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Oxazolidinones

A Review

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Abstract

The oxazolidinones represent a novel chemical class of synthetic antimicrobial agents. They exhibit an unique mechanism of protein synthesis inhibition and generally display bacteriostatic activity against many important human pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin- and cephalosporin-resistant Streptococcus pneumoniae. Linezolid, the oxazolidinone which has been selected for clinical development, has near complete oral bioavailability plus favourable pharmacokinetic and toxicity profiles. Results from experimental models of infection and phase II trials reveal linezolid to be highly active in vivo against infections due to many common Gram-positive pathogens. The role of linezolid remains to be determined in phase III clinical trials, but it shows great promise as an alternative to glycopeptides and streptogramins to treat serious infections due to resistant Gram-positive organisms. Further modification of the oxazolidinone nucleus may yield agents with even greater potency and with novel spectra of activity.

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References

  1. Spink WW, Ferris V. Quantitative action of penicillin inhibitor from penicillin-resistant strains of staphylococci. Science 1945; 102: 221

    Article  PubMed  CAS  Google Scholar 

  2. Panlilio AL, Culver DH, Gaynes RP, et al. Methicillin-resistant S. aureus in US hospitals, 1975–1991. Infect Control Hosp Epidemiol 1992; 13: 582–6

    Article  PubMed  CAS  Google Scholar 

  3. Schwalbe RS, Stapleton JT, Gilligan PH. Emergence of vancomycin resistance in coagulase-negative staphylococci. N Engl J Med 1987; 316: 927–31

    Article  PubMed  CAS  Google Scholar 

  4. Centers for Disease Control and Prevention. Update: Staphylococcus aureus with reduced susceptibility to vancomycin —United States, 1997. MMWR Morb Mortal Wkly Rep 1997; 46: 813–5

    Google Scholar 

  5. Jones RN, Sader HS, Erwin ME, et al. Emerging multiply resistant enterococci among clinical isolates. I. Prevalence data from 97 medical center surveillance study in the United States. Diag Microbiol Infect Dis 1995; 21: 85–93

    CAS  Google Scholar 

  6. Doern GV, Pfaller MA, Kugler K, et al. Prevalence of antimicrobial resistance among respiratory tract isolates of Streptococcus pneumoniae in North America: 1997 results from the SENTRY antimicrobial surveillance program. Clin Infect Dis 1998; 27: 764–8

    Article  PubMed  CAS  Google Scholar 

  7. Bochud P, Calandra T, Francioli P. Bacteremia due to viridans streptococci in neutropenic patients: a review. Am J Med 1994; 97: 256–64

    Article  PubMed  CAS  Google Scholar 

  8. Pfaller MA, Jones RN, Doern GV, et al. Bacterial pathogens isolated from patients with bloodstream infection: frequencies of occurrence and antimicrobial susceptibility patterns from the SENTRY antimicrobial surveillance program (United States and Canada, 1997). Antimicrob Agents Chemother 1998; 42: 1762–70

    PubMed  CAS  Google Scholar 

  9. Banerjee SN, Emori TG, Culver DH, et al. Secular trends in nosocomial primary bloodstream infections in the United States, 1980–1989. Am J Med 1991; 91 Suppl. 3B: 86S–89S

    Article  PubMed  CAS  Google Scholar 

  10. Marshall SA, Wilke WW, Pfaller MA, et al. Staphylococcus aureus and coagulase-negative staphylococci from blood stream infections: frequency of occurrence, antimicrobial susceptibility, and molecular (mec A) characterisation of oxacillin resistance in the SCOPE program. Diagn Microbiol Infect Dis 1998; 30: 205–14

    Article  PubMed  CAS  Google Scholar 

  11. Moellering RC. Vancomycin-resistant enterococci. Clin Infect Dis 1998; 26: 1196–9

    Article  PubMed  Google Scholar 

  12. Jones RN, Barrett MS. Antimicrobial activity of SCH 27899, oligosaccharide member of the everninomycin class with a wide Gram-positive spectrum. Clin Microbiol Infect 1995; 1: 35–43

    Article  PubMed  CAS  Google Scholar 

  13. Linden PK, Pasculle AW, McDevitt D, et al. Effect of quinupristin-dalfopristin on the outcome of vancomycin-resistant Enterococcus faecium. bacteraemia: Comparison with a control cohort. J Antimicrob Chemother 1997; 39 Suppl. A: 145–51

    Article  PubMed  CAS  Google Scholar 

  14. Jones RN, Barrett MS, Erwin ME. In vitro activity and spectrum of LY333328, a novel glycopeptide derivative. Antimicrob Agents Chemother 1997; 41: 488–93

    PubMed  CAS  Google Scholar 

  15. Chambers HF. In vitro and in vivo antistaphylococcal activities of 1-695,256, a carbapenem with high affinity for the penicillin-binding protein PBP 2a. Antimicrob Agents Chemother 1995; 39: 462–6

