Therapeutic drug monitoring of commonly used anti-infective agents: A nationwide cross-sectional survey of Australian hospital practices

Imani, Sahand; Alffenaar, Jan‐Willem C.; Cotta, Menino Osbert; Daveson, Kathryn; Hal, Sebastiaan J. van; Lau, Cindy; Marriott, Debbie; Penm, Jonathan; Roberts, Jason A.; Tabah, Alexis; Trethewy, Nicholas; Williams, Paul; Sandaradura, Indy

doi:10.1016/j.ijantimicag.2020.106180

Cited by 19 publications

(24 citation statements)

References 31 publications

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“…1,290 Previous studies from Australia suggested that many facilities do not have access to on-site laboratory processing of antifungal serum concentrations, with a turnaround time of 3-5 days for the majority of TDM results. [291][292][293] The time to obtaining optimal drug exposures can commonly take 1-2 weeks in complex cases, and may be longer if the blood test samples are processed off-site. Thus, optimising the timing of samples, reducing processing turnaround times, and streamlining subsequent dose adjustments, could all improve time to adequate drug exposure.…”

Section: Concentration-related Toxicities Of Flucytosinementioning

confidence: 99%

Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy and haemopoietic stem cell transplant recipients, 2021

Chau

Daveson

Alffenaar

et al. 2021

Internal Medicine Journal

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Antifungal agents can have complex dosing and the potential for drug interaction, both of which can lead to subtherapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy and haemopoietic stem cell transplant recipients. Antifungal agents can also be associated with significant toxicities when drug concentrations are too high. Suboptimal dosing can be minimised by clinical assessment, laboratory monitoring, avoidance of interacting drugs, and dose modification. Therapeutic drug monitoring (TDM) plays an increasingly important role in antifungal therapy, particularly for antifungal agents that have an established exposure-response relationship with either a narrow therapeutic window, large dose-exposure variability, cytochrome P450 gene polymorphism affecting drug metabolism, the presence of antifungal drug interactions or unexpected toxicity, and/or concerns for non-compliance or inadequate absorption of oral antifungals. These guidelines provide recommendations on antifungal drug monitoring and TDM-guided dosing adjustment for selected antifungal agents, and include suggested resources for identifying and analysing antifungal drug interactions. Recommended competencies for optimal interpretation of antifungal TDM and dose recommendations are also provided.

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Section: Concentration-related Toxicities Of Flucytosinementioning

confidence: 99%

Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy and haemopoietic stem cell transplant recipients, 2021

Chau

Daveson

Alffenaar

et al. 2021

Internal Medicine Journal

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“…361 A cross-sectional survey of TDM practices in Australia concluded that only 35% of clinical practices were consistent with current TDM recommendations. 362 The inclusion of the pharmacological unit in hospital staff meetings 363 is one aspect of AFS programs that could increase the appropriateness of repetitive TDM and lead to the development of reciprocal levels of education in multidisciplinary collaborations. 364,365 However, the growing number of software suites for dose prediction may be affected by problems of sampling accuracy and infusion time documentation.…”

Section: Recommendations and Practicementioning

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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“…TDM is one such strategy that has traditionally been used to minimise the risk of exposure-related toxicity, particularly in antimicrobials with a narrow therapeutic index, such as the aminoglycosides and glycopeptides. With growing evidence linking sub-therapeutic antimicrobial concentrations with treatment failure [16,71,72], the role of TDM has now expanded to ensure therapeutic effectiveness is maximised [73,74].…”

Section: Dosing Softwarementioning

confidence: 99%

Machines that help machines to help patients: optimising antimicrobial dosing in patients receiving extracorporeal membrane oxygenation and renal replacement therapy using dosing software

et al. 2022

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Intensive care unit (ICU) patients with end-organ failure will require specialised machines or extracorporeal therapies to support the failing organs that would otherwise lead to death. ICU patients with severe acute kidney injury may require renal replacement therapy (RRT) to remove fluid and wastes from the body, and patients with severe cardiorespiratory failure will require extracorporeal membrane oxygenation (ECMO) to maintain adequate oxygen delivery whilst the underlying pathology is evaluated and managed. The presence of ECMO and RRT machines can further augment the existing pharmacokinetic (PK) alterations during critical illness. Significant changes in the apparent volume of distribution (V d ) and drug clearance (CL) for many important drugs have been reported during ECMO and RRT. Conventional antimicrobial dosing regimens rarely consider the impact of these changes and consequently, are unlikely to achieve effective antimicrobial exposures in critically ill patients receiving ECMO and/or RRT. Therefore, an in-depth understanding on potential PK changes during ECMO and/or RRT is required to inform antimicrobial dosing strategies in patients receiving ECMO and/or RRT. In this narrative review, we aim to discuss the potential impact of ECMO and RRT on the PK of antimicrobials and antimicrobial dosing requirements whilst receiving these extracorporeal therapies. The potential benefits of therapeutic drug monitoring (TDM) and dosing software to facilitate antimicrobial therapy for critically ill patients receiving ECMO and/or RRT are also reviewed and highlighted.

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Therapeutic drug monitoring of commonly used anti-infective agents: A nationwide cross-sectional survey of Australian hospital practices

Cited by 19 publications

References 31 publications

Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy and haemopoietic stem cell transplant recipients, 2021

Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy and haemopoietic stem cell transplant recipients, 2021

Antifungal Drugs TDM: Trends and Update

Machines that help machines to help patients: optimising antimicrobial dosing in patients receiving extracorporeal membrane oxygenation and renal replacement therapy using dosing software

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