Candidiasis

History

• Cutaneous candidiasis ^r4
  • Most common symptom is pruritus in affected areas ^c1
• Mucous membrane syndromes
  • Relevant history of predisposing conditions may be obtained, including diabetes mellitus, broad-spectrum antibiotic use, and/or immunosuppression (eg, HIV, malignancy, corticosteroid treatment) ^{r4c2c3c4c5c6c7}
  • Site-specific symptoms:
    • Oral candidiasis (ie, oropharyngeal candidiasis) ^r4
      • Mouth and throat soreness ^c8c9
    • Esophageal candidiasis ^r4
      • Common symptoms include dysphagia, odynophagia with or without dysphagia, epigastric pain, and retrosternal pain; in severe or protracted cases, weight loss ^{c10c11c12c13c14c15}
    • Genitourinary infections
      • Vulvovaginal candidiasis symptoms include pruritus, often but not invariably accompanied by curdy white discharge; occasionally dysuria and dyspareunia may occur ^{r4c16c17c18c19}
      • Balanitis is characterized by penile pruritus ^r4c20
      • Candida cystitis may present asymptomatically or symptomatically with dysuria, urgency, and suprapubic discomfort ^{r14c21c22c23c24}
        • Passage of particulate matter and/or pneumaturia suggest presence of a fungus ball ^c25c26
        • Patients with indwelling catheters rarely have dysuria, but they sometimes have suprapubic or flank pain ^c27c28c29
    • Chronic mucocutaneous candidiasis
      • Characterized by longstanding or recurrent involvement of skin, mucous membranes, and nails
      • Lesions may be granulomatous or fungating in appearance, causing severe disfigurement ^c30c31c32
      • Refractory to usual therapy
• Invasive or systemic candidiasis ^r1
  • Most often presents in setting of prolonged hospitalization ^r1c33c34
    • Prolonged use of central venous catheters ^c35c36
    • Surgery requiring general anesthesia ^c37c38
    • Use of antibiotics, corticosteroids, or parenteral nutrition ^{c39c40c41c42c43c44}
    • May occur in patients with history of cancer and chemotherapy/radiation therapy or immunosuppression for other reasons (eg, organ transplant) ^{c45c46c47c48c49c50c51c52c53c54}
  • Patients are generally quite ill but may have no localizing complaint
  • Central nervous system candidiasis may present with manifestations of meningitis or mycotic aneurysms, including a change in mental status, headache, neck stiffness, or focal weakness ^{r1c55c56c57c58c59c60c61c62c63c64c65c66}
  • Candida endophthalmitis symptoms include eye pain, decreased vision, and eyelid edema ^{r1c67c68c69c70c71c72}
  • Cardiac involvement may cause chest pain or dyspnea ^c73c74c75c76
  • Candida peritonitis symptoms include abdominal pain, nausea, vomiting, and constipation; patients receiving chronic ambulatory peritoneal dialysis may report cloudy postdwell dialysate ^{r1c77c78c79c80c81c82c83c84c85c86}
  • Hepatosplenic candidiasis (chronic disseminated) may present with right upper quadrant abdominal pain ^r1c87c88
    • Usually becomes evident during recovery from immune suppression (this timing is suggestive of diagnosis)
  • Musculoskeletal infection symptoms may include localizing pain or joint swelling ^c89c90c91c92

Physical examination

• Cutaneous candidiasis
  • Generalized erythematous papular rash; lesions may coalesce ^c93c94c95
    • Most common in infants with congenital cutaneous candidiasis ^c96c97
  • Candida folliculitis ^r4
    • Pustulous nodules in areas of hair growth ^c98
  • Intertrigo ^r4
    • Macerated, oozing erosions and exudation in folds and creases of the skin; satellite lesions may be present ^{c99c100c101c102}
    • Commonly seen under breasts and abdominal pannus ^c103c104
  • Perianal candidiasis ^r4
    • Perianal skin reddened, sometimes macerated; satellite lesions are common ^c105c106c107
    • May extend to perineum, particularly when associated with diaper use ^c108c109
  • Interdigital infection
    • Either scaling or maceration evident on a red base ^c110c111c112
  • Paronychia/onychomycosis ^r4
    • Dystrophic, brittle, or lost nails; nail bed inflammation ^{r4c113c114c115c116c117c118c119c120}
• Mucous membrane syndromes
  • Oral candidiasis (ie, oropharyngeal candidiasis)
    • Creamy white patches on the tongue, palate, and/or buccal mucosa; in severe cases, these become confluent, coating the entire surface ^{r4c121c122c123}
    • Transverse fissuring also may be apparent in oral cavity ^r4c124
    • Angular cheilitis appears as chronic reddened, scaly, or macerated lesions at the corners of the mouth and extending from labial to cutaneous surface ^c125c126c127
  • Esophageal candidiasis
    • Presence of oral thrush in the setting of retrosternal chest pain, odynophagia, or dysphagia suggests esophageal thrush (but absence of oral lesions does not rule out esophageal candidiasis) ^c128c129c130
  • Genitourinary infections
    • Vulvovaginal candidiasis ^r4
      • Speculum examination reveals generalized mucosal injection; white plaques may be visible on the vaginal walls, and creamy, curdlike discharge may be present ^c131c132c133
      • Vulvar changes include labial edema, erythema, and fissures
      • Perineal skin may be involved, with erythema and satellite lesions ^c134c135c136
    • Balanitis ^r4
      • Dry, erythematous patches on penis; white plaques or maceration may occur around glans ^{c137c138c139c140}
    • Candida cystitis
      • Suprapubic tenderness may be elicited on palpation, and in women, perineal skin may reveal inflammation and/or satellite lesions ^c141c142c143
  • Chronic mucocutaneous candidiasis ^c144
    • Extensive disfiguring lesions around mouth and nose, on scalp, and on hands
• Invasive candidiasis
  • A common general finding of invasive Candida infection is fever, which is almost universal; signs of sepsis may be present (eg, hypotension, tachycardia, and/or altered mental status) ^{c145c146c147c148c149}
  • Neonates may exhibit lethargy, poor feeding, respiratory distress, abdominal distention, or unstable vital signs ^{r17c150c151c152c153c154}
  • Additional physical examination findings of invasive Candida may be dependent on specific organ involvement:
    • There may be evidence of cutaneous or mucous membrane candidiasis (eg, oral thrush, intertrigo) ^c155c156
    • Generalized erosive skin changes with oozing and crusting in premature newborns who have invasive cutaneous candidiasis ^r17c157c158
    • Disseminated candidiasis in patients with neutropenia may present with a palpable skin eruption consisting of 1 or multiple small (ie, several millimeters) erythematous nodules ^r1c159c160
    • With central nervous system disease (eg, meningitis, intracranial abscess), findings may include neck rigidity, mental confusion or coma, seizures, or focal neurologic deficits ^{r1c161c162c163c164c165c166c167c168c169c170}
    • Endophthalmitis may result in generalized reddening of the eye or in periorbital edema; funduscopic examination may show cotton-wool exudates or a vitreous haze ^r15c171c172
      • Funduscopic examination shows large cotton-wool exudates or off-white lesions with indistinct borders; may also show a vitreous haze ^r1c173c174
    • Tachycardia, new or changing heart murmur, or pericardial friction rub may be noted in cardiac involvement ^{r1c175c176c177}
      • Fungal endocarditis is characterized by large vegetations; evidence of emboli may be present on examination ^c178c179
    • Palpable tender liver, splenomegaly may be detected in hepatosplenic (chronic disseminated) candidiasis ^{r1c180c181c182}
      • Rarely, jaundice may be observed ^r1c183
    • Findings of peritoneal infection include abdominal distention, reduced or absent bowel sounds, generalized tenderness with rebound ^{r1c184c185c186c187c188}
      • A dialysis catheter or surgical incision may be present; surrounding erythema, scaling, or satellite lesions suggest Candida^{c189c190c191c192c193c194}
    • Findings in musculoskeletal infection may include erythema and tenderness in involved area (eg, tenderness on spinal percussion); affected joints may have effusion ^{r1c195c196c197c198}
      • Additional findings may occasionally include a draining fistulous tract ^c199