    Article  PubMed  CAS  Google Scholar 

  16. Rosen H, Silver L, Hammond M. L-786,392: a releasable pharmacophore carbapenem active on MRS, VISA, and VRE. Abstracts of the 36th Annual General Meeting of the Infectious Diseases Society of America; 1998 Nov 12-15: Denver (CO). Alexandria (VA): Infectious Diseases Society of America, 1998

  17. Alborn WE, Allen NE, Preston DA. Daptomycin disrupts membrane potential in growing Staphylococcus aureus. Antimicrob Agents Chemother 1991; 35: 2282–7

    Article  PubMed  CAS  Google Scholar 

  18. Ford CW, Hamel JC, Stapert D, et al. Oxazolidinones: new antibacterial agents. Trends Microbiol 1997; 5: 196–200

    Article  PubMed  CAS  Google Scholar 

  19. Moellering Jr RC. A novel antimicrobial agent joins the battle against resistant bacteria. Ann Intern Med 1999; 130: 155–7

    PubMed  Google Scholar 

  20. Slee AM, Wuonola MA, McRipley RJ, et al. Oxazolidinones, a new class of synthetic antibacterial agents: in vitro and in vivo activities of DuP 105 and DuP 721. Antimicrob Agents Chemother 1987; 31: 1791–7

    Article  PubMed  CAS  Google Scholar 

  21. Brickner SJ. Oxazolidinone antibacterial agents. Curr Pharm Design 1996; 2: 175–94

    CAS  Google Scholar 

  22. Brickner SJ, Hutchinson DK, Barbachyn MR, et al. Synthesis and antibacterial activity of U-100592 and U-100766, two oxazolidinone antibacterial agents for the potential treatment of multidrug-resistant gram-positive bacterial infections. J Med Chem 1996; 39: 673–9

    Article  PubMed  CAS  Google Scholar 

  23. Eustice DC, Feldman PA, Zajaz I, et al. Mechanism of action of DuP-721: inhibition of an early event during initiation of protein synthesis. Antimicrob Agents Chemother 1988; 32: 1218–22

    Article  PubMed  CAS  Google Scholar 

  24. Daly JS, Eliopoulos GM, Reisznerl, et al. Mechanism of action and in vitro studies of DuP-105 and DuP-721, new oxazolidinone antibacterials. J Antimicrob Chemother 1988; 21: 721–30

    Article  PubMed  CAS  Google Scholar 

  25. Shinabarger DL, Marotti KR, Murray RW, et al. Mechanism of action of oxazolidinones: effects of linezolid and eperezolid on translation reactions. Antimicrob Agents Chemother 1997; 41: 2132–6

    PubMed  CAS  Google Scholar 

  26. 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

    PubMed  CAS  Google Scholar 

  27. Swaney SM, Aoki H, Clelia Ganoza M, et al. The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria. Antimicrob Agents Chemother 1998; 42: 3251–5

    PubMed  CAS  Google Scholar 

  28. 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

    PubMed  CAS  Google Scholar 

  29. Murray RW, Schaadt RD, Zurenko GE, et al. Ribosomes from an oxazolidinone-resistant mutant confer resistance to eperezolid in a Staphylococcus aureus cell-free transcription-translation assay. Antimicrob Agents Chemother 1998; 42: 947–50

    PubMed  CAS  Google Scholar 

  30. Kaatz GW, Seo SM. In vitro activities of oxazolidinone compounds U-100592 and U-100766 against Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob Agents Chemother 1996; 40: 799–801

    PubMed  CAS  Google Scholar 

  31. Swaney SM, Shinabarger DL, Schaadt RD, et al. Oxazolidinone resistance is associated with a mutation in the peptidyl transferase region of 23S rRNA [abstract C-104]. In: Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-27: Washington (DC). Washington (DC): American Society for Microbiology, 1998

  32. 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

    PubMed  CAS  Google Scholar 

  33. Mulazimoglu L, Drenning SD, Yu VL. In vitro activities of two novel oxazolidinones (U-100592 and U-100766), a new fluoroquinolone (trovafloxacin), and dalfopristin-quinupristin against Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob Agents Chemother 1996; 40: 2428–30

    PubMed  CAS  Google Scholar 

  34. Jorgensen JH, McElmeel ML, Trippy CW. In vitro activities of the oxazolidinone antibiotics U-100592 and U-100766 against Staphylococcus aureus and coagulase-negative Staphylococcus species. Antimicrob Agents Chemother 1997; 41: 465–7

    PubMed  CAS  Google Scholar 

  35. 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, and Enterococcus faecium. Antimicrob Agents Chemother 1998; 42: 721–4

