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European Journal of Clinical Pharmacology

, Volume 74, Issue 8, pp 1091–1092 | Cite as

Higher than standard meropenem and linezolid dosages needed for appropriate treatment of an intracerebral hemorrhage patient with augmented renal clearance

  • Pier Giorgio Cojutti
  • Cristina Barbarino
  • Amato De Monte
  • William Hope
  • Federico Pea
Letter to the Editor
  • 181 Downloads

A 57-year-old, 49 kg female was admitted at the Emergency Department after severe intracerebral hemorrhage. Head CT-scan revealed rupture of a saccular aneurysm of the right middle cerebral artery. External ventricular drain (EVD) was placed in the right lateral ventricle to treat hydrocephalus, and endovascular coiling of the cerebral aneurysm was performed.

On day 3, an EVD-related infection was suspected [C-reactive protein (C-RP) of 82.56 mg/L, normal range 0–5 mg/L; and pro-calcitonin (PCT) of 0.87 ng/mL, normal range < 0.10 ng/mL], and empirical antimicrobial therapy was started intravenously with cefotaxime 2 g q8h. On day 8, C-RP was 110.03 mg/L, and antimicrobial therapy was escalated to meropenem [500 mg q6h over 6 h (i.e., by continuous infusion, CI) after 2 g loading] plus linezolid (600 mg q12h intravenously).

Despite escalated therapy, C-RP increased furtherly and peaked on day 13 (241.47 mg/L). Therapeutic drug monitoring (TDM) was performed for assessing drug exposure...

Notes

Transparency declaration

W. H. holds or has recently held research grants with F2G, AiCuris, Astellas Pharma, Spero Therapeutics, Matinas Biosciences, Antabio, Amplyx, Allecra, Auspherix and Pfizer and he holds awards from the National Institutes of Health, Medical Research Council, National Institute of Health Research, FDA and the European Commission (FP7 and IMI). W. H. acted as a consultant for F2G, Amplyx, Ausperix, Spero Therapeutics, Medicines Company, Gilead and Basilea in the past 3 years, and he is an Ordinary Council Member for the British Society of Antimicrobial Chemotherapy. F.P. acted as consultants for, and have been on the speakers’ bureau of Angelini, Basilea, Gilead, MSD, Nordic Pharma and Pfizer in the previous 3 years. P.G.C., C.B and A.D.M. had no financial relationships with any organizations that might have an interest in the submitted work.

References

  1. 1.
    Pea F, Viale P, Cojutti P, Del Pin B, Zamparini E, Furlanut M (2012) Therapeutic drug monitoring may improve safety outcomes of long-term treatment with linezolid in adult patients. J Antimicrob Chemother 67(8):2034–2042.  https://doi.org/10.1093/jac/dks153 CrossRefPubMedGoogle Scholar
  2. 2.
    Pea F, Viale P, Cojutti P, Furlanut M (2012) Dosing nomograms for attaining optimum concentrations of meropenem by continuous infusion in critically ill patients with severe gram-negative infections: a pharmacokinetics/pharmacodynamics-based approach. Antimicrob Agents Chemother 56(12):6343–6348.  https://doi.org/10.1128/AAC.01291-12 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Carrie C, Petit L, D'Houdain N, Sauvage N, Cottenceau V, Lafitte M, Foumenteze C, Hisz Q, Menu D, Legeron R, Breilh D, Sztark F (2017) Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill septic patients receiving high doses of beta-lactams administered by continuous infusion. a prospective observational study. Int J Antimicrob Agents doi  https://doi.org/10.1016/j.ijantimicag.2017.11.013
  4. 4.
    MacGowan AP (2003) Pharmacokinetic and pharmacodynamic profile of linezolid in healthy volunteers and patients with Gram-positive infections. J Antimicrob Chemother 51(Suppl 2):ii17–ii25.  https://doi.org/10.1093/jac/dkg248 PubMedCrossRefGoogle Scholar
  5. 5.
    Kees MG, Minichmayr IK, Moritz S, Beck S, Wicha SG, Kees F, Kloft C, Steinke T (2016) Population pharmacokinetics of meropenem during continuous infusion in surgical ICU patients. J Clin Pharmacol 56(3):307–315.  https://doi.org/10.1002/jcph.600 CrossRefPubMedGoogle Scholar
  6. 6.
    Cojutti P, Sartor A, Righi E, Scarparo C, Bassetti M, Pea F (2017) Population pharmacokinetics of high-dose continuous-infusion meropenem and considerations for use in the treatment of infections due to KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 61(10):e00794–e00717.  https://doi.org/10.1128/AAC.00794-17 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Neely MN, van Guilder MG, Yamada WM, Schumitzky A, Jelliffe RW (2012) Accurate detection of outliers and subpopulations with Pmetrics, a nonparametric and parametric pharmacometric modeling and simulation package for R. Ther Drug Monit 34(4):467–476.  https://doi.org/10.1097/FTD.0b013e31825c4ba6 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    May CC, Arora S, Parli SE, Fraser JF, Bastin MT, Cook AM (2015) Augmented renal clearance in patients with subarachnoid hemorrhage. Neurocrit Care 23(3):374–379.  https://doi.org/10.1007/s12028-015-0127-8 CrossRefPubMedGoogle Scholar
  9. 9.
    Carrie C, Bentejac M, Cottenceau V, Masson F, Petit L, Cochard JF, Sztark F (2018) Association between augmented renal clearance and clinical failure of antibiotic treatment in brain-injured patients with ventilator-acquired pneumonia: a preliminary study. Anaesth Crit Care Pain Med 37(1):35–41.  https://doi.org/10.1016/j.accpm.2017.06.006 CrossRefPubMedGoogle Scholar
  10. 10.
    Tang Y, Kong L, Wu C, Zhang X, Lu G, Wu X (2017) Pharmacokinetics of linezolid in plasma and cerebrospinal fluid in patients with cerebral hemorrhage post-surgical intervention. Eur J Clin Pharmacol 73(7):919–921.  https://doi.org/10.1007/s00228-017-2239-x CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Clinical PharmacologySanta Maria della Misericordia University Hospital of Udine, Azienda Sanitaria Universitaria Integrata di UdineUdineItaly
  2. 2.Department of MedicineUniversity of UdineUdineItaly
  3. 3.Department of Anaesthesia and Intensive CareAzienda Sanitaria Universitaria Integrata di UdineUdineItaly
  4. 4.Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, Institute of Translational MedicineUniversity of LiverpoolLiverpoolUK

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