Candidiasis Xử trí

When choosing an antifungal agent, the following factors are considered:

• 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

It must be noted that premature discontinuation of antifungal therapy may lead to recurrent infection. Treatment duration depends on the extent of the organs involved as well. In patients with documented candidemia, duration of therapy with systemic antifungal agents should be 14 days after the first negative blood culture. Lastly, oral therapy may start after 10 days of IV therapy.

Echinocandins

Example drugs: Anidulafungin, Caspofungin, Micafungin

Echinocandins are alternative agents for patients with oropharyngeal or esophageal candidiasis unresponsive to azole therapy. They have low minimum inhibitory concentrations for Candida sp, which provides good efficacy against esophageal and invasive candidiasis with less adverse events. They are the preferred empiric treatment in non-neutropenic intensive care unit (ICU) patients suspected with candidiasis and patients requiring intravenous therapy. Caspofungin requires dosage reduction for moderate to severe hepatic dysfunction.

Flucytosine

Flucytosine has broad antifungal activity against most Candida species with the exception of C krusei. It is 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. It is also occasionally used for symptomatic urinary tract candidiasis due to Fluconazole-resistant C glabrata.

Imidazoles

Example drugs: Clotrimazole, Miconazole

Imidazoles are the preferred topical therapy for mild oropharyngeal candidiasis and vulvovaginal candidiasis. Clotrimazole pessary is also recommended for suppression in patients with recurrent vulvovaginal candidiasis. While Miconazole gel and Clotrimazole lozenges are alternative agents in patients with severe oral candidiasis unresponsive to azole therapy.

Polyenes

Amphotericin B

Amphotericin B is 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. Amphotericin B is a treatment alternative for patients with Fluconazole-refractory oropharyngeal or esophageal candidiasis. Vaginal preparations may be used as an alternative to Fluconazole for the treatment of recurrent vulvovaginal candidiasis and may be given in combination with vaginal Flucytosine against C glabrata infection. Urinary candidiasis may be the only candidal infection where lipid-associated formulas are contraindicated because it is theorized that the lipid-associated formulas will potentially reduce delivery of AmB and thus slow the pace of response. Amphotericin B is also used as alternative treatment in patients who are intolerant with other antifungal agents.

Nystatin

Nystatin is the preferred oral therapy for mild oropharyngeal candidiasis and also an effective treatment option for candidal skin infections and paronychia. It is used for the prevention of recurrent oropharyngeal candidiasis. Additionally, vaginal preparations may be used as an alternative to Fluconazole for the treatment of acute and recurrent vulvovaginal candidiasis. However, Nystatin may cause dental caries when used over a prolonged period.

Triazoles

Fluconazole

Fluconazole is the preferred initial therapy for most adult patients with candidiasis. It is highly effective for the treatment of superficial and invasive candidal infections. Oral Fluconazole is recommended in patients with moderate to severe oropharyngeal candidiasis, especially those who are unable to apply topical agents, with high aspiration risk, or in immunocompromised patients at risk for disseminated disease, and vulvovaginal candidiasis. Oral or IV Fluconazole is the preferred treatment for patients with esophageal candidiasis. Though it is inferior to Anidulafungin, Fluconazole is better than echinocandins against C parapsilosis. Fluconazole is used as an alternative treatment for patients with no recent exposure to azole and those who are not colonized by azole-resistant Candida sp. It is also the recommended chronic suppressive therapy for patients with recurrent esophageal, vulvovaginal or oropharyngeal candidiasis.

Isavuconazole

Isavuconazole is a recently approved expanded-spectrum triazole with good in vitro activity against Candida sp. It is an alternative treatment option to Fluconazole against uncomplicated esophageal candidiasis. It is suggested by preliminary analysis of the recently completed international double-blind trial that Isavuconazole did not meet criteria for non-inferiority when compared to an echinocandin.

