María Eugenia Navarrete-Rouco1, Sònia Luque2,3,4,5, Luisa Sorlí6,7,8,9,10, Adela Benítez-Cano6,11, Jason A Roberts12,13,14, Santiago Grau1,6,7,8,10. 1. Pharmacy Department, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. 2. Pharmacy Department, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. sluque@psmar.cat. 3. Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain. sluque@psmar.cat. 4. Spanish Network for Research in Infectious Diseases (REIPI), Madrid, Spain. sluque@psmar.cat. 5. CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain. sluque@psmar.cat. 6. Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain. 7. Spanish Network for Research in Infectious Diseases (REIPI), Madrid, Spain. 8. CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain. 9. Infectious Diseases Department, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. 10. Universitat Pompeu Fabra (UPF), Barcelona, Spain. 11. Department of Anaesthesiology and Surgical Intensive Care, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. 12. University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia. 13. Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia. 14. Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France.
Abstract
BACKGROUND AND OBJECTIVE: Prolonged infusion of ceftolozane/tazobactam (C/T) is a strategy used to increase achievement of pharmacokinetic/pharmacodynamic targets for the treatment of multi- or extensively drug-resistant MDR/XDR Gram-negative microorganisms. The objective of this study was to describe our therapeutic drug monitoring (TDM) experience of C/T administered by prolonged infusion or intermittent infusion to patients with MDR/XDR Pseudomonas aeruginosa infections. Our outcomes of interest were pharmacokinetic/pharmacodynamic target achievement and clinical cure. METHODS: Patients with MDR/XDR P. aeruginosa infections treated with C/T were enrolled between February 2018 and February 2020. Blood samples were obtained as part of a TDM program. The pharmacokinetic/pharmacodynamic therapeutic target of C/T was defined as 100% of the duration of the dosing interval that free concentrations are above the minimum inhibitory concentration (MIC) (100 %ƒT ≥ MIC) of the causative pathogen. Dose changes were performed according to TDM results. RESULTS: Forty patients were included: 13 (32.5%) with a proven MDR and 27 (67.5%) with a XDR P. aeruginosa infection. C/T was administered by prolonged infusion in 32 (80%) patients and by intermittent infusion in 8 (20%) patients. Lower doses were administered in the prolonged infusion compared to the intermittent infusion group [3 (9.4%) vs. 5 (62.5%] patients received a dose of 9 g/day (ceftolozane 2 g + tazobactam 1 g, every 8 h; p = 0.004). All patients achieved the pharmacokinetic/pharmacodynamic target and C/T concentrations exceeded 10 × MIC in > 50% of patients in both groups. TDM-recommended dose reductions occurred in 19 (47.5%) patients, being 16 (84.2%) in the prolonged infusion group. A high proportion of patients achieved clinical cure (82.5%). CONCLUSIONS: The administration of C/T by prolonged infusion with TDM-guided dosing allowed the achievement of a pharmacokinetic/pharmacodynamic target even at lower doses. C/T showed a high efficacy for treating MDR/XDR P. aeruginosa infections.
BACKGROUND AND OBJECTIVE: Prolonged infusion of ceftolozane/tazobactam (C/T) is a strategy used to increase achievement of pharmacokinetic/pharmacodynamic targets for the treatment of multi- or extensively drug-resistant MDR/XDR Gram-negative microorganisms. The objective of this study was to describe our therapeutic drug monitoring (TDM) experience of C/T administered by prolonged infusion or intermittent infusion to patients with MDR/XDR Pseudomonas aeruginosa infections. Our outcomes of interest were pharmacokinetic/pharmacodynamic target achievement and clinical cure. METHODS: Patients with MDR/XDR P. aeruginosa infections treated with C/T were enrolled between February 2018 and February 2020. Blood samples were obtained as part of a TDM program. The pharmacokinetic/pharmacodynamic therapeutic target of C/T was defined as 100% of the duration of the dosing interval that free concentrations are above the minimum inhibitory concentration (MIC) (100 %ƒT ≥ MIC) of the causative pathogen. Dose changes were performed according to TDM results. RESULTS: Forty patients were included: 13 (32.5%) with a proven MDR and 27 (67.5%) with a XDR P. aeruginosa infection. C/T was administered by prolonged infusion in 32 (80%) patients and by intermittent infusion in 8 (20%) patients. Lower doses were administered in the prolonged infusion compared to the intermittent infusion group [3 (9.4%) vs. 5 (62.5%] patients received a dose of 9 g/day (ceftolozane 2 g + tazobactam 1 g, every 8 h; p = 0.004). All patients achieved the pharmacokinetic/pharmacodynamic target and C/T concentrations exceeded 10 × MIC in > 50% of patients in both groups. TDM-recommended dose reductions occurred in 19 (47.5%) patients, being 16 (84.2%) in the prolonged infusion group. A high proportion of patients achieved clinical cure (82.5%). CONCLUSIONS: The administration of C/T by prolonged infusion with TDM-guided dosing allowed the achievement of a pharmacokinetic/pharmacodynamic target even at lower doses. C/T showed a high efficacy for treating MDR/XDR P. aeruginosa infections.
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