Open Access

Absence of obvious link between supra-therapeutic serum levels of β lactams and clinical toxicity in ICU patients with acute renal failure treated with intermittent hemodialysis

  • Faten May1, 7Email author,
  • Najouah El-Helali2,
  • Jean-François Timsit3, 4, 5 and
  • Benoît Misset1, 6
Critical Care201620:220

https://doi.org/10.1186/s13054-016-1394-2

Received: 10 June 2016

Accepted: 27 June 2016

Published: 1 August 2016

The Letter to this article has been published in Critical Care 2016 20:350

Early and adequate antibiotic therapy increases the likelihood of survival in intensive care unit (ICU) patients with sepsis [1]. Beta-lactams (BL) are the most frequently prescribed antibiotics because of their broad spectrum and low toxicity [2]. Supra-therapeutic serum levels have been suggested to be associated with clinical toxicity, mainly neurological. In the clinical settings, determining the optimal dosage is not obvious because it should take into account the distribution volume and renal elimination, both being highly variable among septic patients [3]. Consequently, serum levels of BL are unpredictable during acute renal failure (ARF) and renal replacement therapy (RRT).

To describe the prevalence of supra-therapeutic BL serum levels in septic ICU patients requiring RRT and their link with toxicity we conducted an observational retrospective cohort study. We included consecutive patients who had been sampled for a BL trough serum level assessment within 7 days of sepsis and 3 days after intermittent dialysis. Sera were sampled before the next administration in case of intermittent infusion, and at 24 h in case of continuous infusion. Table 1 shows the thresholds used and the distribution of the observed trough levels for each BL.
Table 1

Antibiotics assessed, thresholds used, and trough serum levels (mg/l)

 

Upper therapeutic trough levela

Observed trough level median (interquartile range)

Piperacillin

20

77 (44–109)

Tazobactam

5

13 (6–20)

Cloxacillin

20

60 (35–103)

Amoxicillin

20

31 (19–42)

Imipenem

3

3 (1.1–4.2)

Clavulanate

0.5

2 (1.3–3.6)

Ceftazidim

20

71 (49–87)

Cefepime

10

27 (16–47)

a Five times bacterial modal minimal inhibitory concentration [4, 5]

We included 108 patients, who developed 180 episodes of sepsis and were sampled 460 times. Their median Simplified Acute Physiology Score (SAPS) II was 53 (39–66) points. Seventy-four percent of the patients required vasopressors, and the overall mortality rate in the ICU was 58 %. Piperacillin (25 %), tazobactam (20 %), and cloxacillin (18 %) were the most assayed antibiotics. The distribution of the serum levels was scattered (Table 1). A supra-therapeutic serum level for at least one BL was observed in 96/108 (89 %) patients and 156/180 (86 %) septic events. A level in the highest quartile was observed for at least one BL in 54/108 (50 %) patients and 80/180 (45 %) septic events. Supra-therapeutic serum levels of piperacillin, tazobactam, and cloxacillin were observed in 66, 55, and 31, and were in the highest quartile in 33, 23, and 14 septic events, respectively. Using a univariate logistic marginal regression model to account for the correlation of successive infections in the same patient, we did not observe a statistical link between serum overdose and convulsions (n = 8; odds ratio 1.68 (0.15–18.9); p = 0.67) and mortality (n = 40; odds ratio 1.28 (0.38–4.33); p = 0.69).

Supra-therapeutic serum levels of BL antibiotics are commonly observed in our ICU patients with ARF and RRT. We could not find an association between supra-therapeutic levels and clinical toxicity.

Abbreviations

ARF, acute renal failure; BL, beta-lactams; ICU, intensive care unit; RRT, renal replacement therapy

Notes

Declarations

Authors’ contributions

All authors read and approved the final manuscript.

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

The collection and use of data from the Outcomerea database was approved by the Clermond-Ferrand Hospital Institutional Review Board (CECIC, IRB 5891) and by the Pitié-Salpêtrière Hospital Ethics Committee, which waived the need for informed consent for patients included in the database.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Medical Surgical ICU, Groupe Hospitalier Paris Saint Joseph, Service de Médecine Intensive et Réanimation
(2)
Clinical Microbiology Unit, Saint-Joseph Hospital Network
(3)
Department of Biostatistics, Outcomerea
(4)
Medical ICU, Bichat hospital, Assistance Publique-Hôpitaux de Paris
(5)
Infection, Antimicrobials, Modelling, Evolution (IAME), UMR 1137, INSERM and Paris Diderot University, Department of Biostatistics - HUPNVS. - AP-HP, UFR de Médecine, Bichat University Hospital
(6)
Paris Descartes University
(7)
Groupe hospitalier Paris Saint Joseph, Service de médecine intensive et réanimation

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Copyright

© The Author(s). 2016

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