Managing Candida Infections

Oropharyngeal Candidiasis (thrush, Candida stomatitis) causes raised white plaques on the tongue and inside the mouth.

--information in this section is from reference 1, unless otherwise denoted--

How do you treat mild thrush?

Clotrimazole oral troche 10 mg (US only; Mycelex) five times per day for 7 to 14 days OR miconazole mucoadhesive buccal 50 mg tablet (US only; Oravig) once daily for 7 to 14 days.

Alternative in US, choice in Canada: nystatin oral suspension 100,000 units/mL 4 to 6 mL QID for 7 to 14 days.

How is moderate to severe thrush treated?

Fluconazole oral 100 to 200 mg once daily for 7 to 14 days.

How do you treat recurrent thrush?

Fluconazole oral 100 mg three times weekly.

Long-term suppressive therapy with fluconazole is usually unnecessary. It may reduce relapse; however, does result in resistance.

How do you treat fluconazole-refractory thrush?

Fluconazole-refractory disease is typically seen in patients who are persistently immunosuppressed (e.g., patients with AIDS and low CD4 cell counts [<50 cells/mcL]). It can be caused by C. glabrata.

Usually treat with itraconazole oral solution 200 mg once daily for up to 28 days OR posaconazole oral suspension
400 mg BID for 3 days, then 400 mg daily for up to 28 days.

Alternatives include (choice based on clinical considerations):

• voriconazole oral 200 mg BID
• amphotericin B oral suspension 100 mg/mL QID (compounded product)
• caspofungin IV 70 mg loading dose, then 50 mg once daily
• micafungin IV 100 mg daily
• anidulafungin IV 200 mg loading dose, then 100 mg once daily
• amphotericin B deoxycholate IV 0.3 mg/kg once daily
• occasionally tried: immunomodulation with GM-CSF or interferon–alpha

What are important considerations when treating pregnant patients with thrush?

Pregnant patients should start with treatment options for mild thrush (above section).

If needed, amphotericin B IV 0.3 mg/kg once daily can be used.

Systemic azoles (including single 150 mg doses of oral fluconazole [based on limited data]) should be avoided during pregnancy due to a potential for increased risk of miscarriage and possible birth defects.^1-4

There are little data with use of echinocandins during pregnancy. Animal data suggest low to moderate risk.⁵

Vulvovaginal Candidiasis (VVC) symptoms include:pruritus, vaginal soreness, dyspareunia, abnormal vaginal discharge.^4,6

What are the first line treatments for uncomplicated VVC?

Short-course (single dose or once daily for three days) vaginal azole (any)^4,6,b,c

OR

Oral fluconazole 150 mg x 1 dose (<$10 [US])^4,6,d

What are the first line treatments for complicated VVC?

Pregnancy: vaginal azole^b,c for 7 days.^4,6 Up to 14 days and/or repeat treatments may be required.⁶ Avoid oral fluconazole and intravaginal boric acid.^4,6

Severe infection (e.g., extensive vulvar erythema, edema, excoriation, fissures). US guidelines recommend one of the following:⁴

Recurrent infection (≥3 episodes/year [Canada: ≥4 episodes/year]):^4,6

• Maintenance should start immediately after induction and typically continue for six months:^4,6
  • once weekly oral fluconazole (100, 150, or 200 mg) for at least six months (US preferred) (Canadian guidelines specify the 150 mg dose).^4,6
  • intermittent vaginal azoleb,c (US, not preferred)⁴
  • Canadian guidelines also include choices of:⁶
    • boric acid capsule (compounded) vaginally 300mg for five days at the beginning of each menstrual cycle.
    • ketoconazole oral 100 mg once daily (Canada). Must be monitored for hepatoxicity and drug interactions.

What are other treatments options for VVC?

For non-albicans infections (usually C. glabrata) consider:

What is the role of ibrexafungerp for VVC?

Ibrexafungerp (Brexafemme, US only [$475]) is an oral triterpenoid antifungal for vulvovaginal candidiasis.⁷

What is the role of oteseconazole for VVC?

Oteseconazole (Vivjoa, US only [$2,700]) is an oral azole antifungal for recurrent vulvovaginal candidiasis.^7,d

Non-neutropenic Candidemia

What are risk factors for invasive candidiasis?

Risk factors for the development of invasive candidiasis include comorbid conditions (e.g., colonization with Candida, immunosuppression, diabetes, sepsis) and the following recent medical interventions:^8,9

When should empiric antifungal therapy be considered?

Guidance is NOT clear on who is most likely to benefit from, or when to start, empiric antifungal therapy.

Use clinical judgment of invasive candidiasis risk factors.¹⁰ Consider starting empiric therapy in patients:

Which empiric antifungal should be used?