Causes

• Under normal circumstances, Candida albicans and other species of Candida are commensal organisms ^r21
  • Prevalence of carriage (colonization) of Candida varies from 45% to 65% in healthy infants and 30% to 55% in healthy adults ^r5r15
  • Candida carriage occurs in up to 65% of patients who wear dentures, 78% of patients older than 65 years who are hospitalized, and more than 90% of patients who are immunocompromised (eg, those who are HIV-positive or who are receiving chemotherapy) ^r5
  • Host susceptibility (eg, alteration in immune function or mucosal barrier) favors transition from colonization to infection ^r22
• Most common cause of cutaneous and mucocutaneous candidiasis is Candida albicans ^c200c201
  • Other common causes are Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei ^{r2c202c203c204c205c206c207c208c209}
  • Less common causative pathogens include Candidadubliniensis, Candida guilliermondii, Candida lusitaniae, and Candida kefyr^{r2c210c211c212c213c214c215c216c217}
• Together, Candida albicans and Candida glabrata account for 70% to 80% of invasive Candida infections ^r1c218c219
  • Commonly circulating Candida species can vary widely by institution; rarer/more resistant forms (as opposed to Candida albicans) are more commonly seen in large cancer treatment centers and transplant centers
  • Candida parapsilosis is associated with vascular catheters and prosthetic devices, as well as with illicit drug injection ^{r1r15c220c221c222}

Risk factors and/or associations

Primary diagnostic tools

• Cutaneous and mucous membrane syndromes
  • Diagnosis often can be made clinically by typical appearance of lesions ^r15c261
  • Diagnosis is confirmed by obtaining scrapings from skin, oral or vaginal mucosa, or nails for microscopic examination ^r4
    • Presence of hyphae/pseudohyphae or budding yeasts on potassium hydroxide preparation is suggestive of Candida infection ^r4
  • Upper endoscopy with biopsy is necessary for definitive diagnosis of esophageal candidiasis; in practice, a clinical diagnosis is often made in the setting of dysphagia or odynophagia in a patient with oropharyngeal thrush ^r2
  • Urinalysis and urine culture may detect pyuria and Candida, but distinction between colonization and infection may be difficult ^r26
    • Imaging such as ultrasonography may be used in symptomatic or critically ill patients to detect pyelonephritis and hydronephrosis, as well as fungus balls
      • Preferred initial study in patients in the ICU or in those with impaired renal function
  • In cutaneous and mucous membrane syndromes, culture results alone may be misleading, as a positive result from these sites does not distinguish colonization from infection; however, it may be helpful in directing antifungal therapy once infection is determined to be present
• Invasive candidiasis ^r27
  • High index of clinical suspicion is necessary, as most laboratory tests are nonspecific, and several diagnostic measures may be needed to confirm diagnosis ^r27
  • Clinical risk factors and evidence of simultaneous Candida colonization or mucocutaneous infection at multiple sites (eg, mouth, vagina, urinary tract) have been combined in various scoring systems to predict presence of invasive candidiasis ^r27
    • However, none provide high specificity; these scoring systems provide suggestive but not diagnostic information ^r2
  • Perform blood cultures in all patients in whom invasive candidiasis is suspected, but in whom sensitivity is limited ^r27
  • Culture samples from other clinically suspected sites of infection; a positive result in cultures from a normally sterile site (eg, cerebrospinal or synovial fluid) confirms infection, but negative culture results do not rule out infection
    • Obtain cell count and differential of normally sterile fluid in conjunction with culture
    • Analysis and culture of cerebrospinal fluid is recommended in children in whom blood culture results are positive for Candida, because there is a high frequency of central nervous system involvement in this population ^r17
    • Perform aspiration or biopsy at sites of suspected deep tissue invasion if diagnosis cannot be achieved by less invasive means; culture tissue and examine histologically
  • Non–culture-based diagnostic tests such as serum (1,3)-β-D-glucan detection assay may provide supportive information ^r27
  • Routine blood work is nonspecific
    • Leukocytosis may be present; conversely, neutropenia is a risk factor for invasive candidiasis
    • Serum alkaline phosphatase levels commonly are elevated in hepatosplenic candidiasis ^r4
  • Imaging is generally not required but may provide indirect evidence for diagnosis, and it may identify focal area for biopsy ^r1
    • CT may be useful in identifying hepatosplenic (ie, chronic disseminated) candidiasis and renal/intra-abdominal abscesses ^r1
    • CT or MRI may reveal parenchymal brain lesions in suspected central nervous system infection
      • Recommended for infants who have blood cultures positive for Candida because there is a high incidence of central nervous system involvement, and cerebrospinal fluid may not reflect brain infection ^r17
    • Echocardiogram (preferably transesophageal) is required for diagnosis of endocarditis; transthoracic or transesophageal echocardiogram may reveal evidence of myocarditis or pericarditis

