The ADMIN-ICU survey: a survey on antimicrobial dosing and monitoring in ICUs

Tabah, Alexis; Waele, Jan J. De; Lipman, Jeffrey; Zahar, Jean Ralph; Cotta, Menino Osbert; Barton, Greg; Timsit, Jean‐François; Roberts, Jason A.

doi:10.1093/jac/dkv165

Cited by 113 publications

(122 citation statements)

References 20 publications

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“…Mutation frequencies were determined at baseline (0 h) and at 23,47,71,95,119,143,167,191,215, and 239 h to quantify less-susceptible subpopulations. A 200-l sample of appropriately diluted log-phase growth suspension was manually plated onto CAMHA containing no antibiotic and meropenem at 5ϫ and 10ϫ MIC (i.e., 1.25 and 2.5 mg/liter meropenem).…”

Section: Methodsmentioning

confidence: 99%

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Substantial Impact of Altered Pharmacokinetics in Critically Ill Patients on the Antibacterial Effects of Meropenem Evaluated via the Dynamic Hollow-Fiber Infection Model

Bergen

Bulitta

Kirkpatrick

et al. 2017

Antimicrob Agents Chemother

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Critically ill patients frequently have substantially altered pharmacokinetics compared to non-critically ill patients. We investigated the impact of pharmacokinetic alterations on bacterial killing and resistance for commonly used meropenem dosing regimens. A Pseudomonas aeruginosa isolate (MIC meropenem 0.25 mg/ liter) was studied in the hollow-fiber infection model (inoculum ϳ10 7.5 CFU/ml; 10 days). Pharmacokinetic profiles representing critically ill patients with augmented renal clearance (ARC), normal, or impaired renal function (creatinine clearances of 285, 120, or ϳ10 ml/min, respectively) were generated for three meropenem regimens (2, 1, and 0.5 g administered as 8-hourly 30-min infusions), plus 1 g given 12 hourly with impaired renal function. The time course of total and less-susceptible populations and MICs were determined. Mechanism-based modeling (MBM) was performed using S-ADAPT. All dosing regimens across all renal functions produced similar initial bacterial killing (Յϳ2.5 log 10 ). For all regimens subjected to ARC, regrowth occurred after 7 h. For normal and impaired renal function, bacterial killing continued until 23 to 47 h; regrowth then occurred with 0.5-and 1-g regimens with normal renal function (fT Ͼ5ϫMIC ϭ 56 and 69%, fC min /MIC Ͻ 2); the emergence of less-susceptible populations (Ն32-fold increases in MIC) accompanied all regrowth. Bacterial counts remained suppressed across 10 days with normal (2-g 8-hourly regimen) and impaired (all regimens) renal function (fT Ͼ5ϫMIC Ն 82%, fC min /MIC Ն 2). The MBM successfully described bacterial killing and regrowth for all renal functions and regimens simultaneously. Optimized dosing regimens, including extended infusions and/or combinations, supported by MBM and Monte Carlo simulations, should be evaluated in the context of ARC to maximize bacterial killing and suppress resistance emergence.

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Section: Methodsmentioning

confidence: 99%

“…However, the impact of a wide range of renal functions, including ARC, on bacterial killing and resistance emergence has not been quantified for meropenem. At present, clinicians still rely predominantly on the product information when selecting dosing regimens instead of adjusting the doses for patients with ARC (22,23).…”

mentioning

confidence: 99%

Substantial Impact of Altered Pharmacokinetics in Critically Ill Patients on the Antibacterial Effects of Meropenem Evaluated via the Dynamic Hollow-Fiber Infection Model

Bergen

Bulitta

Kirkpatrick

et al. 2017

Antimicrob Agents Chemother

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“…4,24 Hypothesized hospital-level factors contributing to variation in highly resistant microorganisms include differing infection prevention and control practices, antimicrobial use practices, hospital size, staffing (nurse ratios, infection prevention and/or hospital epidemiology staffing) and characteristics of the patient populations served. [25][26][27][28] All sites that contributed data to this study were located within academic/teaching hospitals, which suggests that the variability was not due to hospital teaching status. Rates of highly resistant microorganisms were lowest in Manitoba and Quebec (5% each) and highest in Alberta, British Columbia and Ontario (20%, 16% and 15%, respectively).…”

