Linezolid: A promising option in the treatment of Gram-positives

Journal of Antimicrobial Chemotherapy

Volumn 72, Issue 2, 2017, Pages 354-364

  Bialvaei, Abed Zahedi ^a   Rahbar, Mohammad ^b   Yousefi, Mehdi ^c   Asgharzadeh, Mohammad ^d   Kafil, Hossein Samadi ^e  

^a IRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b MINISTRY OF HEALTH AND MEDICAL EDUCATION   (Iran)

^c TABRIZ UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^d TABRIZ UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^e TABRIZ UNIVERSITY OF MEDICAL SCIENCES   (Iran)

Author keywords

[No Author keywords available]

Indexed keywords

CHLORAMPHENICOL; CLINDAMYCIN; DICLOXACILLIN; IMMUNOGLOBULIN; LINCOSAMIDE; LINEZOLID; MACROLIDE; OXACILLIN; OXAZOLIDINONE DERIVATIVE; PENICILLIN DERIVATIVE; RIFAMPICIN; STREPTOGRAMIN DERIVATIVE; TEDIZOLID; TETRACYCLINE DERIVATIVE; VANCOMYCIN; ANTIINFECTIVE AGENT; PROTEIN SYNTHESIS INHIBITOR;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ANTIBIOTIC THERAPY; APLASTIC ANEMIA; AREA UNDER THE CURVE; ARTICLE; BACTERIUM ISOLATE; BONE MARROW SUPPRESSION; CLINICAL LABORATORY; CYTOPENIA; DIAGNOSTIC PROCEDURE; DIARRHEA; DRUG CLEARANCE; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG SCREENING; EXTENSIVELY DRUG RESISTANT TUBERCULOSIS; GRAM POSITIVE BACTERIUM; GRAM POSITIVE INFECTION; HUMAN; MINIMUM INHIBITORY CONCENTRATION; MULTICENTER STUDY (TOPIC); NAUSEA; NONHUMAN; PHARMACODYNAMICS; PHARMACOKINETIC PARAMETERS; PHASE 3 CLINICAL TRIAL (TOPIC); PREVALENCE; SKIN INFECTION; SOFT TISSUE INFECTION; THROMBOCYTOPENIA; VENTILATOR ASSOCIATED PNEUMONIA; VOMITING; DRUG EFFECTS; GRAM-POSITIVE BACTERIAL INFECTIONS; MICROBIAL SENSITIVITY TEST; UTILIZATION;

ANTI-BACTERIAL AGENTS; DRUG RESISTANCE, BACTERIAL; GRAM-POSITIVE BACTERIA; GRAM-POSITIVE BACTERIAL INFECTIONS; HUMANS; LINEZOLID; MICROBIAL SENSITIVITY TESTS; PROTEIN SYNTHESIS INHIBITORS;

EID: 85014574590     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dkw450     Document Type: Article

References (127)

