Candidiasis%20(pediatric) Treatment

• 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
    • Longer duration may be required for candidemia with central venous catheter retention and deep-seated invasive candidiasis
  • 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 and/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 antifungal agents vary between adult and pediatric patients
• In order that the most effective antifungal agent will be administered to the patient, Candida sp should be isolated and its antifungal susceptibility should be determined

Echinocandins

• Eg Caspofungin, Micafungin, Anidulafungin
• For treatment of candidemia in neonates that is refractory or resistant to conventional therapy with Amphotericin B (AmB) or Fluconazole
• United States Food and Drug Administration (US FDA) approved its use against invasive candidiasis in children
• Not recommended for candidiasis involving the eyes, CNS, or urinary tract because of poor penetration to these sites
• Mechanism of action: 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)
• Well-tolerated with minimum adverse effects

Flucytosine

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

Polyenes

• Mechanism of action: Binds to ergosterol in the fungal cell membrane leading to cell leakage and death

Amphotericin B (AmB)

• Eg AmB deoxycholate, liposomal AmB B, AmB lipid complex (ABLC), and AmB colloidal dispersion (ABCD)
• AmB deoxycholate is the most commonly used antifungal agent for neonatal invasive candidiasis including disseminated neonatal candidemia as it is efficacious and well-tolerated
  • Lipid formulations are reserved for neonates who are intolerant to AmB deoxycholate but should be used with caution
• AmB deoxycholate pharmacokinetics are highly variable in neonates and adults
• Lipid formulations have the ability to deliver a higher dose of medication with lower levels of toxicity
• The cost of lipid formulations and the small number of organized clinical data tend to limit use in patients at high risk of being intolerant of AmB deoxycholate
• Nephrotoxicity (eg acute kidney injury, tubular acidosis) is the most common serious adverse effect of AmB deoxycholate
  • In contrast to older children and adults, AmB deoxycholate does not appear to be associated with risk for nephrotoxicity in neonates
• Urinary candidiasis may be the only candidal infection where lipid-associated formulas are contraindicated

Nystatin

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

Triazoles

• Eg Fluconazole, Voriconazole
• Depending on the type of candidal infection, triazoles are commonly used in neonates as an alternative to AmB and in children with invasive candidiasis

Fluconazole

• Most commonly used triazole in neonates as an alternative to AmB and in children with invasive candidiasis
• Recommended prophylactic agent against invasive candidiasis in neonates with extremely low birth weights (<1000 g)
• Rapidly cleared in children; daily dose is necessary for neonates and children
• Mechanism of action: Inhibits the fungal enzyme 14-alpha-sterol demethylase, which is necessary for the production of ergosterol, a major component of the fungal cell membrane
• In children with neutropenia, had recent triazole use, or if Candida krusei is suspected, Fluconazole should not be used due to resistance

Voriconazole

• Alternative treatment for invasive candidiasis if Fluconazole is contraindicated in children
• Not recommended for candidiasis involving the urinary tract because of poor urinary excretion

Pharmacological Therapy for Specific Type of Candidiasis
Mucocutaneous Candidiasis

Oropharyngeal Candidiasis

• Neonates:
  • Topical Nystatin are highly effective
• 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

• Children ≥12 months old:
  • Topical Nystatin or Clotrimazole for 7-14 days for mild oral candidiasis
  • Nystatin and 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) AmB (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, and 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 and Sertaconazole

Chronic Mucocutaneous Candidiasis

• The preferred treatment is Fluconazole or Itraconazole

Invasive Candidiasis

Neonates

• There is a high likelihood of disseminated disease and the possibility of infection within the CNS thus treatment is complicated
• The following can be potentially used for treatment: AmB deoxycholate, liposomal AmB, AmB lipid complex, Fluconazole, Micafungin and Caspofungin
• AmB is recommended as first line treatment while Fluconazole as the alternative 1st-line agent

Children

• With several exceptions, recommendations for the treatment are extrapolated from the adult studies, with concomitant pharmacokinetic studies
• AmB deoxycholate, liposomal AmB, AmB lipid complex, Micafungin, Caspofungin, Anidulafungin, Fluconazole, and Voriconazole can all be used
• Echinocandins are the 1st-line agents for the treatment of invasive candidiasis in children
• Liposomal AmB is an alternative 1st-line agent

Remove Possible Source of Infection

• Existing central venous catheters or bladder catheter, or infected CNS devices (eg ventriculostomy drains and shunts) should be removed, when feasible
• Intravascular catheter removal is strongly recommended
• 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

Sterilization or Decolonization

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