Laboratory

• Cultures of blood, deep tissue, and normally sterile fluids may be diagnostic ^r27
  • Blood culture results are positive in only 50% to 70% of patients with Candida bloodstream infection ^c262c263c264
  • Invasive candidiasis may be present without concurrent candidemia
    • Blood culture results are positive in only approximately 50%^r20 of patients with deep-seated candidiasis ^r27
    • Culture of tissue may yield fungal growth; important for antifungal susceptibility testing
    • Histologic evidence of tissue invasion, even with negative tissue culture results, confirms diagnosis
• Urinalysis and urine culture ^r26c265c266
  • Pyuria is common in catheterized patients; thus, it is not a reliable distinguishing feature of infection in catheterized patients with candiduria
  • Colony counts have not clearly correlated with infection versus colonization
• Cerebrospinal fluid analysis ^r15c267c268
  • Yeast may be visible on Gram stain or wet mount in 40% of cases
  • Cell count and differential usually reveal a lymphocytic pleocytosis
• Peritoneal fluid analysis ^{c269c270c271c272}
  • Culture peritoneal fluid during surgery, or culture dialysate of patients undergoing peritoneal dialysis ^r28
  • WBC count of dialysate may range from hundreds to thousands of WBC per mm³ ^r29
• Synovial fluid analysis ^c273c274
  • Yeast may be visible on Gram stain and recoverable by culture; synovial biopsy may reveal evidence of tissue invasion
• Serum (1,3)-β-D-glucan detection assay ^r24c275
  • A level higher than 80 pg/mL on 2 successive measurements suggests invasive fungal infection, but it is not specific for Candida because it also detects Aspergillus and Pneumocystis^r20
    • Negative results carry a high negative predictive value
    • Decline of elevated levels in response to treatment is associated with a favorable outcome ^r30
• Serum alkaline phosphatase ^r1c276c277
  • Elevated in hepatosplenic candidiasis ^r4
• Sputum culture
  • Given the widespread frequency of sputum cultures that are positive for Candida in hospitalized, critically ill patients, sputum culture has little value

Imaging ^{c278c279c280c281c282}

• CT ^{r31c283c284c285}
  • Lesion enhancement pattern differs for acute, subacute, and chronic stage of disease (ie, hepatosplenic candidiasis)
  • Most sensitive CT phase for liver involvement is arterial dominant phase (25-35 seconds after contrast injection)
    • Shows a hyperattenuating rim surrounding a hypoattenuating center or bulls-eye lesion
• Ultrasonography ^{r31c286c287c288}
  • Typical ultrasonography phenotype of hepatic candidiasis is similar to that of CT ^r31
    • Appears as a bull's eye or target pattern with a peripheral hypoechoic halo encircling a central hyperechoic core
    • As disease advances, hyperechoic lesions with dorsal shadowing may occur
  • Ultrasonography in Candida urinary tract infection may reveal focal, segmental, hypoechoic renal lesions when pyelonephritis is present ^r14
    • Separation of central renal echoes or dilated calyces and renal pelvis may be apparent when hydronephrosis is present