1. Lohray BB, Baskaran S, Rao BS et al. A short synthesis of oxazolidinone derivatives linezolid and eperezolid: a new class of antibacterials. Tetrahedron Lett 1999; 40: 4855-6.
2. CDC. Nosocomial enterococci resistant to vancomycin-United States, 1989-1993.MMWR 1993; 42: 597-9.
3. Mutnick AH, Biedenbach DJ, Turnidge JD et al. Spectrum and potency evaluation of a new oxazolidinone, linezolid: report from the SENTRY antimicrobial surveillance program, 1998-2000. Diagn Microbiol Infect Dis 2002; 43: 65-73.
4. Khare M, Keady D. Antimicrobial therapy of methicillin resistant Staphylococcus aureus infection. Expert Opin Pharmacother 2003; 4: 165-77.
5. López H, Li JZ, Balan DA et al. Hospital resource use and cost of treatment with linezolid versus teicoplanin for treatment of serious gram-positive bacterial infections among hospitalized patients from South America and Mexico: results fromamulticenter trial. Clin Ther 2003; 25: 1846-71.
6. Carbon C. Costs of treating infections caused by methicillin-resistant staphylococci and vancomycin-resistant enterococci. J Antimicrob Chemother 1999; 44: 31-6.
7. Naimi TS, LeDell KH, Como-Sabetti K et al. Comparison of community-and health care-associatedmethicillin-resistant Staphylococcus aureus infection. JAMA 2003; 290: 2976-84.
8. Itani KM, Weigelt J, Li JZ et al. Linezolid reduces length of stay and duration of intravenous treatment compared with vancomycin for complicated skin and soft tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). Int J Antimicrob Agents 2005; 26: 442-8.
9. Diekema D, Pfaller M, Schmitz F et al. Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY antimicrobial surveillance program, 1997-1999. Clin Infect Dis 2001; 32 Suppl 2: S114-32.
10. Livermore DM. Linezolid in vitro:mechanismand antibacterial spectrum. J Antimicrob Chemother 2003; 51 Suppl 2: ii9-16.
11. Brickner SJ, Barbachyn MR, Hutchinson DK et al. Linezolid (Zyvox), the first member of a completely new class of antibacterial agents for treatment of serious gram-positive infections. JMed Chem2008; 51: 1981-90.
12. Viale P, Pagani L, Cristini F et al. Linezolid for the treatment of central nervous system infections in neurosurgical patients. Scand J Infect Dis 2002; 34: 456-9.
13. Diekema DJ, Jones RN. Oxazolidinone antibiotics. Lancet 2001; 358: 1975-82.
14. Jones RN, Ross JE, Bell JM et al. ZyvoxVR Annual Appraisal of Potency and Spectrum program: linezolid surveillance program results for 2008. Diagn Microbiol Infect Dis 2009; 65: 404-13.
15. Zurenko GE, Yagi BH, Schaadt RD et al. In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents. Antimicrob Agents Chemother 1996; 40: 839-45.
16. Rybak MJ, Cappelletty DM, Moldovan T et al. 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, andEnterococcus faecium. Antimicrob Agents Chemother 1998; 42: 721-4.
17. Brown-Elliott BA, Ward SC, Crist CJ et al. In vitro activities of linezolid against multiple Nocardia species. Antimicrob Agents Chemother 2001; 45: 1295-7.
18. Boal AK, Grove TL, McLaughlinMI et al. Structural basis formethyl transfer by a radical SAMenzyme. Science 2011; 332: 1089-92.
19. Buysse J, Demyan W, Dunyak D et al. Mutation of the AcrAB antibiotic efflux pumpin Escherichia coli confers susceptibility to oxazolidinone antibiotics. Abstract C-42. In: Abstracts of the Thirty-sixth Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC, USA: American Society for Microbiology.
20. Hamel J, Stapert D, Moermann J et al. Linezolid, critical characteristics. Infection 2000; 28: 60-4.
21. Dresser LD, Rybak MJ. The pharmacologic and bacteriologic properties of oxazolidinones, a new class of synthetic antimicrobials. Pharmacotherapy 1998; 18: 456-62.
22. Wunderink RG, Mendelson MH, Somero MS et al. Early microbiological response to linezolid vs vancomycin in ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus. Chest 2008; 134: 1200-7.
