Therapeutic drug monitoring of meropenem and piperacillin-tazobactam in the Singapore critically ill population – A prospective, multi-center, observational study (BLAST 1)

Chua, Nathalie Grace; Loo, Liwen; Hee, Daryl Kim Hor; Lim, Tze Peng; Ng, Tat Ming; Hoo, Grace Si Ru; Soong, Jie Lin; Ong, Jasmine Chiat Ling; Tang, Sarah Si Lin; Zhou, Yvonne Peijun; Lee, Winnie; Lee, Lawrence Soon-U; Cove, Matthew E.; L, Li; Kwa, Andrea Lay-Hoon

doi:10.1016/j.jcrc.2021.12.013

Cited by 20 publications

(21 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, the observed concentrations for TZP and MEM were comparable to previously reported concentrations. For TZP, other studies reported both higher and lower median concentrations, while for MEM higher median concentrations were frequently reported [ 19 – 23 ]. The crude percentages of over- and underdosing reported here are difficult to compare with other studies, as a multitude of therapeutic targets and ranges are used in the literature.…”

Section: Discussionmentioning

confidence: 99%

Pathogen-based target attainment of optimized continuous infusion dosing regimens of piperacillin-tazobactam and meropenem in surgical ICU patients: a prospective single center observational study

Corte

Verhaeghe

Dhaese

et al. 2023

Ann. Intensive Care

View full text Add to dashboard Cite

Background Several studies have indicated that commonly used piperacillin-tazobactam (TZP) and meropenem (MEM) dosing regimens lead to suboptimal plasma concentrations for a range of pharmacokinetic/pharmacodynamic (PK/PD) targets in intensive care unit (ICU) patients. These targets are often based on a hypothetical worst-case scenario, possibly overestimating the percentage of suboptimal concentrations. We aimed to evaluate the pathogen-based clinically relevant target attainment (CRTA) and therapeutic range attainment (TRA) of optimized continuous infusion dosing regimens of TZP and MEM in surgical ICU patients. Methods A single center prospective observational study was conducted between March 2016 and April 2019. Free plasma concentrations were calculated by correcting total plasma concentrations, determined on remnants of blood gas samples by ultra-performance liquid chromatography with tandem mass spectrometry, for their protein binding. Break points (BP) of identified pathogens were derived from epidemiological cut-off values. CRTA was defined as a corrected measured total serum concentration above the BP and calculated for increasing BP multiplications up to 6 × BP. The upper limit of the therapeutic range was set at 157.2 mg/L for TZP and 45 mg/L for MEM. As a worst-case scenario, a BP of 16 mg/L for TZP and 2 mg/L for MEM was used. Results 781 unique patients were included with 1036 distinctive beta-lactam antimicrobial prescriptions (731 TZP, 305 MEM) for 1003 unique infections/prophylactic regimens (750 TZP, 323 MEM). 2810 samples were available (1892 TZP, 918 MEM). The median corrected plasma concentration for TZP was 86.4 mg/L [IQR 56.2–148] and 16.2 mg/L [10.2–25.5] for MEM. CRTA and TRA was consistently higher for the pathogen-based scenario than for the worst-case scenario, but nonetheless, a substantial proportion of samples did not attain commonly used PK/PD targets. Conclusion Despite these pathogen-based data demonstrating that CRTA and TRA is higher than in the often-used theoretical worst-case scenario, a substantial proportion of samples did not attain commonly used PK/PD targets when using optimised continuous infusion dosing regimens. Therefore, more dosing optimization research seems warranted. At the same time, a ‘pathogen-based analysis’ approach might prove to be more sensible than a worst-case scenario approach when evaluating target attainment and linked clinical outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Pathogen-based target attainment of optimized continuous infusion dosing regimens of piperacillin-tazobactam and meropenem in surgical ICU patients: a prospective single center observational study

Corte

Verhaeghe

Dhaese

et al. 2023

Ann. Intensive Care

View full text Add to dashboard Cite

show abstract

“…In a recent prospective multi‐center observational study (BLAST‐1) conducted in Singapore, critically ill patients who did not achieve adequate ß‐lactam drug levels had higher mortality rates. In contrast, those with adequate ß‐lactam drug levels (achieved 100%fT > 5x MIC) had a significantly shorter duration of hospitalization 89 . Although ß‐lactam TDM is currently only a research tool, we expect this to be made more widely available in time to come and is a useful stewardship tool that could potentially improve outcomes of MDRO infections in our transplant recipients.…”

Section: Looking Beyond the Current Core Strategies In Stewardshipmentioning

confidence: 99%

“…In contrast, those with adequate ß-lactam drug levels (achieved 100%fT > 5x MIC) had a significantly shorter duration of hospitalization. 89 Although ß-lactam TDM is currently only a research tool, we expect this to be made more widely available in time to come and is a useful stewardship tool that could potentially improve outcomes of MDRO infections in our transplant recipients.…”

