemia (weak recommendation; low-quality evidence).
  • For patients who have no clinical response to empiric antifungal therapy at 4–5 days and who do not have subsequent evidence of invasive candidiasis after the start of empiric therapy or have a negative non-culture-based diagnostic assay with a high negative predictive value, consideration should be given to stopping antifungal therapy (strong recommendation; low-quality evidence).

VI. Should Prophylaxis Be Used to Prevent Invasive Candidiasis in the Intensive Care Unit Setting?

Recommendations

  • Fluconazole, 800-mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily, could be used in high-risk patients in adult ICUs with a high rate (>5%) of invasive candidiasis (weak recommendation; moderate-quality evidence).
  • An alternative is to give an echinocandin (caspofungin: 70-mg loading dose, then 50 mg daily; anidulafungin: 200-mg loading dose and then 100 mg daily; or micafungin: 100 mg daily) (weak recommendation; low-quality evidence).
  • Daily bathing of ICU patients with chlorhexidine, which has been shown to decrease the incidence of bloodstream infections including candidemia, could be considered (weak recommendation; moderate-quality evidence).

VII. What Is the Treatment for Neonatal Candidiasis, Including Central Nervous System Infection?

What Is the Treatment for Invasive Candidiasis and Candidemia?

Recommendations

  • AmB deoxycholate, 1 mg/kg daily, is recommended for neonates with disseminated candidiasis (strong recommendation; moderate-quality evidence).
  • Fluconazole, 12 mg/kg intravenous or oral daily, is a reasonable alternative in patients who have not been on fluconazole prophylaxis (strong recommendation; moderate-quality evidence).
  • Lipid formulation AmB, 3–5 mg/kg daily, is an alternative, but should be used with caution, particularly in the presence of urinary tract involvement (weak recommendation; low-quality evidence).
  • Echinocandins should be used with caution and generally limited to salvage therapy or to situations in which resistance or toxicity preclude the use of AmB deoxycholate or fluconazole (weak recommendation; low-quality evidence).
  • A lumbar puncture and a dilated retinal examination are recommended in neonates with cultures positive for Candida species from blood and/or urine (strong recommendation; low-quality evidence).
  • Computed tomographic or ultrasound imaging of the genitourinary tract, liver, and spleen should be performed if blood cultures are persistently positive for Candida species (strong recommendation; low-quality evidence).
  • CVC removal is strongly recommended (strong recommendation; moderate-quality evidence).
  • The recommended duration of therapy for candidemia without obvious metastatic complications is for 2 weeks after documented clearance of Candidaspecies from the bloodstream and resolution of signs attributable to candidemia (strong recommendation; low-quality evidence).

What Is the Treatment for Central Nervous System Infections in Neonates?

Recommendations

  • For initial treatment, AmB deoxycholate, 1 mg/kg intravenous daily, is recommended (strong recommendation; low-quality evidence).
  • An alternative regimen is liposomal AmB, 5 mg/kg daily (strong recommendation; low-quality evidence).
  • The addition of flucytosine, 25 mg/kg 4 times daily, may be considered as salvage therapy in patients who have not had a clinical response to initial AmB therapy, but adverse effects are frequent (weak recommendation; low-quality evidence).
  • For step-down treatment after the patient has responded to initial treatment, fluconazole, 12 mg/kg daily, is recommended for isolates that are susceptible to fluconazole (strong recommendation; low-quality evidence).
  • Therapy should continue until all signs, symptoms, and cerebrospinal fluid (CSF) and radiological abnormalities, if present, have resolved (strong recommendation; low-quality evidence).
  • Infected central nervous system (CNS) devices, including ventriculostomy drains and shunts, should be removed if at all possible (strong recommendation; low-quality evidence).

What Are the Recommendations for Prophylaxis in the Neonatal Intensive Care Unit Setting?