Procedures

Most common

• Cutaneous infections
  • Generalized cutaneous infection
    • Impetigo ^c292d1
      • Infection with Streptococcus pyogenes and/or Staphylococcus aureus
      • Similar to generalized cutaneous candidiasis, characterized by erythematous lesions that may coalesce
      • Impetigo lesions evolve to oozing, crusting to a greater extent than lesions of generalized candidiasis; the latter usually occupies more surface area than impetigo
      • Differentiated by cultures revealing Streptococcus pyogenes and/or Staphylococcus aureus
    • Cellulitis ^c293d2
      • Bacterial infection of skin and subcutaneous tissue
      • Like cutaneous candidiasis, presents with erythematous skin changes
      • Fever is common and skin changes are usually confined to 1 area (eg, a lower extremity)
      • Distinction is usually based on clinical appearance, epidemiology, and risk factors
        • Skin scrapings that demonstrate yeast or hyphal elements support diagnosis of candidiasis rather than cellulitis
    • Erythema multiforme ^c294d3
      • Generalized cutaneous allergic reaction
      • Similar to generalized cutaneous candidiasis, characterized by erythematous lesions that may coalesce
      • Lesions expand and coalesce, and central clearing is often evident (ie, target lesions)
        • May involve palms and soles
        • Usually intensely pruritic
        • Trigger may be identified (eg, medication or other exposure, viral infection)
      • Diagnosis is primarily clinical
    • Psoriasis ^c295d4
      • Autoimmune disease characterized by skin inflammation and hyperproliferation
      • Similar to cutaneous candidiasis, psoriasis presents with a palpable red skin rash; it is associated with pruritus
      • Unlike cutaneous candidiasis, psoriatic lesions have a characteristic finding of pinpoint bleeding when psoriatic scale is lifted, called the Auspitz sign
      • Psoriasis is differentiated from cutaneous candidiasis using clinical signs and, in some cases, a skin biopsy
  • Folliculitis
    • Bacterial folliculitis ^c296
      • Bacterial infection of hair follicles, usually caused by Staphylococcus aureus
      • Clinically indistinguishable from Candida folliculitis
      • Conditions distinguished by microscopic examination of skin scrapings and results of cultures
  • Intertrigo ^c297
    • Maceration of skin folds
      • Occurs from excessive and prolonged moisture in skin folds
      • Appearance is similar to that of intertrigo due to Candida, but satellite lesions are absent
      • Distinguished clinically and by absence of yeast on skin scrapings
  • Perianal dermatitis ^c298
    • Diaper rash ^c299c300d5
      • Inflammation caused by prolonged moisture and contact with irritants in urine and feces
      • Appearance is similar to perianal and perineal candidiasis, although satellite lesions are not a regular feature
      • Distinction is clinical; however, in many cases, the 2 conditions coexist
    • Allergic contact dermatitis ^c301
      • Allergy to chemical components of diapers, residual detergent, or skin cleansing agents
      • Appearance is similar to perianal and perineal candidiasis; satellite lesions are not seen
      • In some cases, appearance of rash is diagnostic (eg, rash shape conforms to shape of adhesive strip only)
      • Positive response to changing products also supports diagnosis
    • Perianal streptococcal infection ^{c302c303c304c305c306}
      • Caused by group A streptococci; more common in young children than in adults
      • Characterized by bright red perianal patches, fiery-red erythema, and maceration in intertriginous folds; satellite lesions are not present
      • Pain, low-grade fever, and malaise may be present
      • Group A streptococci can be cultured using a perirectal swab
  • Interdigital
    • Eczema ^c307d6
      • Inflammatory skin condition associated with atopy; may involve interdigital web spaces
      • Similar presentation of pruritic, scaly, erythematous rash at web spaces
      • Many patients also have involvement elsewhere (eg, flexor surfaces of elbows and knees)
      • Distinguished clinically and by skin scrapings
  • Paronychia ^d7
    • Bacterial infection ^c308
      • May be caused by Staphylococcus aureus, streptococci, or gram-negative bacilli
      • Appears similar to paronychia caused by Candida, with erythema, tenderness, and edema or fluctuance at nail bed
      • May be distinguished by acute presentation, whereas Candida infection tends to be more indolent and chronic
      • Definitive diagnosis made by microscopic examination and culture of expressed or aspirated drainage
  • Onychomycosis ^c309
    • Dermatophyte nail infections may be clinically indistinguishable from Candida onychomycosis
    • Differentiation is based on microscopic examination of the nail and subungual material
• Mucosal candidiasis
  • Oral candidiasis (ie, thrush)
    • Herpes simplex stomatitis ^c310
      • Initial infection with HSV
      • Like oral candidiasis, presents with diffuse painful lesions of tongue and oral mucosa
      • Clinically differentiated in most cases by vesicular nature of the lesions, which (unlike thrush) often involve lips and periorbital skin; cervical lymphadenopathy often occurs with herpetic infections but is not common with thrush
      • Definitive distinction can be made by polymerase chain reaction for herpes simplex
    • Oral leukoplakia ^c311
      • Lesion of the tongue or oral mucosa; often associated with tobacco use and may be premalignant in some cases
      • Like thrush, appears as white plaque
      • Unlike thrush, cannot be rubbed off or dislodged
      • Diagnosis is confirmed by biopsy
    • Streptococcal pharyngitis ^c312
      • Bacterial infection of tonsils and pharynx
      • Tonsils and peritonsillar region are covered by patches of white or yellow exudate; swallowing is painful
      • Unlike thrush, pretracheal lymphadenopathy is often prominent; fever is usually present
      • Diagnosis is confirmed by rapid antigen test or culture
  • Esophageal candidiasis
    • Viral esophagitis ^c313
      • HSV or cytomegalovirus infection of the esophagus, usually due to reactivation infection in severely immunocompromised persons
      • Like esophageal candidiasis, presents with retrosternal pain, odynophagia, and/or dysphagia
      • Clinically indistinguishable from esophageal candidiasis and sometimes coinfecting
      • Can diagnose by endoscopy and biopsy
    • Gastroesophageal reflux ^c314d8
      • Reflux of stomach contents through lower esophageal sphincter
      • Like esophageal candidiasis, may be associated with dysphagia or retrosternal pain
      • Unlike esophageal candidiasis, usually relieved by antacids or proton pump inhibitors
      • Demonstrated on barium swallow
    • Esophageal spasm ^c315
      • Severe, involuntary contraction of the esophagus
      • Like esophageal candidiasis, may cause severe retrosternal pain
      • Unlike esophagitis, spasms (and symptoms) occur episodically
      • Demonstrated on barium swallow or manometry
  • Genitourinary
    • Vaginal yeast infection
      • Trichomoniasis ^c316
        • Caused by Trichomonas vaginalis, a sexually transmitted organism
        • Presentation is similar to that for vaginal candidiasis with pruritus and discharge
          • Discharge of candidiasis more likely to be white and curdlike, and perineal satellite lesions may be seen
          • Discharge of trichomoniasis may be foul-smelling and have a thinner consistency
        • Diagnosis is suggested by relatively high vaginal pH and positive test results with polymerase chain reaction; motile trichomonads usually can be seen on wet mount
      • Bacterial vaginosis ^c317d9
        • Caused primarily by Gardnerella vaginalis and the facultative anaerobes
        • Presents similar to vaginal candidiasis, with pruritus and discharge
          • Candidiasis discharge is more likely to be white and curdlike, and perineal satellite lesions may be seen
          • Bacterial vaginosis discharge is described as having a fishy odor
        • Diagnosis is made by appearance of clue cells on wet mount and increased pH
    • Cystitis
      • Bacterial cystitis ^c318
        • Bacterial bladder infection
        • In catheterized patients (the usual setting for urinary candidiasis), presentation is similar, with fever and cloudy urine
        • There are no distinguishing clinical features; culture is required
    • Balanitis
      • Leukoplakia ^c319
        • Penile skin condition of unknown cause, seen mainly in diabetic men; may be associated with penile malignancy
        • Appears as white plaque; unlike Candida, it cannot be scraped off
        • Diagnosis is made by biopsy
      • Lichen sclerosus ^c320
        • Pruritic lesion occurring on glans and inner prepuce (ie, foreskin) in uncircumcised men
        • White or cream-colored plaque that cannot be scraped off, unlike Candida
        • Diagnosis is made by biopsy
      • Plasma cell balanitis ^c321
        • Penile lesion occurring in uncircumcised men
        • Appears as smooth, well-demarcated plaques on glans penis
        • Diagnosis is made by biopsy
• Invasive candidiasis
  • Bacterial infection ^c322
    • Bacterial infection, whether in the bloodstream or deep tissue, has presentation similar to a Candida infection in the same location
    • No clinical features can definitively differentiate bacterial infection from invasive candidiasis
    • Distinction is based on cultures of blood and other clinically relevant sites, and on epidemiologic risk factors