Itraconazole

Itraconazole is a useful agent for dermatologic and mucosal candidal infections but its role in invasive candidal infections has yet to be determined. It is a second-line treatment to Fluconazole in patients with oropharyngeal, esophageal and vulvovaginal candidiasis. It is used as a suppressive therapy for patients with recurrent vulvovaginal candidiasis.

Oteseconazole

Oteseconazole may be considered in patients with recurrent vulvovaginal candidiasis who are not of reproductive potential.

Posaconazole

Posaconazole is an alternative treatment for Fluconazole- or Itraconazole-refractory oropharyngeal and esophageal candidiasis. It is also an alternative suppressive therapy for patients with recurrent esophageal candidiasis.

Voriconazole

Voriconazole is as active as Fluconazole against esophageal candidiasis. It is used for mucosal and invasive candidiasis as step-down oral therapy in patients with candidal infection caused by C krusei and Fluconazole-resistant, Voriconazole-susceptible C glabrata. It is an alternative treatment for Fluconazole-resistant oropharyngeal and esophageal candidiasis. It must be noted that Voriconazole should not be used for urinary candidiasis as it does not accumulate in active form in the urine.

Ibrexafungerp

Ibrexafungerp is an alternative agent to Fluconazole, Itraconazole and other azoles for the treatment of acute vulvovaginal, oropharyngeal and esophageal candidiasis.

Other Agents

Topical gentian violet may be considered for mild oropharyngeal candidiasis. Boric acid is an alternative to Fluconazole for the treatment of recurrent vulvovaginal candidiasis and in pregnant patients with vulvovaginal candidiasis. Lastly, Cetirizine in combination with Fluconazole has been studied for the treatment of recurrent vulvovaginal.

Antifungal Therapy Based on Site of Infection

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)	Nystatin (topical)
Onychomycosis1	Itraconazole (oral) or Terbinafine (oral)	Griseofulvin (oral)
Mucosal Candidiasis
Oropharyngeal (thrush)	Fluconazole (oral) For mild disease: Clotrimoxazole (lozenges) or  Miconazole (mucoadhesive buccal) or  Nystatin (suspension/pastilles) For moderate to severe disease: Fluconazole (oral) or Clotrimazole (lozenges) or Posaconazole (oral) or Miconazole (gel or mucoadhesive buccal tablet)	Itraconazole (oral solution) or Posaconazole (oral suspension) or Voriconazole (oral) or Amphotericin B deoxycholate (oral suspension/IV) or  Echinocandin (IV) or Ibrexafungerp (oral)
Esophageal	Fluconazole (oral/IV) or Itraconazole (oral solution)	Voriconazole (oral) or Isavuconazole (roal) or Echinocandin (IV) or Posaconazole (oral suspension) or Amphotericin B deoxycholate (IV) or Ibrexafungerp (oral)
Vulvovaginal candidiasis2	Uncomplicated: Fluconazole (oral) or Topical agents (ie Clotrimazole, Miconazole, Boric acid, Nystatin) Severe/recurrent: Fluconazole (oral) or Clotrimazole (pessary)	Fluconazole (IV/oral) or Azole (topical) or  Ibrexafungerp (oral) or Itraconazole (oral) or Flucytosine (vaginal) Severe/recurrent:\ Boric acid (topical) or Fluconazole (oral) plus Cetirizine (oral) or Itraconazole (oral) or Nystatin (topical) or Osteseconazole (oral)
Chronic mucocutaneous candidiasis	Fluconazole (oral)	Itraconazole (oral) or Ketoconazole (oral)3

¹Please see Tinea Unguium disease management chart for further information.
²Please see Vaginitis: Trichomoniasis, Candidiasis, Bacterial Vaginosis disease management chart for further information.
³Serious hepatotoxicity may occur with the use of oral Ketoconazole. Please see Dosage Guidelines for more information. 

Steps for infection control include screening of individuals at high risk and close contacts of infected patients, isolating patients, and performing environmental cleaning. Hydrogen peroxide, sodium hypochlorite and peracetic acid, chlorine-based disinfectants, octenidine dihydrochloride and quarternary ammonium are recommended for effective control of Candida spp.