Skip to main content

Advertisement

SpringerLink
Log in

Use of linezolid in neonatal and pediatric inpatient facilities—results of a retrospective multicenter survey

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

The purpose of this investigation was to describe the use of linezolid in pediatric inpatient facilities. A retrospective multicenter survey including data from nine participating tertiary care pediatric inpatient facilities in Germany and Austria was undertaken. Data on 126 off-label linezolid treatment courses administered to 108 patients were documented. The survey comprises linezolid treatment in a broad spectrum of clinical indications to children of all age groups; the median age was 6.8 years (interquartile range 0.6–15.5 years; range 0.1–21.2 years; ten patients were older than 18 years of age but were treated in pediatric inpatient units). Of the 126 treatment courses, 27 (21%) were administered to preterm infants, 64 (51%) to pediatric oncology patients, and 5% to patients soon after liver transplantation. In 25%, the infection was related to a medical device. Linezolid iv treatment was started after intensive pre-treatment (up to 11 other antibiotics for a median duration of 14 days) and changed to enteral administration in only 4% of all iv courses. In 39 (53%) of 74 courses administered to children older than 1 week and younger than 12 years of age, the dose was not adjusted to age-related pharmacokinetic parameters. In only 17 courses (13%) was a pediatric infectious disease consultant involved in the clinical decision algorithm. Linezolid seemed to have contributed to a favorable outcome in 70% of all treatment courses in this survey. Although retrospective, this survey generates interesting data on the off-label use of linezolid and highlights several important clinical aspects in which the use of this rescue antibiotic in children might be improved.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

caMRSA:

Community-acquired MRSA

CNS:

Central nervous system

EMEA:

European Medicines Evaluation Agency

MRSA:

Methicillin-resistant Staphylococcus aureus

MRCoNS:

Methicillin-resistant coagulase-negative Staphylococcus spp.

NICU:

Neonatal intensive care unit

PICU:

Pediatric intensive care unit

PIDC:

Pediatric infectious disease consultant

PRSP:

Penicillin-resistant Streptococcus pneumoniae

VRE:

Vancomycin-resistant Enterococcus spp.

References

  1. Arias CA, Murray BE (2009) Antibiotic-resistant bugs in the 21st century—a clinical super-challenge. N Engl J Med 360(5):439–443. doi:10.1056/NEJMp0804651

    Article  PubMed  CAS  Google Scholar 

  2. Kaplan SL, Deville JG, Yogev R, Morfin MR, Wu E, Adler S, Edge-Padbury B, Naberhuis-Stehouwer S, Bruss JB; Linezolid Pediatric Study Group (2003) Linezolid versus vancomycin for treatment of resistant Gram-positive infections in children. Pediatr Infect Dis J 22(8):677–686

    Article  PubMed  Google Scholar 

  3. Kaplan SL, Afghani B, Lopez P, Wu E, Fleishaker D, Edge-Padbury B, Naberhuis-Stehouwer S, Bruss JB (2003) Linezolid for the treatment of methicillin-resistant Staphylococcus aureus infections in children. Pediatr Infect Dis J 22(9 Suppl):S178–S185

    PubMed  Google Scholar 

  4. Isaacson G, Aronoff SC (2008) Linezolid for tympanostomy tube otorrhea caused by methicillin-resistant Staphylococcus aureus and multiple drug-resistant Streptococcus pneumoniae. Int J Pediatr Otorhinolaryngol 72(5):647–651

    Article  PubMed  Google Scholar 

  5. Kaplan SL, Patterson L, Edwards KM, Azimi PH, Bradley JS, Blumer JL, Tan TQ, Lobeck FG, Anderson DC; Linezolid Pediatric Pneumonia Study Group. Pharmacia and Upjohn (2001) Linezolid for the treatment of community-acquired pneumonia in hospitalized children. Linezolid Pediatric Pneumonia Study Group. Pediatr Infect Dis J 20(5):488–494

