International Journal of Clinical Pharmacy

, Volume 36, Issue 5, pp 1059–1068 | Cite as

Antimicrobial stewardship and linezolid

  • Pauline GuillardEmail author
  • Arnaud de La Blanchardière
  • Vincent Cattoir
  • Marc-Olivier Fischer
  • Renaud Verdon
  • Guillaume Saint-Lorant
Research Article


Background Since 2002, linezolid, the first representative of the oxazolidinone class, has been widely prescribed, sometimes outside of approved indications. However, several cases of clinical outbreaks due to linezolid-resistant organisms have been reported, and its relatively high cost represents an economic challenge for hospital settings. Objectives The aim of this study was to assess the impact of different actions conducted by an antimicrobial stewardship team (AST) to control over-prescription of linezolid with regard to the defined daily dose (DDD) per 1,000 inhabitants per day. Setting This work was conducted in a 1,495-bed hospital from 2009 to 2013. An AST, gathering the departments of pharmacy, microbiology, and infectious diseases, assessed the pertinence of linezolid use and associated effect on the prescriber. Method A retrospective study was conducted throughout 2009. Three different evaluations were prospectively carried out, each for 3 months, between 2011 and 2013. Main outcome measure The indicators chosen to monitor the consumption of linezolid were the DDD per 1,000 inhabitants per day, which enabled a comparison to be made between hospitals from 2004 to 2012, and of the pertinence of its prescription by different departments. Results From 2009 to 2013, 239 patients were evaluated through three 3-month stages. Prescriptions were for off-label use in 45 % of cases. Prescriptions were considered appropriate in 60 % of cases. Unsuitable treatment was either modified or discontinued (62 and 38 % of cases, respectively). Mean duration of linezolid treatment was 8 days, i.e. below the national mean duration reported in the literature. To highlight the impact of action taken by the team, a consensual strategy to treat ventilator-acquired pneumonia was elaborated with principal prescribers. Throughout the study, the mean DDD per 1,000 inhabitants per day increased very slowly and was lower than the eleven other French hospitals, which were secondarily included in this study. Conclusion The multidisciplinary approach that was adopted for therapeutic education and delivery control led to an improvement in the proper use of linezolid. Similar strategy should be extended to other antimicrobial agents, such as carbapenems, for which both cost and risk of resistance emergence are of major concern.


Antimicrobial stewardship Clinical impact France Linezolid use MRSA 



The authors thank the following pharmacists for their contribution to data collection: Anne-Laure Cordonnier, Albane Degrassat-Théas, Thierry Henon, Dominique Breilh, Caroline Hadjadj, Angelique Cotteau-Leroy, Charleric Bornet, Marie-Christine Douet, Florence Lieutier, Benedicte Gourieux, Anne Elaatmani, Patrick Votte, Nathalie Pelloquin, Stéphanie Provot and Morgane Bonnet. The authors also wish to thank Jean-Jacques Parienti (biostatistician), department of Clinical Investigation and Biostatistics, for his assistance in statistical analysis for the present study.


The authors received no funding for this study.

Conflicts of interest

The authors declare they have no conflict of interest concerning this article.


