Candidiasis

Essentials of Diagnosis

• Common normal flora but opportunistic pathogen

• Typically mucosal disease, particularly vaginitis, oral thrush, and esophagitis

• Persistent, unexplained oral or vaginal candidiasis: check for HIV or diabetes mellitus

• (1,3)-beta-D-glucan results may be positive in candidemia even when blood cultures are negative

General Considerations

• Candida albicans can be cultured from the mouth, vagina, and feces of most people

• Cellular immunodeficiency predisposes to mucocutaneous disease

• Risk factors for vulvovaginal candidiasis

  • Pregnancy, uncontrolled diabetes mellitus, broad-spectrum antimicrobial treatment, corticosteroid use, and HIV infection

  • Symptoms include

    • Acute vulvar pruritus

    • Burning vaginal discharge

    • Dyspareunia

• Risk factors for invasive candidiasis

  • Prolonged neutropenia

  • Recent abdominal surgery

  • Broad-spectrum antibiotics

  • Kidney disease

  • Intravascular catheters (especially for total parenteral nutrition)

Demographics

• Vulvovaginal candidiasis occurs in an estimated 75% of women during their lifetime

• Esophageal involvement is the most frequent type of significant mucosal disease

Symptoms and Signs

• Esophageal candidiasis

  • Substernal odynophagia, gastroesophageal reflux, or nausea without substernal pain

  • Oral candidiasis may not be present

• Vulvovaginal candidiasis

  • Acute vulvar pruritus

  • Burning vaginal discharge

  • Dyspareunia

• Invasive candidiasis

  • Candidemia without deep seated infection

  • Candidemia with deep seated infection (typically eyes, kidney, or abdomen)

  • Deep-seated candidiasis in the absence of bloodstream infection (ie, hepatosplenic candidiasis)

  • Clinical presentation of candidemia ranges from minimal fever to septic shock

• Candidal funguria

  • Asymptomatic and typically represents specimen contamination or bladder colonization

  • However, signs and symptoms of true Candida urinary tract infections (UTIs) are indistinguishable from bacterial UTIs and can include urgency, hesitancy, fever, chills, or flank pain

• Hepatosplenic candidiasis: fever and variable abdominal pain weeks after chemotherapy for hematologic cancers, when neutrophil counts have recovered

• Candidal endocarditis

  • Rare

  • Affects patients with prosthetic heart valves or prolonged candidemia, such as with indwelling catheters

Differential Diagnosis

• Esophageal candidiasis

  • Herpes simplex virus (HSV) esophagitis

  • Cytomegalovirus (CMV) esophagitis

  • Varicella-zoster virus esophagitis

  • Pill esophagitis, eg, nonsteroidal anti-inflammatory drugs, bisphosphonates, KCl

  • Gastroesophageal reflux disease

• Vulvovaginal candidiasis

  • Bacterial vaginosis

  • Trichomonas vaginitis

  • Normal vaginal discharge

• Candidemia

  • Histoplasmosis

  • Coccidioidomycosis

  • Tuberculosis

  • Bacterial endocarditis

  • Aspergillosis

Laboratory Tests

• Esophageal candidiasis: Best confirmed by endoscopy with biopsy and culture

• Invasive candidiasis

  • Blood cultures are positive in only about 50% of cases

  • While candidemia can be benign (transient, eg, catheter-related), positive blood cultures are sufficient to initiate treatment for disseminated disease

  • Consecutively positive 1,3-beta-D-glucan results may be used to guide empiric therapy in high-risk patients even in the absence of positive blood cultures

  • Positive mucosal cultures (urine, sputum) may be a clue to underlying disseminated candidiasis

• Hepatosplenic candidiasis

  • Can occur following prolonged neutropenia in patients with underlying hematologic cancers but this entity is less common in the era of widespread antifungal prophylaxis

  • Typically, fever and variable abdominal pain present weeks after chemotherapy, when neutrophil counts have recovered

  • Blood cultures are generally negative

• Candidal endocarditis: diagnosis is established definitively by culturing Candida from vegetations at the time of valve replacement