    Article  PubMed  CAS  Google Scholar 

  6. Yogev R, Patterson LE, Kaplan SL, Adler S, Morfin MR, Martin A, Edge-Padbury B, Naberhuis-Stehouwer S, Bruss JB (2003) Linezolid for the treatment of complicated skin and skin structure infections in children. Pediatr Infect Dis J 22(9 Suppl):S172–S177

    PubMed  Google Scholar 

  7. Chen CJ, Chiu CH, Lin TY, Lee ZL, Yang WE, Huang YC (2007) Experience with linezolid therapy in children with osteoarticular infections. Pediatr Infect Dis J 26(11):985–988

    Article  PubMed  Google Scholar 

  8. Milstone AM, Bryant KA, Huskins WC, Zerr DM (2010) The past, present, and future of healthcare-associated infection prevention in pediatrics: multidrug-resistant organisms. Infect Control Hosp Epidemiol 31(Suppl 1):S18–S21. doi:10.1086/656001

    Article  PubMed  Google Scholar 

  9. Milstone AM, Maragakis LL, Carroll KC, Perl TM (2010) Targeted surveillance to identify children colonized with vancomycin-resistant Enterococcus in the pediatric intensive care unit. Infect Control Hosp Epidemiol 31(1):95–98. doi:10.1086/649221

    Article  PubMed  Google Scholar 

  10. Milstone AM, Song X, Beers C, Berkowitz I, Carroll KC, Perl TM (2008) Unrecognized burden of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus carriage in the pediatric intensive care unit. Infect Control Hosp Epidemiol 29(12):1174–1176. doi:10.1086/592093

    Article  PubMed  Google Scholar 

  11. Deville JG, Goldfarb J, Kaplan SL, Equils O, Huang DB, Ang JY, Salazar JC (2010) The use of linezolid in the treatment of paediatric patients with infections caused by enterococci including strains resistant to vancomycin. J Antimicrob Chemother 65(10):2267–2270. doi:10.1093/jac/dkq300

    Article  PubMed  CAS  Google Scholar 

  12. Jantausch BA, Deville J, Adler S, Morfin MR, Lopez P, Edge-Padbury B, Naberhuis-Stehouwer S, Bruss JB (2003) Linezolid for the treatment of children with bacteremia or nosocomial pneumonia caused by resistant gram-positive bacterial pathogens. Pediatr Infect Dis J 22(9 Suppl):S164–S171

    PubMed  Google Scholar 

  13. Moellering RC (2003) Linezolid: the first oxazolidinone antimicrobial. Ann Intern Med 138(2):135–142

    PubMed  CAS  Google Scholar 

  14. Beibei L, Yun C, Mengli C, Nan B, Xuhong Y, Rui W (2010) Linezolid versus vancomycin for the treatment of gram-positive bacterial infections: meta-analysis of randomised controlled trials. Int J Antimicrob Agents 35(1):3–12. doi:10.1016/j.ijantimicag.2009.09.013

    Article  PubMed  Google Scholar 

  15. Chiappini E, Conti C, Galli L, de Martino M (2010) Clinical efficacy and tolerability of linezolid in pediatric patients: a systematic review. Clin Ther 32(1):66–88

    Article  PubMed  CAS  Google Scholar 

  16. Dotis J, Iosifidis E, Ioannidou M, Roilides E (2010) Use of linezolid in pediatrics: a critical review. Int J Infect Dis 14(8):e638–e648. doi:10.1016/j.ijid.2009.10.002

    Article  PubMed  CAS  Google Scholar 

  17. Kocher S, Müller W, Resch B (2010) Linezolid treatment of nosocomial bacterial infection with multiresistant Gram-positive pathogens in preterm infants: a systematic review. Int J Antimicrob Agents 36(2):106–110. doi:10.1016/j.ijantimicag.2010.03.030

    Article  PubMed  CAS  Google Scholar 

  18. U.S. Food and Drug Administration, Center for Drug Evaluation and Research (2000) Drug approval package: Zyvox. Available online at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21130_Zyvox.cfm. Accessed April 23, 2011

