Paediatric Fungal Infections – Antifungal Treatments

Use of antifungal treatment and outcomes for Invasive Aspergillosis  with a summary of notable factors in children.

(*This summary has been compiled from published data – it should not be substituted as a treatment protocol, original references should be consulted, ,not all antifungal drugs are licensed for paediatric use; no liability will be undertaken by the Aspergillus website or its staff)

Drug Target fungal infections Dose per day Pharmacokinetics Important notes
Polyenes Binds ergosterol in fungal cell membrane
Amphotericin B
deoxycholate
Candidiasis
Cryptococcal meningitis
0.7- 1.0 mg/kg daily over 2-4 h [1] Similar to adult High individual variation, renal toxicity.
Amph B lipid formulations:
Abelcet
AmBisome
Amphocil
Candidiasis
Aspergillosis
Zygomycosis
3-5mg/kg daily for lipid forms,
3-4 mg/kg for colloidal [2]
Safety data same as adult Less renal toxicity than Amphotericin B parent compd. Less fever, chills and rigors
Antimetabolites Inhibitor of pyrimidine salvage pathway
5-fluorocytosine Candidiasis
(in combination with Amphotericin B)
100mg/kg (in four doses) day
Peak plasma levels for antifungal active 40-60 ug/ml [3]
Insufficient data in children

neonates?

Variable drug clearance data
Triazoles Inhibits lanosterol 14- a- demethylase
Fluconazole Candida, Cryptococcus, Dermatophyte infection 12 mg/kg for neonates and 12 mg/kg in paediatric patients. [4] See table 2 groll Greater plasma clearance with shorter 1/2 life( not in premature) side effects include gastro intest disturbances and hepatic transaminase levels increased.
Itraconazole Candida
Aspergillus
Dermatophyte infection
Oral soln >2yrs suggest starting dose 5mg/kg in 2 doses daily (to attain trough level of 0.5ug/ml [5]
IV data lacking
In immunocompromised patients only here Adverse effects vomiting, abnormal liver function, abdominal pain

*itra not approved for<18yrs so off label

Voriconazole Invasive Aspergillosis Fusarium
Scedosporium Candidiasis in non- neutropenics
9 mg/kg/dose IV load day 1, then 8 mg/kg/dose or 9 mg/kg/dose PO maintainance. If >12 years, then load 6 mg/kg/dose and the 4 mg/kg/dose or give 200-300 mg PO per dose *1 Immunocompromised paediatricss with inv mycosis – has approval from FDA
Table 3 ??groll??
No data for <2 yrs so empirical .
Ages 2-11 have higher elimination rates than adult which may result in lower non therapeutic doses.
No data <2 yrs on pharmacokinetics
Posaconazole Active against zygomycetes, broad spectrum.
Approved 2nd line treatment for:aspergollosis fusariosis, chrmoblastomycosis coccidioidomycosis >18yrs. Approved prophylaxis for AML , myelodysplasia, hematopoietic, GVHD and stem cell transplant
No pharmacokinetcs <18yrs. In 12 patients less than 8yrs no basic differences in trough levels. Successful salvage reported in 5/11 and 6/10 with IF ie. similar to adult. Dosage safety and tolerance has been initiated by manufacturers for paediatrics. [6]  
Echinocandins Inhibit 1,3 beta-D glucan synth in fungal cell wall
Anidulafungin In adults licensed for candida 0.7-1.5mg/kg/day in children. Study of 19 granulocytopenic children w cancer similar to adults re plasma conc. [7] No serious side effects in paediatric trial of cancer patients
Caspofungin Candida
Aspergillus
50mg/m2 daily(70 mg day 1)for 3months –17yrs [8]. In 0-3months, 25mg/m2 gave same exposure as for 3 month-17yrs. [9] Very few serious side effects well tolerated, favourable safety profile. Success rates comparable to Amph B lipo.
Micafungin   100 mg/day <40 kg weight(2mg/kg) or 150 mg /day(4mg/kg), for oesophageal candidiasis and 50 mg/day for prevention. [10] Licensed in EU for invasive candida and as prophylaxis for candida with allogeneic stem cell tr
Similar to adults
In Neonates micafungin has a shorter half life – clearance is more rapid, so need a larger dose.
Recommend 4mg/kg in neonates with invasive candidiasis, higher dose 10 mg/kg with CNS involvement. Recommend liver monitoring (Alanine transaminase & Aspartate transaminase) during treatment

Data is mainly compiled from Groll & Tragiannidis 2010,

This website specialises in Aspergillus infections – but the lack of paediatric data has meant that we have included data for other types of fungal infections – where it may be useful.

*1 W. Steinbach, personal communication.

Important information: At no time should the information compiled here be used as a treatment protocol or for any other purpose except to provide the latest available summary of information relating to paediatric patients for educational and scientific purpose. We accept no liability for the use of data gathered here.
Treatments should always be carried out according to manufacturers instructions. Not all antifungal treatments are licensed for use in paediatric patients – please check this.

 


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