General Therapy Principles

• When choosing an antifungal agent, consider the following factors:
  • Patient’s clinical status
  • Physician’s knowledge of the species and/or antifungal susceptibility of the infecting isolate
  • Relative drug toxicity
  • Presence of organ dysfunction that would affect drug clearance
  • Available knowledge of use of the drug in the given patient population
  • Patient’s prior exposure to antifungal agents

• Premature discontinuation of antifungal therapy may lead to recurrent infection
• Treatment duration depends on extent of involved organs
  • Treat for 14 days after resolution of candidemia for uncomplicated cases (eg end of candidemia documented by a negative blood culture and absence of organ involvement)
  • Oral therapy may start after 10 days of intravenous (IV) therapy

• Efficacious for Candida but has well-documented significant toxicity
• Lipid formulations [eg Amphotericin B lipid complex (ABLC), Amphotericin B colloidal dispersion (ABCD), liposomal Amphotericin B] are less toxic but as effective as Amphotericin B deoxycholate (AmB-d) when used in appropriate dosages
• There is no known specific form of candidiasis for which a lipid formulation of Amphotericin B (LFAmB) is superior to Amphotericin B deoxycholate
• The cost of lipid formulations and the small number of organized clinical data tend to limit use in patients at high risk of being intolerant of Amphotericin B deoxycholate
• Urinary candidiasis may be the only candidal infection where lipid-associated formulas are contraindicated
  • It is theorized that the lipid-associated formulas will potentially reduce delivery of Amphotericin B and thus slow the pace of response

• Used as alternative treatment in patients who are intolerant with other antifungal agents

• Eg Anidulafungin, Caspofungin, Micafungin
• Preferred agents for most episodes of candidemia and invasive candidiasis except for those infections in the central nervous system, eye and urinary tract infection
• Agents of choice for patients with moderately severe to severe illness or those who have had recent azole exposure
• Preferred empiric treatment in non-neutropenic intensive care unit (ICU) patients suspected with Candidiasis
• Strongly recommended for targeted primary treatment of candidemia
• Only Caspofungin requires dosage reduction for moderate to severe hepatic dysfunction

• Has broad antifungal activity against most Candida species with the exception of Candida krusei
• Primarily used in combination with Amphotericin B with more refractory infections such as Candida endocarditis, meningitis and endophthalmitis
• Occasionally used for symptomatic urinary tract candidiasis due to Fluconazole-resistant Candida glabrata

• Appropriate as initial therapy for most adult patients
• Highly effective for the treatment of superficial and invasive candidal infections
• Inferior to Anidulafungin but better than echinocandins against Candida parapsilosis
• Used as an alternative treatment for patients with no recent exposure to azole & those who are not colonized by azole-resistant Candida sp

• Itraconazole is a useful agent for dermatologic and mucosal candidal infections but its role in invasive candidal infections has yet to be determined

• Posaconazole has in vitro activity against Candida sp but there is limited evidence for its use in candidal infections other than oropharyngeal candidiasis

• Voriconazole is as active as Fluconazole against esophageal candidiasis
• Has been used for candidemia in non-neutropenic patients, candida infection in the central nervous system and for other deep tissue Candida infections
• Also used as step-down oral therapy in patients with Candidal infection caused by Candida krusei & Fluconazole-resistant, Voriconazole-susceptible Candida glabrata
• Should not be used for urinary candidiasis as it does not accumulate in active form in the urine

• Recently approved expanded-spectrum triazole with good in vitro activity against Candida sp
• It is suggested by preliminary analysis of the recently completed international double-blind trial that compared Isavuconazole to an echinocandin that Isavuconazole did not meet criteria for noninferiority

• Existing central venous catheters should be removed, when feasible
• All patients with candidemia should undergo at least 1 ophthalmological exam to exclude the possibility of candidal endophthalmitis

• Both native valve and prosthetic valve infection should be managed with surgical replacement of the infected valve, the native valve within 1 week and the prosthetic valve even earlier
• If valve replacement is not possible, the patient may require long-term suppressive therapy

• Removal of intraocular lens implant if infection is due to implant

• Removal of urinary tract instruments, including stents and Foley catheters, is often helpful
• If complete removal is not possible, placement of new devices may be beneficial
• Surgical intervention in adults with candida urinary tract infection associated with fungus balls

• For candidal meningitis associated with neurosurgical procedures, treatment should include removal of any prosthetic devices