Admission criteria

Patients with invasive infections require hospital admission

• Note: most (but not all) invasive infections occur in patients who are already hospitalized

Recommendations for specialist referral

• Refer any patient with suspected invasive candidiasis to infectious disease specialist; any subsequent referral will depend on organ site or patient involved ^r1

Drug therapy ^r2

• Triterpenoid antifungal
  • Ibrexafungerp
    • For vulvovaginal candidiasis (VVC)
      • Ibrexafungerp Oral tablet; Children and Adolescents (post-menarchal): 300 mg PO every 12 hours for 1 day. Coadministration of certain other drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Ibrexafungerp Oral tablet; Adults: 300 mg PO every 12 hours for 1 day. Coadministration of certain other drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • For recurrent vulvovaginal candidiasis (RVVC)
      • Ibrexafungerp Oral tablet; Children and Adolescents (post-menarchal): 300 mg PO every 12 hours for 1 day of every month for 6 months. Coadministration of certain other drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Ibrexafungerp Oral tablet; Adults: 300 mg PO every 12 hours for 1 day of every month for 6 months. Coadministration of certain other drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
• Pyridone antifungal ^c323
  • Ciclopirox ^c324
    • For cutaneous candidiasis
      • Ciclopirox Olamine Topical cream; Children and Adolescents 10 to 17 years: Apply to affected area(s) twice daily for 4 weeks.
      • Ciclopirox Olamine Topical cream; Adults: Apply to affected area(s) twice daily for 4 weeks.
• Triazole antifungals ^c325
  • Clotrimazole ^c326c327
    • For oropharyngeal candidiasis (thrush)
      • Clotrimazole Oral troche; Children and Adolescents 3 to 17 years: 10 mg PO 5 times daily for 7 to 14 days.
      • Clotrimazole Oral troche; Adults: 10 mg PO 5 times daily for 7 to 14 days.
  • Oteseconazole
    • For recurrent vulvovaginal candidiasis (RVVC)
      • Oteseconazole Oral capsule; Children and Adolescents 10 to 17 years (post-menarchal): 600 mg PO as single dose on day 1, followed by 450 mg PO as a single dose on day 2, and then beginning on day 14, 150 mg PO once weekly for 11 weeks.
      • Oteseconazole Oral capsule; Adults: 600 mg PO as single dose on day 1, followed by 450 mg PO as a single dose on day 2, and then beginning on day 14, 150 mg PO once weekly for 11 weeks.
  • Miconazole ^c328c329
    • For cutaneous candidiasis
      • Miconazole Nitrate Topical cream; Children and Adolescents 2 to 17 years: Apply to affected area(s) twice daily for 2 weeks.
      • Miconazole Nitrate Topical cream; Adults: Apply to affected area(s) twice daily for 2 weeks.
    • For uncomplicated vulvovaginal candidiasis (VVC)
      • Topical dosage
        • NOTE: Vaginal miconazole products are often packaged with additional miconazole cream for external vulvar symptoms (eg, itching, irritation).
        • Miconazole Nitrate Topical cream, Miconazole Nitrate Vaginal cream; Children and Adolescents 12 to 17 years: Apply externally to the vulva twice daily for up to 7 days in combination with intravaginal miconazole.
        • Miconazole Nitrate Topical cream, Miconazole Nitrate Vaginal cream; Adults: Apply externally to the vulva twice daily for up to 7 days in combination with intravaginal miconazole.
      • Intravaginal dosage 1-day regimen, vaginal suppository
        • NOTE: For use in nonpregnant persons
        • Miconazole Nitrate Vaginal suppository; Children and Adolescents 12 to 17 years: 1,200 mg (1 suppository) intravaginally as a single dose at bedtime.
        • Miconazole Nitrate Vaginal suppository; Adults: 1,200 mg (1 suppository) intravaginally as a single dose at bedtime.
      • Intravaginal dosage 3-day regimen, vaginal suppository or cream
        • NOTE: For use in nonpregnant persons
        • Miconazole Nitrate Vaginal cream, Miconazole Nitrate Vaginal suppository; Children and Adolescents 12 to 17 years: 200 mg (1 applicatorful or suppository) intravaginally once daily at bedtime for 3 days.
        • Miconazole Nitrate Vaginal cream, Miconazole Nitrate Vaginal suppository; Adults: 200 mg (1 applicatorful or suppository) intravaginally once daily at bedtime for 3 days.
      • Intravaginal dosage 7-day regimen, vaginal suppository or cream
        • NOTE: For use in pregnant and nonpregnant persons
        • Miconazole Nitrate Vaginal cream, Miconazole Nitrate Vaginal suppository; Children and Adolescents 12 to 17 years: 100 mg (1 applicatorful or suppository) intravaginally once daily at bedtime for 7 days.
        • Miconazole Nitrate Vaginal cream, Miconazole Nitrate Vaginal suppository; Adults: 100 mg (1 applicatorful or suppository) intravaginally once daily at bedtime for 7 days.
    • For complicated vulvovaginal candidiasis (VVC)
      • Miconazole Nitrate Vaginal cream, Miconazole Nitrate Vaginal suppository; Adolescents: 100 mg (1 applicatorful or suppository) intravaginally once daily at bedtime for 7 to 14 days; subsequent intermittent topical treatment may be considered.
      • Miconazole Nitrate Vaginal cream, Miconazole Nitrate Vaginal suppository; Adults: 100 mg (1 applicatorful or suppository) intravaginally once daily at bedtime for 7 to 14 days; subsequent intermittent topical treatment may be considered.
  • Fluconazole ^{c330c331c332c333c334c335c336c337c338c339c340c341c342c343c344}
    • For oropharyngeal candidiasis (thrush)
      • For oropharyngeal candidiasis (thrush) in persons without HIV
        • Fluconazole Oral tablet; Neonates†: 6 mg/kg/dose PO once, then 3 to 6 mg/kg/dose PO once daily for 7 to 14 days.
        • Fluconazole Oral tablet; Infants 1 to 5 months†: 6 mg/kg/dose PO once, then 3 to 6 mg/kg/dose PO once daily for 7 to 14 days.
        • Fluconazole Oral tablet; Infants, Children, and Adolescents 6 months to 17 years: 6 mg/kg/dose (Max: 200 mg/dose) PO once, then 3 to 6 mg/kg/dose (Max: 100 mg/dose) PO once daily for 7 to 14 days.
        • Fluconazole Oral tablet; Adults: 100 to 200 mg PO once daily for 7 to 14 days.
