Treatment of Candida endocarditis and suppurative thrombophlebitis

Treatment of Candida endocarditis and suppurative thrombophlebitis

Condition or treatment group	Therapy
Condition or treatment group	Primary	Step-down	Comments
Candida endocarditis
Native valve endocarditis	A lipid formulation of amphotericin B (3 to 5 mg/kg IV daily) with or without flucytosine* (25 mg/kg orally four times daily); OR High-dose echinocandin (caspofungin 150 mg IV daily, micafungin 150 mg IV daily, or anidulafungin 200 mg IV daily).	For patients who are clinically stable, have isolates that are susceptible to fluconazole, and have negative repeat blood cultures following initiation of a lipid formulation of amphotericin B or high-dose echinocandin therapy, transition to oral fluconazole^¶ 400 to 800 mg (6 to 12 mg/kg) daily is appropriate. Oral voriconazole^Δ 200 to 300 mg (3 to 4 mg/kg) twice daily or delayed-release posaconazole tablets^Δ 300 mg daily can be used for step-down therapy in clinically stable patients who have isolates susceptible to these agents but not susceptible to fluconazole.	Valve replacement is recommended; treatment should continue for at least 6 weeks after surgery. For patients who cannot undergo valve replacement, long-term suppression with an oral azole (fluconazole^¶ 400 to 800 mg [6 to 12 mg/kg] daily if the isolate is susceptible^◊) is recommended following initial antifungal therapy.
Prosthetic valve endocarditis	A lipid formulation of amphotericin B (3 to 5 mg/kg IV daily) with or without flucytosine* (25 mg/kg orally four times daily); OR High-dose echinocandin (caspofungin 150 mg IV daily, micafungin 150 mg IV daily, or anidulafungin 200 mg IV daily).	For patients who are clinically stable, have isolates that are susceptible to fluconazole, and have negative repeat blood cultures following initiation of a lipid formulation of amphotericin B or high-dose echinocandin therapy, transition to oral fluconazole^¶ 400 to 800 mg (6 to 12 mg/kg) daily is appropriate. Oral voriconazole^Δ 200 to 300 mg (3 to 4 mg/kg) twice daily or delayed-release posaconazole tablets^Δ 300 mg daily can be used for step-down therapy in clinically stable patients who have isolates susceptible to these agents but not susceptible to fluconazole.	Valve replacement is recommended. Lifelong suppression with an oral azole (fluconazole^¶ 400 to 800 mg [6 to 12 mg/kg] daily if the isolate is susceptible^◊) is recommended to prevent recurrence following initial antifungal therapy in all patients.
Candida suppurative thrombophlebitis
	A lipid formulation of amphotericin B (3 to 5 mg/kg IV daily); OR Fluconazole^¶ 400 to 800 mg (6 to 12 mg/kg) IV or orally daily; OR High-dose echinocandin (caspofungin 150 mg IV daily, micafungin 150 mg IV daily, or anidulafungin 200 mg IV daily).	For patients who are clinically stable, have isolates that are susceptible to fluconazole, and have negative repeat blood cultures following initiation of amphotericin B or high-dose echinocandin therapy, transition to oral fluconazole^¶ 400 to 800 mg (6 to 12 mg/kg) daily is appropriate.	Catheter removal and incision and drainage or resection of the vein is recommended if feasible. Treat with one of the options for primary therapy for at least two weeks after candidemia has cleared, before transitioning to step-down therapy. Resolution of thrombus can be used as evidence to discontinue antifungal therapy if clinical and culture data are supportive.

The doses above are intended for patients with normal organ function. The dose of fluconazole and flucytosine must be adjusted in the setting of renal insufficiency; the caspofungin and voriconazole dose may require adjustment in hepatic insufficiency. Refer to the Lexicomp drug-specific monographs for additional information including specific dose adjustment recommendations.

IV: intravenously.
* Toxic effects on bone marrow and liver require careful monitoring preferably with frequent serum flucytosine levels; refer to accompanying text for discussion of benefits and risks of combined flucytosine and amphotericin B therapy.
¶ Since fluconazole is highly bioavailable, oral therapy is appropriate for most patients. IV therapy (at the same dose) should be given to patients who are unable to take oral medications, who are not expected to have good gastrointestinal absorption, or who are severely ill.
Δ Therapeutic drug monitoring should be considered due to widely variable pharmacokinetics; refer to the topic review on pharmacology of azoles for detail.
◊ In patients with endocarditis caused by a Candida species that is not susceptible to fluconazole, oral voriconazole (200 or 300 mg [3 to 4 mg/kg] twice daily) or delayed-release posaconazole tablets (300 mg daily) should be used for chronic suppressive therapy if the organism is susceptible.

Data from: Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2015; 62:e1.

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Treatment of Candida endocarditis and suppurative thrombophlebitis