23. Rubinstein E, Cammarata SK, Oliphant TH et al. Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patientswith nosocomial pneumonia: a randomized, double-blind, multicenter study. Clin Infect Dis 2001; 32: 402-12.
24. Wunderink RG, Rello J, Cammarata SK et al. Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest 2003; 124: 1789-97.
25. Stalker DJ, Jungbluth GL. Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial. Clin Pharmacokinet 2003; 42: 1129-40.
26. Dehghanyar P, Bürger C, Zeitlinger M et al. Penetration of linezolid into soft tissues of healthy volunteers after single andmultiple doses. Antimicrob Agents Chemother 2005; 49: 2367-71.
27. Lovering A, Zhang J, Bannister G et al. Penetration of linezolid into bone, fat, muscle and haematomaof patients undergoing routine hip replacement. JAntimicrobChemother 2002; 50: 73-7.
28. Moellering RC. Linezolid: the first oxazolidinone antimicrobial. Ann Intern Med 2003; 138: 135-42.
29. MacGowan AP. Pharmacokinetic and pharmacodynamic profile of linezolid in healthy volunteers and patients with Gram-positive infections. JAntimicrobChemother 2003; 51 Suppl 2: ii17-25.
30. Adembri C, Fallani S, Cassetta MI et al. Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septic patients: intermittent versus continuous infusion. Int J Antimicrob Agents 2008; 31: 122-9.
31. Tsuji Y, Hiraki Y, Matsumoto K et al. Thrombocytopenia and anemia caused by a persistent high linezolid concentration inpatientswith renaldysfunction. J Infect Chemother 2011; 17: 70-5.
32. Lin Y-H, Wu V-C, Tsai I-J et al. High frequency of linezolid-associated thrombocytopenia among patients with renal insufficiency. Int J Antimicrob Agents 2006; 28: 345-51.
33. Attassi K, Hershberger E, AlamR et al. Thrombocytopenia associatedwith linezolid therapy. Clin Infect Dis 2002; 34: 695-8.
34. Park I-N, Hong S-B, Oh Y-M et al. Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis. JAntimicrobChemother 2006; 58: 701-4.
35. Migliori GB, Eker B, Richardson M et al. A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis. Eur Respir J 2009; 34: 387-93.
36. Matsumoto K, Takeshita A, Ikawa K et al. Higher linezolid exposure and higher frequency of thrombocytopenia in patients with renal dysfunction. Int J Antimicrob Agents 2010; 36: 179-81.
37. Matsumoto K, Takeda Y, Takeshita A et al. Renal function as a predictor of linezolid-induced thrombocytopenia. Int J Antimicrob Agents 2009; 33: 98-9.
38. Shinabarger DL, Marotti KR, Murray RWet al. Mechanism of action of oxazolidinones: effects of linezolid and eperezolid on translation reactions. Antimicrob Agents Chemother 1997; 41: 2132-6.
39. Eustice D, Feldman P, Slee A. Themechanism of action of DuP 721, a new antibacterial agent: effects on macromolecular synthesis. Biochem Biophys Res Commun 1988; 150: 965-71.
40. Daly JS, Eliopoulos GM, Reiszner E et al. Activity andmechanismof action of DuP 105 and DuP 721, new oxazolidinone compounds. J Antimicrob Chemother 1988; 21: 721-30.
41. Lin AH, Murray RW, Vidmar TJ et al. The oxazolidinone eperezolid binds to the 50S ribosomal subunit and competes with binding of chloramphenicol and lincomycin. Antimicrob Agents Chemother 1997; 41: 2127-31.
42. Gemmell CG, Ford CW. Virulence factor expression by Gram-positive cocci exposed to subinhibitory concentrations of linezolid. J Antimicrob Chemother 2002; 50: 665-72.
43. Tsiodras S, Gold HS, Sakoulas G et al. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet 2001; 358: 207-8.
44. Prystowsky J, Siddiqui F, Chosay J et al. Resistance to linezolid: characterization of mutations in rRNA and comparison of their occurrences in vancomycinresistant enterococci. Antimicrob Agents Chemother 2001; 45: 2154-6.
