Candidiasis%20(pediatric) Treatment
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