    Article  PubMed  CAS  Google Scholar 

  36. Spangler SK, Jacobs MR, Appelbaum PC. Activities of RPR 106972 (a new oral streptogramin), cefditoren (a new oral cephalosporin), two new oxazolidinones (U-100592 and U-100766), and other oral and parenteral agents against 203 penicillin-susceptible and -resistant pneumococci. Antimicrob Agents Chemother 1996; 40: 481–4

    PubMed  CAS  Google Scholar 

  37. Mason EO,Lamberth LB, Kaplan SL. In vitro activities of oxazolidinones U-100592 and U-100766 against penicillin-resistant and cephalosporin-resistant strains of Streptococcus pneumoniae. Antimicrob Agents Chemother 1996; 40: 1039–40

    PubMed  CAS  Google Scholar 

  38. Mercier RC, Penzak SR, Rybak MJ. In vitro activities of an investigational quinolone, glycylcycline, glycopeptide, streptogramin, and oxazolidinone tested alone and in combinations against vancomycin-resistant Enterococcus faecium. Antimicrob Agents Chemother 1997; 41: 2573–5

    PubMed  CAS  Google Scholar 

  39. Bostic GD, Perri MB, Thal LA, et al. Comparative in vitro and bactericidal activity of oxazolidinone antibiotics against multidrug-resistant enterococci. Diagn Microbiol Infect Dis 1998; 30: 109–12

    Article  PubMed  CAS  Google Scholar 

  40. Eliopoulos GM, Wennersten CB, Gold HS, et al. In vitro activities of new oxazolidinone antimicrobial agents against enterococci. Antimicrob Agents Chemother 1996; 40: 1745–7

    PubMed  CAS  Google Scholar 

  41. Biedenbach DJ, Jones RN. Disk diffusion test interpretive criteria and quality control recommendation for testing linezolid (U-1007660 and eperezolid (U-100592) with commercially prepared reagents. J Clin Microbiol 1997; 35: 3198–202

    PubMed  CAS  Google Scholar 

  42. Data on file, Upjohn Co., 1997

  43. Salmon SA, Portis EL, Case CA, et al. Minimum inhibitory concentration determinations for oxazolidinone antimicrobial agents and comparator agents against strains of Rhodococcus equi [abstract E-129]. In: Program and Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-27: Washington (DC). Washington (DC): American Society for Microbiology, 1998

  44. Schulin T, Wennersten CB, Ferraro MJ, et al. Susceptibilities of Legionella spp. to newer antimicrobials in vitro. Antimicrob Agents Chemother 1998; 42: 1520–3

    PubMed  CAS  Google Scholar 

  45. Goldstein EJ, Citron DM, Gerardo SH, et al. Linezolid compared with other macrolides against Pasteurella species [abstract E-147]. In: Program and Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-27: Washington (DC). Washington (DC): American Society for Microbiology, 1998

  46. Di Pentima MC, Mason Jr EO, Kaplan SL. In vitro antibiotic synergy against Flavobacterium. meningosepticum: implications for therapeutic options. Clin Infect Dis 1998; 26: 1169–76

    Article  PubMed  Google Scholar 

  47. Yagi BH, Zurenko GE. In vitro activity of linezolid and eperezolid, two novel oxazolidinone antimicrobial agents, against anaerobic bacteria. Anaerobe 1997; 3: 301–6

    Article  PubMed  CAS  Google Scholar 

  48. Ashtekar DR, Costa-Periera R, Shrinivasan T, et al. Oxazolidinones, a new class of synthetic antituberculous agent; in vitro and in vivo activities of DuP-721 against Mycobacterium tuberculosis. Diagn Microbiol Infect Dis 1991; 14: 465–71

    Article  PubMed  CAS  Google Scholar 

  49. Peters J, Kondo KL, Lee RK, et al. In vitro activity of oxazolidinones against Mycobacterium. avium complex. J Antimicrob Chemother 1995; 35: 675–9

    Article  PubMed  CAS  Google Scholar 

  50. Wu M, Aralor P, Nash K, et al. Linezolid, a new oxazolidinone, has activity in vitro and in macrophage culture system against Mycobacterium. avium. complex (MAC) [abstract E-142]. In: Program and Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-27: Washington (DC). Washington (DC): American Society for Microbiology, 1998

  51. Barbachyn MR, Hutchinson DK, Brickner SJ, et al. Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity. J Med Chem 1996; 39: 680–5

    Article  PubMed  CAS  Google Scholar 

  52. Cynamon MH, Klemens SP, Sharpe CA, et al. Activities of several novel oxazolidinones against Mycobacterium tuberculosis in a murine model. Antimicrob Agents Chemother 1999; 43: 1189–91

