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.

Candidiasis Treatment

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
    • In patients with documented candidemia, duration of therapy with systemic antifungal agents should be 14 days after the first negative blood culture
    • 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
  • Treatment alternative for patients with Fluconazole-refractory oropharyngeal or esophageal candidiasis
  • Topical formulation when combined with Flucytosine cream is used as an alternative treatment option against C glabrata infection
  • 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
  • Alternative agents for patients with oropharyngeal or esophageal candidiasis unresponsive to azole therapy
  • Preferred agents for most episodes of candidemia and invasive candidiasis except for those infections in the central nervous system, eye and urinary tract infection
  • With low minimum inhibitory concentrations for Candida sp, which provides good efficacy against esophageal and invasive candidiasis with less adverse events
  • Preferred empiric treatment in non-neutropenic intensive care unit (ICU) patients suspected with Candidiasis
  • Strongly recommended for targeted primary treatment of candidemia
  • 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, and Fluconazole-resistant C glabrata vulvovaginal candidiasis
  • 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 and those who are not colonized by azole-resistant Candida sp
  • Recommended chronic suppressive therapy for patients with recurrent esophageal, vulvovaginal or oropharyngeal candidiasis
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
  • Alternative treatment for Fluconazole-refractory oropharyngeal and esophageal candidiasis 
Voriconazole
  • 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
  • Used as step-down oral therapy in patients with Candidal infection caused by Candida krusei and 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 Isavuconazole did not meet criteria for noninferiority when compared to an echinocandin
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 solution) or
Posaconazole (oral suspension)
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) -
*Please see Vaginitis: Trichomoniasis, Candidiasis, Bacterial Vaginosis disease management chart for further information
**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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