We have read the recent letter by Honore et al. [1] about our findings published in this journal regarding the influence of continuous renal replacement therapy (CRRT) on the pharmacokinetics of ceftolozane-tazobactam (C/T) [2]. In our report, we decided to administer a 3 g/iv dose every 8 h taking into account two previous studies referenced in our paper [2] and another one 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 [3].
As Honore et al. explain in their paper, the C/T eliminitation was assumed by hemodiafiltration and the adsorption was not assessed [1]. However, there is a misunderstanding in this letter [1], because we used a polysulphone membrane (Fresenius, Germany) instead of an acrylonitrile 69 Multiflow (AN-69-M). In contrast to highly adsorptive membranes (HAM; e.g., AN69 surface-treated, AN69-ST), the antibiotic adsorption with polysulphone ones is negligible, which facilitates antibiotic adaptation during CRRT [4].
Our data should not be extrapolated to other clinical scenarios, as noted by Honore et al. [1]. In our report, ceftolozane and tazobactam plasma concentrations remained above the minimal inhibitory concentration (MIC), for MICs of up to 8 μg/mL, but we estimated that the administration of standard doses of 1 g/0.5 g, even with polysulphone membranes, could compromise the effectiveness of C/T for not reaching adequate tazobactam concentrations. Thus, the use of HAM would represent a real risk factor of clinical failure when a C/T dose of 1.5 g every 8 h is administered, especially in multidrug-resistant infections [3]. Therefore, we agree with Honore et al. [1] that therapeutic drug monitoring (TDM) is critical when using C/T for patients receiving CRRT, especially when MICs of bacteria like multidrug-resistant (MDR) Pseudomonas aeruginosa are considered very high. However, the recommendation of continuous (over 24 h) vs extended (over 2 to 4 h) or intermittent (over 30 to 60 min) infusion of beta-lactams is still under debate [5].
Acknowledgements
None
Abbreviations
- AN-69-M
Acrylonitrile 69 Multiflow
- AN-69-ST
AN69-surface treated
- C/T
Ceftolozane-tazobactam
- CRRT
Continuous renal replacement therapy
- HAM
Highly adsorptive membranes
- MDR
Multidrug-resistant
- MIC
Minimal inhibitory concentration
Authors’ contributions
GA, RF, and DN designed the paper. All authors participated in drafting and reviewing the manuscript. All authors read and approved the final version of the manuscript.
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The authors declare that they have no competing interests.
Footnotes
This reply refers to the comment available at: 10.1186/s13054-019-2692-2.
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Contributor Information
Gerardo Aguilar, Email: gerardo.aguilar@uv.es.
Rafael Ferriols, Email: rafael.ferriols@uv.es.
Sara Martínez-Castro, Email: saradacuris@hotmail.com.
Carlos Ezquer, Email: cezquer@incliva.es.
Ernesto Pastor, Email: ernesto.pastormz@gmail.com.
Jose A. Carbonell, Email: joseacarbonell19@gmail.com
Manuel Alós, Email: manuel.alos@uv.es.
David Navarro, Email: david.navarro@uv.es.
References
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