Recommendations

  • In nurseries with high rates (>10%) of invasive candidiasis, intravenous or oral fluconazole prophylaxis, 3–6 mg/kg twice weekly for 6 weeks, in neonates with birth weights <1000 g is recommended (strong recommendation; high-quality evidence)
  • Oral nystatin, 100 000 units 3 times daily for 6 weeks, is an alternative to fluconazole in neonates with birth weights <1500 g in situations in which availability or resistance preclude the use of fluconazole (weak recommendation; moderate-quality evidence).
  • Oral bovine lactoferrin (100 mg/day) may be effective in neonates <1500 g but is not currently available in US hospitals (weak recommendation; moderate-quality evidence).

VIII. What Is the Treatment for Intra-abdominal Candidiasis?

Recommendations

  • Empiric antifungal therapy should be considered for patients with clinical evidence of intra-abdominal infection and significant risk factors for candidiasis, including recent abdominal surgery, anastomotic leaks, or necrotizing pancreatitis (strong recommendation; moderate-quality evidence).
  • Treatment of intra-abdominal candidiasis should include source control, with appropriate drainage and/or debridement (strong recommendation; moderate-quality evidence).
  • The choice of antifungal therapy is the same as for the treatment of candidemia or empiric therapy for nonneutropenic patients in the ICU (See sections I and V) (strong recommendation; moderate-quality evidence).
  • The duration of therapy should be determined by adequacy of source control and clinical response (strong recommendation; low-quality evidence).

IX. Does the Isolation of Candida Species From the Respiratory Tract Require Antifungal Therapy?

Recommendation

  • Growth of Candida from respiratory secretions usually indicates colonization and rarely requires treatment with antifungal therapy (strong recommendation; moderate-quality evidence).

X. What Is the Treatment for Candida Intravascular Infections, Including Endocarditis and Infections of Implantable Cardiac Devices?

What Is the Treatment for Candida Endocarditis?

Recommendations

  • For native valve endocarditis, lipid formulation AmB, 3–5 mg/kg daily, with or without flucytosine, 25 mg/kg 4 times daily, OR high-dose echinocandin (caspofungin 150 mg daily, micafungin 150 mg daily, or anidulafungin 200 mg daily) is recommended for initial therapy (strong recommendation; low-quality evidence).
  • Step-down therapy to fluconazole, 400–800 mg (6–12 mg/kg) daily, is recommended for patients who have susceptible Candida isolates, have demonstrated clinical stability, and have cleared Candida from the bloodstream (strong recommendation; low-quality evidence).
  • Oral voriconazole, 200–300 mg (3–4 mg/kg) twice daily, or posaconazole tablets, 300 mg daily, can be used as step-down therapy for isolates that are susceptible to those agents but not susceptible to fluconazole (weak recommendation; very low-quality evidence).
  • Valve replacement is recommended; treatment should continue for at least 6 weeks after surgery and for a longer duration in patients with perivalvular abscesses and other complications (strong recommendation; low-quality evidence).
  • For patients who cannot undergo valve replacement, long-term suppression with fluconazole, 400–800 mg (6–12 mg/kg) daily, if the isolate is susceptible, is recommended (strong recommendation; low-quality evidence).
  • For prosthetic valve endocarditis, the same antifungal regimens suggested for native valve endocarditis are recommended (strong recommendation; low-quality evidence). Chronic suppressive antifungal therapy with fluconazole, 400–800 mg (6–12 mg/kg) daily, is recommended to prevent recurrence (strong recommendation; low-quality evidence).

What Is the Treatment for Candida Infection of Implantable Cardiac Devices?

Recommendations

  • For pacemaker and implantable cardiac defibrillator infections, the entire device should be removed (strong recommendation; moderate-quality evidence).
  •  Antifungal therapy is the same as that recommended for native valve endocarditis (strong recommendation; low-quality evidence).
  • For infections limited to generator pockets, 4 weeks of antifungal therapy after removal of the device is recommended (strong recommendation; low-quality evidence).
  • For infections involving the wires, at least 6 weeks of antifungal therapy after wire removal is recommended (strong recommendation; low-quality evidence).
  • For ventricular assist devices that cannot be removed, the antifungal regimen is the same as that recommended for native valve endocarditis (strong recommendation; low-quality evidence). Chronic suppressive therapy with fluconazole if the isolate is susceptible, for as long as the device remains in place is recommended (strong recommendation; low-quality evidence).

