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
- 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
- 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
- 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
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 is a useful agent for dermatologic and mucosal candidal infections but its role in invasive candidal infections has yet to be determined
- Alternative treatment for Fluconazole-refractory oropharyngeal and esophageal candidiasis
- 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
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) | - |
**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
- 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
- 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
- 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
- Surgical incision and drainage or resection of the involved vein segment is recommended