  19. Porta A, Esposito S, Menson E, Spyridis N, Tsolia M, Sharland M, Principi N (2010) Off-label antibiotic use in children in three European countries. Eur J Clin Pharmacol 66(9):919–927. doi:10.1007/s00228-010-0842-1

    Article  PubMed  Google Scholar 

  20. U.S. Food and Drug Administration (2007) Information for healthcare professionals: Linezolid (marketed as Zyvox). FDA ALERT [3/16/2007]. Available online at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm085249.htm Accessed April 23, 2011

  21. Ang JY, Lua JL, Turner DR, Asmar BI (2003) Vancomycin-resistant Enterococcus faecium endocarditis in a premature infant successfully treated with linezolid. Pediatr Infect Dis J 22(12):1101–1103

    Article  PubMed  Google Scholar 

  22. Sung TJ, Kim HM, Kim MJ (2008) Methicillin-resistant Staphylococcus aureus endocarditis in an extremely low-birth-weight infant treated with linezolid. Clin Pediatr (Phila) 47(5):504–506. doi:10.1177/0009922807311736

    Article  Google Scholar 

  23. Di Paolo A, Malacarne P, Guidotti E, Danesi R, Del Tacca M (2010) Pharmacological issues of linezolid: an updated critical review. Clin Pharmacokinet 49(7):439–447. doi:10.2165/11319960-000000000-00000

    Article  PubMed  Google Scholar 

  24. Yilmaz A, Dalgic N, Müslüman M, Sancar M, Colak I, Aydin Y (2010) Linezolid treatment of shunt-related cerebrospinal fluid infections in children. J Neurosurg Pediatr 5(5):443–448. doi:10.3171/2009.12.PEDS09421

    Article  PubMed  Google Scholar 

  25. Prusseit J, Simon M, von der Brelie C, Heep A, Molitor E, Volz S, Simon A (2009) Epidemiology, prevention and management of ventriculoperitoneal shunt infections in children. Pediatr Neurosurg 45(5):325–336. doi:10.1159/000257520

    Article  PubMed  Google Scholar 

  26. Yogev R, Damle B, Levy G, Nachman S (2010) Pharmacokinetics and distribution of linezolid in cerebrospinal fluid in children and adolescents. Pediatr Infect Dis J 29(9):827–830. doi:10.1097/INF.0b013e3181df4b9a

    Article  PubMed  Google Scholar 

  27. Malacarne P, Viaggi B, Di Paolo A, Danesi R, Del Tacca M (2007) Linezolid cerebrospinal fluid concentration in central nervous system infection. J Chemother 19(1):90–93

    PubMed  CAS  Google Scholar 

  28. Webster DP, Griffiths S, Bowler IC (2009) Failure of linezolid therapy for post-neurosurgical meningitis due to Enterococcus faecium. J Antimicrob Chemother 63(3):622–623. doi:10.1093/jac/dkn519

    Article  PubMed  CAS  Google Scholar 

  29. Metaxas EI, Falagas ME (2009) Update on the safety of linezolid. Expert Opin Drug Saf 8(4):485–491. doi:10.1517/14740330903049706

    Article  PubMed  CAS  Google Scholar 

  30. Linam WM, Wesselkamper K, Gerber MA (2009) Peripheral neuropathy in an adolescent treated with linezolid. Pediatr Infect Dis J 28(2):149–151. doi:10.1097/INF.0b013e3181945999

    Article  PubMed  Google Scholar 

  31. Javaheri M, Khurana RN, O’Hearn TM, Lai MM, Sadun AA (2007) Linezolid-induced optic neuropathy: a mitochondrial disorder? Br J Ophthalmol 91(1):111–115

    Article  PubMed  CAS  Google Scholar 

  32. Brennan K, Jones BL, Jackson L (2009) Auditory nerve neuropathy in a neonate after linezolid treatment. Pediatr Infect Dis J 28(2):169. doi:10.1097/INF.0b013e31818fd8f5

    PubMed  Google Scholar 

  33. Serisier DJ, Jones G, Carroll M (2004) Eradication of pulmonary methicillin-resistant Staphylococcus aureus (MRSA) in cystic fibrosis with linezolid. J Cyst Fibros 3(1):61