Imaging Studies

• Usually normal in invasive disease

Diagnostic Procedures

• Esophageal candidiasis is best confirmed by endoscopy with biopsy and culture

• For mucosal disease, KOH prep will demonstrate yeast and pseudohyphae

• For invasive disease, definitive proof requires sterile site histologic tests or culture or both

• A dilated fundoscopic examination is recommended for all patients with candidemia to exclude endophthalmitis

• Repeat blood cultures should be drawn to demonstrate organism clearance

Medications

• Vulvovaginal candidiasis

  • Oral fluconazole

    • Dose: Single 150-mg oral dose; equivalent to topical treatments with better patient acceptance

    • 150 weekly can decrease disease recurrence

  • Topical azole preparations include

    • Clotrimazole, 100-mg vaginal tablet for 7 days

    • Miconazole, 200-mg vaginal suppository for 3 days

  • For non-albicans strains (eg, Candida glabrata), alternative therapies (such as intravaginal boric acid) in the setting of azole resistance may be required

• Esophageal candidiasis

  • If patients are able to swallow and take adequate amounts of fluid orally, fluconazole, 200–400 mg daily for 14-21 days, is recommended

  • Patients who are unable to tolerate oral therapy should receive intravenous fluconazole, 400 mg daily; or an echinocandin

  • Options for patients with fluconazole-refractory disease include

    • Oral itraconazole solution, 200 mg daily

    • Oral or intravenous voriconazole, 200 mg twice daily

    • An intravenous echinocandin (caspofungin,70 mg loading dose, then 50 mg/day; anidulafungin, 200 mg/day; or intravenous micafungin, 150 mg/day)

    • Posaconazole tablets, 300 mg/day

• Candidal funguria

  • Benefit from treatment of asymptomatic candiduria has not been demonstrated

  • Frequently resolves without therapy following discontinuation of antibiotics or removal of bladder catheter

  • Fluconazole, 200 mg orally once daily for 7–14 days, if symptoms persist

  • Newer generation azoles (eg, voriconazole) and echinocandins are not considered standard therapy due to low levels of active drug in the urine

• Invasive candidiasis

  • Intravenous echinocandin as first-line therapy

    • Caspofungin, 70 mg once, then 50 mg daily

    • Micafungin, 100 mg daily

    • Anidulafungin, 200 mg once, then 100 mg daily

  • Intravenous or oral fluconazole (800 mg once, then 400 mg daily) is an acceptable alternative for less critically ill patients without recent azole exposure

  • Voriconazole, 400 mg twice daily for two doses, then 200 mg twice daily

    • Also effective for candidemia

    • However, offers little advantage over fluconazole unless infection is due to fluconazole-resistant isolates

  • Non-albicans species of Candida

    • An echinocandin is recommended for treatment of C glabrata infection with transition to oral fluconazole or voriconazole reserved for when isolates are known to be susceptible to these agents

    • Lipid formulation amphotericin B (3–5 mg/kg intravenously daily) may be used for isolates with resistance to azoles and echinocandins

• Candidal endocarditis

  • Best results are achieved with a combination of medical and surgical therapy (valve replacement)

  • Initial therapy recommendations

    • Lipid formulation amphotericin B (3–5 mg/kg/day) or

    • High-dose echinocandin: caspofungin 150 mg/day, micafungin 150 mg/day, or anidulafungin 200 mg/day

  • Step-down or long-term suppressive therapy for nonsurgical candidates may be done with fluconazole at 6–12 mg/kg/day for susceptible organisms

Complications

• Candidal fungemia: endophthalmitis; often no complications if fungemia resolves with removal of intravenous catheters

• Candidal endocarditis

  • Valve destruction (usually aortic or mitral)

  • Myocardial ring abscess

  • Systemic embolization

Prognosis

• Esophageal candidiasis: relapse common in HIV infection without adequate immune reconstitution

Prevention

• Fluconazole prophylaxis for high-risk patients undergoing induction chemotherapy

• Minimize unnecessary broad-spectrum antibiotics and intravenous catheters