45. Flamm RK, Farrell DJ, Mendes RE et al. LEADER surveillance program results for 2010: an activity and spectrum analysis of linezolid using 6801 clinical isolates from the United States (61 medical centers). Diagn Microbiol Infect Dis 2012; 74: 54-61.
46. Diaz L, Kiratisin P, Mendes RE et al. Transferable plasmid-mediated resistance to linezolid due to cfr in a human clinical isolate of Enterococcus faecalis. Antimicrob Agents Chemother 2012; 56: 3917-22.
47. Hillemann D, Rüsch-Gerdes S, Richter E. In vitro-selected linezolid-resistant Mycobacterium tuberculosis mutants. Antimicrob Agents Chemother 2008; 52: 800-1.
48. Kaatz GW, Seo SM. In vitro activities of oxazolidinone compounds U100592 and U100766 against Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob Agents Chemother 1996; 40: 799-801.
49. Jones RN, Ross JE, Fritsche TR et al. Oxazolidinone susceptibility patterns in 2004: report from the ZyvoxVR Annual Appraisal of Potency and Spectrum (ZAAPS) Program assessing isolates from 16 nations. J Antimicrob Chemother 2006; 57: 279-87.
50. Kloss P, Xiong L, Shinabarger DL et al. Resistance mutations in 23 S rRNA identify the site of action of the protein synthesis inhibitor linezolid in the ribosomal peptidyl transferase center. JMol Biol 1999; 294: 93-101.
51. Liakopoulos A, Neocleous C, Klapsa D et al. A T2504A mutation in the 23S rRNA gene responsible for high-level resistance to linezolid of Staphylococcus epidermidis. J Antimicrob Chemother 2009; 64: 206-7.
52. Wada A, Ohta H, Kulthanan K et al. Molecular cloning and mapping of 16S-23S rRNA gene complexes of Staphylococcus aureus. J Bacteriol 1993; 175: 7483-7.
53. Seedat J, Zick G, Klare I et al. Rapid emergence of resistance to linezolid during linezolid therapy of an Enterococcus faecium infection. Antimicrob Agents Chemother 2006; 50: 4217-9.
54. Long KS, Poehlsgaard J, Kehrenberg C et al. The Cfr rRNAmethyltransferase confers resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antibiotics. Antimicrob Agents Chemother 2006; 50: 2500-5.
55. Kehrenberg C, Aarestrup FM, Schwarz S. IS21-558 insertion sequences are involved in the mobility of themultiresistance gene cfr. Antimicrob Agents Chemother 2007; 51: 483-7.
56. Schwarz S, Werckenthin C, Kehrenberg C. Identification of a plasmidborne chloramphenicol-florfenicol resistance gene in Staphylococcus sciuri. Antimicrob Agents Chemother 2000; 44: 2530-3.
57. Kehrenberg C, Schwarz S, Jacobsen L et al. A new mechanism for chloramphenicol, florfenicol and clindamycin resistance: methylation of 23S ribosomal RNA at A2503. MolMicrobiol 2005; 57: 1064-73.
58. Wang Y, Lv Y, Cai J et al. A novel gene, optrA, that confers transferable resistance to oxazolidinones and phenicols and its presence in Enterococcus faecalis and Enterococcus faeciumof human and animal origin. J Antimicrob Chemother 2015; 70: 2182-90.
59. Itani KM, Shorr AF. FDA guidance for ABSSSI trials: implications for conducting and interpreting clinical trials. Clin Infect Dis 2014; 58: S4-9.
60. Locke JB, Zurenko GE, Shaw KJ et al. Tedizolid for the management of human infections: in vitro characteristics. Clin Infect Dis 2014; 58: S35-42.
61. Cai J, Wang Y, Schwarz S et al. Enterococcal isolates carrying the novel oxazolidinone resistance gene optrA from hospitals in Zhejiang, Guangdong, and Henan, China, 2010-2014. ClinMicrobiol Infect 2015; 21: 1095.e1-4.
62. Mendes RE, Hogan PA, Jones RN et al. Surveillance for linezolid resistance via the ZyvoxVR Annual Appraisal of Potency and Spectrum (ZAAPS) programme (2014): evolving resistance mechanisms with stable susceptibility rates. JAntimicrobChemother 2016; 71: 1860-5.
63. O'Driscoll C, Murphy V, Doyle O et al. First outbreak of linezolid-resistant vancomycin-resistant Enterococcus faecium in an Irish hospital, February to September 2014.JHosp Infect 2015; 91: 367-70.
