Treatment Guideline Chart

Infections caused by Candida sp that is associated w/ candidemia & metastatic organ involvement.

Most common pathogens of invasive candidiasis are Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida krusei

Early initiation of antifungal therapy w/ adequate source control is essential in the management of invasive candidiasis.

Invasive%20candidiasis Treatment

Removal of Possible Reservoirs of Infection


  • 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

Central Nervous System (CNS)

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


  • 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

Genitourinary Tract (GUT)

  • 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 UTI associated with fungal balls

Infections of the Vasculature

  • Catheter removal
  • Surgical incision and drainage or resection of the involved vein segment is recommended


  • Adequate drainage of involved joints is critical to successful therapy
    • Candida arthritis of the hip, in particular, requires open drainage
  • If a prosthetic joint is involved, a resection arthroplasty is generally required


  • Remove peritoneal dialysis catheter, if the patient has one
    • After removal and a delay of at least 2 weeks, a new catheter may be placed
  • Proper surgical repair and drainage must be done for patients in whom Candida peritonitis is related to intra-abdominal leakage of fecal material

Principles of Therapy

  • Early initiation of antifungal therapy with adequate source control is essential in the management of invasive candidiasis
    • Empirical antifungal therapy should be considered in patients with neutropenic fever, non-neutropenic patients who have persistent fever or unexplained hypotension despite broad-spectrum antibacterial agents, and patients with septic shock and multiorgan failure with >1 proven colonization outside of the gastrointestinal (GI) tract
  • 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
  • De-escalation from an echinocandin to Fluconazole may be considered in non-neutropenic critically ill patients if clinically stable and isolate with proven susceptibility to Fluconazole, and without central venous catheter or any other foreign material
  • Step-down to Fluconazole may also be considered in patients with persistent neutropenia who are clinically stable, with Fluconazole-susceptible isolates and documented clearance of Candida sp from the bloodstream
  • 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 BC and absence of organ involvement)
    • Oral therapy may start after 10 days of IV therapy
  • Premature discontinuation of antifungal therapy may lead to recurrent infection
    • May consider discontinuation of antifungal therapy once with negative BC results in previously suspected patients
  • Routine antifungal prophylactic or pre-emptive therapy for critically ill patients at high risk for severe infection is not recommended
    • Only patients with risk factors for invasive disease (eg central venous catheters, parenteral nutrition, hemodialysis, trauma, broad-spectrum antibiotics, recent surgery) should be considered
    • Immunosuppressed patients anticipated to develop profound, protracted neutropenia and grade III/IV mucositis at high risk for invasive candidiasis may be given antifungal prophylaxis during the expected period of neutropenia

Pharmacological Therapy


  • Eg Anidulafungin, Caspofungin, Micafungin
  • First-line therapy for most episodes of candidemia and invasive candidiasis except for those infections in the CNS, eye and UTIs
  • Agents of choice for patients with moderately severe to severe illness, critically ill patients with septic shock and multiorgan failure, 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
  • Mechanism of action: Inhibit synthesis of glucan, which is an important component of fungal cell wall


  • Has broad antifungal activity against most Candida sp with the exception of C 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 C glabrata
  • Mechanism of action: Deaminated to 5-fluorouracil, which inhibits RNA and protein synthesis


  • Eg Amphotericin B deoxycholate (AmB-d), lipid formulations [eg Amphotericin B lipid complex (ABLC), Amphotericin B colloidal dispersion (ABCD), liposomal Amphotericin B, lipid formulation of Amphotericin B (LFAmB)]
  • Efficacious for Candida sp but has well-documented significant toxicity
  • Lipid formulations are less toxic but as effective as AmB-d when used in appropriate dosages
  • LFAmB is preferred over other lipid formulations for critically ill patients with history of treatment failure with echinocandins and azoles
  • 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 AmB-d
  • 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
  • Mechanism of action: Increase cytoplasmic permeability


  • Mechanism of action: Inhibit synthesis of ergosterol, which is a fungal cell component
  • Should not be used as initial therapy in neutropenic patients who require antifungal therapy


  • Appropriate as initial therapy for hemodynamically stable patients with no recent exposure to azole and those who are not colonized by azole-resistant Candida sp (eg C krusei, C glabrata) if access to echinocandins is limited
    • Should be considered 1st-line treatment option for critically ill patients with low disease severity
  • Highly effective for the treatment of superficial and invasive candidal infections
  • Inferior to Anidulafungin but better than echinocandins against C parapsilosis


  • 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
  • May be used as alternative treatment in patients who are intolerant to Voriconazole


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

Other Triazole


  • An expanded-spectrum triazole with good in vitro activity against Candida sp
  • Clinical trials are ongoing to prove the use of Isavuconazole for the treatment of candidiasis
    • 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
Site of Candidal Infection Antifungal of Choice Alternative Antifungal Drugs
Invasive Candidiasis
CNS LFAmB (IV) ± Flucytosine (oral) followed by Fluconazole (IV/oral) Fluconazole (IV/oral) as step-down therapy
Chronic disseminated (Hepatosplenic) LFAmB or Echinocandin (IV) initially, followed by Fluconazole (oral) -
Endocarditis LFAmB (IV) ± Flucytosine (oral) or
AmB-d (IV) ± Flucytosine (oral) or
Echinocandin (IV)
Fluconazole (IV/oral) or Voriconazole (oral) as step-down therapy
Endophthalmitis Candida chorioretinitis without vitritis:
Flucytosine (oral) or
Voriconazole (oral) or
Candida chorioretinitis with vitritis:
AmB-d (intravitreal inj) + Flucytosine (oral) or
Voriconazole (oral)
Pericarditis or myocarditis LFAmB (IV) or
Fluconazole (IV/oral) or
Echinocandin (IV)
Fluconazole (IV/oral) as step-down therapy
Peritonitis AmB-d (IV) or
Fluconazole (IV/oral)
Suppurative thrombophlebitis LFAmB (IV) or
Fluconazole (IV/oral) or
Echinocandin (IV)
Fluconazole (IV/oral) as step-down therapy
Genitourinary Tract (GUT)
Asymptomatic candiduria For high-risk patients:
Treat as candidemia
For patients undergoing urologic procedures:
Fluconazole (IV/oral) or
AmB-d (IV) daily for several days before and after the procedure
Pyelonephritis Fluconazole (IV/oral) LFAmB (IV) ± Flucytosine (oral) or
Flucytosine (oral) alone
Symptomatic cystitis Fluconazole (IV/oral) AmB-d (IV) or
Flucytosine (oral)
Urinary fungus balls Fluconazole (IV/oral) or
AmB-d (IV) ± Flucytosine (oral)
Osteoarticular Infection
Osteomyelitis Fluconazole (IV/oral) or
Echinocandin (IV)
LFAmB (IV), followed by Fluconazole (IV/oral)
Septic arthritis Fluconazole (IV/oral) or
Echinocandin (IV)
LFAmB (IV) followed by Fluconazole (IV/oral)
Other musculoskeletal infections AmB-d (IV) or
Fluconazole (IV/oral)

± with or without

Treatments Under Investigation

  • Rezafungin, a novel semi-synthetic 1,3-β-D-glucan synthase-targeting echinocandin, is undergoing clinical trials for its use in the treatment of candidiasis
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