What Is the Treatment for Candida Suppurative Thrombophlebitis?

Recommendations

  • Catheter removal and incision and drainage or resection of the vein, if feasible, is recommended (strong recommendation; low-quality evidence).
  • Lipid formulation AmB, 3–5 mg/kg daily, OR fluconazole, 400–800 mg (6–12 mg/kg) daily, OR an echinocandin (caspofungin 150 mg daily, micafungin 150 mg daily, or anidulafungin 200 mg daily) for at least 2 weeks after candidemia (if present) has cleared is recommended (strong recommendation; low-quality evidence).
  • Step-down therapy to fluconazole, 400–800 mg (6–12 mg/kg) daily, should be considered for patients who have initially responded to AmB or an echinocandin, are clinically stable, and have a fluconazole-susceptible isolate (strong recommendation; low-quality evidence).
  • Resolution of the thrombus can be used as evidence to discontinue antifungal therapy if clinical and culture data are supportive (strong recommendation; low-quality evidence).

XI. What Is the Treatment for Candida Osteoarticular Infections?

What Is the Treatment for Candida Osteomyelitis?

Recommendations

  • Fluconazole, 400 mg (6 mg/kg) daily, for 6–12 months OR an echinocandin (caspofungin 50–70 mg daily, micafungin 100 mg daily, or anidulafungin 100 mg daily) for at least 2 weeks followed by fluconazole, 400 mg (6 mg/kg) daily, for 6–12 months is recommended (strong recommendation; low-quality evidence).
  • Lipid formulation AmB, 3–5 mg/kg daily, for at least 2 weeks followed by fluconazole, 400 mg (6 mg/kg) daily, for 6–12 months is a less attractive alternative (weak recommendation; low-quality evidence).
  • Surgical debridement is recommended in selected cases (strong recommendation; low-quality evidence).

What Is the Treatment for Candida Septic Arthritis?

  • Fluconazole, 400 mg (6 mg/kg) daily, for 6 weeks OR an echinocandin (caspofungin 50–70 mg daily, micafungin 100 mg daily, or anidulafungin 100 mg daily) for 2 weeks followed by fluconazole, 400 mg (6 mg/kg) daily, for at least 4 weeks is recommended (strong recommendation; low-quality evidence)
  • Lipid formulation AmB, 3–5 mg/kg daily, for 2 weeks, followed by fluconazole, 400 mg (6 mg/kg) daily, for at least 4 weeks is a less attractive alternative (weak recommendation; low-quality evidence).
  • Surgical drainage is indicated in all cases of septic arthritis (strong recommendation; moderate-quality evidence).
  • For septic arthritis involving a prosthetic device, device removal is recommended (strong recommendation; moderate-quality evidence).
  • If the prosthetic device cannot be removed, chronic suppression with fluconazole, 400 mg (6 mg/kg) daily, if the isolate is susceptible, is recommended (strong recommendation; low-quality evidence).

XII. What Is the Treatment for Candida Endophthalmitis?

What Is the General Approach to Candida Endophthalmitis?

Recommendations

  • All patients with candidemia should have a dilated retinal examination, preferably performed by an ophthalmologist, within the first week of therapy in nonneutropenic patients to establish if endophthalmitis is present (strong recommendation; low-quality evidence). For neutropenic patients, it is recommended to delay the examination until neutrophil recovery (strong recommendation; low-quality evidence).
  • The extent of ocular infection (chorioretinitis with or without macular involvement and with or without vitritis) should be determined by an ophthalmologist (strong recommendation; low-quality evidence).
  • Decisions regarding antifungal treatment and surgical intervention should be made jointly by an ophthalmologist and an infectious diseases physician (strong recommendation; low-quality evidence).

What Is the Treatment for Candida Chorioretinitis Without Vitritis?