64. Mendes RE, Deshpande LM, Jones RN. Linezolid update: stable in vitro activity following more than a decade of clinical use and summary of associated resistance mechanisms. Drug Resist Updat 2014; 17: 1-12.
65. Rai S, Rani M, Choudhury DD et al. Failure to decolonize mupirocin and linezolid resistant MRSA from a patient with necrotizing soft tissue infection. J Infect Public Health 2016; 9: 667-9.
66. Sierra JM, Camoez M, Tubau F et al. Low prevalence of Cfr-mediated linezolid resistance among methicillin-resistant Staphylococcus aureus in a Spanish hospital: case report on linezolid resistance acquired during linezolid therapy. PLoS One 2013; 8: e59215.
67. Alonso M, Marín M, Iglesias C et al. Rapid identification of linezolid resistance in Enterococcus spp. based on high-resolution melting analysis. JMicrobiol Methods 2014; 98: 41-3.
68. Sinclair A, Arnold C, Woodford N. Rapid detection and estimation by pyrosequencing of 23S rRNA genes with a single nucleotide polymorphism conferring linezolid resistance in enterococci. Antimicrob Agents Chemother 2003; 47: 3620-2.
69. Rao N, Ziran BH, Hall RA et al. Successful treatment of chronic bone and joint infectionswith oral linezolid. Clin Orthop Relat Res 2004; 427: 67-71.
70. Bassetti M, Vitale F, Melica G et al. Linezolid in the treatment of Gram-positive prosthetic joint infections. J Antimicrob Chemother 2005; 55: 387-90.
71. Senneville E, Legout L, Valette M et al. Effectiveness and tolerability of prolonged linezolid treatment for chronic osteomyelitis: a retrospective study. Clin Ther 2006; 28: 1155-63.
72. Ford CW, Hamel JC, Wilson DM et al. In vivo activities of U-100592 and U-100766, novel oxazolidinone antimicrobial agents, against experimental bacterial infections. Antimicrob Agents Chemother 1996; 40: 1508-13.
73. Moran GJ, Abrahamian FM, LoVecchio F et al. Acute bacterial skin infections: developments since the 2005 Infectious Diseases Society of America (IDSA) guidelines. J EmergMed2013; 44: e397-412.
74. Stevens DL, Smith LG, Bruss JB et al. Randomized comparison of linezolid (PNU-100766) versus oxacillin-dicloxacillin for treatment of complicated skin and soft tissue infections. Antimicrob Agents Chemother 2000; 44: 3408-13.
75. Serisier DJ, Jones G, Carroll M. Eradication of pulmonary methicillinresistant Staphylococcus aureus (MRSA) in cystic fibrosis with linezolid. J Cyst Fibros 2004; 3: 61.
76. Sharpe JN, Shively EH, Polk HC. Clinical and economic outcomes of oral linezolid versus intravenous vancomycin in the treatment of MRSAcomplicated, lower-extremity skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. AmJ Surg 2005; 189: 425-8.
77. Biedenbach DJ, Farrell DJ, Mendes RE et al. Stability of linezolid activity in an era of mobile oxazolidinone resistance determinants: results from the 2009. ZyvoxVR Annual Appraisal of Potency and Spectrum Program. Diagn Microbiol Infect Dis 2010; 68: 459-67.
78. Mendes RE, Flamm RK, Hogan PA et al. Summary of linezolid activity and resistance mechanisms detected during the 2012 surveillance program for the United States (LEADER). Antimicrob Agents Chemother 2014; 58: 1243-7.
79. Mutnick AH, Enne V, Jones RN. Linezolid resistance since 2001: SENTRY antimicrobial surveillance program. Ann Pharmacother 2003; 37: 769-74.
80. Mendes RE, Hogan PA, Streit JM et al. ZyvoxVR Annual Appraisal of Potency and Spectrum (ZAAPS) Program: report of linezolid activity over 9 years (2004-12). J Antimicrob Chemother 2014; 69: 1582-8.
81. Eliopoulos GM, Meka VG, Gold HS. Antimicrobial resistance to linezolid. Clin Infect Dis 2004; 39: 1010-5.
82. Jones RN, Della-Latta P, Lee LV et al. Linezolid-resistant Enterococcus faecium isolated from a patient without prior exposure to an oxazolidinone: report from the SENTRY antimicrobial surveillance program. Diagn Microbiol Infect Dis 2002; 42: 137-9.
83. Gu B, Kelesidis T, Tsiodras S et al. The emerging problem of linezolidresistant Staphylococcus. JAntimicrobChemother 2013; 68: 4-11.
