Population pharmacokinetics and probability of target attainment of meropenem in critically ill patients

Mattioli, Francesca; Fucile, Carmen; Bono, Valerio Del; Marini, Valéria; Parisini, Andrea; Molin, Alexandre; Zuccoli, Maria Laura; Milano, Giulia; Danesi, Romano; Marchese, Anna; Polillo, Marialuisa; Viscoli, Claudio; Pelosi, Paolo; Martelli, Antonietta; Paolo, Antonello Di

doi:10.1007/s00228-016-2053-x

Cited by 67 publications

(43 citation statements)

References 38 publications

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“…A flowchart of study selection for each drug is provided in Figure . A total of 2082 articles were identified and screened, with 130 studies included in the final analysis . Some studies provided PK parameters for two drugs (e.g.…”

Section: Resultsmentioning

confidence: 99%

Scaling beta‐lactam antimicrobial pharmacokinetics from early life to old age

Lonsdale

Baker

Kipper

et al. 2018

Brit J Clinical Pharma

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Section: Resultsmentioning

confidence: 99%

Scaling beta‐lactam antimicrobial pharmacokinetics from early life to old age

Lonsdale

Baker

Kipper

et al. 2018

Brit J Clinical Pharma

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“…Although the population pharmacokinetics of meropenem was investigated in various patient populations (15)(16)(17)(18)(19), this is the first time that it was assessed during HDCI. The final model accounted for up to 94% of the variability in meropenem concentrations and adequately fitted the drug concentration-time data.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of High-Dose Continuous-Infusion Meropenem and Considerations for Use in the Treatment of Infections Due to KPC-Producing Klebsiella pneumoniae

Cojutti

Sartor

Righi

et al. 2017

Antimicrob Agents Chemother

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We assessed the population pharmacokinetics of high-dose continuous-infusion (HDCI) meropenem in a cohort of patients with carbapenemase (KPC)-producing (KPC-Kp) infections. Monte Carlo simulations were used to define the permissible HDCI meropenem regimens that could be safely considered for the treatment of KPC-Kp infections due to meropenem-resistant strains. Permissible doses were arbitrarily defined as those associated with a ≤10% to 15% likelihood of meropenem steady-state concentrations () of >100 mg/liter. Probabilities of target attainment (PTA) of four incremental pharmacodynamic determinants for meropenem efficacy (100% T, 100% T, 100% T, and 100% T, where "T" represents the time during which the plasma concentration of this time-dependent antibacterial agent is maintained above the MIC for the pathogen) in relation to different classes of renal function were calculated. The cumulative fractions of response (CFR) for the permissible HDCI meropenem regimens were calculated against the MIC distribution of the KPC-Kp clinical isolates that were collected routinely at our University Hospital between 2013 and 2016 ( = 169). Ninety-seven meropenem were included in the analysis. The final model included creatinine clearance (CrCL) as a covariate and explained 94% of the population variability. Monte Carlo simulations based on licensed dosages of up to 6 g/day predicted an acceptable PTA (>80%) of 100% T against KPC-Kp with a meropenem MIC of ≤32 mg/liter in patients with a CrCL level of <130 ml/min. Dosages of 8 g/day were needed for achieving the same target in patients with CrCL at levels of 130 to 200 ml/min. In dealing with pathogens with a meropenem MIC of 64 mg/liter, HDCI regimens using meropenem at higher than licensed levels should be considered. In these cases, real-time therapeutic drug monitoring could be a useful adjunct for optimized care. The predicted CFR were >75% in all of the classes of renal function.

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“…The general target population were and still are patients in acute care situations or those hospitalized for longer term care and treatment (e.g. [5]). A more advanced TDM practice, however, is emerging with an aim to ensure efficacy as well as minimizing toxicity of a broader spectrum of antibiotics with relatively wider therapeutic indices.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and medical needs for therapeutic drug monitoring of antibiotics

Mabilat

Gros

Nicolau

et al. 2019

Eur J Clin Microbiol Infect Dis

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Therapeutic drug monitoring (TDM) of antibiotics has been practiced for more than half a century, but it is still not widely applied for infected patients. It has a traditional focus on limiting toxicity of specific classes of antibiotics such as aminoglycosides and vancomycin. With more patients in critical care with higher levels of sickness severity and immunosuppression as well as an increasingly obese and ageing population, an increasing risk of suboptimal antibiotic exposure continues to escalate. As such, the value of TDM continues to expand, especially for beta-lactams which constitute the most frequently used antibiotic class. To date, the minimum inhibitory concentration (MIC) of infectious microbes rather than classification in terms of susceptible and resistant can be reported. In parallel, increasingly sophisticated TDM technology is becoming available ensuring that TDM is feasible and can deliver personalized antibiotic dosing schemes. There is an obvious need for extensive studies that will quantify the improvements in clinical outcome of individual TDM-guided dosing. We suggest that a broad diagnostic and medical investigation of the TDM arena, including market analyses and analytical technology assessment, is a current priority.

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Population pharmacokinetics and probability of target attainment of meropenem in critically ill patients

Abstract: Several factors may influence meropenem pharmacokinetics in ICU patients. Continuous i.v. infusions of meropenem seem to be more effective than standard regimens to achieve optimal therapeutic targets.

Cited by 67 publications

References 38 publications

Scaling beta‐lactam antimicrobial pharmacokinetics from early life to old age

Scaling beta‐lactam antimicrobial pharmacokinetics from early life to old age

Population Pharmacokinetics of High-Dose Continuous-Infusion Meropenem and Considerations for Use in the Treatment of Infections Due to KPC-Producing Klebsiella pneumoniae

Diagnostic and medical needs for therapeutic drug monitoring of antibiotics

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