A protocol for an international, multicentre pharmacokinetic study for Screening Antifungal Exposure in Intensive Care Units: The SAFE-ICU study

Roberts, Jason A.; Sime, Fekade Bruck; Lipman, Jeffrey; Hernández-Mitre, María Patricia; Baptista, João Pedro; Brüggemann, Roger J. M.; Darvall, Jai; Waele, Jan J. De; Dimοpoulos, George; Lefrant, Jean‐Yves; Nor, Mohd Basri Mat; Rello, Jordi; Seoane, Leonardo; Slavin, Monica; Valkonen, Miia; Venditti, Mario; Jorda, Anselm; Roger, Claire

doi:10.1016/j.ccrj.2023.04.002

Cited by 2 publications

(2 citation statements)

References 19 publications

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“…The differences between the PK/PD of L-amb and DamB are underemphasized, such that a lower DamB C max /MIC ratio of 5–10 is improperly applied to studies using L-amb. One L-amb paediatric TDM study by Tortora et al , 34 which was excluded due to the paediatric patient numbers (<5), and another adult multicentre study currently underway by Roberts et al , 35 use a lower C max /MIC target of >4.5 for L-amb.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic drug monitoring of liposomal amphotericin B in children. Are we there yet? A systematic review

Lai,

Yeo,

Rockliff

et al. 2024

Journal of Antimicrobial Chemotherapy

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Introduction Therapeutic drug monitoring (TDM) is a tool that supports personalized dosing, but its role for liposomal amphotericin B (L-amb) is unclear. This systematic review assessed the evidence for L-amb TDM in children. Objectives To evaluate the concentration–efficacy relationship, concentration–toxicity relationship and pharmacokinetic/pharmacodynamic (PK/PD) variability of L-amb in children. Methods We systematically reviewed PubMed and Embase databases following PRISMA guidelines. Eligible studies included L-amb PK/PD studies in children aged 0–18 years. Review articles, case series of <five patients, editorials and animal studies were excluded. Quality assessment was performed using the Critical Appraisal of Clinical Pharmacokinetics tool. The concentration–efficacy and concentration–toxicity relationships and PK/PD variability were analysed. Results In total, 4220 studies were screened; 6 were included, presenting data on 195 children. Invasive candidiasis and aspergillosis were the two most common infections treated with L-amb. Studies showed significant PK variability due to age (mean age ranged from 14 days to 17 years), body weight, non-linear PK and changes in the volume of distribution. Limited evidence supported a peak concentration/MIC (Cmax/MIC) of 25–50 for optimal efficacy and an AUC24 of >600 mg·h/L for nephrotoxicity. L-amb doses of 2.5–10 mg/kg/day were reported to achieve Cmax/MIC > 25 using an MIC of 1 mg/L. Conclusions While significant PK variability was observed in children, evidence to support routine L-amb TDM was limited. Further studies on efficacy and toxicity benefits are required before routine TDM of L-amb can be recommended.

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Section: Discussionmentioning

confidence: 99%

Therapeutic drug monitoring of liposomal amphotericin B in children. Are we there yet? A systematic review

Lai,

Yeo,

Rockliff

et al. 2024

Journal of Antimicrobial Chemotherapy

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“…Suboptimal drug concentrations in peritoneal fluid represent a risk for emergence of antifungal resistance in intraabdominal Candida , making of intraabdominal microbiota a reservoir of non-susceptible isolates, as occurs with bacteria. Further studies determining concentrations of antifungals in peritoneal samples as the one planned [ 110 ] or the recently published with voriconazole [ 111 ] represent the first step to achieve the adequate dosing in this entity. A current opinion in the literature indicates that guidelines should be updated by separating the recommendations for candidemia and abdominal candidiasis with a revision of echinocandin doses and the inclusion of other antifungals such as liposomal amphotericin B.…”

Section: Discussionmentioning

confidence: 99%

Critical appraisal beyond clinical guidelines for intraabdominal candidiasis

Maseda,

Martín-Loeches,

Zaragoza

et al. 2023

Crit Care

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Background Regardless of the available antifungals, intraabdominal candidiasis (IAC) mortality continues to be high and represents a challenge for clinicians. Main body This opinion paper discusses alternative antifungal options for treating IAC. This clinical entity should be addressed separately from candidemia due to the peculiarity of the required penetration of antifungals into the peritoneal cavity. Intraabdominal concentrations may be further restricted in critically ill patients where pathophysiological facts alter normal drug distribution. Echinocandins are recommended as first-line treatment in guidelines for invasive candidiasis. However, considering published data, our pharmacodynamic analysis suggests the required increase of doses, postulated by some authors, to attain adequate pharmacokinetic (PK) levels in peritoneal fluid. Given the limited evidence in the literature on PK/PD-based treatments of IAC, an algorithm is proposed to guide antifungal treatment. Liposomal amphotericin B is advocated as first-line therapy in patients with sepsis/septic shock presenting candidemia or endophthalmitis, or with prior exposure to echinocandins and/or fluconazole, or with infections by Candida glabrata. Other situations and alternatives, such as new compounds or combination therapy, are also analysed. Conclusion There is a critical need for more robust clinical trials, studies examining patient heterogeneity and surveillance of antifungal resistance to enhance patient care and optimise treatment outcomes. Such evidence will help refine the existing guidelines and contribute to a more personalised and effective approach to treating this serious medical condition. Meanwhile, it is suggested to broaden the consideration of other options, such as liposomal amphotericin B, as first-line treatment until the results of the fungogram are available and antifungal stewardship could be implemented to prevent the development of resistance.

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A protocol for an international, multicentre pharmacokinetic study for Screening Antifungal Exposure in Intensive Care Units: The SAFE-ICU study

Cited by 2 publications

References 19 publications

Therapeutic drug monitoring of liposomal amphotericin B in children. Are we there yet? A systematic review

Therapeutic drug monitoring of liposomal amphotericin B in children. Are we there yet? A systematic review

Critical appraisal beyond clinical guidelines for intraabdominal candidiasis

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