Pharmacokinetic, efficacy, and safety considerations for the use of antifungal drugs in the neonatal population

Scott, Briana; Hornik, Chi Dang; Zimmerman, Kanecia O.

doi:10.1080/17425255.2020.1773793

Cited by 14 publications

(8 citation statements)

References 137 publications

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“…To date, Amphotericin B deoxycholate or liposomal amphotericin B are recommended as first-line therapies for invasive fungal infections in neonates, but their use can be limited by nephrotoxicity [ 18 ]. Fluconazole is recommended as a second-line drug, but hepatotoxicity and azole resistance can limit its use [ 16 , 19 ]; furthermore, fluconazole prophylaxis is recommended against invasive candidiasis in very low and extremely low-birth-weight preterm neonates or in those carriers of central venous catheters [ 20 , 21 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma and Cerebrospinal Fluid Concentrations of Micafungin Administered at High Doses in Critically Ill Infants with Systemic Candidiasis: A Pooled Analysis of Two Studies

et al. 2023

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Background: Neonates may require higher doses of micafungin than adults to reach the therapeutic effect for increased plasma clearance. Only poor and inconclusive data are available still now to support this hypothesis, especially with regard to central nervous system micafungin concentrations. To assess the pharmacokinetics of increased doses (8 to 15 mg/kg/day) of micafungin in preterm and term neonates with invasive candidiasis and to complete previously presented results, we analyzed the pharmacokinetic data on a total of 53 newborns treated with micafungin, whereby 3 of them had Candida meningitis and hydrocephalus. Methods: Fifty-three neonates with systemic candidiasis, three of them with meningitis, were treated for at least 14 days with intravenous micafungin (Mycamine®) at a dosage ranging from 8 to 15 mg/kg/day. Plasma and cerebrospinal fluid (CSF) concentrations of micafungin were measured before the drug administration and at 1, 2, and 8 h after the end of the infusion using high-performance liquid chromatography (HPLC). Systemic exposure was assessed according to AUC0–24, plasma clearance (CL), and half-life measured in 52/53 patients, divided by chronological age. Results and conclusions: The mean micafungin clearance is higher in neonates than in older infants (0.036 L/h/kg before 28 days of life versus 0.028 L/h/kg after 120 days). The drug half-life is shorter in neonates than in older patients (13.5 h before 28 days of life versus 14.4 h after 120 days). With doses ranging between 8 and 15 mg/kg/day, micafungin crosses the blood–brain barrier reaching therapeutic levels in CSF.

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Section: Discussionmentioning

confidence: 99%

Plasma and Cerebrospinal Fluid Concentrations of Micafungin Administered at High Doses in Critically Ill Infants with Systemic Candidiasis: A Pooled Analysis of Two Studies

et al. 2023

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“…Es por esto, que los resultados favorecen la decisión como institución de no usar profilaxis antifúngica ni probióticos, y da pie para continuar fortaleciendo los programas y equipos de trabajo actuales. Además, esta conducta está también sustentada en la morbilidad adicional que generan los antimicóticos, en pacientes que de por sí ya tienen una condición de riesgo significativa [28][29][30][31] .…”

Section: Discussionunclassified

Incidencia de fungemia en la unidad de recién nacidos del Hospital Universitario San Ignacio de Bogotá en el periodo comprendido desde el 01 de enero de 2008 hasta el 31 de diciembre de 2018

Sánchez-Tordecilla

Bertolotto

Vargas-Vaca

et al. 2022

Infect

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Objetivo: determinar la incidencia de fungemia en neonatos del Hospital Universitario San Ignacio de Bogotá, y caracterizar a los que desarrollaron infección fúngica invasora, en el periodo entre 2008 y 2018. Material y método: estudio de casos y controles anidado a una cohorte retrospectiva, con información obtenida de las bases de datos de los departamentos de microbiología y estadística, así como las historias clínicas. Resultados: En el periodo de estudio se atendieron en total 12.905 neonatos; población en la cual se encontró una tasa de incidencia de 6,2 por 10.000 pacientes con una distribución equitativa por sexos y una mediana de edad gestacional de 36,5 semanas, siendo el principal agente causal la Candida albicans (50%). En los casos se reportó uso de antibiótico de amplio espectro en el 75%, de nutrición parenteral en el 100%, cirugía previa en el 75% (principalmente de tipo gastrointestinal 83,3%), uso de catéter venoso central en el 100% e inicio de alimentación trófica temprana en el 12,5%. Finalmente, no se documentó uso de corticoides postnatales en la muestra. Conclusiones: se encontró una baja incidencia de fungemia en el HUSI, lo que refuerza la no necesidad de implementar el uso de profilaxis antimicótica de forma estandarizada en nuestra institución. Entre los casos identificados, la patología quirúrgica gastrointestinal surgió como la condición clínica prevalente debido a los requerimientos de uso de nutrición parenteral por catéter venoso central.

