Skip to main content
  • Correspondence
  • Open access
  • Published:

No evidence for relevant impact of renal replacement therapy on clinical effect of erythromycin in critically ill patients with sepsis

The Original Article was published on 07 February 2023

The Original Article was published on 24 May 2022

We appreciate the insightful comments by Prof. Honoré and colleagues regarding our target trial emulation on the effect of erythromycin in critically ill patients with sepsis [1, 2]. Prof. Honoré and colleagues suggest that, in theory, removal of erythromycin from the circulation by renal replacement therapy (RRT) could dilute the potential effect of erythromycin, and that it may therefore be necessary to exclude patients undergoing RRT.

To test their hypothesis, we reanalysed our data after excluding patients that received RRT within 72 h of ICU admission (the exposure period) and considered RRT initiated > 72 h after admission as a secondary outcome (these patients were not excluded to avoid immortal time bias and selection bias). After excluding 43/235 (18.3%) erythromycin-treated patients and 75/470 (16.0%) control patients, 192 patients remained in the erythromycin group and 395 patients in the control group (Additional file 1: Table S1). When compared with the original study population [2], this subpopulation was similar in terms of baseline demographics, comorbidities and chronic medications, but demonstrated lower disease severity (e.g. APACHE-IV score in the original erythromycin group mean [standard deviation] 90.9 [28.5], new erythromycin group 84.8 [24.1]; in the original control group 85.0 [28.4], new control group 81.4 [26.9]). Within this subpopulation, the number of patients receiving RRT > 72 h after admission was low and not different between groups: 13/192 (6.8%) in the erythromycin group and 26/395 (6.6%) in the control group. Propensity score (PS) matching and (inverse probability of treatment) weighting resulted in well-balanced groups. After matching and weighting, we found no differences in mortality rate up to 90 days: matching HR 0.87 (95% confidence interval [CI] 0.59–1.26), weighting HR 0.91 (95% CI 0.60–1.37) nor in secondary clinical outcomes (aside from a slightly longer ICU length of stay in the erythromycin group in the weighted analysis; P = 0.025).

Thus, in our study, RRT does not appear to impact the effect of erythromycin on 90-day mortality to a clinically relevant degree. We would like to emphasize that the pharmacokinetics of macrolide antibiotics in the critically ill are complex, understudied, and affected by other factors, such as accumulation in white blood cells (which are not removed by RRT) [3, 4]. We would very much welcome new studies aimed at better characterizing the pharmacokinetics of macrolide antibiotics in critically ill patients, including the possible elimination by RRT—particularly if these studies also attempt to quantify minimum dosages needed to achieve measurable immunomodulatory effects.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.



Acute physiology and chronic health evaluation IV


Confidence interval


Hazard ratio


Intensive care unit


Propensity score


Renal replacement therapy


  1. Honore PM, Blackman S, Perriens E, Bousbiat I. Study claiming target in sepsis with erythromycin has no effect upon mortality and secondary outcomes includes patients with CRRT and RRT. Critical Care 2023 27:1. 2023;27:1–2.

  2. Reijnders TDY, Peters-Sengers H, van Vught LA, Uhel F, Bonten MJM, Cremer OL, et al. Effect of erythromycin on mortality and the host response in critically ill patients with sepsis: a target trial emulation. Crit Care. 2022;26:1–15.

    Article  Google Scholar 

  3. Pea F, Viale P, Furlanut M. Antimicrobial therapy in critically Ill patients. Clin Pharmacokinet. 2005;44:1009–34.

    Article  CAS  PubMed  Google Scholar 

  4. Pea F. Intracellular pharmacokinetics of antibacterials and their clinical implications. Clin Pharmacokinet. 2018;57:177–89.

    Article  CAS  PubMed  Google Scholar 

Download references


The MARS project was performed within the framework of the Center for Translational Molecular Medicine (CTMM;; grant 04I-201). TDYR is supported by research program ‘NACTAR’, project ‘MDR-phage’ (grant number 16447) which is financed by the Dutch research council (NWO). HPS is supported by the Dutch Kidney Foundation (Kolff Grant 19OK009). The funders had no role in the data analysis or the decision to publish.

Author information

Authors and Affiliations



TDYR, HPS, and TvdP contributed to the design of the analyses. TDYR performed the statistical analyses and drafted the manuscript. All authors contributed to careful reviewing and editing of the manuscript content. All authors approved the final manuscript.

Corresponding author

Correspondence to Tom D. Y. Reijnders.

Ethics declarations

Ethical approval and consent to participate

All patients were included via an opt-out consent procedure approved by the institutional medical ethics committees of both participating hospitals (Amsterdam University Medical Center, location AMC, Amsterdam; University Medical Center Utrecht, Utrecht, IRB No. 10-056C).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1

. Supplementary Table 1. Baseline characteristics and clinical outcomes.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reijnders, T.D.Y., Peters-Sengers, H. & van der Poll, T. No evidence for relevant impact of renal replacement therapy on clinical effect of erythromycin in critically ill patients with sepsis. Crit Care 27, 70 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: