Optimizing ceftolozane-tazobactam dosage in critically ill patients during continuous venovenous hemodiafiltration

• Published in: Critical care (London, England) England), 2019-04, Vol.23 (1), p.145-3, Article 145
• Main Authors: Aguilar, Gerardo, Ferriols, Rafael, Martínez-Castro, Sara, Ezquer, Carlos, Pastor, Ernesto, Carbonell, José A, Alós, Manuel, Navarro, David
• Format: Article
• Language: English
• Subjects: Acute kidney failure; Aged; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics; Beta lactamases; Cephalosporins; Cephalosporins - administration & dosage; Cephalosporins - pharmacology; Cephalosporins - therapeutic use; Chromatography; Combination drug therapy; Critical care; Critical Illness - therapy; Critically ill persons; Dosage and administration; Dose-Response Relationship, Drug; Drug dosages; Drug therapy; Hemofiltration; Hemofiltration - methods; Humans; Kidney failure; Letter; Male; Methods; Patients; Peritonitis; Renal replacement therapy; Septic shock; Shock; Tazobactam; Tazobactam - administration & dosage; Tazobactam - pharmacology; Tazobactam - therapeutic use
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1366-609X
• DOI: 10.1186/s13054-019-2434-5

(The figure is original for this article) Table 1 Concentrations of ceftolozane and tazobactam in pre-filter and post-filter plasma samples obtained after the fourth dose of 2 g/1 g ceftolozane-tazobactam administered as intravenous 1-h infusion Sampling time Ceftolozane (mg/L) Tazobactam (mg/L) Pre-filter Post-filter Pre-filter Post-filter 0 h (pre dose) 41.9 20.7 10.6 5.8 1.5 h post dose 89.1 45.2 28.3 12.2 2 h post dose 80.3 38.4 21.6 10.3 2.5 h post dose 77.1 36.1 19.0 9.0 3 h post dose 73.8 34.7 16.3 8.2 5 h post dose 66.6 30.6 14.2 7.4 7 h post dose 60.2 28.7 12.7 6.0 8 h post dose 55.8 25.8 11.4 5.1 Table 2 Pharmacokinetic parameters of ceftolozane and tazobactam Parameter Ceftolozane Tazobactam Pre-filter Post-filter Pre-filter Post-filter Clearance (L/h) 2.1 5.4 6.4 17.4 Volume of distribution (L) 53.9 97.5 108.9 194.2 Half-life (h) 17.9 12.6 11.9 7.8 AUC (h mg/L) 960 373 157 57.6 Maximum concentration (mg/L) 99 53 37 14.5 Minimum concentration (mg/L) 55.9 25.8 11.4 5.1 AUC area under the concentration-time curve We decided on a 3 g/iv dose every 8 h, taking into account two previous studies [3, 4] and a recent study which showed CRRT to be an independent predictor of clinical failure (OR 4.5, 95% CI 1.18–17.39, p = 0.02) when C/T is administered at 1.5 g every 8 h [5]. [...]our data underscore that a dosage of 3 g every 8 h can be used safely to prevent the potential harm of underdosing ceftolozane/tazobactam during CRRT; larger studies are however needed to confirm our findings. Ethics approval and consent to participate The study protocol (TC-TCRR-2018) was approved by the local ethics committee (INCLIVA Health Research Institute) and written informed consent obtained from the patients or their relatives prior to study inclusion.