Clinical Pharmacokinetics

, Volume 57, Issue 5, pp 559–575 | Cite as

Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones

  • Claire Roger
  • Jason A. Roberts
  • Laurent Muller
Review Article


Oxazolidinones are a class of synthetic antimicrobial agents with potent activity against a wide range of multidrug-resistant Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Oxazolidinones exhibit their antibacterial effects by inhibiting protein synthesis acting on the ribosomal 50S subunit of the bacteria and thus preventing formation of a functional 70S initiation complex. Currently, two oxazolidinones have been approved by the US Food and Drug Administration: linezolid and more recently tedizolid. Other oxazolidinones are currently under investigation in clinical trials. These antimicrobial agents exhibit a favourable pharmacokinetic profile with an excellent bioavailability and a good tissue and organ penetration. In-vitro susceptibility studies have shown that oxazolidinones are bacteriostatic against enterococci and staphylococci, and bactericidal for the majority of strains of streptococci. In the context of emergence of resistance to glycopeptides, oxazolidinones have become an effective alternative to vancomycin treatment frequently associated with nephrotoxicity. However, oxazolidinones, and linezolid in particular, are associated with significant adverse events, myelosuppression representing the main unfavourable side effect. More recently, tedizolid has been shown to effectively treat acute bacterial skin and skin structure infections. This newer oxazolidinone offers the advantages of once-daily dosing and a better safety profile in healthy volunteer studies (fewer gastrointestinal and haematological side effects). The potential use of tedizolid for other infections that could require longer therapy warrants further studies for positioning this new oxazolidinone in the available antimicrobial armamentarium. Moreover, other oxazolidinones are currently under active investigation.


Compliance with Ethical Standards


No funding was received for the preparation of this article. The authors acknowledge funding from the Australian National Health and Medical Research Council for a Centre of Research Excellence (APP1099452).

Conflict of interest

Jason A. Roberts is funded in part by a Practitioner Fellowship (APP1117065) from the National Health and Medical Research Council of Australia. Claire Roger and Laurent Muller have no conflicts of interest directly relevant to the content of this article.

Author Contributions

CR made substantial contributions to the literature search, interpretation and synthesis of published data, drafting the manuscript and approved the final version to be published. JAR made substantial contributions to revising the manuscript for important intellectual content and approved the final version to be published. LM made substantial contributions to the literature search, interpretation and synthesis of published data, drafting the manuscript and approved the final version to be published.


  1. 1.
    Johnson AP, Warner M, Livermore DM. Activity of linezolid against multi-resistant gram-positive bacteria from diverse hospitals in the United Kingdom. J Antimicrob Chemother. 2000;45(2):225–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Full prescribing information: Sivextro®. 2015. Accessed 7 May 2017.
  3. 3.
    European public assessment report summary for the public: Sivextro®. 2015. Accessed 7 May 2017.
  4. 4.
    Mutnick AH, Biedenbach DJ, Turnidge JD, Jones RN. Spectrum and potency evaluation of a new oxazolidinone, linezolid: report from the SENTRY Antimicrobial Surveillance Program, 1998–2000. Diagn Microbiol Infect Dis. 2002;43(1):65–73.PubMedCrossRefGoogle Scholar
  5. 5.
    Rybak MJ, Cappelletty DM, Moldovan T, Aeschlimann JR, Kaatz GW. Comparative in vitro activities and postantibiotic effects of the oxazolidinone compounds eperezolid (PNU-100592) and linezolid (PNU-100766) versus vancomycin against Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, and Enterococcus faecium. Antimicrob Agents Chemother. 1998;42(3):721–4.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Brown-Elliott BA, Ward SC, Crist CJ, Mann LB, Wilson RW, Wallace RJ Jr. In vitro activities of linezolid against multiple Nocardia species. Antimicrob Agents Chemother. 2001;45(4):1295–7.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Dresser LD, Rybak MJ. The pharmacologic and bacteriologic properties of oxazolidinones, a new class of synthetic antimicrobials. Pharmacotherapy. 1998;18(3):456–62.PubMedGoogle Scholar
  8. 8.
    Gee T, Ellis R, Marshall G, Andrews J, Ashby J, Wise R. Pharmacokinetics and tissue penetration of linezolid following multiple oral doses. Antimicrob Agents Chemother. 2001;45(6):1843–6.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Slatter JG, Stalker DJ, Feenstra KL, Welshman IR, Bruss JB, Sams JP, et al. Pharmacokinetics, metabolism, and excretion of linezolid following an oral dose of [(14)C]linezolid to healthy human subjects. Drug Metab Dispos. 2001;29(8):1136–45.PubMedGoogle Scholar
  10. 10.
    Stalker DJ, Jungbluth GL, Hopkins NK, Batts DH. Pharmacokinetics and tolerance of single- and multiple-dose oral or intravenous linezolid, an oxazolidinone antibiotic, in healthy volunteers. J Antimicrob Chemother. 2003;51(5):1239–46.PubMedCrossRefGoogle Scholar
  11. 11.
    Wiskirchen DE, Shepard A, Kuti JL, Nicolau DP. Determination of tissue penetration and pharmacokinetics of linezolid in patients with diabetic foot infections using in vivo microdialysis. Antimicrob Agents Chemother. 2011;55(9):4170–5.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Diekema DJ, Jones RN. Oxazolidinone antibiotics. Lancet. 2001;358(9297):1975–82.PubMedCrossRefGoogle Scholar
  13. 13.
    Full prescribing information: Zyvox®. Accessed 25 Jun 2015.
  14. 14.
