Dosing Antifungals in Obesity: a Literature Review

Amsden, Jarrett R.; Slain, Douglas

doi:10.1007/s12281-019-0335-3

Cited by 4 publications

(4 citation statements)

References 73 publications

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“…For obese critically ill patients, weight-based dosing is challenging as antifungal pharmacokinetics vary, specifically the volume of distribution. This could impact the efficacy and toxicity of treatment 32 like voriconazole and L-AMB, which both involve weight-based dosing 33 , 34 or posaconazole, which may have lower plasma drug concentrations in patients >120kg. 35 In these patients, treatment options without weight-based dosing requirements and without trough level concentration difference between obese and non-obese patients as well as minimizing drug–drug interactions would be preferable and make suboptimal dosing less likely.…”

Section: Discussionmentioning

confidence: 99%

Patient Characteristics and Risk Factors in Invasive Mold Infections: Comparison from a Systematic Review and Database Analysis

Sung

Martin

Phan

et al. 2021

CEOR

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Introduction Diagnosis and treatment of invasive mold infections (IMI) can be challenging and IMI is a significant source of morbidity and mortality. Invasive aspergillosis (IA) and invasive mucormycosis (IM) are two of the most common mold infections. A better understanding of patient comorbidities and risk factors that predispose IMI may help clinicians to refine the difficult diagnostic and treatment process. Methods A systematic literature review (SLR) was conducted (January 2008–October 2019) for studies reporting comorbidities/risk factors of patients with IA or IM (Phase I), followed by an analysis on the Optum ® US EHR database of prominent risk factor cohorts based on SLR findings and expert opinion (Phase II). From the four identified patient cohorts: 1) patients undergoing solid organ transplant (SOT) and patients with 2) hematologic cancers, 3) diabetes, or 4) lung disease, rates of IA, IM, or concurrent IA and IM; patient comorbidities; and Charlson Comorbidity Index (CCI) scores were reported. Results The SLR included 88 studies, and 46 were used to select comorbidities/risk factors cohorts in IA and IM patients. The most important comorbidities/risk factors in IA and IM patients were diabetes, lung disease, hematological malignances, and SOT. In the Optum database (N=101,340,454 patients), IA rates were highest in lung transplant (10.81%) patients and IM rates were highest in intestine transplant (0.83%) patients, lung transplant (0.43%), and hematopoietic stem cell transplant (0.49%). CCI scores were elevated in all mold infection groups compared to the total Optum cohort. Conclusion The current study describes patient comorbidity and risk factors associated with IA and IM. These data can be used to refine clinical decision-making regarding when to suspect mold infections. Future research should focus on identifying whether patients respond differently to various antifungal treatments to determine if strategic recommendations should be made for certain patient groups.

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Section: Discussionmentioning

confidence: 99%

Patient Characteristics and Risk Factors in Invasive Mold Infections: Comparison from a Systematic Review and Database Analysis

Sung

Martin

Phan

et al. 2021

CEOR

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Section: Pharmacokinetic Variability and Therapeutic Drug Monitoringmentioning

confidence: 99%

“…All three echinocandins exhibit altered pharmacokinetics as weight increases above 65–75 kg [ 30 ]. In a recent empirical trial of micafungin for critically ill mechanically ventilated patients, micafungin 100 mg daily was found to be associated with at relatively lower (< 80%) probability of PK/PD target attainment for C. albicans, C. glabrata and C. parapsilosis in patients weighing more than 80 kg [ 33 ].…”

Section: Pharmacokinetic Variability and Therapeutic Drug Monitoringmentioning

confidence: 99%

“…Fluconazole and voriconazole require dosage adjustment based on total body weight an adjusted body weight, respectively [30]. Although conflicting data have been reported for itraconazole and posaconazole based on TDM studies, Wasmann et al [31] found that higher doses of the intravenous posaconazole (400 mg twice daily loading, then 400 mg daily) were required to achieve similar exposures to standard 300 mg intravenous doses in patients weighing more than 140 kg.…”

Section: Pharmacokinetic Variability and Therapeutic Drug Monitoringmentioning

confidence: 99%

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Managing uncertainty in antifungal dosing: antibiograms, therapeutic drug monitoring and drug-drug interactions

Lewis

Andes

2021

Current Opinion in Infectious Diseases

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Purpose of reviewA number of pharmacokinetic and pharmacodynamic factors in critically ill or severely immunosuppressed patients influence the effectiveness of antifungal therapy making dosing less certain. Recent position papers from infectious diseases societies and working groups have proposed methods for dosage individualization of antibiotics in critically ill patients using a combination of population pharmacokinetic models, Monte-Carlo simulation and therapeutic drug monitoring (TDM) to guide dosing. In this review, we examine the current limitations and practical issues of adapting a pharmacometrics-guided dosing approaches to dosing of antifungals in critically ill or severely immunosuppressed populations.Recent findingsWe review the current status of antifungal susceptibility testing and challenges in incorporating TDM into Bayesian dose prediction models. We also discuss issues facing pharmacometrics dosage adjustment of newer targeted chemotherapies that exhibit severe pharmacokinetic drug-drug interactions with triazole antifungals.SummaryAlthough knowledge of antifungal pharmacokinetic/pharmacodynamic is maturing, the practical application of these concepts towards point-of-care dosage individualization is still limited. User-friendly pharmacometric models are needed to improve the utility of TDM and management of a growing number of severe pharmacokinetic antifungal drug-drug interactions with targeted chemotherapies.

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Dosificación de fármacos en el paciente obeso crítico, una revisión bibliográfica

García-Díaz,

Sánchez-Sancho,

Lalueza-Broto

et al. 2024

Farmacia Hospitalaria

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Dosing Antifungals in Obesity: a Literature Review

Cited by 4 publications

References 73 publications

Patient Characteristics and Risk Factors in Invasive Mold Infections: Comparison from a Systematic Review and Database Analysis

Patient Characteristics and Risk Factors in Invasive Mold Infections: Comparison from a Systematic Review and Database Analysis

Managing uncertainty in antifungal dosing: antibiograms, therapeutic drug monitoring and drug-drug interactions

Dosificación de fármacos en el paciente obeso crítico, una revisión bibliográfica

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