Recommendations

  • For fluconazole-/voriconazole-susceptible isolates, fluconazole, loading dose, 800 mg (12 mg/kg), then 400–800 mg (6–12 mg/kg) daily OR voriconazole, loading dose 400 mg (6 mg/kg) intravenous twice daily for 2 doses, then 300 mg (4 mg/kg) intravenous or oral twice daily is recommended (strong recommendation; low-quality evidence).
  • For fluconazole-/voriconazole-resistant isolates, liposomal AmB, 3–5 mg/kg intravenous daily, with or without oral flucytosine, 25 mg/kg 4 times daily is recommended (strong recommendation; low-quality evidence).
  • With macular involvement, antifungal agents as noted above PLUS intravitreal injection of either AmB deoxycholate, 5–10 µg/0.1 mL sterile water, or voriconazole, 100 µg/0.1 mL sterile water or normal saline, to ensure a prompt high level of antifungal activity is recommended (strong recommendation; low-quality evidence).
  • The duration of treatment should be at least 4–6 weeks, with the final duration depending on resolution of the lesions as determined by repeated ophthalmological examinations (strong recommendation; low-quality evidence).

What Is the Treatment for Candida Chorioretinitis With Vitritis?

Recommendations

  • Antifungal therapy as detailed above for chorioretinitis without vitritis, PLUS intravitreal injection of either amphotericin B deoxycholate, 5–10 µg/0.1 mL sterile water, or voriconazole, 100 µg/0.1 mL sterile water or normal saline is recommended (strong recommendation; low-quality evidence).
  • Vitrectomy should be considered to decrease the burden of organisms and to allow the removal of fungal abscesses that are inaccessible to systemic antifungal agents (strong recommendation; low-quality evidence).
  • The duration of treatment should be at least 4–6 weeks, with the final duration dependent on resolution of the lesions as determined by repeated ophthalmological examinations (strong recommendation; low-quality evidence).

XIII. What Is the Treatment for Central Nervous System Candidiasis?

Recommendations

  • For initial treatment, liposomal AmB, 5 mg/kg daily, with or without oral flucytosine, 25 mg/kg 4 times daily is recommended (strong recommendation; low-quality evidence).
  • For step-down therapy after the patient has responded to initial treatment, fluconazole, 400–800 mg (6–12 mg/kg) daily, is recommended (strong recommendation; low-quality evidence).
  • Therapy should continue until all signs and symptoms and CSF and radiological abnormalities have resolved (strong recommendation; low-quality evidence).
  • Infected CNS devices, including ventriculostomy drains, shunts, stimulators, prosthetic reconstructive devices, and biopolymer wafers that deliver chemotherapy should be removed if possible (strong recommendation; low-quality evidence).
  • For patients in whom a ventricular device cannot be removed, AmB deoxycholate could be administered through the device into the ventricle at a dosage ranging from 0.01 mg to 0.5 mg in 2 mL 5% dextrose in water (weak recommendation; low-quality evidence).

XIV. What Is the Treatment for Urinary Tract Infections Due to Candida Species?

What Is the Treatment for Asymptomatic Candiduria?

Recommendations

  • Elimination of predisposing factors, such as indwelling bladder catheters, is recommended whenever feasible (strong recommendation; low-quality evidence).
  • Treatment with antifungal agents is NOT recommended unless the patient belongs to a group at high risk for dissemination; high-risk patients include neutropenic patients, very low-birth-weight infants (<1500 g), and patients who will undergo urologic manipulation (strong recommendation; low-quality evidence).
  • Neutropenic patients and very low–birth-weight infants should be treated as recommended for candidemia (see sections III and VII) (strong recommendation; low-quality evidence).
  • Patients undergoing urologic procedures should be treated with oral fluconazole, 400 mg (6 mg/kg) daily, OR AmB deoxycholate, 0.3–0.6 mg/kg daily, for several days before and after the procedure (strong recommendation; low-quality evidence).

What Is the Treatment for Symptomatic Candida Cystitis?

Recommendations

  • For fluconazole-susceptible organisms, oral fluconazole, 200 mg (3 mg/kg) daily for 2 weeks is recommended (strong recommendation; moderate-quality evidence).
  • For fluconazole-resistant C. glabrata, AmB deoxycholate, 0.3–0.6 mg/kg daily for 1–7 days OR oral flucytosine, 25 mg/kg 4 times daily for 7–10 days is recommended (strong recommendation; low-quality evidence).
  • For C. krusei, AmB deoxycholate, 0.3–0.6 mg/kg daily, for 1–7 days is recommended (strong recommendation; low-quality evidence).
  • Removal of an indwelling bladder catheter, if feasible, is strongly recommended (strong recommendation; low-quality evidence).
  • AmB deoxycholate bladder irrigation, 50 mg/L sterile water daily for 5 days, may be useful for treatment of cystitis due to fluconazole-resistant species, such as C. glabrata and C. krusei (weak recommendation; low-quality evidence).

