• General management principles that is mostly derived from adults’ candidiasis management:
  • Antifungal therapy should be administered as soon as possible
  • Ideal duration of therapy is 14 days after blood cultures are sterile
  • Due to reduced susceptibility or resistance of some species to certain antifungal classes/agents, the appropriate choice of an anti-Candida agent may be influenced by local epidemiology
  • In all cases of candidemia, clinical evaluation for deep sites of infection, including ophthalmological examination is advised to be done
  • Removal or at least replacing intravenous (IV) catheters &/or other implanted prosthetic devices in a timely manner should be considered
  • Combination antifungal chemotherapy may be considered in some situations as there is no firm recommendation regarding this
  • There are limited data on dosing for antifungal agents in pediatric patients while pharmacokinetics of antifungalagents vary between adult & pediatric patients
  • In order that the most effective antifungal agent will be administered to the patient, the species of Candida should be isolated & its antifungal susceptibility should be determined

Polyenes

• Binds to ergosterol in the fungal cell membrane leading to cell leakage & death

Amphotericin B

• Most commonly used antifungal agent for disseminated neonatal candidemia as it is efficacious & well-tolerated
• Kinetics are the same in neonates & adults
• Lipid formulations have the ability to deliver a higher dose of medication w/ lower levels of toxicity
• The cost of lipid formulations & 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

Nystatin

• Used in patients w/ noninvasive mucocutaneous candidiasis w/ a low risk for disseminated systemic infection
• Alternative prophylactic agent to Fluconazole used against invasive candidiasis in neonates w/ birth weights <1500 g
• It is not absorbed systemically from the gastrointestinal tract

Echinocandins

• Eg Caspofungin, Micafungin, Anidulafungin
• Inhibits 1,3-beta-D-glucan synthetase enzyme complex that can prevent the formation of glucan polymers (a major component of the fungal cell wall)
• For treatment of candidemia in neonates that is refractory or resistant to conventional therapy w/ Amphotericin B or Fluconazole
• Well-tolerated w/ minimum adverse effects

Triazoles

• Depending on the type of candidal infection, triazoles are commonly used in neonates as an alternative to Amphotericin B

Fluconazole

• Inhibits the fungal enzyme 14-alpha-sterol demethylase, which is necessary for the production of ergosterol, a major component of the fungal cell membrane
• Most commonly used triazole in neonates as an alternative to Amphotericin B
• Recommended prophylactic agent against invasive candidiasis in neonates w/ low birth weights (<1000 g)
• Rapidly cleared in children

Flucytosine

• Inhibits thymidylate synthetase, which disrupts DNA synthesis that is not specific to Candida thus there are significant side effects
• Clinical use is limited; it is primarily used in combination w/ Amphotericin B in neonates w/ central nervous system candidal infections
• It is discouraged to use Flucytosine in infants w/ very low birthweight because of poor renal function due to immaturity

Pharmacological Therapy for Specific Type of Candidiasis

Oropharyngeal Ccandidiasis

Infants

• Nystatin is recommended as initial treatment for immunocompetent infants
• Oral Fluconazole may be used as an alternative to Nystatin
• Gentian violet (0.5% or 1%) applied to the buccal mucosa once or twice daily is also effective

Older Children

• Topical Nystatin or Clotrimazole for 7-14 days for mild oral candidiasis
• Nystatin & Clotrimazole lozenges should not be used in children <4 years old because they are choking hazard
• Fluconazole is indicated for moderate to severe oropharyngeal candidiasis
• Intravenous (IV) Amphotericin (deoxycholate or lipid formulation) or an echinocandin is the treatment for severe oropharyngeal candidiasis refractory to oral or IV Fluconazole

Diaper Dermatitis

• Antifungal agents such as Nystatin, Clotrimazole, Miconazole, & Ketoconazole or other
• Imidazole creams are effective topical therapies for candidal diaper dermatitis
• Antifungal creams or ointments are applied to the diaper area beneath the barrier ointment at least two to three times a day until rash has resolved

Intertrigo

• The most commonly used antifungal agents are Nystatin (polyene), Miconazole, Clotrimazole, Ketoconazole, Econazole & Sertaconazole

Chronic Mucocutaneous Candidiasis

• The preferred treatment is Fluconazole or Itraconazole

Invasive Candidiasis

Neonates

• There is a high likelihood of disseminated disease & the possibility of infection w/in the central nervous system thus treatment is complicated
• The following can be potentially used for treatment: Amphotericin B deoxycholate, liposomal amphotericin B, amphotericin B lipid complex, Fluconazole, Micafungin & Caspofungin
• Amphotericin B is recommended as first line treatment while Fluconazole as the alternative first-line agent

Children

• W/ several exceptions, recommendations for the treatment are extrapolated from the adult studies, w/ concomitant pharmacokinetic studies
• Amphotericin B deoxycholate, liposomal amphotericin B, amphotericin B lipid complex, Micafungin, Caspofungin, Anidulafungin, Fluconazole, & Voriconazole can all be used
• Echinocandins are the first-line agents for the treatment of invasive candidiasis in children
• Liposomal amphotericin B is an alternative first-line agent

Remove Possible Source of Infection

• Existing central venous catheters or bladder catheter should be removed, when feasible
• Intravascular catheter removal is strongly recommended
• Removal of urinary tract instruments, including stents & Foley catheters, is often helpful
• If complete removal is not possible, placement of new devices may be beneficial

Sterilization or Decolonization

• Measures to prevent reinfection includes sterilization or decolonization of items & body sites that are placed in the infant’s mouth
  
  • Bottle nipples & pacifiers that are to be reused should be boiled after each use