    Dehghanyar P, Burger C, Zeitlinger M, Islinger F, Kovar F, Muller M, et al. Penetration of linezolid into soft tissues of healthy volunteers after single and multiple doses. Antimicrob Agents Chemother. 2005;49(6):2367–71.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Welshman IR, Sisson TA, Jungbluth GL, Stalker DJ, Hopkins NK. Linezolid absolute bioavailability and the effect of food on oral bioavailability. Biopharm Drug Dispos. 2001;22(3):91–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Meagher AK, Forrest A, Rayner CR, Birmingham MC, Schentag JJ. Population pharmacokinetics of linezolid in patients treated in a compassionate-use program. Antimicrob Agents Chemother. 2003;47(2):548–53.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Mandell LA, Wunderink R. Methicillin-resistant Staphylococcus aureus and community-acquired pneumonia: an evolving relationship. Clin Infect Dis. 2012;54(8):1134–6.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Griffin AT, Peyrani P, Wiemken TL, Ramirez JA, Arnold FW. Empiric therapy directed against MRSA in patients admitted to the intensive care unit does not improve outcomes in community-acquired pneumonia. Infection. 2013;41(2):517–23.PubMedCrossRefGoogle Scholar
  19. 19.
    Self WH, Wunderink RG, Williams DJ, Zhu Y, Anderson EJ, Balk RA, et al. Staphylococcus aureus community-acquired pneumonia: prevalence, clinical characteristics, and outcomes. Clin Infect Dis. 2016;63(3):300–9.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Takada H, Hifumi T, Nishimoto N, Kanemura T, Yoshioka H, Okada I, et al. Linezolid versus vancomycin for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus in the elderly: a retrospective cohort analysis. Effectiveness of linezolid in the elderly. Am J Emerg Med. 2017;35(2):245–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Boselli E, Breilh D, Rimmele T, Djabarouti S, Saux MC, Chassard D, et al. Pharmacokinetics and intrapulmonary diffusion of levofloxacin in critically ill patients with severe community-acquired pneumonia. Crit Care Med. 2005;33(1):104–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Boselli E, Breilh D, Caillault-Sergent A, Djabarouti S, Guillaume C, Xuereb F, et al. Alveolar diffusion and pharmacokinetics of linezolid administered in continuous infusion to critically ill patients with ventilator-associated pneumonia. J Antimicrob Chemother. 2012;67(5):1207–10.PubMedCrossRefGoogle Scholar
  23. 23.
    Luna CM, Bruno DA, Garcia-Morato J, Mann KC, Risso Patron J, Sagardia J, et al. Effect of linezolid compared with glycopeptides in methicillin-resistant Staphylococcus aureus severe pneumonia in piglets. Chest. 2009;135(6):1564–71.PubMedCrossRefGoogle Scholar
  24. 24.
    De Pascale G, Fortuna S, Tumbarello M, Cutuli SL, Vallecoccia M, Spanu T, et al. Linezolid plasma and intrapulmonary concentrations in critically ill obese patients with ventilator-associated pneumonia: intermittent vs continuous administration. Intensive Care Med. 2015;41(1):103–10.PubMedCrossRefGoogle Scholar
  25. 25.
    Nau R, Sorgel F, Eiffert H. Penetration of drugs through the blood–cerebrospinal fluid/blood–brain barrier for treatment of central nervous system infections. Clin Microbiol Rev. 2010;23(4):858–83.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Cottagnoud P, Gerber CM, Acosta F, Cottagnoud M, Neftel K, Tauber MG. Linezolid against penicillin-sensitive and -resistant pneumococci in the rabbit meningitis model. J Antimicrob Chemother. 2000;46(6):981–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Cabellos C, Garrigos C, Taberner F, Force E, Pachon-Ibanez ME. Experimental study of the efficacy of linezolid alone and in combinations against experimental meningitis due to Staphylococcus aureus strains with decreased susceptibility to beta-lactams and glycopeptides. J Infect Chemother. 2014;20(9):563–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Villani P, Regazzi MB, Marubbi F, Viale P, Pagani L, Cristini F, et al. Cerebrospinal fluid linezolid concentrations in postneurosurgical central nervous system infections. Antimicrob Agents Chemother. 2002;46(3):936–7.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Beer R, Engelhardt KW, Pfausler B, Broessner G, Helbok R, Lackner P, et al. Pharmacokinetics of intravenous linezolid in cerebrospinal fluid and plasma in neurointensive care patients with staphylococcal ventriculitis associated with external ventricular drains. Antimicrob Agents Chemother. 2007;51(1):379–82.PubMedCrossRefGoogle Scholar
  30. 30.
    Myrianthefs P, Markantonis SL, Vlachos K, Anagnostaki M, Boutzouka E, Panidis D, et al. Serum and cerebrospinal fluid concentrations of linezolid in neurosurgical patients. Antimicrob Agents Chemother. 2006;50(12):3971–6.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Luque S, Grau S, Alvarez-Lerma F, Ferrandez O, Campillo N, Horcajada JP, et al. Plasma and cerebrospinal fluid concentrations of linezolid in neurosurgical critically ill patients with proven or suspected central nervous system infections. Int J Antimicrob Agents. 2014;44(5):409–15.PubMedCrossRefGoogle Scholar
  32. 32.
    Zeitlinger BS, Zeitlinger M, Leitner I, Muller M, Joukhadar C. Clinical scoring system for the prediction of target site penetration of antimicrobials in patients with sepsis. Clin Pharmacokinet. 2007;46(1):75–83.PubMedCrossRefGoogle Scholar
  33. 33.
    Majcher-Peszynska J, Haase G, Sass M, Mundkowski R, Pietsch A, Klammt S, et al. Pharmacokinetics and penetration of linezolid into inflamed soft tissue in diabetic foot infections. Eur J Clin Pharmacol. 2008;64(11):1093–100.PubMedCrossRefGoogle Scholar
  34. 34.