      • For oropharyngeal candidiasis (thrush) in persons living with HIV
        • Fluconazole Oral tablet; Infants 1 to 5 months†: 6 to 12 mg/kg/dose PO once daily for 7 to 14 days.
        • Fluconazole Oral tablet; Infants and Children 6 months to 12 years: 6 to 12 mg/kg/dose (Max: 200 mg/dose) PO once daily for 7 to 14 days.
        • Fluconazole Oral tablet; Adolescents: 100 to 200 mg PO once daily for 7 to 14 days.
        • Fluconazole Oral tablet; Adults: 100 to 200 mg PO once daily for 7 to 14 days.
    • For esophageal candidiasis
      • For esophageal candidiasis in persons without HIV
        • Fluconazole Oral tablet; Neonates†: 6 mg/kg/dose PO once, then 3 to 6 mg/kg/dose PO once daily for 14 to 21 days. Doses up to 12 mg/kg/day PO may be used if clinical condition warrants more aggressive dosing.
        • Fluconazole Oral tablet; Infants 1 to 5 months†: 6 mg/kg/dose PO once, then 3 to 6 mg/kg/dose PO once daily for 14 to 21 days. Doses up to 12 mg/kg/day PO may be used if clinical condition warrants more aggressive dosing.
        • Fluconazole Oral tablet; Infants, Children, and Adolescents 6 months to 17 years: 6 mg/kg/dose (Max: 400 mg/dose) PO once, then 3 to 6 mg/kg/dose (Max: 400 mg/dose) PO once daily for 14 to 21 days. Doses up to 12 mg/kg/day (Max: 400 mg/day) PO may be used if clinical condition warrants more aggressive dosing.
        • Fluconazole Oral tablet; Adults: 200 to 400 mg PO once daily for 14 to 21 days.
      • For esophageal candidiasis in persons living with HIV
        • Fluconazole Oral tablet; Infants 1 to 5 months†: 6 to 12 mg/kg/dose PO once daily for 14 to 21 days.
        • Fluconazole Oral tablet; Infants and Children 6 months to 12 years: 6 to 12 mg/kg/dose (Max: 400 mg/dose) PO once daily for 14 to 21 days.
        • Fluconazole Oral tablet; Adolescents: 100 to 400 mg PO once daily for 14 to 21 days.
        • Fluconazole Oral tablet; Adults: 100 to 400 mg PO once daily for 14 to 21 days.
      • For secondary esophageal candidiasis prophylaxis (ie, long-term suppressive therapy) in persons without HIV with recurrent infections
        • Fluconazole Oral tablet; Adults: 100 to 200 mg PO 3 times weekly.
      • For secondary esophageal candidiasis prophylaxis (ie, long-term suppressive therapy) in persons living with HIV with recurrent infections
        • Fluconazole Oral tablet; Infants and Children: 3 to 6 mg/kg/dose (Max: 200 mg/dose) PO once daily.
        • Fluconazole Oral tablet; Adolescents: 100 to 200 mg PO once daily.
        • Fluconazole Oral tablet; Adults: 100 to 200 mg PO once daily.
    • For vulvovaginal candidiasis (VVC)
      • For uncomplicated vulvovaginal candidiasis (VVC)
        • Fluconazole Oral tablet; Adolescents†: 150 mg PO as a single dose.
        • Fluconazole Oral tablet; Adults: 150 mg PO as a single dose.
      • For severe vulvovaginal candidiasis (VVC) in persons without HIV
        • Fluconazole Oral tablet; Adolescents: 150 mg PO every 3 days for 2 to 3 doses.
        • Fluconazole Oral tablet; Adults: 150 mg PO every 3 days for 2 to 3 doses.
      • For severe vulvovaginal candidiasis (VVC) in persons living with HIV
        • Fluconazole Oral tablet; Adolescents: 100 to 200 mg PO daily for at least 7 days.
        • Fluconazole Oral tablet; Adults: 100 to 200 mg PO daily for at least 7 days.
      • For recurrent vulvovaginal candidiasis (RVVC) in persons without HIV
        • Fluconazole Oral tablet; Adolescents: 100 to 200 mg PO every 3 days for a total of 3 doses or daily therapy with oral fluconazole for 10 to 14 days, followed by long-term suppressive therapy.
        • Fluconazole Oral tablet; Adults: 100 to 200 mg PO every 3 days for a total of 3 doses or daily therapy with oral fluconazole for 10 to 14 days, followed by long-term suppressive therapy.
      • For recurrent vulvovaginal candidiasis (RVVC) in persons living with HIV
        • Fluconazole Oral tablet; Adolescents: 100 to 200 mg PO daily for at least 7 days, followed by long-term suppressive therapy.
        • Fluconazole Oral tablet; Adults: 100 to 200 mg PO daily for at least 7 days, followed by long-term suppressive therapy.
      • For secondary vulvovaginal candidiasis prophylaxis (ie, long-term suppressive therapy) in persons without HIV with RVVC
        • Fluconazole Oral tablet; Adolescents: 100 to 200 mg PO once weekly for 6 months.
        • Fluconazole Oral tablet; Adults: 100 to 200 mg PO once weekly for 6 months.
      • For secondary vulvovaginal candidiasis prophylaxis (ie, long-term suppressive therapy) in persons living with HIV with RVVC
        • Fluconazole Oral tablet; Adolescents: 150 mg PO once weekly.
        • Fluconazole Oral tablet; Adults: 150 mg PO once weekly.
    • For invasive candidiasis (not central nervous system)
      • Fluconazole Solution for injection; Neonates†: 12 mg/kg/dose IV once daily; loading dose of 25 mg/kg IV on day 1 is recommended to achieve therapeutic concentrations faster. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
      • Fluconazole Solution for injection; Infants 1 to 5 months†: 12 mg/kg/dose IV once daily. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
      • Fluconazole Solution for injection; Infants, Children, and Adolescents 6 months to 17 years: 12 mg/kg/dose (Usual Max: 600 mg/dose) IV once daily. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
      • Fluconazole Solution for injection; Adults: 800 mg IV once, then 400 mg IV once daily. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
  • Voriconazole ^c345c346c347
    • For invasive candidiasis (not central nervous system)
      • Voriconazole Solution for injection; Neonates†: Safe and effective use not established; very limited data available. 2 mg/kg/dose IV every 12 hours to 6 mg/kg/dose IV every 8 hours. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Voriconazole Solution for injection; Infants† and Children younger than 2 years†: Optimal dosing not well established. 9 mg/kg/dose IV every 12 hours on day 1, followed by 8 mg/kg/dose IV every 12 hours. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Some pediatric patients will require higher doses to achieve therapeutic concentrations.
