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Optimizing ceftolozane-tazobactam dosage during continuous renal replacement therapy: additional insights
Critical Care volume 23, Article number: 406 (2019)
The original article was published in Critical Care 2019 23:145
The Letter to this article has been published in Critical Care 2020 24:11
We read the recent report by Aguilar et al., who concluded that among patients with nosocomial peritonitis who are on continuous renal replacement therapy (CRRT), ceftolozane-tazobactam (C/T) at a dose of 3 g every 8 h is safe . This finding was additional information following the notion that CRRT was an independent predictor of clinical failure when C/T was administered at 1.5 g every 8 h . The Aguilar et al. protocol included a short infusion time, i.e., 1 h . Previously described extended-infusion over 4 h was found to reach above the minimal inhibitory concentration (MIC), given that beta-lactam antibiotics exhibit time-dependent antibacterial activity . This might prevent underdosing during CRRT . Besides, the C/T elimination was explained by diffusion . However, adsorption was not assessed. The acrylonitrile 69 Multiflow (AN-69-M) membrane, used in this study, has a lower adsorptive capacity compared with the AN69 surface-treated (AN69-ST) membrane, which is considered a highly adsorptive membrane (HAM). In a recent comparison of polysulphone versus AN-69-M for C/T extraction by CRRT in an ex vivo model , there was no difference in adsorption. In a case report, a continuous infusion (CI) of 6 g in 24 h of C/T was used in a cystic fibrosis patient with a multidrug-resistant (MDR) Pseudomonas aeruginosa and augmented renal clearance to optimize time-dependent antibacterial activity . In this patient, therapeutic drug monitoring (TDM) confirmed adequate exposure . CI and TDM are two critical parameters when using C/T for patients receiving CRRT especially when MICs of bacteria like MDR P. aeruginosa are considered very high.
Availability of data and materials
Acrylonitrile 69 Multiflow
Continuous renal replacement therapy
Highly adsorptive membranes
Minimal inhibitory concentration
Aguilar G, Ferriols R, Martínez-Castro S, Ezquer C, Pastor E, Carbonell JA, Alós M, Navarro D. Optimizing ceftolozane-tazobactam dosage in critically ill patients during continuous venovenous hemodiafiltration. Crit Care. 2019;23(1):145. https://doi.org/10.1186/s13054-019-2434-5.
Mussini C, Righi E, Tascini C, et al. Ceftolozane/tazobactam for the treatment of serious P. aeruginosa infections: a multicenter nationwide clinical experience. Int J Antimicrob Agents. 2018;53(4):408–15. https://doi.org/10.1016/j.ijantimicag.2018.11.001 Epub 2018 Nov 8.
Oliver WD, Heil EL, Gonzales JP, Mehrotra S, Robinett K, Saleeb P, Nicolau DP. Ceftolozane-tazobactam pharmacokinetics in a critically ill patient on continuous venovenous hemofiltration. Antimicrob Agents Chemother. 2015;60(3):1899–901. https://doi.org/10.1128/AAC.02608-15.
Chaijamorn W, Shaw AR, Lewis SJ, Mueller BA. Ex vivo ceftolozane/tazobactam clearance during continuous renal replacement therapy. Blood Purif. 2017;44(1):16–23. https://doi.org/10.1159/000455897 Epub 2017 Feb 25.
Elizabeth Davis S, Ham J, Hucks J, Gould A, Foster R, Ann Justo J, Nicolau DP, Bookstaver PB. Use of continuous infusion ceftolozane-tazobactam with therapeutic drug monitoring in a patient with cystic fibrosis. Am J Health Syst Pharm. 2019;76(8):501–4. https://doi.org/10.1093/ajhp/zxz011.
We would like to thank Prof. Kianoush Kashani, MD, PhD, FCCP (Mayo Clinic, Rochester, USA) for critically reviewing the manuscript.
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Honore, P.M., Mugisha, A., Barreto Gutierrez, L. et al. Optimizing ceftolozane-tazobactam dosage during continuous renal replacement therapy: additional insights. Crit Care 23, 406 (2019) doi:10.1186/s13054-019-2692-2