BACKGROUND/AIMS: To determine ceftolozane/tazobactam transmembrane clearances (CLTM) in continuous hemofiltration (CHF) and continuous hemodialysis (CHD) and to determine optimal ceftolozane/tazobactam dosing regimens for patients receiving continuous renal replacement therapy (CRRT). METHOD: Validated, ex vivo CHF and CHD bovine blood models using polysulfone (HF1400) and AN69 (Multiflow 150-M) hemofilters were used to evaluate adsorption and CLTM at different effluent flow rates. Monte Carlo simulations (MCS) using pharmacokinetic parameters from published studies and CLTM from this study were used to generate ceftolozane/tazobactam dosing for patients receiving CRRT. RESULTS: CHF and CHD CLTM did not differ at equivalent effluent rates. CLTM approximated effluent flow rates. No adsorption of ceftolozane/tazobactam occurred for either hemofilter. Effluent flow was the most important determinant of MCS-derived doses. CONCLUSION: CRRT clearances of ceftolozane/tazobactam depended on effluent flow rates but not hemofilter types. MCS-derived ceftolozane/tazobactam doses of 750 (500/250)-1,500 (1,000/500) mg every 8 h met pharmacodynamic targets for virtual patients receiving CRRT at contemporary effluent rates.
BACKGROUND/AIMS: To determine ceftolozane/tazobactam transmembrane clearances (CLTM) in continuous hemofiltration (CHF) and continuous hemodialysis (CHD) and to determine optimal ceftolozane/tazobactam dosing regimens for patients receiving continuous renal replacement therapy (CRRT). METHOD: Validated, ex vivo CHF and CHD bovine blood models using polysulfone (HF1400) and AN69 (Multiflow 150-M) hemofilters were used to evaluate adsorption and CLTM at different effluent flow rates. Monte Carlo simulations (MCS) using pharmacokinetic parameters from published studies and CLTM from this study were used to generate ceftolozane/tazobactam dosing for patients receiving CRRT. RESULTS:CHF and CHD CLTM did not differ at equivalent effluent rates. CLTM approximated effluent flow rates. No adsorption of ceftolozane/tazobactam occurred for either hemofilter. Effluent flow was the most important determinant of MCS-derived doses. CONCLUSION: CRRT clearances of ceftolozane/tazobactam depended on effluent flow rates but not hemofilter types. MCS-derived ceftolozane/tazobactam doses of 750 (500/250)-1,500 (1,000/500) mg every 8 h met pharmacodynamic targets for virtual patients receiving CRRT at contemporary effluent rates.
Authors: Fekade B Sime; Melissa Lassig-Smith; Therese Starr; Janine Stuart; Saurabh Pandey; Suzanne L Parker; Steven C Wallis; Jeffrey Lipman; Jason A Roberts Journal: Antimicrob Agents Chemother Date: 2020-12-16 Impact factor: 5.191
Authors: Laura Butragueño-Laiseca; Iñaki F Troconiz; Santiago Grau; Nuria Campillo; Xandra García; Belén Padilla; Sarah N Fernández; María José Santiago Journal: Antibiotics (Basel) Date: 2020-12-10
Authors: Fekade B Sime; Saurabh Pandey; Nermin Karamujic; Suzanne Parker; Elizabeth Alexander; Jeffery Loutit; Stephanie Durso; David Griffith; Jeffrey Lipman; Steven C Wallis; Jason A Roberts Journal: Antimicrob Agents Chemother Date: 2018-09-24 Impact factor: 5.191
Authors: Fekade B Sime; Melissa Lassig-Smith; Therese Starr; Janine Stuart; Saurabh Pandey; Suzanne L Parker; Steven C Wallis; Jeffrey Lipman; Jason A Roberts Journal: Antimicrob Agents Chemother Date: 2019-12-20 Impact factor: 5.191
Authors: M G Vossen; S Pferschy; C Milacek; M Haidinger; Mario Karolyi; Zoltan Vass; Heinz Burgmann; Alexandra Maier-Salamon; S G Wicha; W Jäger; M Zeitlinger; T Stimpfl; T Wittek; F Thalhammer Journal: Front Pharmacol Date: 2021-06-24 Impact factor: 5.810