An innovative population pharmacokinetic/pharmacodynamic strategy for attaining aggressive joint PK/PD target of continuous infusion ceftazidime/avibactam against KPC- and OXA-48- producing Enterobacterales and preventing resistance development in critically ill patients DOI
Pier Giorgio Cojutti, Manjunath P. Pai, Milo Gatti

et al.

Journal of Antimicrobial Chemotherapy, Journal Year: 2024, Volume and Issue: 79(11), P. 2801 - 2808

Published: Aug. 19, 2024

Abstract Objectives Ceftazidime/avibactam is a key antibiotic for carbapenemase-producing Enterobacterales (CPE) Gram-negative infections, but current dosing may be suboptimal to grant activity. This study explores the population pharmacokinetics/pharmacodynamics (PK/PD) of continuous infusion (CI) ceftazidime/avibactam maximizing treatment efficacy in critically ill patients. Methods A retrospective analysis adult patients receiving CI and therapeutic drug monitoring (TDM) both compounds was performed. Population PK/PD modelling identified most accurate method estimating clearance based on kidney function Monte Carlo simulations investigated relationship between various regimens aggressive joint target attainment ceftazidime/avibactam. Results The European Kidney Function Consortium (EKFC) equation best described clearance. findings challenge approach only reducing dose by identifying adjustments with augmented function. Our strategies, adjusted TDM, showed promise achieving optimal targets potentially improving clinical/microbiological outcomes against KPC- OXA-48-producing Enterobacterales. risk neurotoxicity associated these strategies appears acceptable. Conclusions suggests that adjusting regimen solely eCLcr might Higher daily doses delivered TDM have potential improve outcomes. Further investigations are warranted confirm establish TDM-guided clinical practice.

Language: Английский

The Synergy of Machine Learning and Epidemiology in Addressing Carbapenem Resistance: A Comprehensive Review DOI Creative Commons
Aikaterini Sakagianni, Christina Koufopoulou,

Petros Koufopoulos

et al.

Antibiotics, Journal Year: 2024, Volume and Issue: 13(10), P. 996 - 996

Published: Oct. 21, 2024

Carbapenem resistance poses a significant threat to public health by undermining the efficacy of one last lines antibiotic defense. Addressing this challenge requires innovative approaches that can enhance our understanding and ability combat resistant pathogens. This review aims explore integration machine learning (ML) epidemiological understand, predict, carbapenem-resistant It examines how leveraging large datasets advanced computational techniques identify patterns, predict outbreaks, inform targeted intervention strategies.

Language: Английский

Citations

4
Utility of a TDM-Guided Expert Clinical Pharmacological Advice Program for Optimizing the Use of Novel Beta-Lactam/Beta-Lactamase Inhibitor Combinations and Cefiderocol in a Tertiary University Hospital: An Interim Analysis DOI
Milo Gatti, Pier Giorgio Cojutti, Matteo Rinaldi

et al.

Therapeutic Drug Monitoring, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Background: This study assessed the utility of a therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program to optimize aggressive pharmacokinetic/pharmacodynamic (PK/PD) target attainment novel beta-lactam/beta-lactamase inhibitor (BL/BLIc) combinations and cefiderocol. Methods: All hospitalized patients who received TDM-guided ECPA with BL/BLIc (ceftazidime–avibactam, ceftolozane–tazobactam, or meropenem–vaborbactam) cefiderocol were retrospectively. Three performance indicators identified: average number ECPAs delivered per month availability ratio between total recommending dosing adjustment ECPAs, at first subsequent TDM assessments. The relationships PK/PD microbiological outcomes assessed. Results: A 595 administered 263 319 treatment courses. Novel agents mostly used for targeted therapy (79.6%) by continuous infusion (CI; 82.8%). In assessment, dose increases required receiving intermittent/extended (II/EI) (51.9% vs. 6.4%; P < 0.0001), whereas decreases recommended CI (60.3% 23.1%; 0.001). assessments, overall proportion adjustments decreased in both groups (57.1% 39.3% II/EI groups, respectively). Aggressive was associated highest eradication rate ceftazidime–avibactam (79.6% out 86.0%; 0.001), cure (64.2% 78.1%; 0.001) (50.0% 51.5%; = 0.006). Conclusions: dedicated may be helpful optimizing use settings high prevalence multidrug-resistant pathogens.

Language: Английский

Citations

0
An innovative population pharmacokinetic/pharmacodynamic strategy for attaining aggressive joint PK/PD target of continuous infusion ceftazidime/avibactam against KPC- and OXA-48- producing Enterobacterales and preventing resistance development in critically ill patients DOI
Pier Giorgio Cojutti, Manjunath P. Pai, Milo Gatti

et al.

Journal of Antimicrobial Chemotherapy, Journal Year: 2024, Volume and Issue: 79(11), P. 2801 - 2808

Published: Aug. 19, 2024

Abstract Objectives Ceftazidime/avibactam is a key antibiotic for carbapenemase-producing Enterobacterales (CPE) Gram-negative infections, but current dosing may be suboptimal to grant activity. This study explores the population pharmacokinetics/pharmacodynamics (PK/PD) of continuous infusion (CI) ceftazidime/avibactam maximizing treatment efficacy in critically ill patients. Methods A retrospective analysis adult patients receiving CI and therapeutic drug monitoring (TDM) both compounds was performed. Population PK/PD modelling identified most accurate method estimating clearance based on kidney function Monte Carlo simulations investigated relationship between various regimens aggressive joint target attainment ceftazidime/avibactam. Results The European Kidney Function Consortium (EKFC) equation best described clearance. findings challenge approach only reducing dose by identifying adjustments with augmented function. Our strategies, adjusted TDM, showed promise achieving optimal targets potentially improving clinical/microbiological outcomes against KPC- OXA-48-producing Enterobacterales. risk neurotoxicity associated these strategies appears acceptable. Conclusions suggests that adjusting regimen solely eCLcr might Higher daily doses delivered TDM have potential improve outcomes. Further investigations are warranted confirm establish TDM-guided clinical practice.

Language: Английский

Citations

2