invasive%20candidiasis
INVASIVE CANDIDIASIS
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

Candidemia

  • 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

Endocarditis

  • 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

Endophthalmitis

  • 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

Musculoskeletal

  • 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

Peritonitis

  • 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

Echinocandins

  • 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

Flucytosine

  • 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

Polyenes

  • 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 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

Triazoles

  • Mechanism of action: Inhibit synthesis of ergosterol, which is a fungal cell component

Fluconazole

  • 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

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

Posaconazole

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

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

Isavuconazole

  • 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
RECOMMENDED SITE-SPECIFIC ANTIFUNGAL THERAPY
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
LFAmB (IV)
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
Editor's Recommendations
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