  1. 1.
    Dutronc H, Bocquentin F, Galpérine T, Lafarie-Castet S, Dupon M (2005) Le linezolide, premier antibiotique de la famille des oxazolidinones. [Linezolid, the first oxazolidinone antibiotic]. Med Maladies Infect 35:427–434. (French).Google Scholar
  2. 2.
    Perry CM, Jarvis B. Linezolid: a review of its use in the management of serious Gram-positive infections. Drugs. 2001;61:525–51.PubMedCrossRefGoogle Scholar
  3. 3.
    Plouffe JF. Emerging Therapies for Serious Gram-positive bacterial infections: a focus on linezolid. Clin Infect Dis. 2000;31(Supplement 4):S144–9.PubMedCrossRefGoogle Scholar
  4. 4.
  5. 5.
    Anstead GM, Cadena J, Javeri H. Treatment of infections due to resistant Staphylococcus aureus. Methods Mol Biol. 2014;1085:259–309.PubMedCrossRefGoogle Scholar
  6. 6.
    Wunderink RG, Niederman MS, Kollef MH, Shorr AF, Kunkel MJ, Baruch A, et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis. 2012;54(5):621–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Gee T, Ellis R, Marshall G, Andrews J, Ashby J, Wise R. Pharmacokinetics and tissue penetration of linezolid following multiple oral doses. Antimicrob Agent Chemother. 2001;45:1843–6.CrossRefGoogle Scholar
  8. 8.
    Conte JE, Golden JA, Kipps J, Zurlinden E. Intrapulmonary pharmacokinetics of linezolid. Antimicrob Agent Chemother. 2002;46:1475–80.CrossRefGoogle Scholar
  9. 9.
    Haute Autorité de Santé, commission de transparence (FR) (2004). Avis de la commission de la transparence du 14 janvier 2004., pp 1–7. Accessed 22 July 2013.
  10. 10.
    Cattoir V, Daurel C(2010) Quelles nouveautés en antibiothérapie? [Update on antimicrobial chemotherapy]. Med Maladies Infect 40:135–154. (French).Google Scholar
  11. 11.
    Liverore DM. Linezolid in vitro: mechanism and antibacterial spectrum. J Antimicrob Chemother. 2003;51(Suppl. 2):ii9–16.Google Scholar
  12. 12.
    Jones RN, Johnson DM, Erwin ME. In vitro antimicrobial activities and spectra of U-100592 and U-100766, two novel fluorinated oxazolidinones. Antimicrob Agents Chemother. 1996;40:720–6.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Zurenko GE, Yagi BH, Schaadt RD, Allison JW, Kilburn JO, Glickman SE, et al. In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents. Antimicrob Agents Chemother. 1996;43:1469–74.Google Scholar
  14. 14.
    Goldstein EJ, Citron DM, Merriam CV. Linezolid activity compared to those of selected macrolides and other agents against aerobic and anaerobic pathogens isolated from soft tissue bite infections in humans. Antimicrob Agents Chemother. 1999;43:1469–74.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Agence nationale de sécurité du médicament et des produits de santé (FR) (2013). Évolution des consommations d’antibiotiques en France entre 2000 et 2012., pp 1–32. Accessed 20 June 2013.
  16. 16.
    Marchiset-Ferlay N, Pernot C, Guenfoudi MP, Albuisson, Garnier N, Lazzarotti A (2003). Mise en place d’un indicateur d’exposition aux antibiotiques au centre hospitalier universitaire de Dijon. [Implementation of a monitoring system for the consumption of antibiotics in the Dijon university hospital]. Med Maladies Infect 33:84–92. (French).Google Scholar
  17. 17.
    Réseau d’alerte, d’investigation et de surveillance des infections nosocomiales (Raisin) (2013). Surveillance de la consommation des antibiotiques ATB-Raisin—Synthèse des données 2011. Institut de veille sanitaire (FR) pp 1–92. ISSN: 1956-6956, ISBN NET: 978-2-11-131123-7.Google Scholar
  18. 18.
    Aubin G, Lebland C, Corvec S, Thomaré P, Potel G, Caillon J, et al. Good practice in antibiotic use: what about linezolid in a French university hospital? Int J Clin Pharm. 2011;33:925–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Megne Wabo M, Girol B, Renon-Carron F, Pariscoat G, Weinbreck P, M.Javerliat (2013) Utilisation clinique du linezolide: intérêt d’une démarche d’EPP (Evaluation des pratiques professionnelles). [Clinical use of linezolid: Interest of an approach of evaluation of the professional practices]. Le Pharmacien Hospitalier et Clinicien 46(3):188–199. (French).Google Scholar
  20. 20.
    Duhalde V, Lahille B, Camou F, Pedebosq S, Pometan JP (2007) Bon usage des antibiotiques: étude prospective sur l’utilisation du linézolide dans un hôpital universitaire français. [Proper use of antibiotics: a prospective study on the use of linezolid in a french university hospital]. Pathol Biol 55: 478–481. (French).Google Scholar
  21. 21.
    Etienne P, Roger PM, Brofferio P, Labate C, Blanc V, Tiger F, et al. Antimicrobial stewardship program and quality of antibiotic prescriptions. Med Maladies Infect. 2011;41:608–12.CrossRefGoogle Scholar
  22. 22.
    Dellit TH, Owens RC, McGowan JE, Gerding DN, Weinstein RA, Burke JP, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship. Clin Infect Dis. 2007;44(2):159–77.PubMedCrossRefGoogle Scholar
  23. 23.
    Garcia MS, De la Torre MA, Morales G, Pelaez B, Tolon MJ, Domingo S, et al. Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit. JAMA. 2010;303(22):2260–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Kanafani ZA, Corey GR. Tedizolid (TR-701): a new oxazolidinone with enhanced potency. Expert Opin Investig Drugs. 2012;21(4):515–22.PubMedCrossRefGoogle Scholar
  25. 25.
    Arnold Louie, Liu W, Drusano GL, Kulawy R. In vivo pharmacodynamics of Torezolid phosphate (TR-701), a new oxazolidinone antibiotic, against methicillin-susceptible and methicillin-resistant Staphylococcus aureus strains in a mouse thigh infection model. Antimicrob Agents Chemother. 2011;55:3453–60.CrossRefGoogle Scholar

Copyright information

© Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014

Authors and Affiliations

  • Pauline Guillard
    • 1
    Email author
  • Arnaud de La Blanchardière
    • 2
  • Vincent Cattoir
    • 3
  • Marc-Olivier Fischer
    • 4
  • Renaud Verdon
    • 2
  • Guillaume Saint-Lorant
    • 1
  1. 1.Service de PharmacieCHU de CaenCaenFrance
  2. 2.Service des Maladies Infectieuses et TropicalesCHU de CaenCaenFrance
  3. 3.Service de MicrobiologieCHU de CaenCaenFrance
  4. 4.Service de Réanimation ChirurgicaleCHU de CaenCaenFrance

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