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Thrombocytopenia risks in ARDS COVID-19 patients treated with high-dose linezolid during vvECMO therapy: an observational study

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Abstract

Patients treated with ECMO are at great risk of nosocomial infections, and around 10% of isolates are gram-positive pathogens. Linezolid (LZD) is effective in the treatment of these infections but appropriate dosing is challenging. The aim was to evaluate the occurrence of thrombocytopenia during ECMO when treated with LZD. An LZD trough concentration of 8 mg/L was set as the cutoff value for thrombocytopenia occurrence among critically ill patients who received parenteral LZD therapy at a dose of 600 mg every 8 h during ECMO. Eleven patients were included in this prospective observational study. Median LZD trough concentrations were 7.85 (interquartile range (IQR), 1.95-11) mg/L. Thrombocytopenia was found in 81.8% of patients. Based on the median LZD trough concentrations cutoff value, patients were divided into two groups, 1.95 (IQR, 0.91–3.6) and 10.3 (IQR, 9.7–11.7) mg/L, respectively. Median platelet values differed significantly between groups on admission, ECMO day 0, ECMO day 1, and LZD sampling day [194 and 152.5, (p < 0.05)], [113 and 214, (p < 0.05)], [76 and 147.5, (p < 0.01)], and [26 and 96.5, (p < 0.01)], respectively. Duration of LZD therapy was similar between the groups. Significant platelet reduction was observed in both groups, emphasizing the need for closer monitoring to prevent LZD-associated thrombocytopenia.

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Acknowledgements

This study was conducted in low-resource settings during the COVID-19 pandemic, a time of extreme challenges for hospitals, medical staff, and patients. Therefore, the authors would like to acknowledge the Medical Intensive Care Unit at the University Clinical Centre of the Republic of Srpska, Banja Luka, for providing an excellent environment and facilities to conduct this research under these extreme conditions.

Funding

This research was funded by the Ministry of Education, Science and Technological Development, Republic of Serbia through Grant Agreement with University of Belgrade-Faculty of Pharmacy No: 451–03-47/2023–01/200161. In 2022, a research grant support was approved for this study by the Zoll Foundation.

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Authors and Affiliations

  1. Medical Intensive Care Unit, University Clinical Centre of the Republic of Srpska, Dvanaest Beba Bb, 78000, Banja Luka, The Republic of Srpska, Bosnia and Herzegovina

    Pedja Kovacevic, Dragana Milakovic, Tijana Kovacevic, Vedrana Barisic, Sasa Dragic & Biljana Zlojutro

  2. Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, 78000, Banja Luka, Bosnia and Herzegovina

    Pedja Kovacevic, Tijana Kovacevic, Vedrana Barisic, Sasa Dragic & Biljana Zlojutro

  3. Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade Faculty of Pharmacy, Vojvode Stepe 40, 11221, Belgrade, Republic of Serbia

    Branislava Miljkovic & Katarina Vucicevic

  4. Department of Pharmacy, Mayo Clinic, Rochester, USA

    Zeeshan Rizwan

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  1. Pedja Kovacevic
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Contributions

PK and DM were responsible for the study design. PK, KV, and ZR critically reviewed the study proposal. VB, SD, and BZ: original draft preparation. DM, TK, BM, DM, SD, and BZ performed research and data collection. All authors were involved in writing the manuscript, and read and approve the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Pedja Kovacevic.

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Ethics approval and consent to participate

The study protocol was approved by the Ethics Committee of University Clinical Centre of the Republic of Srpska (approval no.: 01–19-651–2/20). All procedures performed in study were in accordance with the ethical standards of the institution. Written informed consent was obtained from the patient or patient representative under consent procedure.

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Keypoints

• Higher doses of linezolid, proposed during vvECMO treatment, are significantly associated with the precipitation of thrombocytopenia (LZD-associated thrombocytopenia) in patients with ARDS related to COVID-19 who are treated with vvECMO.

• While other risk factors in this population can contribute to thrombocytopenia, they do so to a significantly lesser extent than linezolid itself.

• The introduction of TDM and the individualization of antimicrobial therapy in critically ill patients treated with vvECMO in a low-resource setting represent a key intervention.

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Kovacevic, P., Milakovic, D., Kovacevic, T. et al. Thrombocytopenia risks in ARDS COVID-19 patients treated with high-dose linezolid during vvECMO therapy: an observational study. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03136-1

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