    Buerger C, Plock N, Dehghanyar P, Joukhadar C, Kloft C. Pharmacokinetics of unbound linezolid in plasma and tissue interstitium of critically ill patients after multiple dosing using microdialysis. Antimicrob Agents Chemother. 2006;50(7):2455–63.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Thallinger C, Buerger C, Plock N, Kljucar S, Wuenscher S, Sauermann R, et al. Effect of severity of sepsis on tissue concentrations of linezolid. J Antimicrob Chemother. 2008;61(1):173–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Lovering AM, Zhang J, Bannister GC, Lankester BJ, Brown JH, Narendra G, et al. Penetration of linezolid into bone, fat, muscle and haematoma of patients undergoing routine hip replacement. J Antimicrob Chemother. 2002;50(1):73–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Traunmuller F, Schintler MV, Spendel S, Popovic M, Mauric O, Scharnagl E, et al. Linezolid concentrations in infected soft tissue and bone following repetitive doses in diabetic patients with bacterial foot infections. Int J Antimicrob Agents. 2010;36(1):84–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Kutscha-Lissberg F, Hebler U, Muhr G, Koller M. Linezolid penetration into bone and joint tissues infected with methicillin-resistant staphylococci. Antimicrob Agents Chemother. 2003;47(12):3964–6.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Rana B, Butcher I, Grigoris P, Murnaghan C, Seaton RA, Tobin CM. Linezolid penetration into osteo-articular tissues. J Antimicrob Chemother. 2002;50(5):747–50.PubMedCrossRefGoogle Scholar
  40. 40.
    Metallidis S, Nikolaidis J, Lazaraki G, Koumentaki E, Gogou V, Topsis D, et al. Penetration of linezolid into sternal bone of patients undergoing cardiopulmonary bypass surgery. Int J Antimicrob Agents. 2007;29(6):742–4.PubMedCrossRefGoogle Scholar
  41. 41.
    Papadopoulos A, Plachouras D, Giannitsioti E, Poulakou G, Giamarellou H, Kanellakopoulou K. Efficacy and tolerability of linezolid in chronic osteomyelitis and prosthetic joint infections: a case–control study. J Chemother. 2009;21(2):165–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Rayner CR, Baddour LM, Birmingham MC, Norden C, Meagher AK, Schentag JJ. Linezolid in the treatment of osteomyelitis: results of compassionate use experience. Infection. 2004;32(1):8–14.PubMedCrossRefGoogle Scholar
  43. 43.
    Senneville E, Legout L, Valette M, Yazdanpanah Y, Beltrand E, Caillaux M, et al. Effectiveness and tolerability of prolonged linezolid treatment for chronic osteomyelitis: a retrospective study. Clin Ther. 2006;28(8):1155–63.PubMedCrossRefGoogle Scholar
  44. 44.
    Rao N, Ziran BH, Hall RA, Santa ER. Successful treatment of chronic bone and joint infections with oral linezolid. Clin Orthop Relat Res. 2004;427:67–71.CrossRefGoogle Scholar
  45. 45.
    Falagas ME, Manta KG, Ntziora F, Vardakas KZ. Linezolid for the treatment of patients with endocarditis: a systematic review of the published evidence. J Antimicrob Chemother. 2006;58(2):273–80.PubMedCrossRefGoogle Scholar
  46. 46.
    Chiang FY, Climo M. Efficacy of linezolid alone or in combination with vancomycin for treatment of experimental endocarditis due to methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2003;47(9):3002–4.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Jacqueline C, Batard E, Perez L, Boutoille D, Hamel A, Caillon J, et al. In vivo efficacy of continuous infusion versus intermittent dosing of linezolid compared to vancomycin in a methicillin-resistant Staphylococcus aureus rabbit endocarditis model. Antimicrob Agents Chemother. 2002;46(12):3706–11.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Bernardo K, Pakulat N, Fleer S, Schnaith A, Utermohlen O, Krut O, et al. Subinhibitory concentrations of linezolid reduce Staphylococcus aureus virulence factor expression. Antimicrob Agents Chemother. 2004;48(2):546–55.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Diep BA, Afasizheva A, Le HN, Kajikawa O, Matute-Bello G, Tkaczyk C, et al. Effects of linezolid on suppressing in vivo production of staphylococcal toxins and improving survival outcomes in a rabbit model of methicillin-resistant Staphylococcus aureus necrotizing pneumonia. J Infect Dis. 2013;208(1):75–82.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Stevens DL, Herr D, Lampiris H, Hunt JL, Batts DH, Hafkin B. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis. 2002;34(11):1481–90.PubMedCrossRefGoogle Scholar
  51. 51.
    Rubinstein E, Cammarata S, Oliphant T, Wunderink R, Linezolid Nosocomial Pneumonia Study Group. Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study. Clin Infect Dis. 2001;32(3):402–12.PubMedCrossRefGoogle Scholar
  52. 52.
    Wunderink RG, Rello J, Cammarata SK, Croos-Dabrera RV, Kollef MH. Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest. 2003;124(5):1789–97.PubMedCrossRefGoogle Scholar
  53. 53.
    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
  54. 54.
    Ferrer MD, Rodriguez JC, Alvarez L, Artacho A, Royo G, Mira A. Effect of antibiotics on biofilm inhibition and induction measured by real-time cell analysis. J Appl Microbiol. 2017;122(3):640–50.PubMedCrossRefGoogle Scholar
  55. 55.
    Andes D, van Ogtrop ML, Peng J, Craig WA. In vivo pharmacodynamics of a new oxazolidinone (linezolid). Antimicrob Agents Chemother. 2002;46(11):3484–9.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Rayner CR, Forrest A, Meagher AK, Birmingham MC, Schentag JJ. Clinical pharmacodynamics of linezolid in seriously ill patients treated in a compassionate use programme. Clin Pharmacokinet. 2003;42(15):1411–23.PubMedCrossRefGoogle Scholar
  57. 57.