Section: Figurementioning

confidence: 99%

Pathogens and antimicrobial susceptibility profiles in critically ill patients with bloodstream infections: a descriptive study

Savage

Fowler

Rishu³

et al. 2016

CMAJ Open

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“…Sepsis has been a major health issue in the Australian Indigenous population and is associated with a high morbidity and mortality rate (2, Meropenem is a broad spectrum antibiotic commonly used in the ICU (335). Its PK/PD properties show a time dependent bacterial kill characteristic with a target of maintaining free drug concentration above the MIC for at least 40% of the dosing interval (>40%fT >MIC ) .…”

Section: Introductionmentioning

confidence: 99%

“…TDM is almost always utilised for vancomycin therapy in the ICU due to its narrow therapeutic window (335). Vancomycin exhibits a mixed concentration dependent and time dependent bacterial kill characteristic, that appears best represented by the AUC 0-24 :MIC (38), and the commonly accepted PK/PD target is an AUC 0-24 :MIC ratio of ≥400.…”

Section: Introductionmentioning

confidence: 99%

Improving antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis

Tsai¹

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Sepsis is a major health issue in the Australian Indigenous population. Unfortunately, the high rates of mortality and morbidity caused by sepsis or severe sepsis in this population have not significantly reduced over recent decades. Research into the role of optimisation of antibiotic therapy for improving patient outcomes is certainly an important area of need. In other patient populations, there is increasing evidence of an improvement of clinical cure rates and survival in patients with severe sepsis when antibiotic dosing results in therapeutic concentrations, that is, achieves pharmacokinetic/pharmacodynamic (PK/PD) targets. However, numerous PK changes caused by the altered physiology associated with critical illness may reduce the likelihood of such effective dosing.Previous studies have identified a number of physiological characteristics in the Australian Indigenous population which suggest that interethnic PK differences are likely in comparison with the non-Indigenous. As most PK data of antibiotics were obtained from healthy Caucasian volunteers, whether these data can be extrapolated to the critically ill Indigenous patients requires investigation.The aims of this thesis are to describe the PK of meropenem, ceftriaxone, vancomycin and piperacillin in severely septic Indigenous patients; compare the PK with existing data from nonIndigenous patients; design optimised dosing regimens for each of the study antibiotics; and quantify the variation in renal function of critically ill Indigenous patients. This thesis consists of nine Chapters:Chapter one provides an overview of the current clinical challenges encountered in antibiotic dosing in critically ill patients. It also discusses specific physiological characteristics of Australian Indigenous patients which may lead to different PK compared with non-Indigenous comparators.Chapter two comprises of a narrative review which discusses the PK/PD factors that should be considered when prescribing antibiotics to critically ill patients. This Chapter summarises data which describe an improvement in clinical outcome when antibiotics achieve PK/PD targets. ThisChapter concludes to support an individualised approach to dosing antibiotics as opposed to the 'one dose fits all' approach that is common to clinical practice.ii Chapter three incorporates a systematic review which investigates the published data describing differences in antibiotic PK between different ethnic groups. No reports on PK in Indigenous Australians were found. The predominant data described differences in PK between the Asian and Caucasian ethnicities. Typically, Asian subjects manifested higher antibiotic concentrations for antibiotics that have significant hepatic metabolism, are substrates to p-glycoprotein or other forms of active transport and/or have high alpha-1-acid glycoprotein binding.Chapter four incorporates a study which described the renal function of critically ill Australian Indigenous patients. This study found a numerically higher incidence of augmented renal clea...

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The ADMIN-ICU survey: a survey on antimicrobial dosing and monitoring in ICUs

Abstract: We found wide variability in reported practices for antibiotic dosing and monitoring. Research is required to develop evidence-based guidelines to standardize practices.

Cited by 113 publications

References 20 publications

Substantial Impact of Altered Pharmacokinetics in Critically Ill Patients on the Antibacterial Effects of Meropenem Evaluated via the Dynamic Hollow-Fiber Infection Model

Substantial Impact of Altered Pharmacokinetics in Critically Ill Patients on the Antibacterial Effects of Meropenem Evaluated via the Dynamic Hollow-Fiber Infection Model

Pathogens and antimicrobial susceptibility profiles in critically ill patients with bloodstream infections: a descriptive study

Improving antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis

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