What Is the Treatment for Symptomatic Ascending Candida Pyelonephritis?

Recommendations

  • For fluconazole-susceptible organisms, oral fluconazole, 200–400 mg (3–6 mg/kg) daily for 2 weeks is recommended (strong recommendation; low-quality evidence).
  • For fluconazole-resistant C. glabrata, AmB deoxycholate, 0.3–0.6 mg/kg daily for 1–7 days with or without oral flucytosine, 25 mg/kg 4 times daily, is recommended (strong recommendation; low-quality evidence).
  • For fluconazole-resistant C. glabrata, monotherapy with oral flucytosine, 25 mg/kg 4 times daily for 2 weeks, could be considered (weak recommendation; low-quality evidence)
  • For C. krusei, AmB deoxycholate, 0.3–0.6 mg/kg daily, for 1–7 days is recommended (strong recommendation; low-quality evidence).
  • Elimination of urinary tract obstruction is strongly recommended (strong recommendation; low-quality evidence).
  • For patients who have nephrostomy tubes or stents in place, consider removal or replacement, if feasible (weak recommendation; low-quality evidence).

What Is the Treatment for Candida Urinary Tract Infection Associated With Fungus Balls?

Recommendations

  • Surgical intervention is strongly recommended in adults (strong recommendation; low-quality evidence).
  • Antifungal treatment as noted above for cystitis or pyelonephritis is recommended (strong recommendation; low-quality evidence).
  • Irrigation through nephrostomy tubes, if present, with AmB deoxycholate, 25–50 mg in 200–500 mL sterile water, is recommended (strong recommendation; low-quality evidence).

XV. What Is the Treatment for Vulvovaginal Candidiasis?

Recommendations

  • For the treatment of uncomplicated Candida vulvovaginitis, topical antifungal agents, with no one agent superior to another, are recommended (strong recommendation; high-quality evidence).
  • Alternatively, for the treatment of uncomplicated Candida vulvovaginitis, a single 150-mg oral dose of fluconazole is recommended (strong recommendation; high-quality evidence).
  • For severe acute Candida vulvovaginitis, fluconazole, 150 mg, given every 72 hours for a total of 2 or 3 doses, is recommended (strong recommendation; high-quality evidence).
  • For C. glabrata vulvovaginitis that is unresponsive to oral azoles, topical intravaginal boric acid, administered in a gelatin capsule, 600 mg daily, for 14 days is an alternative (strong recommendation; low-quality evidence).
  • Another alternative agent for C. glabrata infection is nystatin intravaginal suppositories, 100 000 units daily for 14 days (strong recommendation; low-quality evidence).
  • A third option for C. glabrata infection is topical 17% flucytosine cream alone or in combination with 3% AmB cream administered daily for 14 days (weak recommendation; low-quality evidence).
  • For recurring vulvovaginal candidiasis, 10–14 days of induction therapy with a topical agent or oral fluconazole, followed by fluconazole, 150 mg weekly for 6 months, is recommended (strong recommendation; high-quality evidence).