    Morata L, Cuesta M, Rojas JF, Rodriguez S, Brunet M, Casals G, et al. Risk factors for a low linezolid trough plasma concentration in acute infections. Antimicrob Agents Chemother. 2013;57(4):1913–7.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Pea F, Furlanut M, Cojutti P, Cristini F, Zamparini E, Franceschi L, et al. Therapeutic drug monitoring of linezolid: a retrospective monocentric analysis. Antimicrob Agents Chemother. 2010;54(11):4605–10.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Adembri C, Fallani S, Cassetta MI, Arrigucci S, Ottaviano A, Pecile P, et al. Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septic patients: intermittent versus continuous infusion. Int J Antimicrob Agents. 2008;31(2):122–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Lopez-Garcia B, Luque S, Roberts JA, Grau S. Pharmacokinetics and preliminary safety of high dose linezolid for the treatment of Gram-positive bacterial infections. J Infect. 2015;71(5):604–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Pea F, Cojutti PG, Baraldo M. A 10-year experience of therapeutic drug monitoring (TDM) of linezolid in a hospital-wide population of patients receiving conventional dosing: is there enough evidence for suggesting TDM in the majority of patients? Basic Clin Pharmacol Toxicol. 2017;121(4):303–8.PubMedCrossRefGoogle Scholar
  62. 62.
    Pea F, Viale P, Cojutti P, Del Pin B, Zamparini E, Furlanut M. Therapeutic drug monitoring may improve safety outcomes of long-term treatment with linezolid in adult patients. J Antimicrob Chemother. 2012;67(8):2034–42.PubMedCrossRefGoogle Scholar
  63. 63.
    Jones RN, Fritsche TR, Sader HS, Ross JE. Zyvox annual appraisal of potency and spectrum program results for 2006: an activity and spectrum analysis of linezolid using clinical isolates from 16 countries. Diagn Microbiol Infect Dis. 2007;59(2):199–209.PubMedCrossRefGoogle Scholar
  64. 64.
    Boak LM, Rayner CR, Grayson ML, Paterson DL, Spelman D, Khumra S, et al. Clinical population pharmacokinetics and toxicodynamics of linezolid. Antimicrob Agents Chemother. 2014;58(4):2334–43.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Matsumoto K, Shigemi A, Takeshita A, Watanabe E, Yokoyama Y, Ikawa K, et al. Analysis of thrombocytopenic effects and population pharmacokinetics of linezolid: a dosage strategy according to the trough concentration target and renal function in adult patients. Int J Antimicrob Agents. 2014;44(3):242–7.PubMedCrossRefGoogle Scholar
  66. 66.
    Rybak JM, Roberts K. Tedizolid phosphate: a next-generation oxazolidinone. Infect Dis Ther. 2015;4(1):1–14.Google Scholar
  67. 67.
    Long KS, Poehlsgaard J, Kehrenberg C, Schwarz S, Vester B. The Cfr rRNA methyltransferase confers resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antibiotics. Antimicrob Agents Chemother. 2006;50(7):2500–5.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Prystowsky J, Siddiqui F, Chosay J, Shinabarger DL, Millichap J, Peterson LR, et al. Resistance to linezolid: characterization of mutations in rRNA and comparison of their occurrences in vancomycin-resistant enterococci. Antimicrob Agents Chemother. 2001;45(7):2154–6.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Vazquez JA, Arnold AC, Swanson RN, Biswas P, Bassetti M. Safety of long-term use of linezolid: results of an open-label study. Ther Clin Risk Manag. 2016;12:1347–54.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Bialvaei ZA, Rahbar M, Yousefi M, Asgharzadeh M, Samadi Kafil H. Linezolid: a promising option in the treatment of Gram-positives. J Antimicrob Chemother. 2017;72(2):354–64.CrossRefGoogle Scholar
  71. 71.
    Flanagan S, McKee EE, Das D, Tulkens PM, Hosako H, Fiedler-Kelly J, et al. Nonclinical and pharmacokinetic assessments to evaluate the potential of tedizolid and linezolid to affect mitochondrial function. Antimicrob Agents Chemother. 2015;59(1):178–85.PubMedCrossRefGoogle Scholar
  72. 72.
    Tsuji Y, Holford NHG, Kasai H, Ogami C, Heo YA, Higashi Y, et al. Population pharmacokinetics and pharmacodynamics of linezolid-induced thrombocytopenia in hospitalized patients. Br J Clin Pharmacol. 2017;83(8):1758–72.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Tsuji Y, Hiraki Y, Matsumoto K, Mizoguchi A, Kobayashi T, Sadoh S, et al. Thrombocytopenia and anemia caused by a persistent high linezolid concentration in patients with renal dysfunction. J Infect Chemother. 2011;17(1):70–5.PubMedCrossRefGoogle Scholar
  74. 74.
    Lodise TP, Bidell MR, Flanagan SD, Zasowski EJ, Minassian SL, Prokocimer P. Characterization of the haematological profile of 21 days of tedizolid in healthy subjects. J Antimicrob Chemother. 2016;71(9):2553–8.PubMedCrossRefGoogle Scholar
  75. 75.
    Soriano A, Ortega M, Garcia S, Penarroja G, Bove A, Marcos M, et al. Comparative study of the effects of pyridoxine, rifampin, and renal function on hematological adverse events induced by linezolid. Antimicrob Agents Chemother. 2007;51(7):2559–63.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Kuter DJ, Tillotson GS. Hematologic effects of antimicrobials: focus on the oxazolidinone linezolid. Pharmacotherapy. 2001;21(8):1010–3.PubMedCrossRefGoogle Scholar
  77. 77.
