Matthew Rawlins1, Vesa Cheng2, Edward Raby3, John Dyer3, Adrian Regli4, Paul Ingram3, Brett C McWhinney5, Jacobus P J Ungerer2,5, Jason A Roberts6,7,8,9. 1. Department of Pharmacy, Fiona Stanley Hospital, Perth, Washington, Australia. 2. University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. 3. Department of Infectious Diseases, Fiona Stanley Hospital, Perth, Washington, Australia. 4. Department of Intensive Care Medicine, Fiona Stanley Hospital, Perth, Washington, Australia. 5. Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. 6. University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australiaj.roberts2@uq.edu.au. 7. Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australiaj.roberts2@uq.edu.au. 8. Pharmacy Department, Royal Brisbane and Womens' Hospital, Brisbane, Queensland, Australiaj.roberts2@uq.edu.au. 9. Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australiaj.roberts2@uq.edu.au.
Abstract
BACKGROUND: Prolonged intermittent renal replacement therapy (PIRRT) eliminates many drugs, and without dosing data, for new antibiotics like ceftolozane/tazobactam, suboptimal concentrations and treatment failure are likely. OBJECTIVES: Herein, we describe the effect of PIRRT on the plasma pharmacokinetics of ceftolozane/tazobactam ad-ministered in a critically ill 55-year-old patient with a polymicrobial sternal wound osteomyelitis, including a multiresistant Pseudomonas aeruginosa. METHOD: Blood samples were taken over 4 days where the patient received a 7.5-h PIRRT treatment. One- and 2-compartment models were tested for ceftolozane and tazobactam separately, and the log-likelihood ratio and goodness-of-fit plots were used to select the final model. RESULTS: Two-compartment models were developed for ceftolozane and tazobactam separately and described significant differences in clearance of ceftolozane and tazobactam with and without PIRRT (8.273 vs. 0.393 and 8.020 vs. 0.767 L/h, respectively). CONCLUSIONS: A ceftolozane/tazobactam dose of 500 mg/250 mg appears to be sufficient to attain pharmacokinetic/pharmacodynamic targets during PIRRT while the manufacturer's recommended dosing of 100 mg/50 mg every 8 h was sufficient during non-PIRRT periods.
BACKGROUND: Prolonged intermittent renal replacement therapy (PIRRT) eliminates many drugs, and without dosing data, for new antibiotics like ceftolozane/tazobactam, suboptimal concentrations and treatment failure are likely. OBJECTIVES: Herein, we describe the effect of PIRRT on the plasma pharmacokinetics of ceftolozane/tazobactam ad-ministered in a critically ill 55-year-old patient with a polymicrobial sternal wound osteomyelitis, including a multiresistant Pseudomonas aeruginosa. METHOD: Blood samples were taken over 4 days where the patient received a 7.5-h PIRRT treatment. One- and 2-compartment models were tested for ceftolozane and tazobactam separately, and the log-likelihood ratio and goodness-of-fit plots were used to select the final model. RESULTS: Two-compartment models were developed for ceftolozane and tazobactam separately and described significant differences in clearance of ceftolozane and tazobactam with and without PIRRT (8.273 vs. 0.393 and 8.020 vs. 0.767 L/h, respectively). CONCLUSIONS: A ceftolozane/tazobactam dose of 500 mg/250 mg appears to be sufficient to attain pharmacokinetic/pharmacodynamic targets during PIRRT while the manufacturer's recommended dosing of 100 mg/50 mg every 8 h was sufficient during non-PIRRT periods.
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