Use echinocandins (e.g., caspofungin, micafungin, anidulafungin) first line, especially in patients with hemodynamic instability, recent azole exposure, or known colonization with fluconazole-resistant Candida.^11,12

Azoles: use fluconazole in non-critically ill patients if your hospital’s main pathogen is fluconazole-susceptible Candida albicans and the patient has NOT recently received an azole.^1,13  Note: voriconazole is primarily used as oral step-down therapy for specific Candida species.¹

Use amphotericin B lipid formulation last-line, due its significant adverse effects (e.g., kidney toxicity).⁹

What are pregnancy considerations for antifungal therapy?

Amphotericin B is the preferred antifungal during pregnancy.¹

There are little data with use of echinocandins during pregnancy. Animal data suggest low to moderate risk.¹⁵

Avoid fluconazole use, especially in the first trimester, due to potential for increased risk of miscarriage.^1,3,7

Avoid voriconazole use, especially in the first trimester, due to fetal abnormalities seen in animal studies.^1,5

What antifungal doses should be used?

Echinocandins (Generally considered interchangeable; use formulary echinocandin.):¹

Fluconazole:¹ 12 mg/kg IV or 800 mg, followed by 6 mg/kg or 400 mg IV once daily. Adjust for kidney impairment.⁷

Voriconazole:¹ 6 mg/kg or 400 mg PO x 2 doses 12 hours apart, followed by 3 to 4 mg/kg or 200 mg PO every 12 hrs.

Amphotericin B (lipid formulation):¹ 3 to 5 mg/kg IV once daily.

What susceptibility testing is recommended?

Test all patients with candidemia or other cases of invasive candidiasis for azole susceptibility.¹

Consider echinocandin susceptibility testing:^1,17

How should echinocandin or amphotericin B antifungal therapy be stepped down?

Step down to oral fluconazole 6 mg/kg or 400 mg once daily (usually within three to seven days) when isolates show susceptibility to fluconazole.^1,14

For infections due to C. glabrata, transition to:¹

What is the duration of therapy for empiric antifungals?

Generally, continue empiric therapy for two weeks in patients who respond.^1,12,14

Consider stopping empiric therapy after four or five days in patients who are NOT improving and don’t have other signs of a fungal infection.^1,12,14

What is the duration of therapy of invasive candidiasis?

Generally, recommend two weeks of therapy AFTER negative cultures and resolution of symptoms.¹

Longer therapy may be required for patients with complications of invasive candidiasis (e.g., metastatic organ involvement such as Candida endocarditis or endophthalmitis).¹

What is the role for non-culture-based testing (NCBTs) and antifungal therapy?

Some institutions may use NCBTs (e.g., PCR) along WITH blood cultures and other clinical data to assist with decisions about antifungal therapy, due to blood culture limitations (e.g., sensitivity, timeliness, contamination versus infection).¹¹

NCBTs do NOT provide definitive results, they assess the likelihood of infection.¹¹

Candida auris

C. auris is an emerging multidrug-resistant yeast, associated with a high mortality rate (~30% to 50%).¹⁸

It is easily spread within healthcare settings (unlike other Candida infections).¹⁹

In the US, resistance to fluconazole is ~90% and to amphotericin B is ~30% (range of 5% to 85%, depending on the region).^20,23

Associated with various infections (bloodstream, CNS, intra-abdominal, osteomyelitis, pericarditis).

Appears to colonize respiratory and urine specimens; however, risk of infections in these sites is unclear.

Risk factors for C. auris include:

• hospitalizations, especially in an ICU, long admissions, in non-US countries (e.g., India, Pakistan, South Africa).
• nursing home care, especially homes that use ventilators.
• use of invasive devices (central venous catheter, breathing tube, feeding tube).
• history of broad-spectrum antibiotic or antifungal use.
• immunosuppression.
• recent surgery. 

Consult the infectious disease team if a C. auris infection is suspected.¹⁹

Treat only if there is evidence of infection (e.g., fever, increased white blood cell count).

Consider treatment with anidulafungin, caspofungin, micafungin, or rezafungin.^16,19

• Consider switching to (or adding)²² liposomal amphotericin B for patients who do not respond to initial therapy.¹⁹
• For CNS infections, the ID team may choose flucytosine plus liposomal amphotericin B.¹  

Patients (with or without prior infection) may be colonized with C. auris for long periods of time (maybe indefinitely).¹⁹ Decolonization is not recommended due to lack of data.¹⁹

Use standard and contact precautions (including proper hand hygiene) when caring for patients with C. auris infections or colonization for the duration of their stay in all healthcare facilities.¹⁹

• In nursing homes, Enhanced Barrier Precautions may be recommended.  See CDC’s guidance on the prevention of spread of multidrug-resistant organisms at https://www.cdc.gov/hai/containment/PPE-Nursing-Homes.html.

C. auris can persist on surfaces outside of the human body for weeks.¹⁹

Rooms should be cleaned daily with an agent from EPA’s “List P.”  If unavailable, use disinfectants active against C. diff spores (i.e., EPA List K).²¹