    French G. Safety and tolerability of linezolid. J Antimicrob Chemother. 2003;51(Suppl. 2):ii45–53.PubMedGoogle Scholar
  78. 78.
    Soriano A, Gomez J, Gomez L, Azanza JR, Perez R, Romero F, et al. Efficacy and tolerability of prolonged linezolid therapy in the treatment of orthopedic implant infections. Eur J Clin Microbiol Infect Dis. 2007;26(5):353–6.PubMedCrossRefGoogle Scholar
  79. 79.
    Corallo CE, Paull AE. Linezolid-induced neuropathy. Med J Aust. 2002;177(6):332.PubMedGoogle Scholar
  80. 80.
    Bressler AM, Zimmer SM, Gilmore JL, Somani J. Peripheral neuropathy associated with prolonged use of linezolid. Lancet Infect Dis. 2004;4(8):528–31.PubMedCrossRefGoogle Scholar
  81. 81.
    Rho JP, Sia IG, Crum BA, Dekutoski MB, Trousdale RT. Linezolid-associated peripheral neuropathy. Mayo Clin Proc. 2004;79(7):927–30.PubMedCrossRefGoogle Scholar
  82. 82.
    Kishor K, Dhasmana N, Kamble SS, Sahu RK. Linezolid induced adverse drug reactions: an update. Curr Drug Metab. 2015;16(7):553–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Narita M, Tsuji BT, Yu VL. Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome. Pharmacotherapy. 2007;27(8):1189–97.PubMedCrossRefGoogle Scholar
  84. 84.
    Mehta S, Das M, Laxmeshwar C, Jonckheere S, Thi SS, Isaakidis P. Linezolid-associated optic neuropathy in drug-resistant tuberculosis patients in Mumbai, India. PLoS One. 2016;11(9):e0162138.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Leach KL, Swaney SM, Colca JR, McDonald WG, Blinn JR, Thomasco LM, et al. The site of action of oxazolidinone antibiotics in living bacteria and in human mitochondria. Mol Cell. 2007;26(3):393–402.PubMedCrossRefGoogle Scholar
  86. 86.
    De Vriese AS, Coster RV, Smet J, Seneca S, Lovering A, Van Haute LL, et al. Linezolid-induced inhibition of mitochondrial protein synthesis. Clin Infect Dis. 2006;42(8):1111–7.PubMedCrossRefGoogle Scholar
  87. 87.
    Palenzuela L, Hahn NM, Nelson RP Jr, Arno JN, Schobert C, Bethel R, et al. Does linezolid cause lactic acidosis by inhibiting mitochondrial protein synthesis? Clin Infect Dis. 2005;40(12):e113–6.PubMedCrossRefGoogle Scholar
  88. 88.
    Protti A, Ronchi D, Bassi G, Fortunato F, Bordoni A, Rizzuti T, et al. Changes in whole-body oxygen consumption and skeletal muscle mitochondria during linezolid-induced lactic acidosis. Crit Care Med. 2016;44(7):e579–82.PubMedCrossRefGoogle Scholar
  89. 89.
    Zuccarini NS, Yousuf T, Wozniczka D, Rauf AA. Lactic acidosis induced by linezolid mimics symptoms of an acute intracranial bleed: a case report and literature review. J Clin Med Res. 2016;8(10):753–6.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Im JH, Baek JH, Kwon HY, Lee JS. Incidence and risk factors of linezolid-induced lactic acidosis. Int J Infect Dis. 2015;31:47–52.PubMedCrossRefGoogle Scholar
  91. 91.
    Apodaca AA, Rakita RM. Linezolid-induced lactic acidosis. N Engl J Med. 2003;348(1):86–7.PubMedCrossRefGoogle Scholar
  92. 92.
    Johnson PC, Vaduganathan M, Phillips KM, O’Donnell WJ. A triad of linezolid toxicity: hypoglycemia, lactic acidosis, and acute pancreatitis. Proc (Bayl Univ Med Cent). 2015;28(4):466–8.CrossRefGoogle Scholar
  93. 93.
    Hoyo I, Martinez-Pastor J, Garcia-Ramiro S, Climent C, Brunet M, Cuesta M, et al. Decreased serum linezolid concentrations in two patients receiving linezolid and rifampicin due to bone infections. Scand J Infect Dis. 2012;44(7):548–50.PubMedCrossRefGoogle Scholar
  94. 94.
    Pea F, Cadeo B, Cojutti PG, Pecori D, Bassetti M. Linezolid underexposure in a hypothyroid patient on levothyroxine replacement therapy: a case report. Ther Drug Monit. 2014;36(5):687–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Sakai Y, Naito T, Arima C, Miura M, Qin L, Hidaka H, et al. Potential drug interaction between warfarin and linezolid. Intern Med. 2015;54(5):459–64.PubMedCrossRefGoogle Scholar
  96. 96.
    Kalil AC, Klompas M, Haynatzki G, Rupp ME. Treatment of hospital-acquired pneumonia with linezolid or vancomycin: a systematic review and meta-analysis. BMJ Open. 2013;3(10):e003912.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Wang Y, Zou Y, Xie J, Wang T, Zheng X, He H, et al. Linezolid versus vancomycin for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a systematic review employing meta-analysis. Eur J Clin Pharmacol. 2015;71(1):107–15.PubMedCrossRefGoogle Scholar
  98. 98.
    Kalil AC, Murthy MH, Hermsen ED, Neto FK, Sun J, Rupp ME. Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: a systematic review and meta-analysis. Crit Care Med. 2010;38(9):1802–8.PubMedCrossRefGoogle Scholar
  99. 99.
    Jiang H, Tang RN, Wang J. Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: meta-analysis of randomised controlled trials. Eur J Clin Microbiol Infect Dis. 2013;32(9):1121–8.PubMedCrossRefGoogle Scholar
  100. 100.
