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Optimizing ceftolozane-tazobactam dosage during continuous renal replacement therapy: additional insights

  • 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 [1]. 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 [2]. The Aguilar et al. protocol included a short infusion time, i.e., 1 h [1]. 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 [3]. This might prevent underdosing during CRRT [3]. Besides, the C/T elimination was explained by diffusion [1]. 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 [4], 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 [5]. In this patient, therapeutic drug monitoring (TDM) confirmed adequate exposure [5]. 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.

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Abbreviations

AN-69-M:

Acrylonitrile 69 Multiflow

AN-69-ST:

AN69-surface treated

C/T:

Ceftolozane-tazobactam

CI:

Continuous infusion

CRRT:

Continuous renal replacement therapy

HAM:

Highly adsorptive membranes

MDR:

Multi-drug resistant

MIC:

Minimal inhibitory concentration

References

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    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.

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    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.

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    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.

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    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.

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    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.

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Acknowledgements

We would like to thank Prof. Kianoush Kashani, MD, PhD, FCCP (Mayo Clinic, Rochester, USA) for critically reviewing the manuscript.

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PMH and DDB designed the paper. All authors participated in the drafting and reviewing. All authors read and approved the final version of the manuscript.

Correspondence to Patrick M. Honore.

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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). https://doi.org/10.1186/s13054-019-2692-2

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