Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 36-02: Candidiasis + Key Features Download Section PDF Listen +++ +++ 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 + Clinical Findings Download Section PDF Listen +++ +++ 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 + Diagnosis Download Section PDF Listen +++ +++ 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 + Treatment Download Section PDF Listen +++ +++ 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 + Outcome Download Section PDF Listen +++ +++ 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 + References Download Section PDF Listen +++ + +Bradley SF. JAMA patient page. Candida auris infection. JAMA. 2019 Oct 15;322(15):1526. [PubMed: 31613347] + +Eyre DW et al. A Candida auris outbreak and its control in an intensive care setting. N Engl J Med. 2018 Oct 4;379(14):1322–31. [PubMed: 30281988] + +Kullberg BJ et al. Isavuconazole versus caspofungin in the treatment of candidemia and other invasive Candida infections: the ACTIVE trial. Clin Infect Dis. 2019 May 30;68(12):1981–9. [PubMed: 30289478] + +Murri R et al. Systematic clinical management of patients with candidemia improves survival. J Infect. 2018 Aug;77(2):145–50. [PubMed: 29742466] + +Pappas PG et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Feb 15;62(4):e1–50. [PubMed: 26679628] + +Pristov KE et al. Resistance of Candida to azoles and echinocandins worldwide. Clin Microbiol Infect. 2019 Jul;25(7):792–8. [PubMed: 30965100]