Section: Looking Beyond the Current Core Strategies In Stewardshipmentioning

confidence: 99%

Current state of antimicrobial stewardship in organ transplantation in Singapore

Chung

Liew

Lee

et al. 2022

Transplant Infectious Dis

View full text Add to dashboard Cite

Background Antibiotic stewardship programs (ASPs) are well established in the public hospitals in Singapore, but they are not mandatory for transplant programs. Given the positive impact of ASPs in non‐organ transplant patients (improved use of broad‐spectrum antibiotics, reduced length of stay, and lower healthcare costs), stewardship principles are likely to benefit transplant recipients. Methods We reviewed the progress made in ASPs in the Asia Pacific region as well as the progress of our ASP over the last decade since it was established. We also described how stewardship strategies have evolved for the purposes of our transplant program. Results Currently, pressing stewardship issues for our transplant program include high antibiotic consumption, as well as the burden, morbidity, and mortality associated with drug‐resistant bacterial infections. Transplanting the model of stewardship onto a transplant program ignores the intricacies of transplant patients; the bespoke form of stewardship, “handshake stewardship”, is more appropriate. Conclusion To advance the cause of ASP in the transplant unit in Singapore, stakeholder buy‐in is key; empowering transplant physicians to be stewardship‐focused would be more sustainable in the long run. In addition, expanding our diagnostic armamentarium, optimizing existing therapeutics and multi‐disciplinary team involvement (including stakeholders from microbiology, and infection prevention teams) are vital.

show abstract

“…Great controversy exists surrounding the optimal PK/PD target(s) for BL TDM 1,7,15,33–36 . When selecting the Mayo Clinic BL TDM PK/PD target, we considered published data, the use of total drug concentration assays 25 which could be potentially up to 20% higher than circulating free drug concentrations for these agents, 37 the complexity of PK calculations, and resistance patterns.…”

Section: Establishing Clinical Workflowsmentioning

confidence: 99%

“…Great controversy exists surrounding the optimal PK/PD target(s) for BL TDM. 1,7,15,[33][34][35][36] When selecting the Mayo Clinic BL TDM PK/PD target, we considered published data, the use of total drug concentration assays 25 which could be potentially up to 20% higher than circulating free drug concentrations for these agents, 37 the complexity of PK calculations, and resistance patterns. To optimize practice uptake, we deemed it preferable to select a single PK/PD target for all scenarios rather than a target tailored to the type of bacteria (i.e., gram negative vs. gram positive), site of infection (e.g., pneumonia vs. skin and soft tissue), or severity of illness.…”

Section: Pharmacokinetic/pharmacodynamic Targetmentioning

confidence: 99%

“How to” guide for pharmacist‐led implementation of beta‐lactam therapeutic drug monitoring in the critically ill

Ausman

Moreland‐Head

Saleh

et al. 2023

J Am Coll Clin Pharm

View full text Add to dashboard Cite

Beta‐lactam therapeutic drug monitoring (TDM) can improve precision dosing and clinical outcomes in critically ill patients, but has not been implemented widely in the United States. Mayo Clinic recently implemented a beta‐lactam TDM program. This single‐center experience forms the basis of the manuscript which outlines practical considerations involved with beta‐lactam TDM implementation, including the pharmacist's role as a leader. Our implementation effort focused on three primary domains. First, we aimed to ensure a supportive organizational infrastructure. Early leadership engagement by the pharmacist‐led core team facilitated advocacy for the clinical need, allocation of resources, and assay development. Second, core clinical workflows were developed that addressed the preferred patient population for use, desirable pharmacokinetic and pharmacodynamic targets, and the preferred sampling strategy. Clinical tools to guide pharmacists in interpreting the results (e.g., pharmacokinetics calculator) and documenting decisions were developed. Third, stakeholders were offered repeated exposure to evidence and expertise to facilitate understanding and application of the new practice. This act of ‘individual internalization’ seems to be uniquely important to beta‐lactam TDM implementation compared with the implementation of other antimicrobial TDM programs. Educational strategies and supportive materials that were developed were focused on providing substantive and varied information tailored to the stakeholders' role in the process. For pharmacists, this included both clinical and operational considerations. A continuous improvement plan to support management of the process was instituted to address necessary updates and changes that inevitably emerged. In summary, the described approach to implementation of a pharmacist‐led beta‐lactam TDM program could be used as a roadmap to aid other institutions that aim to develop such a program.

show abstract

Therapeutic drug monitoring of meropenem and piperacillin-tazobactam in the Singapore critically ill population – A prospective, multi-center, observational study (BLAST 1)

Cited by 20 publications

References 37 publications

Pathogen-based target attainment of optimized continuous infusion dosing regimens of piperacillin-tazobactam and meropenem in surgical ICU patients: a prospective single center observational study

Pathogen-based target attainment of optimized continuous infusion dosing regimens of piperacillin-tazobactam and meropenem in surgical ICU patients: a prospective single center observational study

Current state of antimicrobial stewardship in organ transplantation in Singapore

“How to” guide for pharmacist‐led implementation of beta‐lactam therapeutic drug monitoring in the critically ill

Contact Info

Product

Resources

About