    Caffrey AR, Morrill HJ, Puzniak LA, Laplante KL. Comparative effectiveness of linezolid and vancomycin among a national veterans affairs cohort with methicillin-resistant Staphylococcus aureus pneumonia. Pharmacotherapy. 2014;34(5):473–80.PubMedCrossRefGoogle Scholar
  101. 101.
    Sinha Ray A, Haikal A, Hammoud KA, Yu AS. Vancomycin and the risk of AKI: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2016;11(12):2132–40.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Patel DA, Michel A, Stephens J, Weber B, Petrik C, Charbonneau C. An economic model to compare linezolid and vancomycin for the treatment of confirmed methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Germany. Infect Drug Resist. 2014;7:273–80.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Patel DA, Shorr AF, Chastre J, Niederman M, Simor A, Stephens JM, et al. Modeling the economic impact of linezolid versus vancomycin in confirmed nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus. Crit Care. 2014;18(4):R157.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Shorr AF, Puzniak LA, Biswas P, Niederman MS. Predictors of clinical success in the treatment of patients with methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia (NP). PLoS One. 2015;10(7):e0131932.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Niederman MS, Chastre J, Solem CT, Wan Y, Gao X, Myers DE, et al. Health economic evaluation of patients treated for nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus: secondary analysis of a multicenter randomized clinical trial of vancomycin and linezolid. Clin Ther. 2014;36(9):1233 e1–1243 e1.CrossRefGoogle Scholar
  106. 106.
    Lin PC, Wang BC, Kim R, Magyar A, Lai CC, Yang YW, et al. Estimating the cost-effectiveness of linezolid for the treatment of methicillin-resistant Staphylococcus aureus nosocomial pneumonia in Taiwan. J Microbiol Immunol Infect. 2016;49(1):46–51.PubMedCrossRefGoogle Scholar
  107. 107.
    Rello J, Bin C. Cost of nosocomial pneumonia: the example of vancomycin versus linezolid-shorter stay or fewer complications? Int J Infect Dis. 2016;51:1–3.PubMedCrossRefGoogle Scholar
  108. 108.
    Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61–111.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Thom H, Thompson JC, Scott DA, Halfpenny N, Sulham K, Corey GR. Comparative efficacy of antibiotics for the treatment of acute bacterial skin and skin structure infections (ABSSSI): a systematic review and network meta-analysis. Curr Med Res Opin. 2015;31(8):1539–51.PubMedCrossRefGoogle Scholar
  110. 110.
    Yue J, Dong BR, Yang M, Chen X, Wu T, Liu GJ. Linezolid versus vancomycin for skin and soft tissue infections. Cochrane Database Syst Rev. 2013;9(7):CD008056.Google Scholar
  111. 111.
    Yue J, Dong BR, Yang M, Chen X, Wu T, Liu GJ. Linezolid versus vancomycin for skin and soft tissue infections. Cochrane Database Syst Rev. 2016;9(1):CD008056.Google Scholar
  112. 112.
    Bounthavong M, Hsu DI. Efficacy and safety of linezolid in methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infection (cSSTI): a meta-analysis. Curr Med Res Opin. 2010;26(2):407–21.PubMedCrossRefGoogle Scholar
  113. 113.
    Beibei L, Yun C, Mengli C, Nan B, Xuhong Y, Rui W. Linezolid versus vancomycin for the treatment of gram-positive bacterial infections: meta-analysis of randomised controlled trials. Int J Antimicrob Agents. 2010;35(1):3–12.PubMedCrossRefGoogle Scholar
  114. 114.
    Dodds TJ, Hawke CI. Linezolid versus vancomycin for MRSA skin and soft tissue infections (systematic review and meta-analysis). ANZ J Surg. 2009;79(9):629–35.PubMedCrossRefGoogle Scholar
  115. 115.
    Nemeth J, Oesch G, Kuster SP. Bacteriostatic versus bactericidal antibiotics for patients with serious bacterial infections: systematic review and meta-analysis. J Antimicrob Chemother. 2015;70(2):382–95.PubMedCrossRefGoogle Scholar
  116. 116.
    Tsoulas C, Nathwani D. Review of meta-analyses of vancomycin compared with new treatments for Gram-positive skin and soft-tissue infections: are we any clearer? Int J Antimicrob Agents. 2015;46(1):1–7.PubMedCrossRefGoogle Scholar
  117. 117.
    Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18–55.PubMedCrossRefGoogle Scholar
  118. 118.
    Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10–52.PubMedCrossRefGoogle Scholar
  119. 119.
    Bounthavong M, Hsu DI. Cost-effectiveness of linezolid in methicillin-resistant Staphylococcus aureus skin and skin structure infections. Expert Rev Pharmacoecon Outcomes Res. 2012;12(6):683–98.PubMedCrossRefGoogle Scholar
  120. 120.
    Bounthavong M, Zargarzadeh A, Hsu DI, Vanness DJ. Cost-effectiveness analysis of linezolid, daptomycin, and vancomycin in methicillin-resistant Staphylococcus aureus: complicated skin and skin structure infection using Bayesian methods for evidence synthesis. Value Health. 2011;14(5):631–9.PubMedCrossRefGoogle Scholar
  121. 121.
    Falagas ME, Siempos II, Papagelopoulos PJ, Vardakas KZ. Linezolid for the treatment of adults with bone and joint infections. Int J Antimicrob Agents. 2007;29(3):233–9.PubMedCrossRefGoogle Scholar
  122. 122.
    Osmon DR, Berbari EF, Berendt AR, Lew D, Zimmerli W, Steckelberg JM, et al. Executive summary: diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2013;56(1):1–10.PubMedCrossRefGoogle Scholar
  123. 123.
    Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Michael Scheld W, et al. Infectious Diseases Society of America’s Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clin Infect Dis. 2017;64(6):e34–65.Google Scholar
  124. 124.
    Shorr AF, Kunkel MJ, Kollef M. Linezolid versus vancomycin for Staphylococcus aureus bacteraemia: pooled analysis of randomized studies. J Antimicrob Chemother. 2005;56(5):923–9.PubMedCrossRefGoogle Scholar
  125. 125.
    Wilcox MH, Tack KJ, Bouza E, Herr DL, Ruf BR, Ijzerman MM, et al. Complicated skin and skin-structure infections and catheter-related bloodstream infections: noninferiority of linezolid in a phase 3 study. Clin Infect Dis. 2009;48(2):203–12.PubMedCrossRefGoogle Scholar
  126. 126.
    Whang DW, Miller LG, Partain NM, McKinnell JA. Systematic review and meta-analysis of linezolid and daptomycin for treatment of vancomycin-resistant enterococcal bloodstream infections. Antimicrob Agents Chemother. 2013;57(10):5013–8.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011;52(3):285–92.PubMedCrossRefGoogle Scholar
  128. 128.
    Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Tleyjeh IM, Rybak MJ, et al. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132(15):1435–86.PubMedCrossRefGoogle Scholar
  129. 129.
    Roberts JA, Kumar A, Lipman J. Right dose, right now: customized drug dosing in the critically ill. Crit Care Med. 2017;45(2):331–6.PubMedCrossRefGoogle Scholar
  130. 130.
    Roberts JA, Abdul-Aziz MH, Lipman J, Mouton JW, Vinks AA, Felton TW, et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis. 2014;14(6):498–509.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Tsai D, Lipman J, Roberts JA. Pharmacokinetic/pharmacodynamic considerations for the optimization of antimicrobial delivery in the critically ill. Curr Opin Crit Care. 2015;21(5):412–20.PubMedCrossRefGoogle Scholar
  132. 132.
    Zoller M, Maier B, Hornuss C, Neugebauer C, Dobbeler G, Nagel D, et al. Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study. Crit Care. 2014;18(4):R148.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Neri M, Villa G, Garzotto F, Bagshaw S, Bellomo R, Cerda J, et al. Nomenclature for renal replacement therapy in acute kidney injury: basic principles. Crit Care. 2016;20(1):318.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    KDIGO. Clinical practice guidelines for acute kidney injury. 2012. Accessed 17 Sept 2017.
  135. 135.
    Jamal JA, Mueller BA, Choi GY, Lipman J, Roberts JA. How can we ensure effective antibiotic dosing in critically ill patients receiving different types of renal replacement therapy? Diagn Microbiol Infect Dis. 2015;82(1):92–103.PubMedCrossRefGoogle Scholar
  136. 136.
    Roger C, Wallis SC, Muller L, Saissi G, Lipman J, Lefrant JY, et al. Influence of renal replacement modalities on Amikacin population pharmacokinetics in critically ill patients on continuous renal replacement therapy. Antimicrob Agents Chemother. 2016;60(8):4901–9.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Roger C, Wallis SC, Muller L, Saissi G, Lipman J, Bruggemann RJ, et al. Caspofungin population pharmacokinetics in critically ill patients undergoing continuous veno-venous haemofiltration or haemodiafiltration. Clin Pharmacokinet. 2017;56(9):1057–68.Google Scholar
  138. 138.
    Roger C, Wallis SC, Louart B, Lefrant JY, Lipman J, Muller L, et al. Comparison of equal doses of continuous venovenous haemofiltration and haemodiafiltration on ciprofloxacin population pharmacokinetics in critically ill patients. J Antimicrob Chemother. 2016;71(6):1643–50.PubMedCrossRefGoogle Scholar
  139. 139.
    Villa G, Di Maggio P, De Gaudio AR, Novelli A, Antoniotti R, Fiaccadori E, et al. Effects of continuous renal replacement therapy on linezolid pharmacokinetic/pharmacodynamics: a systematic review. Crit Care. 2016;20(1):374.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Roger C, Muller L, Wallis SC, Louart B, Saissi G, Lipman J, et al. Population pharmacokinetics of linezolid in critically ill patients on renal replacement therapy: comparison of equal doses in continuous venovenous haemofiltration and continuous venovenous haemodiafiltration. J Antimicrob Chemother. 2016;71(2):464–70.PubMedCrossRefGoogle Scholar
  141. 141.
    Bhalodi AA, Papasavas PK, Tishler DS, Nicolau DP, Kuti JL. Pharmacokinetics of intravenous linezolid in moderately to morbidly obese adults. Antimicrob Agents Chemother. 2013;57(3):1144–9.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Srinivas NR. Influence of morbidly obesity on the clinical pharmacokinetics of various anti-infective drugs: reappraisal using recent case studies-issues, dosing implications, and considerations. Am J Ther. 2016. doi: 10.1097/MJT.0000000000000401.
  143. 143.
    Corcione S, Pagani N, Baietto L, Fanelli V, Urbino R, Ranieri VM, et al. Pharmacokinetics of high dosage of linezolid in two morbidly obese patients. J Antimicrob Chemother. 2015;70(10):2925.PubMedCrossRefGoogle Scholar
  144. 144.
    Stein GE, Schooley SL, Peloquin CA, Kak V, Havlichek DH, Citron DM, et al. Pharmacokinetics and pharmacodynamics of linezolid in obese patients with cellulitis. Ann Pharmacother. 2005;39(3):427–32.PubMedCrossRefGoogle Scholar
  145. 145.