84. Wilson P, Andrews J, Charlesworth R et al. Linezolid resistance in clinical isolates of Staphylococcus aureus. J Antimicrob Chemother 2003; 51: 186-8.
85. Menichetti F. Current and emerging serious Gram-positive infections. Clin Microbiol Infect 2005; 11: 22-8.
86. Toh SM, Xiong L, Arias CA et al. Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid. MolMicrobiol 2007; 64: 1506-14.
87. Mendes RE, Deshpande LM, Castanheira M et al. First report of cfrmediated resistance to linezolid in human staphylococcal clinical isolates recovered in the United States. Antimicrob Agents Chemother 2008; 52: 2244-6.
88. Feßler AT, Calvo N, Gutiérrez N et al. Cfr-mediated linezolid resistance in methicillin-resistant Staphylococcus aureus and Staphylococcus haemolyticus associated with clinical infections in humans: two case reports. J Antimicrob Chemother 2014; 69: 268-270.
89. Chien JW, Kucia ML, Salata RA. Use of linezolid, an oxazolidinone, in the treatment of multidrug-resistant gram-positive bacterial infections. Clin Infect Dis 2000; 30: 146-51.
90. Kaplan SL, Patterson L, Edwards KM et al. Linezolid for the treatment of community-acquired pneumonia in hospitalized children. Pediatr Infect Dis J 2001; 20: 488-94.
91. Waldrep TW, Skiest DJ. Linezolid-induced anemia and thrombocytopenia. Pharmacotherapy 2002; 22: 109-12.
92. French G. Safety and tolerability of linezolid. J Antimicrob Chemother 2003; 51 Suppl 2: ii45-53.
93. BernsteinWB, Trotta RF, Rector JT et al. Mechanisms for linezolid-induced anemia and thrombocytopenia. Ann Pharmacother 2003; 37: 517-20.
94. Narita M, Tsuji BT, Yu VL. Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome. Pharmacotherapy 2007; 27: 1189-97.
95. Kuter DJ, Tillotson GS. Hematologic effects of antimicrobials: focus on the oxazolidinone linezolid. Pharmacotherapy 2001; 21: 1010-3.
96. Green SL, Maddox JC, Huttenbach ED. Linezolid and reversible myelosuppression. JAMA 2001; 285: 1291.
97. Moran GJ, Fang E, Corey GR et al. 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: 696-705.
98. Livermore DM, Mushtaq S, Warner M et al. Activity of oxazolidinone TR-700 against linezolid-susceptible and-resistant staphylococci and enterococci. J Antimicrob Chemother 2009; 63: 713-5.
99. Dietze R, Hadad DJ, McGee B et al. Early and extended early bactericidal activity of linezolid in pulmonary tuberculosis. Am J Respir Crit Care Med 2008; 178: 1180-5.
100. Livermore DM, WarnerM, Mushtaq S et al. In vitro activity of the oxazolidinone RWJ-416457 against linezolid-resistant and-susceptible staphylococci and enterococci. Antimicrob Agents Chemother 2007; 51: 1112-4.
101. Auckland C, Teare L, Cooke F et al. Linezolid-resistant enterococci: report of the first isolates inthe United Kingdom. JAntimicrob Chemother 2002; 50: 743-6.
102. Krawczyk B, Samet A, BronkMet al. Emerging linezolid-resistant, vancomycin resistant Enterococcus faecium from a patient of a haematological unit in Poland. Pol JMicrobiol 2004; 53: 193-6.
103. Bersos Z, Maniati M, Kontos F et al. First report of a linezolid-resistant vancomycin-resistant Enterococcus faecium strain in Greece. J Antimicrob Chemother 2004; 53: 685-6.
104. Potoski BA, Adams J, Clarke L et al. Epidemiological profile of linezolidresistant coagulase-negative staphylococci. Clin Infect Dis 2006; 43: 165-71.
105. Richter E, Rüsch-Gerdes S, Hillemann D. First linezolid-resistant clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother 2007; 51: 1534-6.
106. Kainer MA, Devasia RA, Jones TF et al. Response to emerging infection leading to outbreak of linezolid-resistant enterococci. Emerg Infect Dis 2007; 13: 1024-30.
107. Flamm RK, Mendes RE, Ross JE et al. Linezolid surveillance results for the United States (LEADER Surveillance Program 2011). Antimicrob Agents Chemother 2013; 57: 1077-81.