      • Voriconazole Solution for injection; Children 2 to 11 years: 9 mg/kg/dose IV every 12 hours on day 1, followed by 8 mg/kg/dose IV every 12 hours. May increase the dose by 1 mg/kg increments for inadequate response; if not tolerated, reduce dose by 1 mg/kg increments. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Voriconazole Solution for injection; Children and Adolescents 12 to 14 years weighing less than 50 kg: 9 mg/kg/dose IV every 12 hours on day 1, followed by 8 mg/kg/dose IV every 12 hours. May increase the dose by 1 mg/kg increments for inadequate response; if not tolerated, reduce dose by 1 mg/kg increments. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Voriconazole Solution for injection; Children and Adolescents 12 to 14 years weighing 50 kg or more: 6 mg/kg/dose IV every 12 hours on day 1, followed by 3 to 4 mg/kg/dose IV every 12 hours. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Voriconazole Solution for injection; Adolescents 15 to 17 years: 6 mg/kg/dose IV every 12 hours on day 1, followed by 3 to 4 mg/kg/dose IV every 12 hours. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. 
      • Voriconazole Solution for injection; Adults: 6 mg/kg/dose IV every 12 hours on day 1, followed by 3 to 4 mg/kg/dose IV every 12 hours. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. 
• Echinocandins ^{r40c348c349c350c351c352c353c354c355c356c357c358c359c360c361}
  • Caspofungin ^{c362c363c364c365}
    • For invasive candidiasis (not central nervous system)
      • Caspofungin Solution for injection; Neonates†: Very limited data available. 25 mg/m2/dose IV once daily may provide comparable exposure to usual dose in adults. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Caspofungin Solution for injection; Infants 1 to 2 months†: Very limited data available. 25 mg/m2/dose IV once daily may provide comparable exposure to usual dose in adults. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Caspofungin Solution for injection; Infants, Children, and Adolescents 3 months to 17 years: 70 mg/m2/dose (Max: 70 mg/dose) IV loading dose on day 1, followed by 50 mg/m2/dose (Max: 70 mg/dose) IV once daily. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. May increase dose to 70 mg/m2/dose (Max: 70 mg/dose) if there is an inadequate clinical response. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Caspofungin Solution for injection; Adults: 70 mg IV loading dose on day 1, then 50 mg IV once daily. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
  • Micafungin ^{c366c367c368c369}
    • For invasive candidiasis (not central nervous system)
      • Micafungin Sodium Solution for injection; Neonates: 4 mg/kg/dose IV once daily; however, higher doses (10 to 15 mg/kg/dose IV once daily) have been used off-label. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications
      • Micafungin Sodium Solution for injection; Infants 1 to 3 months: 4 mg/kg/dose IV once daily. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
      • Micafungin Sodium Solution for injection; Infants, Children, and Adolescents 4 months to 17 years weighing 40 kg or less: 2 mg/kg/dose IV once daily; if response inadequate after 5 days, may increase the dose to 4 mg/kg/dose IV once daily. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
      • Micafungin Sodium Solution for injection; Children and Adolescents weighing more than 40 kg: 2 mg/kg/dose (Max: 100 mg/dose) IV once daily; if response inadequate after 5 days, may increase the dose to 200 mg IV once daily. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
      • Micafungin Sodium Solution for injection; Adults: 100 mg IV once daily. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
  • Anidulafungin ^{c370c371c372c373}
    • For invasive candidiasis (not central nervous system)
      • Anidulafungin Solution for injection; Neonates†: Very limited data available. 3 mg/kg IV loading dose, then 1.5 mg/kg/dose IV once daily appears to provide comparable exposure to that seen in children receiving similar weight-based dosing and adults receiving a 200 mg IV loading dose, followed by 100 mg IV once daily. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
      • Anidulafungin Solution for injection; Infants, Children, and Adolescents: 3 mg/kg/dose (Max: 200 mg/dose) IV loading dose on day 1, then 1.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
      • Anidulafungin Solution for injection; Adults: 200 mg IV loading dose on day 1, then 100 mg IV once daily for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
• Polyene antifungals
  • Nystatin
    • For cutaneous candidiasis
      • Nystatin Topical powder; Neonates: Apply to affected area(s) 2 to 3 times daily until healing is complete.
      • Nystatin Topical powder; Infants, Children, and Adolescents: Apply to affected area(s) 2 to 3 times daily until healing is complete.
      • Nystatin Topical powder; Adults: Apply to affected area(s) 2 to 3 times daily until healing is complete.
    • For oropharyngeal candidiasis (thrush)
      • Nystatin Oral suspension; Neonates: 200,000 units (2 mL) PO 4 times daily for 7 to 14 days; divide dose so that one-half of each dose is placed in each side of the mouth.
      • Nystatin Oral suspension; Infants: 200,000 units (2 mL) PO 4 times daily for 7 to 14 days; divide dose so that one-half of each dose is placed in each side of the mouth.
      • Nystatin Oral suspension; Children and Adolescents: 400,000 to 600,000 units (4 to 6 mL) PO 4 times daily for 7 to 14 days; divide dose so that one-half of each dose is placed in each side of the mouth.
      • Nystatin Oral suspension; Adults: 400,000 to 600,000 units (4 to 6 mL) PO 4 times daily for 7 to 14 days; divide dose so that one-half of each dose is placed in each side of the mouth.
  • Amphotericin B ^{c374c375c376c377c378c379c380c381c382c383c384c385c386c387c388c389c390}