XVI. What Is the Treatment for Oropharyngeal Candidiasis?

Recommendations

  • For mild disease, clotrimazole troches, 10 mg 5 times daily, OR miconazole mucoadhesive buccal 50-mg tablet applied to the mucosal surface over the canine fossa once daily for 7–14 days are recommended (strong recommendation; high-quality evidence).
  • Alternatives for mild disease include nystatin suspension (100 000 U/mL) 4–6 mL 4 times daily, OR 1–2 nystatin pastilles (200 000 U each) 4 times daily, for 7–14 days (strong recommendation; moderate-quality evidence).
  • For moderate to severe disease, oral fluconazole, 100–200 mg daily, for 7–14 days is recommended (strong recommendation; high-quality evidence).
  • For fluconazole-refractory disease, itraconazole solution, 200 mg once daily OR posaconazole suspension, 400 mg twice daily for 3 days then 400 mg daily, for up to 28 days are recommended (strong recommendation; moderate-quality evidence).
  • Alternatives for fluconazole-refractory disease include voriconazole, 200 mg twice daily, OR AmB deoxycholate oral suspension, 100 mg/mL 4 times daily (strong recommendation; moderate-quality evidence).
  • Intravenous echinocandin (caspofungin: 70-mg loading dose, then 50 mg daily; micafungin: 100 mg daily; or anidulafungin: 200-mg loading dose, then 100 mg daily) OR intravenous AmB deoxycholate, 0.3 mg/kg daily, are other alternatives for refractory disease (weak recommendation; moderate-quality evidence).
  • Chronic suppressive therapy is usually unnecessary. If required for patients who have recurrent infection, fluconazole, 100 mg 3 times weekly, is recommended (strong recommendation; high-quality evidence).
  • For HIV-infected patients, antiretroviral therapy is strongly recommended to reduce the incidence of recurrent infections (strong recommendation; high-quality evidence).
  • For denture-related candidiasis, disinfection of the denture, in addition to antifungal therapy is recommended (strong recommendation; moderate-quality evidence).

XVII. What Is the Treatment for Esophageal Candidiasis?

Recommendations

  • Systemic antifungal therapy is always required. A diagnostic trial of antifungal therapy is appropriate before performing an endoscopic examination (strong recommendation; high-quality evidence).
  • Oral fluconazole, 200–400 mg (3–6 mg/kg) daily, for 14–21 days is recommended (strong recommendation; high-quality evidence).
  • For patients who cannot tolerate oral therapy, intravenous fluconazole, 400 mg (6 mg/kg) daily, OR an echinocandin (micafungin, 150 mg daily, caspofungin, 70-mg loading dose, then 50 mg daily, or anidulafungin, 200 mg daily) is recommended (strong recommendation; high-quality evidence).
  • A less preferred alternative for those who cannot tolerate oral therapy is AmB deoxycholate, 0.3–0.7 mg/kg daily (strong recommendation; moderate-quality evidence).
  • Consider de-escalating to oral therapy with fluconazole 200–400 mg (3–6 mg/kg) daily once the patient is able to tolerate oral intake (strong recommendation; moderate-quality evidence).
  • For fluconazole-refractory disease, itraconazole solution, 200 mg daily, OR voriconazole, 200 mg (3 mg/kg) twice daily either intravenous or oral, for 14–21 days is recommended (strong recommendation; high-quality evidence).
  • Alternatives for fluconazole-refractory disease include an echinocandin (micafungin: 150 mg daily; caspofungin: 70-mg loading dose, then 50 mg daily; or anidulafungin: 200 mg daily) for 14–21 days, OR AmB deoxycholate, 0.3–0.7 mg/kg daily, for 21 days (strong recommendation; high-quality evidence)
  • Posaconazole suspension, 400 mg twice daily, or extended-release tablets, 300 mg once daily, could be considered for fluconazole-refractory disease (weak recommendation; low-quality evidence).
  • For patients who have recurrent esophagitis, chronic suppressive therapy with fluconazole, 100–200 mg 3 times weekly, is recommended (strong recommendation; high-quality evidence).
  • For HIV-infected patients, antiretroviral therapy is strongly recommended to reduce the incidence of recurrent infections (strong recommendation; high-quality evidence).

Prevention

While there is no guaranteed way to prevent a Candida infection, certain actions can reduce the risk of developing a vaginal yeast infection.

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Women who are susceptible are advised to:

  • Avoid douching
  • Do not use feminine deodorant or deodorant pads or tampons
  • Wear underwear made from cotton or other natural fibers
  • Wear loose fitting pants or skirts
  • Wash underwear at a high temperature
  • Avoid tight underwear and pantyhose
  • Eat a healthy, varied diet
  • Promptly change wet clothing, for example bathing suits
  • Avoid hot tubs and hot baths

References

Vulvovaginal candidiasis

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