    Article  PubMed  Google Scholar 

  34. Jaksic B, Martinelli G, Perez-Oteyza J, Hartman CS, Leonard LB, Tack KJ (2006) Efficacy and safety of linezolid compared with vancomycin in a randomized, double-blind study of febrile neutropenic patients with cancer. Clin Infect Dis 42(5):597–607

    Article  PubMed  CAS  Google Scholar 

  35. Falagas ME, Giannopoulou KP, Kokolakis GN, Rafailidis PI (2008) Fosfomycin: use beyond urinary tract and gastrointestinal infections. Clin Infect Dis 46(1):1069–1077

    Article  PubMed  Google Scholar 

  36. Kearns GL, Abdel-Rahman SM, Blumer JL, Reed MD, James LP, Jacobs RF, Bradley JA, Welshman IR, Jungbluth GL, Stalker DJ; Pediatric Pharmacology Research Unit Network (2000) Single dose pharmacokinetics of linezolid in infants and children. Pediatr Infect Dis J 19(12):1178–1184

    Article  PubMed  CAS  Google Scholar 

  37. Kearns GL, Jungbluth GL, Abdel-Rahman SM, Hopkins NK, Welshman IR, Grzebyk RP, Bruss JB, Van Den Anker JN; Pediatric Pharmacology Research Unit Network (2003) Impact of ontogeny on linezolid disposition in neonates and infants. Clin Pharmacol Ther 74(5):413–422

    Article  PubMed  CAS  Google Scholar 

  38. Jungbluth GL, Welshman IR, Hopkins NK (2003) Linezolid pharmacokinetics in pediatric patients: an overview. Pediatr Infect Dis J 22(9 Suppl):S153–S157

    PubMed  Google Scholar 

  39. Di Pentima MC, Chan S, Eppes SC, Klein JD (2009) Antimicrobial prescription errors in hospitalized children: role of antimicrobial stewardship program in detection and intervention. Clin Pediatr (Phila) 48(5):505–512. doi:10.1177/0009922808330774

    Article  Google Scholar 

  40. Sullivan J, Tobias JD (2006) Preliminary experience with the use of oral linezolid in infants for the completion of antibiotic therapy in the outpatient setting after admission to the pediatric intensive care unit. Am J Ther 13(6):473–477

    PubMed  Google Scholar 

  41. Plosker GL, Figgitt DP (2005) Linezolid: a pharmacoeconomic review of its use in serious Gram-positive infections. Pharmacoeconomics 23(9):945–964

    Article  PubMed  Google Scholar 

  42. Schecter GF, Scott C, True L, Raftery A, Flood J, Mase S (2010) Linezolid in the treatment of multidrug-resistant tuberculosis. Clin Infect Dis 50(1):49–55. doi:10.1086/648675

    Article  PubMed  CAS  Google Scholar 

  43. Schaaf HS, Willemse M, Donald PR (2009) Long-term linezolid treatment in a young child with extensively drug-resistant tuberculosis. Pediatr Infect Dis J 28(8):748–750. doi:10.1097/INF.0b013e31819bc491

    Article  PubMed  Google Scholar 

  44. Falagas ME, Vardakas KZ (2008) Benefit–risk assessment of linezolid for serious gram-positive bacterial infections. Drug Saf 31(9):753–768

    Article  PubMed  CAS  Google Scholar 

  45. Bishop E, Melvani S, Howden BP, Charles PG, Grayson ML (2006) Good clinical outcomes but high rates of adverse reactions during linezolid therapy for serious infections: a proposed protocol for monitoring therapy in complex patients. Antimicrob Agents Chemother 50(4):1599–1602. doi:10.1128/AAC.50.4.1599-1602.2006

    Article  PubMed  CAS  Google Scholar 

  46. Seedat J, Zick G, Klare I, Konstabel C, Weiler N, Sahly H (2006) Rapid emergence of resistance to linezolid during linezolid therapy of an Enterococcus faecium infection. Antimicrob Agents Chemother 50(12):4217–4219. doi:10.1128/AAC.00518-06

