Micafungin twice weekly as antifungal prophylaxis in paediatric patients at high risk for invasive fungal disease

Bochennek, Konrad; Balan, Anu; Müller-Scholden, L.; Becker, Martina; Farowski, Fedja; Müller, Carsten; Groll, Andreas H.; Lehrnbecher, Thomas

doi:10.1093/jac/dku544

Cited by 37 publications

(23 citation statements)

References 20 publications

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“…Of note, a recent placebo‐controlled RCT in adult patients with acute lymphoblastic leukaemia did not show good prophylactic effect of L‐AmB (Cornely et al , ). Micafungin may provide an attractive alternative (Bochennek et al , ), but results need prospective validation in paediatric AML patients. Another option is to closely monitor serum galactomannan levels.…”

Section: Discussionmentioning

confidence: 99%

Differences in infection prophylaxis measures between paediatric acute myeloid leukaemia study groups within the international Berlin–Frankfürt–Münster (I‐BFM) study group

et al. 2018

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Prevention of infections is of obvious relevance in paediatric patients with acute myeloid leukaemia (AML). However, recommendations are often non-specific and supported by low-quality evidence, resulting in divergent infection preventive regimens. Using a web-based survey, we investigated the infection prophylaxis guidelines of 22 paediatric AML study groups affiliated to the international Berlin-Frankfürt-Münster study group. In order to evaluate differences in daily practice among hospitals, representatives (n = 27) from the Nordic Society for Paediatric Haematology and Oncology-Dutch-Belgium-Hong Kong - AML study group participated in a slightly modified survey. Seven study groups (32%) advise gram-negative antibiotic prophylaxis, mainly with fluoroquinolones (n = 6). Gram-positive prophylaxis is prescribed by eight groups (36%). Over 60% of the study groups prescribe food and social restrictions, but the specific topics and strictness differ widely. According to the hospital-based survey, sites roughly comply with common study group guidelines. However, the use of any gram-negative antibiotic prophylaxis, the specific prophylactic antifungal agent and the strictness of the food and social restrictions differ substantially between the hospitals. Despite a long history of close collaboration, many differences are still present between the affiliated groups. The results of this survey provide an appropriate baseline measure to study the emergence and impact of future guidelines on infection prophylaxis in paediatric AML.

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Section: Discussionmentioning

confidence: 99%

Differences in infection prophylaxis measures between paediatric acute myeloid leukaemia study groups within the international Berlin–Frankfürt–Münster (I‐BFM) study group

et al. 2018

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“…These concepts have more recently been considered for antifungal drugs meeting these PK/PD criteria in the settings of fungal infection prevention (prophylaxis) and therapy (6)(7)(8)(9).…”

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confidence: 99%

Efficacy of Extended-Interval Dosing of Micafungin Evaluated Using a Pharmacokinetic/Pharmacodynamic Study with Humanized Doses in Mice

Lepak

Marchillo

VanHecker

et al. 2016

Antimicrob Agents Chemother

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The pharmacokinetic/pharmacodynamic (PK/PD) characteristics of the echinocandins favor infrequent administration of large doses. The in vivo investigation reported here tested the utility of a range of humanized dose levels of micafungin using a variety of prolonged dosing intervals for the prevention and therapy of established disseminated candidiasis. Humanized doses of 600 mg administered every 6 days prevented fungal growth in prophylaxis. Humanized doses of 300 to 1,000 mg administered every 6 days demonstrated efficacy for established infections. Several pharmacokinetic and pharmacodynamic (PK/PD) characteristics help to discern optimal antimicrobial dosing frequency. Drugs that exhibit concentration-dependent killing and prolonged postantibiotic effects are most effective when larger dose levels are administered infrequently (1-3). Intuitively, drugs with prolonged elimination half-lives can also be given less frequently than drugs that are rapidly cleared. In addition to enhancing efficacy, extended-interval dosing has the potential to reduce the length of hospitalization, to improve patient compliance and satisfaction, and to reduce the cost of drugs that require parenteral administration.The characteristics of several antibacterial and antiviral compounds have led to less than daily or even weekly dosing intervals (4, 5). These concepts have more recently been considered for antifungal drugs meeting these PK/PD criteria in the settings of fungal infection prevention (prophylaxis) and therapy (6-9).

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“…There are several reported cases of chronic disseminated candidiasis (CDC) in adults with acute myeloid leukemia (AML), typically a childhood cancer, which failed treatment with liposomal amphotericin, azoles, and caspofungin, but responded to micafungin and posaconazole with favorable side effect profiles (10). Micafungin has also been shown to be a successful prophylactic in pediatric populations (11).…”

Section: Discussionmentioning

confidence: 99%

Caspofungin resistant disseminated candidiasis in a 7-year-old girl with T cell lymphoma: a case report

et al. 2018

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Immunocompromised patients are at increased risk of disseminated candidiasis. Guidelines for the treatment of invasive candidiasis were last published in 2009, but resistance to the recommended treatment has recently been described in the literature. Here we present the case of an immunocompromised child with T-cell lymphoma who died secondary to disseminated candidiasis despite prolonged antifungal therapy. Awareness of the increasing resistance patterns of Candida when caring for immunocompromised patients, especially pediatric patients, may improve treatment and create better patient outcomes.

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Micafungin twice weekly as antifungal prophylaxis in paediatric patients at high risk for invasive fungal disease

Abstract: Our data indicate that micafungin administered twice weekly at a dosage of 3-4 mg/kg of bodyweight could be a convenient, safe and efficient alternative for antifungal prophylaxis in children at high risk for IFD.

Cited by 37 publications

References 20 publications

Differences in infection prophylaxis measures between paediatric acute myeloid leukaemia study groups within the international Berlin–Frankfürt–Münster (I‐BFM) study group

Differences in infection prophylaxis measures between paediatric acute myeloid leukaemia study groups within the international Berlin–Frankfürt–Münster (I‐BFM) study group

Efficacy of Extended-Interval Dosing of Micafungin Evaluated Using a Pharmacokinetic/Pharmacodynamic Study with Humanized Doses in Mice

Caspofungin resistant disseminated candidiasis in a 7-year-old girl with T cell lymphoma: a case report

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