    Pfaller MA, Flamm RK, Jones RN, Farrell DJ, Mendes RE. Activities of tedizolid and linezolid determined by the reference broth microdilution method against 3,032 Gram-positive bacterial isolates collected in Asia-Pacific, Eastern Europe, and Latin American countries in 2014. Antimicrob Agents Chemother. 2016;60(9):5393–9.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Chen KH, Huang YT, Liao CH, Sheng WH, Hsueh PR. In vitro activities of tedizolid and linezolid against Gram-positive cocci associated with acute bacterial skin and skin structure infections and pneumonia. Antimicrob Agents Chemother. 2015;59(10):6262–5.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Chen H, Yang Q, Zhang R, He W, Ma X, Zhang J, et al. In vitro antimicrobial activity of the novel oxazolidinone tedizolid and comparator agents against Staphylococcus aureus and linezolid-resistant Gram-positive pathogens: a multicentre study in China. Int J Antimicrob Agents. 2014;44(3):276–7.PubMedCrossRefGoogle Scholar
  148. 148.
    Flanagan S, Fang E, Munoz KA, Minassian SL, Prokocimer PG. Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid. Pharmacotherapy. 2014;34(9):891–900.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Flanagan SD, Bien PA, Munoz KA, Minassian SL, Prokocimer PG. Pharmacokinetics of tedizolid following oral administration: single and multiple dose, effect of food, and comparison of two solid forms of the prodrug. Pharmacotherapy. 2014;34(3):240–50.PubMedCrossRefGoogle Scholar
  150. 150.
    Flanagan S, Passarell J, Lu Q, Fiedler-Kelly J, Ludwig E, Prokocimer P. Tedizolid population pharmacokinetics, exposure response, and target attainment. Antimicrob Agents Chemother. 2014;58(11):6462–70.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Housman ST, Pope JS, Russomanno J, Salerno E, Shore E, Kuti JL, et al. Pulmonary disposition of tedizolid following administration of once-daily oral 200-milligram tedizolid phosphate in healthy adult volunteers. Antimicrob Agents Chemother. 2012;56(5):2627–34.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Sahre M, Sabarinath S, Grant M, Seubert C, Deanda C, Prokocimer P, et al. Skin and soft tissue concentrations of tedizolid (formerly torezolid), a novel oxazolidinone, following a single oral dose in healthy volunteers. Int J Antimicrob Agents. 2012;40(1):51–4.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Louie A, Liu W, Kulawy R, Drusano GL. 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(7):3453–60.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Drusano GL, Liu W, Kulawy R, Louie A. Impact of granulocytes on the antimicrobial effect of tedizolid in a mouse thigh infection model. Antimicrob Agents Chemother. 2011;55(11):5300–5.PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Livermore DM, Mushtaq S, Warner M, Woodford N. Activity of oxazolidinone TR-700 against linezolid-susceptible and -resistant staphylococci and enterococci. J Antimicrob Chemother. 2009;63(4):713–5.PubMedCrossRefGoogle Scholar
  156. 156.
    Locke JB, Morales G, Hilgers M, Kedar GC, Rahawi S, Jose Picazo J, et al. Elevated linezolid resistance in clinical cfr-positive Staphylococcus aureus isolates is associated with co-occurring mutations in ribosomal protein L3. Antimicrob Agents Chemother. 2010;54(12):5352–5.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Shaw KJ, Poppe S, Schaadt R, Brown-Driver V, Finn J, Pillar CM, et al. In vitro activity of TR-700, the antibacterial moiety of the prodrug TR-701, against linezolid-resistant strains. Antimicrob Agents Chemother. 2008;52(12):4442–7.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Moran GJ, Fang E, Corey GR, Das AF, De Anda C, Prokocimer P. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2014;14(8):696–705.PubMedCrossRefGoogle Scholar
  159. 159.
    Prokocimer P, De Anda C, Fang E, Mehra P, Das A. Tedizolid phosphate vs linezolid for treatment of acute bacterial skin and skin structure infections: the ESTABLISH-1 randomized trial. JAMA. 2013;309(6):559–69.PubMedCrossRefGoogle Scholar
  160. 160.
    Shorr AF, Lodise TP, Corey GR, De Anda C, Fang E, Das AF, et al. Analysis of the phase 3 ESTABLISH trials of tedizolid versus linezolid in acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2015;59(2):864–71.PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Flanagan S, Bartizal K, Minassian SL, Fang E, Prokocimer P. In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions. Antimicrob Agents Chemother. 2013;57(7):3060–6.PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Flanagan S, Minassian SL, Morris D, Ponnuraj R, Marbury TC, Alcorn HW, et al. Pharmacokinetics of tedizolid in subjects with renal or hepatic impairment. Antimicrob Agents Chemother. 2014;58(11):6471–6.PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Flanagan S, Minassian SL, Passarell JA, Fiedler-Kelly J, Prokocimer P. Pharmacokinetics of tedizolid in obese and nonobese subjects. J Clin Pharmacol. 2017;57(10):1290–4.PubMedCrossRefGoogle Scholar
  164. 164.
    Phillips OA, Sharaf LH. Oxazolidinone antimicrobials: a patent review (2012–2015). Expert Opin Ther Pat. 2016;26(5):591–605.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Claire Roger
    • 1
    • 2
    • 3
  • Jason A. Roberts
    • 3
    • 4
    • 5
  • Laurent Muller
    • 1
    • 2
  1. 1.Department of Anesthesiology, Intensive Care, Pain and Emergency MedicineNîmes University HospitalNîmes cedex 9France
  2. 2.EA 2992, Faculty of MedicineMontpellier-Nimes UniversityNîmesFrance
  3. 3.Burns Trauma and Critical Care Research CentreThe University of QueenslandBrisbaneAustralia
  4. 4.School of PharmacyThe University of QueenslandBrisbaneAustralia
  5. 5.Department of Intensive Care MedicineRoyal Brisbane and Womens’ HospitalBrisbaneAustralia

Personalised recommendations