    • NOTE: Dosing for conventional amphotericin B deoxycholate and liposomal or lipid complex amphotericin B are NOT interchangeable ^r41
    • Guidelines do not include amphotericin B deoxycholate for invasive candidiasis in adults; a lipid formulation amphotericin B is preferred
    • Amphotericin B liposomal (LAmB)
      • For central nervous system infections
        • Amphotericin B Liposomal Suspension for injection; Neonates†: 3 to 5 mg/kg/dose IV every 24 hours; doses up to 7 mg/kg/dose IV every 24 hours have been used. Continue treatment until all signs and symptoms and CSF and radiologic abnormalities resolve.
        • Amphotericin B Liposomal Suspension for injection; Infants, Children, and Adolescents: 5 mg/kg/dose IV every 24 hours. Continue treatment until all signs and symptoms and CSF and radiologic abnormalities resolve.
        • Amphotericin B Liposomal Suspension for injection; Adults: 5 mg/kg/dose IV every 24 hours. Continue treatment until all signs and symptoms and CSF and radiologic abnormalities resolve.
      • For invasive candidiasis (not central nervous system)
        • Amphotericin B Liposomal Suspension for injection; Neonates†: 3 to 5 mg/kg/dose IV every 24 hours; doses up to 7 mg/kg/dose IV every 24 hours have been used. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
        • Amphotericin B Liposomal Suspension for injection; Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
        • Amphotericin B Liposomal Suspension for injection; Adults: 3 to 5 mg/kg/dose IV every 24 hours. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
    • Amphotericin B lipid complex (ABLC)
      • For invasive candidiasis (not central nervous system)
        • Amphotericin B Phospholipid Complex Suspension for injection; Neonates: 3 to 5 mg/kg/dose IV every 24 hours. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
        • Amphotericin B Phospholipid Complex Suspension for injection; Infants, Children, and Adolescents: 3 to 5 mg/kg/dose IV every 24 hours. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
        • Amphotericin B Phospholipid Complex Suspension for injection; Adults: 3 to 5 mg/kg/dose IV every 24 hours. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
    • Amphotericin B deoxycholate
      • For invasive candidiasis (not central nervous system)
        • Amphotericin B Solution for injection; Neonates†: 1 mg/kg/dose IV every 24 hours. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
        • Amphotericin B Solution for injection; Infants†, Children†, and Adolescents†: 1 mg/kg/dose IV every 24 hours. Treat for 2 weeks after documented clearance from the bloodstream and resolution of signs and symptoms for invasive candidiasis without metastatic complications.
        • Amphotericin B Solution for injection; Adults: Not recommended. 0.25 to 0.3 mg/kg/dose IV every 24 hours; may increase dose by 5 to 10 mg/day to final dose of 0.5 to 0.7 mg/kg/day. Doses up to 1 mg/kg/day or 1.5 mg/kg/dose every other day may be warranted.
• Pyrimidine analogue ^c391
  • Flucytosine ^{c392c393c394c395c396}
    • For central nervous system infections ^c397
      • Flucytosine Oral capsule; Neonates: 50 to 150 mg/kg/day PO divided every 6 hours in combination with amphotericin B; adjust dose, if necessary, based on serum concentrations. Treatment should continue until all signs and symptoms and CSF and radiologic abnormalities have resolved. Not routinely recommended by IDSA for neonatal candidiasis.
      • Flucytosine Oral capsule; Infants, Children, and Adolescents: 25 to 37.5 mg/kg/dose PO 4 times daily in combination with liposomal amphotericin B; adjust dose, if necessary, based on serum concentrations. Treatment should continue until all signs and symptoms and CSF and radiologic abnormalities have resolved.
      • Flucytosine Oral capsule; Adults: 50 to 150 mg/kg/day PO in divided doses every 6 hours; alternately, IDSA recommends 25 mg/kg/dose PO 4 times daily in combination with liposomal amphotericin B. Adjust dose, if necessary, based on serum concentrations. Treatment should continue until all signs and symptoms and CSF and radiologic abnormalities have resolved.
    • For invasive candidiasis (not central nervous system) ^c398
      • Flucytosine Oral capsule; Neonates†: 50 to 150 mg/kg/day PO divided every 6 hours; adjust dose, if necessary, based on serum concentrations.
      • Flucytosine Oral capsule; Infants†, Children†, and Adolescents†: 25 mg/kg/dose PO 4 times daily; adjust dose, if necessary, based on serum concentrations.
      • Flucytosine Oral capsule; Adults: 50 to 150 mg/kg/day PO divided every 6 hours; adjust dose, if necessary, based on serum concentrations.
    • For Candida glabrata vulvovaginal candidiasis (VVC) ^r2r35r36r37
      • NOTE: Flucytosine vaginal cream (12.5%-17%) requires extemporaneous compounding
        • Flucytosine Vaginal Cream; Adults: 1,000 mg (1 applicatorful) intravaginally once daily at bedtime for 14 days.
• Miscellaneous antifungal
  • Boric acid
    • For Candida glabrata vulvovaginal candidiasis (VVC)
      • Boric Acid Vaginal suppository; Adolescents: 600 mg vaginally once daily for 21 days.
      • Boric Acid Vaginal suppository; Adults: 600 mg vaginally once daily for 21 days.

Nondrug and supportive care

Comorbidities

• HIV infection ^c403
  • Use antiretroviral therapy for patients who are HIV-positive, regardless of type of infection or duration of disease
    • Use of antiretroviral therapy typically leads to resolution of oropharyngeal candidiasis as a result of immune recovery ^r2
• Neutropenia (generally a result of chemotherapy for malignancy)
  • Granulocyte transfusions may benefit patients who have persistent candidemia and prolonged neutropenia, as may therapy with an echinocandin ^r2

Special populations

• Neonates are at risk for central nervous system infections ^r2
  • If Candida is in blood or urine, neonate undergoes lumbar puncture and a dilated retinal examination
  • Amphotericin B deoxycholate is recommended as initial treatment