A. Mucosal Candidiasis

B. Candidal Funguria

Most cases of candidal funguria are asymptomatic and represent specimen contamination or bladder colonization (and do not warrant antifungal therapy). However, symptoms and signs of true Candida UTIs are indistinguishable from bacterial UTIs and can include urgency, hesitancy, fever, chills, or flank pain.

C. Invasive Candidiasis

Invasive candidiasis can be (1) candidemia (bloodstream infection) without deep-seated infection; (2) candidemia with deep-seated infection (typically eyes, kidney, or abdomen); and (3) deep-seated candidiasis in the absence of bloodstream infection (ie, hepatosplenic candidiasis). Varying ratios of these clinical entities depends on the predominating risk factors for affected patients (ie, neutropenia, indwelling vascular catheters, postsurgical). Notably, it has been shown that rates of invasive candidiasis decline with implementation of other infection control strategies. The clinical presentation of candidemia varies from minimal fever to septic shock that can resemble a severe bacterial infection. The diagnosis of invasive Candida infection is challenging since Candida species are often isolated from mucosal sites in the absence of invasive disease while blood cultures are positive only 50% of the time in invasive infection. Consecutively positive (1,3)-beta-D-glucan results can guide empiric therapy in high-risk patients even in the absence of positive blood cultures.

Hepatosplenic candidiasis can occur following prolonged neutropenia with 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, though hepatosplenic abscesses may be seen on abdominal imaging.

D. Candidal Endocarditis

Candidal endocarditis is a rare infection affecting patients with prosthetic heart valves or prolonged candidemia, such as with indwelling catheters. The diagnosis is established definitively by culturing Candida from vegetations at the time of valve replacement.

A. Mucosal Candidiasis

B. Candidal Funguria

Candidal funguria frequently resolves with discontinuance of antibiotics or removal of bladder catheters. Clinical benefit from treatment of asymptomatic candiduria has not been demonstrated, but persistent funguria should raise the suspicion of invasive infection. When symptomatic funguria persists, oral fluconazole, 200 mg/day for 7-14 days, can be used. Newer generation azoles (eg, voriconazole) and echinocandins are not considered standard therapy for candidal UTIs due to low levels of active drug in the urine.

C. Invasive Candidiasis

The 2016 Infectious Diseases Society of America guidelines for management of candidemia recommend an intravenous echinocandin as first-line therapy (ie, caspofungin [70 mg once, then 50 mg daily], micafungin [100 mg daily], or 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. Rezafungin (400 mg intravenously once, then 200 mg intravenously weekly) is FDA-approved as a long-acting echinocandin for candidemia and invasive candidiasis when there are limited or no alternative treatment options. Intravenous or oral voriconazole (400 mg twice daily for two doses, then 200 mg twice daily) is also effective for candidemia but offers little advantage over fluconazole unless infection is due to fluconazole-resistant isolates. A 2019 randomized trial failed to demonstrate noninferiority of isavuconazole versus caspofungin for patients with invasive candidiasis; further investigation is needed to establish the roles of posaconazole and isavuconazole in the treatment of candidemia.

Therapy for candidemia should be continued for 2 weeks after the last positive blood culture and resolution of symptoms and signs of infection. The use of rezafungin has not been studied for use beyond 4 weeks. A dilated fundoscopic examination may be advised for patients with candidemia to exclude endophthalmitis and repeat blood cultures should be drawn to demonstrate organism clearance. Susceptibility testing is recommended on all bloodstream Candida isolates; once patients have become clinically stable, parenteral therapy can be discontinued and treatment can be completed with oral fluconazole, 400 mg daily for susceptible isolates. Removal or exchange of intravascular catheters is recommended for patients with candidemia in whom the catheter is the suspected source of infection. Hepatosplenic candidiasis requires treatment until lesions have resolved radiographically.

Non-albicans species of Candida often have resistance patterns that are different from C albicans. An echinocandin is recommended for treatment of Nakaseomyces glabrata (formerly C glabrata) infection with transition to oral fluconazole or voriconazole for patients with susceptible isolates. For isolates with resistance to azoles and echinocandins, lipid formulation amphotericin B (3-5 mg/kg intravenously daily) may be used. C krusei is inherently fluconazole-resistant and should be treated with an alternative agent, such as an echinocandin or voriconazole. Fluconazole may be optimal for Candida parapsilosis due to possible echinocandin resistance in such isolates. Health care-associated infections due to multidrug-resistant Candida auris may be treated with echinocandins plus environmental source control. fosmanogepix, a novel agent inhibiting the enzyme glycosylphosphatidylinositol-anchored wall protein transfer 1 in the glycosylphosphatidylinositol anchor biosynthesis pathway, is under investigation for the treatment of C. auris and other drug-resistant isolates.

D. Candidal Endocarditis

Best results are achieved with a combination of medical and surgical therapy (valve replacement). 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) is recommended as initial therapy. Step-down or long-term suppressive therapy for nonsurgical candidates may be done with fluconazole at 6-12 mg/kg/day for susceptible organisms.

E. Prevention of Invasive Candidiasis

In high-risk patients undergoing induction chemotherapy or hematopoietic stem cell, liver, small bowel, and pancreas transplantation, prophylaxis with antifungal agents has been shown to prevent invasive fungal infections, although the effect on mortality and the preferred agent(s) remain debated. Critically ill patients are at higher risk for invasive candidiasis, but antifungal prophylaxis has not shown clear clinical benefit. Even with prophylaxis, breakthrough infections may occur in high-risk patients.