108. Ikeda-Dantsuji Y, Hanaki H, Nakae T et al. Emergence of linezolidresistant mutants in a susceptible-cell population of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2011; 55: 2466-8.
109. de Almeida LM, Lincopan N, de AraújoMRE et al. Clonal dissemination of linezolid-resistant Staphylococcus haemolyticus exhibiting the G2576Tmutation in the 23S rRNA gene in a tertiary care hospital, Brazil. Antimicrob. Agents Chemother 2012; 56: 2792-3.
110. Ntokou E, Stathopoulos C, Kristo I et al. Intensive care unit dissemination of multiple clones of linezolid-resistant Enterococcus faecalis and Enterococcus faecium. JAntimicrobChemother 2012; 67: 1819-23.
111. Cai JC, Hu YY, Zhang R et al. Linezolid-resistant clinical isolates of meticillin-resistant coagulase-negative staphylococci and Enterococcus faeciumfrom China. JMedMicrobiol 2012; 61: 1568-73.
112. Barros M, Branquinho R, Grosso F et al. Linezolid-resistant Staphylococcus epidermidis, Portugal, 2012. Emerg Infect Diseases 2014; 20: 903.
113. Quiles-Melero I, Gómez-Gil R, Romero-Gómez MP et al. Mechanisms of linezolid resistance among staphylococci in a tertiary hospital. J ClinMicrobiol 2013; 51: 998-1001.
114. Beckert P, Hillemann D, Kohl TA et al. rplC T460C identified as a dominant mutation in linezolid-resistant Mycobacterium tuberculosis strains. Antimicrob Agents Chemother 2012; 56: 2743-5.
115. Patel SN, Memari N, Shahinas D et al. Linezolid resistance in Enterococcus faecium isolated in Ontario, Canada. Diagn Microbiol Infect Dis 2013; 77: 350-3.
116. Román F, Roldán C, Trincado P et al. Detection of linezolid-resistant Staphylococcus aureus with 23S rRNA and novel L4 riboproteinmutations in a cystic fibrosis patient in Spain. Antimicrob Agents Chemother 2013; 57: 2428-9.
117. Yang X-J, Chen Y, Yang Q et al. Emergence of cfr-harbouring coagulasenegative staphylococci among patients receiving linezolid therapy in two hospitals in China. JMedMicrobiol 2013; 62: 845-50.
118. Cui L, Wang Y, Li Y et al. Cfr-mediated linezolid-resistance among methicillin-resistant coagulase-negative staphylococci from infections of humans. PLoS One 2013; 8: e57096.
119. Armin S, Rouhipour A, Fallah F et al. Vancomycin and linezolid resistant staphylococcus in hospitalized children. Arch Pediat Infect Dis 2013; 1: 4-8.
120. de Almeida LM, de Araújo MRE, Iwasaki MF et al. Linezolid resistance in vancomycin-resistant Enterococcus faecalis and Enterococcus faecium isolates in a Brazilian hospital. Antimicrob Agents Chemother 2014; 58: 2993-4.
121. O'Connor C, Powell J, Finnegan C et al. Incidence, management and outcomes of the first cfr-mediated linezolid-resistant Staphylococcus epidermidis outbreak in a tertiary referral centre in the Republic of Ireland. J Hosp Infect 2015; 90: 316-21.
122. Cai JC, Hu YY, Zhou HW et al. Dissemination of the same cfr-carrying plasmid among methicillin-resistant Staphylococcus aureus and coagulasenegative staphylococcal isolates in China. Antimicrob Agents Chemother 2015; 59: 3669-71.
123. Bender J, Strommenger B, SteglichMet al. Linezolid resistance in clinical isolates of Staphylococcus epidermidis from German hospitals and characterization of two cfr-carrying plasmids. J Antimicrob Chemother 2015; 70: 1630-8.
124. Niebel M, Perera M, Shah T et al. Emergence of linezolid resistance in hepatobiliary infections caused by Enterococcus faecium. Liver Transpl 2016; 22: 201-8.
125. Doern CD, Park JY, Gallegos M et al. Investigation of linezolid resistance in staphylococci and enterococci. JClinMicrobiol 2016; 54: 1289-94.
126. Lee M, Lee J, Carroll MW et al. Linezolid for treatment of chronic extensively drug-resistant tuberculosis. NEngl JMed2012; 367: 1508-18.
127. Ippolito JA, Kanyo ZF, Wang D et al. Crystal structure of the oxazolidinone antibiotic linezolid bound to the 50S ribosomal subunit. J Med Chem 2008; 51: 3353-6.