candidiasis
CANDIDIASIS
Candida sp are the most common cause of fungal infections.
 It can cause infections that range from benign mucocutaneous illnesses to invasive process that may affect any organ.
 It is considered as normal flora in the gastrointestinal and genitourinary tracts, but when there is an imbalance in the ecological niche, they can invade and cause disease.
Most common risk factors include broad-spectrum antibiotic use, central venous catheter use, receipt of parenteral nutrition, receipt of renal placement therapy by patients in ICUs, neutropenia, implantable prosthetic device use and receipt of immunosuppressive agents.

Principles of Therapy

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

Pharmacotherapy

Amphotericin B (AmB)
  • 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
Echinocandins
  • 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
Flucytosine
  • 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
Triazoles
Fluconazole
  • 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
  • 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, 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
Other Triazole
Isavuconazole
  • 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
RECOMMENDED SITE-SPECIFIC ANTIFUNGAL THERAPY
Site of Candidal Infection Antifungal of Choice Alternative Antifungal Drugs
Cutaneous Candidiasis
Skin and  paronychia Azole (topical) or Polyene antifungal (topical) -
Onychomycosis Itraconazole (oral) or Terbinafine (oral) Griseofulvin (oral)
Mucosal Candidiasis
Oropharyngeal For mild disease:
Clotrimoxazole (troches) or Miconazole (mucoadhesive buccal)
For moderate to severe disease:
Fluconazole (oral) or Itraconazole (oral soln) or
Posaconazole (oral susp)
For mild disease:
Nystatin (suspension/pastilles)
For moderate to severe disease:
Voriconazole (oral) or AmB-d (oral suspension/IV) or Echinocandin (IV)
Esophageal Fluconazole (oral/IV) or Echinocandin (IV) or AmB-d (oral suspension/IV) Itraconazole (oral solution) or Posaconazole (oral suspension) or Voriconazole (oral)
Vulvovaginal candidiasis Topical agents Fluconazole (IV/oral)
Chronic mucocutaneous candidiasis Fluconazole (oral) Itraconazole (oral) or Ketoconazole (oral)*
Insvasive Candidiasis
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
Pericarditis or myocarditis LFAmB (IV) or Fluconazole (IV/oral) or Echinocandin (IV) Fluconazole (IV/oral) as step-down therapy
Suppurative thrombophlebitis LFAmB (IV) or Fluconazole (IV/oral) or Echinocandin (IV) Fluconazole (IV/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)
-
Central Nervous System LFAmB (IV) ± Flucytosine (oral) followed by Fluconazole (IV/oral) Fluconazole (IV/oral) as step-down therapy
Peritonitis AmB-d (IV) or Fluconazole (IV/oral) -
Candida isolated from respiratory secretions - -
Genitourinary Tract
Asymptomatic candiduria For high-risk patients: Treat as candidiasis
For patients undergoing urologic procedures: Fluconazole (IV/oral) or AmB-d (IV) daily for several days before & after the procedure
-
Symptomatic cystitis Fluconazole (IV/oral) AmB-d (IV) or Flucytosine (oral)
Pyelonephritis Fluconazole (IV/oral) LFAmB (IV) ± Flucytosine (oral) or Flucytosine (oral) alone
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) -
*Serious hepatotoxicity may occur with the use of oral Ketoconazole. Please see Dosage Guidelines for more information
± with or without

Remove 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
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
  • 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
Central Nervous System
  • For candidal meningitis associated with neurosurgical procedures, treatment should include removal of any prosthetic devices
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
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
Infections of the Vasculature
  • Surgical incision and drainage or resection of the involved vein segment is recommended
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