Sofie A M Dhaese1, Alexander D J Thooft2, Andras Farkas3, Jeffrey Lipman4, Alain G Verstraete5, Veronique Stove6, Jason A Roberts7, Jan J De Waele8. 1. Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium. Electronic address: sofie.dhaese@ugent.be. 2. Ghent University, Ghent, Belgium. Electronic address: alexander.thooft@ugent.be. 3. Department of Pharmacy, Mount Sinai West Hospital, New York, United States. Electronic address: andras.farkas@mountsinai.org. 4. University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia. Electronic address: j.lipman@uq.edu.au. 5. Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium. Electronic address: alain.verstraete@ugent.be. 6. Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium. Electronic address: veronique.stove@uzgent.be. 7. University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia; Department of Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia; Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Australia. Electronic address: j.roberts2@uq.edu.au. 8. Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium. Electronic address: jan.dewaele@ugent.be.
Abstract
PURPOSE: To evaluate target attainment of empirically dosed continuous infusion piperacillin/tazobactam (TZP) and meropenem (MER) in critically ill patients. PATIENTS AND METHODS: Patients were sampled on a daily basis. TZP or MER concentrations were evaluated during the first two days antibiotic therapy. The lower limit of the target range was defined as unbound concentrations equaling 4 times the epidemiological cutoff value of P. aeruginosa. The upper limit of the target range was based on the risk of toxicity, i.e. unbound concentrations >160 mg/L for TZP and > 45 mg/L for MER. Multivariable logistic regression was used to evaluate factors associated with target attainment. RESULTS: Data from 253 patients were analyzed. Overall, 76/205 (37.1%) and 36/48 (75%) of the patients receiving TZP or MER respectively, attained target concentrations. In multivariable analysis, estimated creatinine clearance was identified as a risk factor for target non-attainment (OR 0.988, 95%CI [0.982;0.994]). Patients receiving MER were more likely to attain target concentrations compared with patients receiving TZP (OR 6.02, 95%CI [2.12;18.4]). CONCLUSION: Target attainment of empiric antibiotic therapy in critically ill patients was low (37%) for TZP and moderate (75%) for MER, despite the use of a loading dose and despite optimization of the mode of infusion.
PURPOSE: To evaluate target attainment of empirically dosed continuous infusion piperacillin/tazobactam (TZP) and meropenem (MER) in critically illpatients. PATIENTS AND METHODS: Patients were sampled on a daily basis. TZP or MER concentrations were evaluated during the first two days antibiotic therapy. The lower limit of the target range was defined as unbound concentrations equaling 4 times the epidemiological cutoff value of P. aeruginosa. The upper limit of the target range was based on the risk of toxicity, i.e. unbound concentrations >160 mg/L for TZP and > 45 mg/L for MER. Multivariable logistic regression was used to evaluate factors associated with target attainment. RESULTS: Data from 253 patients were analyzed. Overall, 76/205 (37.1%) and 36/48 (75%) of the patients receiving TZP or MER respectively, attained target concentrations. In multivariable analysis, estimated creatinine clearance was identified as a risk factor for target non-attainment (OR 0.988, 95%CI [0.982;0.994]). Patients receiving MER were more likely to attain target concentrations compared with patients receiving TZP (OR 6.02, 95%CI [2.12;18.4]). CONCLUSION: Target attainment of empiric antibiotic therapy in critically illpatients was low (37%) for TZP and moderate (75%) for MER, despite the use of a loading dose and despite optimization of the mode of infusion.
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