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“…92 Dietary differences may also contribute to the difference in bioavailability between children and adults. 92 Age must be taken into account in azole dosing due to age-related PK features and a high interindividual variability in exposure 93–101 referring to weight (above or under 40 kg) and age group [neonates, infants, and children 2–12 years old (yo) or >12 yo]. For example, children ≥12 yo receive VRZ 3–4 mg/kg ×2, whereas the oral dose is 200–300 mg ×2 in patients weighing ≥40 kg versus 100–150 mg ×2 for patients weighing <40 kg.…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…The infant subpopulation has its own PK specificities. 96 Oral drug absorption depends on various patient-related factors, including the functional maturation of organs and systems, such as gastric emptying, which is influenced by milk composition (formula, hydrolysate, or human milk). 113 Gastric pH is higher in newborns compared with infants and children.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Antifungal Drugs TDM: Trends and Update

Kably

Launay

Derobertmasure

et al. 2022

Therapeutic Drug Monitoring

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The increasing burden of invasive fungal infections results in growing challenges to antifungal (AF) therapeutic drug monitoring (TDM). This review aims to provide an overview of recent advances in AF TDM. Methods:We conducted a PubMed search for articles during 2016-2020 using "TDM" or "pharmacokinetics" or "drug-druginteraction" with "antifungal," consolidated for each AF. Selection was limited to English language articles with human data on drug exposure.Results: More than 1000 articles matched the search terms. We selected 566 publications. The latest findings tend to confirm previous observations in real-life clinical settings. The pharmacokinetic variability related to special populations is not specific but must be considered. AF benefit-to-risk ratio, drug-drug interaction (DDI) profiles, and minimal inhibitory concentrations for pathogens must be known to manage at-risk situations and patients. Itraconazole has replaced ketoconazole in healthy volunteers DDI studies. Physiologically based pharmacokinetic modeling is widely used to assess metabolic azole DDI. AF prophylactic use was studied more for Aspergillus spp. and Mucorales in oncohematology and solid organ transplantation than for Candida (already studied). Emergence of central nervous system infection and severe infections in immunocompetent individuals both merit special attention. TDM is more challenging for azoles than amphotericin B and echinocandins. Fewer TDM requirements exist for fluconazole and isavuconazole (ISZ); however, ISZ is frequently used in clinical situations in which TDM is recommended. Voriconazole remains the most challenging of the AF, with toxicity limiting high-dose treatments. Moreover, alternative treatments (posaconazole tablets, ISZ) are now available.Conclusions: TDM seems to be crucial for curative and/or longterm maintenance treatment in highly variable patients. TDM poses fewer cost issues than the drugs themselves or subsequent treatment issues. The integration of clinical pharmacology into multidisciplinary management is now increasingly seen as a part of patient care.

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Pharmacokinetic, efficacy, and safety considerations for the use of antifungal drugs in the neonatal population

Cited by 14 publications

References 137 publications

Plasma and Cerebrospinal Fluid Concentrations of Micafungin Administered at High Doses in Critically Ill Infants with Systemic Candidiasis: A Pooled Analysis of Two Studies

Plasma and Cerebrospinal Fluid Concentrations of Micafungin Administered at High Doses in Critically Ill Infants with Systemic Candidiasis: A Pooled Analysis of Two Studies

Incidencia de fungemia en la unidad de recién nacidos del Hospital Universitario San Ignacio de Bogotá en el periodo comprendido desde el 01 de enero de 2008 hasta el 31 de diciembre de 2018

Antifungal Drugs TDM: Trends and Update

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