Micafungin injection for the treatment of invasive candidiasis in pediatric patients under 4 months of age

ABSTRACT

Introduction

Neonates and young infants with invasive candidiasis are particularly at increased risk of dissemination including hematogenous Candida meningoencephalitis. The echinocandins including micafungin have emerged as a preferred agent in most cases of candidemia and invasive candidiasis but data in pediatric patients under 4 months of age are limited.

Areas covered

In this report, we review the micafungin use in infants younger than 4 months of age. Animal studies as well as clinical data that support its use in neonatal candidiasis are reviewed. In addition, the status of FDA approval and the rationale of micafungin dosing recommendations in infants <4 months are discussed.

Expert Opinion

A dose of 4 mg/kg was approved for treatment of candidemia, Candida peritonitis and abscesses excluding meningoencephalitis or ocular involvement in patients younger than 4 months of age. However, because of the risk of central nervous system dissemination as well as the difficulty in establishing this diagnosis, this dose is inadequate to treat ill infants with candidemia. More studies are needed to establish the safety and efficacy of micafungin daily dose of at least 10 mg/kg in infants younger than 4 months of age when hematogenous Candida meningoencephalitis or ocular involvement cannot be excluded.

KEYWORDS:

• Candidiasis
• micafungin
• neonates
• infants
• meningitis

Article highlights

• Neonates with Candida infection are at high risk of dissemination and increased risk of CNS infection including hematogenous Candida meningoencephalitis (HCME).

• Due to the difficulty in excluding CNS infection, treatment of neonatal candidiasis is often empirical and entails CNS and ocular involvement.

• The IDSA guidelines recommend amphotericin B deoxycholate or liposomal amphotericin B as first line therapy for neonatal candidiasis. However, this treatment may not be ideal in all ill neonates due to concerns with side effects.

• Micafungin is becoming a preferred agent to treat candidemia in different age groups.

• In the rabbit model of HCME, which is most close to resemble neonatal candidiasis, micafungin treatment resulted in a significant reduction of fungal burden in different parts of the CNS. However, there are limitations regarding application of data to CNS infection in neonates and the relevance of fungal burden reduction to outcome remains unclear.

• Studies have shown that high doses of micafungin up to 10 mg/kg/d demonstrate linear pharmacokinetics and exposures were above the AUC pharmacodynamic target exposure of 170 µg h/mL that is needed to treat neonatal candidiasis. The safety profile of this high dose of micafungin seems to be favorable.

• Clinical data remain inadequate to support micafungin use in documented HCME.

• The FDA has approved micafungin 4 mg/kg daily dose for treatment of candidemia, acute disseminated candidiasis, Candida peritonitis, and abscesses without meningoencephalitis and/or ocular dissemination in pediatric patients younger than 4 months of age. This dose is likely inadequate to treat CNS infections.

• Ill neonates and young infants <4 months with candidemia should be treated with a daily dose of 10 mg/kg when micafungin therapy is clinically indicated.

Author contributions

All authors have substantially contributed to the production of the article and agreed with its final version.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any or entity with financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Scientific accuracy check

Astellas Pharma provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This paper was not funded.