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candidiasis%20(pediatric)
CANDIDIASIS (PEDIATRIC)
Candida sp are the most common cause of fungal infections.
It can manifests from benign mucocutaneous illnesses to invasive process that may affect any organ.
It is considered as normal flora in the gastrointestinal & genitourinary tracts, but when there is an imbalance in the ecological niche they can invade & cause disease.
The immune response of the patient is the important determinant of the type of infection caused by Candida.
Most common risk factors include: prematurity, very low birth weight, use of broad-spectrum antibiotics use, use of central venous catheters, receipt of parenteral nutrition, receipt of renal placement therapy by patients in intensive care unit (ICU), neutropenia, use of implantable prosthetic devices and receipt of immunosuppressive agents.

Principles of Therapy

  • 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

Pharmacotherapy

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

Non-Pharmacological Therapy

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
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