    PubMed  CAS  Google Scholar 

  53. 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

    PubMed  CAS  Google Scholar 

  54. Batts DH, Stalker DJ, Peel BG, et al. U-100592 phase I, multiple-oral dose, randomized, placebo-controlled, safety, tolerance and pharmacokinetics in healthy volunteers for 14.25 days using bulk drugs in capsules [abstract]. In: Program and Abstracts of the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1995 Sep 17-20: Washington (DC). Washington (DC): American Society for Microbiology, 1995

  55. Stalker DJ, Wajszczuk CP, Batts DH. Linezolid safety, tolerance, and pharmacokinetics following oral dosing twice daily for 14.5 days [abstract A-115]. In: Program and Abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1997 Sep 28-Oct 1: Washington (DC). Washington (DC): American Society for Microbiology, 1997

  56. Stalker DJ, Wajszczuk CP, Batts DH. Linezolid safety, tolerance, and pharmacokinetics after intravenous dosing twice daily for 7.5 days [abstract A-116]. In: Program and Abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1997 Sep 28-Oct 1: Washington (DC). Washington (DC): American Society for Microbiology, 1997

  57. Brier ME, Stalker DJ, Aronoff GR, et al. Pharmacokinetics of linezolid in subjects with various degrees of renal function and on dialysis [abstract A-54]. In: Program and Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-27: Washington (DC). Washington (DC): American Society for Microbiology, 1998

  58. Stalker DJ, Kearns GL, James L, et al. Pharmacokinetics of linezolid in pediatric patients [abstract 749]. In: Program and Abstracts of the 36th meeting of the Infectious Diseases Society of America; 1998 Nov 12-15: Denver(CO). Alexandria (VA): Infectious Diseases Society of America, 1998

  59. Andes D, Vesga O, Batts D, et al. Pharmacodynamic activity of an oxazolidinone in an animal infection model [abstract F-233]. In: Program and Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1996 Sep 15–18: Washington (DC). Washington (DC): American Society for Microbiology, 1996

  60. Andes D, Van Ogtrop ML, Craig WA. Pharmacodynamic activity of a new oxazolidinone, linezolid, in an animal infection model [abstract A-9]. In: Program and Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-27: Washington (DC). Washington (DC): American Society for Microbiology, 1998

  61. Batts DH. Linezolid clinical development program: end of phase II results [abstract]. 2nd European Congress of Chemotherapy: 1998 May 10–13, Hamburg

  62. Birmingham MC, Zimmer GS, Hafkin B, et al. Initial results of linezolid in patients with multidrug-resistant Gram-positive infections [abstract MN-26]. In: Program and Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-27: Washington (DC). Washington (DC): American Society for Microbiology, 1998

  63. Hyatt JM, Ballow CH, Forrest A, et al. Safety and efficacy of linezolid in eradication of nasal Staphylococcus aureus [abstract A-4]. In: Program and Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-27: Washington (DC). Washington (DC): American Society for Microbiology, 1998

  64. Perl TM, Cullen JJ, Pfaller MA, et al. A randomized, double-blind, placebo-controlled trial of intranasal mupirocin ointment for prevention of 5. aureus surgical site infections [abstract 88]. In: Abstracts of the 36th Annual Meeting of the Infectious Diseases Society of America; 1998 Nov 12-15: Denver (CO). Alexandria (VA): Infectious Diseases Society of America, 1998

  65. Dresser LD, Rybak MJ. The pharmacologic and bacteriologic properties of oxazolidinones, a new class of synthetic antimicrobials. Pharmacotherapy 1998; 18: 456–62

    PubMed  CAS  Google Scholar 

  66. Martin JP, Herberg JT, Slatter JG, et al. Although a novel microtiter-plate assay demonstrates that linezolid is a weak, competitive (reversible) inhibitor of human monoamine oxidase (MAO A), no clinical evidence of MAO A inhibition in clinical trials has been observed [abstract A-85]. In: Program and Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-27: Washington (DC). Washington (DC): American Society for Microbiology, 1998

  67. Gadwood RC, Walker EA, Thomasco LM, et al. Synthesis and antibacterial activity of azolylphenyl oxazolidinones having carbon-bound 1,3-thiazolyl rings [abstract F-139]. In: Program and Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-27: Washington (DC). Washington (DC): American Society for Microbiology, 1998

  68. Endermann R, Bartel S, Guarnieri W, et al. Synthesis and antibacterial activity of novel heteroaryl oxazolidinones. III: activities against clinically important Gram-positive pathogens [abstract F-129]. In: Program and Abstracts of the 38th Inter-science Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-27: Washington (DC). Washington (DC): American Society for Microbiology, 1998

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  1. Medical Microbiology Division, Department of Pathology, C606 GH, Iowa City, Iowa, 52242, USA

    Daniel J. Diekema & Ronald N. Jones

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Diekema, D.J., Jones, R.N. Oxazolidinones. Drugs 59, 7–16 (2000). https://doi.org/10.2165/00003495-200059010-00002

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