    Article  PubMed  CAS  Google Scholar 

  47. Roberts SM, Freeman AF, Harrington SM, Holland SM, Murray PR, Zelazny AM (2006) Linezolid-resistant Staphylococcus aureus in two pediatric patients receiving low-dose linezolid therapy. Pediatr Infect Dis J 25(6):562–564

    Article  PubMed  Google Scholar 

  48. Verma N, Clarke RW, Bolton-Maggs PH, van Saene HK (2007) Gut overgrowth of vancomycin-resistant enterococci (VRE) results in linezolid-resistant mutation in a child with severe congenital neutropenia: a case report. J Pediatr Hematol Oncol 29(8):557–560

    Article  PubMed  Google Scholar 

  49. Mulanovich VE, Huband MD, McCurdy SP, Lemmon MM, Lescoe M, Jiang Y, Rolston KV, LaSala PR (2010) Emergence of linezolid-resistant coagulase-negative Staphylococcus in a cancer centre linked to increased linezolid utilization. J Antimicrob Chemother 65(9):2001–2004. doi:10.1093/jac/dkq238

    Article  PubMed  CAS  Google Scholar 

  50. Sánchez García M, De la Torre MA, Morales G, Peláez B, Tolón MJ, Domingo S, Candel FJ, Andrade R, Arribi A, García N, Martínez Sagasti F, Fereres J, Picazo J (2010) Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit. JAMA 303(22):2260–2264. doi:10.1001/jama.2010.757

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

The support of this study by the executive committee of the German Society of Pediatric Infectious Diseases (DGPI) is gratefully appreciated.

Financial disclosure

This survey was supported by an investigator-initiated scientific research grant by Pfizer Pharma GmbH, Berlin, Germany, without influence on the study design, data collection, data analysis, and the publication of the results.

Author information

Authors and Affiliations

  1. Pediatric Hematology and Oncology, Saarland University Hospital, Homburg/Saar, Germany

    A. Simon

  2. Children’s Hospital Medical Center, University of Bonn, Bonn, Germany

    A. Simon, E. Müllenborn & A. Müller

  3. Department of Pediatrics, Pediatrics I, Medical University Innsbruck, Innsbruck, Austria

    M. Prelog

  4. Neonatal and Pediatric Intensive Care, Department of Pediatrics, Klinikum Augsburg, Augsburg, Germany

    W. Schenk & J. Holzapfel

  5. Children’s Hospital, University of Heidelberg, Heidelberg, Germany

    F. Ebinger & A. Klabunde-Cherwon

  6. Children’s Hospital, Pediatric Hematology and Oncology, University of Mainz, Mainz, Germany

    J. Faber

  7. Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children’s Hospital, Muenster, Germany

    A. H. Groll, K. Masjosthusmann & K. Beutel

  8. Department of Pediatrics, University Hospital Essen, Essen, Germany

    C. Dohna-Schwake

  9. Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    K. Beutel

  10. Pediatric Hematology and Oncology, Children’s Hospital III, Johann Wolfgang Goethe-University, Frankfurt, Germany

    E. Dirkwinkel & T. Lehrnbecher

  11. Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland

    R. A. Ammann

  12. Pediatric Hematology and Oncology, Children’s Hospital Medical Center, University of Saarland, Kirrberger Str., 66421, Homburg/Saar, Germany

    A. Simon

Authors
  1. A. Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Müllenborn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Prelog
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W. Schenk
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Holzapfel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. Ebinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Klabunde-Cherwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. Faber
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. H. Groll
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K. Masjosthusmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C. Dohna-Schwake
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. K. Beutel
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. E. Dirkwinkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. T. Lehrnbecher
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. R. A. Ammann
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. A. Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Simon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Simon, A., Müllenborn, E., Prelog, M. et al. Use of linezolid in neonatal and pediatric inpatient facilities—results of a retrospective multicenter survey. Eur J Clin Microbiol Infect Dis 31, 1435–1442 (2012). https://doi.org/10.1007/s10096-011-1461-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-011-1461-1

Keywords

Search

Navigation