medigraphic.com

2002, Number 2

<< Back

Enf Infec Microbiol 2002; 22 (2)

Linezolid: Clinical applications of its pharmacodynamic and pharmacokinetic

Morfín OR, Esparza AS, Rodríguez NE

Language: Spanish
References: 50
Page: 69-74
PDF size: 64.15 Kb.


ABSTRACT

Background. Antimicrobial resistance among Gram-positive organisms is rising. Resistant Staphylococcus aureus, coagulase-negative Staphylococcus, Enterococcus, and Streptococcus pneumoniae, are now common pathogens of a variety of nosocomial and community infections. The treatment of Gram-positive infections is complicated due to the frequent resistance of S. aureus to methicillin, S. pneumoniae to penicillin and the vancomycin resistance of Enterococcus. Purpose. To review the pharmacokinetic and pharmacodynamic properties of linezolid. Data sources. Medline search for studies examining the pharmacokinetics and pharmacodynamics of linezolid. Study selection. Fifty studies reviewed. Data synthesis. Linezolid is a new antibiotic that belongs to the Oxazolidinone class of antimicrobial agents. Linezolid inhibits the initiation of protein synthesis in a variety of bacteria. Linezolid is active against methicillin-resistant S. aureus, penicillin-resistant S. pneumoniae and vancomycin-resistant Enterococcus faecium among other Gram-positive pathogens. After the administration of 600 mg of linezolid the half-life at the elimination phase is 5.5 h, the mean maximum concentration of the drug in plasma at steady state ranges from 15 to 21 μg/mL. The oral bioavailability is 100% after oral administration with a time to maximum concentration after an oral dose of 1.0 to 1.5 h. Linezolid has good tissue penetration including skin and lung. The usual linezolid dosage in adults is 600 mg every 12 h, and in children a dosage of 10 mg/kg every 8 h will be probably approved. A value of › 39% for the percentage of time during which the linezolid concentration exceeds the MIC of susceptible bacteria correlates with therapeutic success. The rapidly and extensively absorption after and oral dose facilitates the early discharge of patients with severe infections. Conclusions. Linezolid pharmacokinetics, pharmacodynamics and pharmacoeconomic properties support the use for the treatment of resistant Gram-positive infections.


REFERENCES

  1. Moellering RC Jr. A novel antimicrobial agent joins the battle against resistant bacteria. Ann Intern Med 1999;130(2):155-7.

  2. 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(1):146-51.

  3. Plouffe JF. Emerging therapies for serious Gram-positive bacterial infections: a focus on linezolid. Clin Infect Dis 2000;31(Suppl 4):S144-9.

  4. Shinabarger DL, et al. Mechanism ofaction of oxazolidinones: effects of linezolid and eperezolid on translation reactions. Antimicrob Agents Chemother 1997;41(10):2132-6.

  5. Swaney SM, et al. The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria. Antimicrob Agents Chemother 1998;42(12):3251-5.

  6. Slee AM, 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(11):1791-7.

  7. Ford CW, et al. In vivo activities of U-100592 and U-100766, novel oxazolidinone antimicrobial agents, against experimental bacterial infections. Antimicrob Agents Chemother 1996;40(6): 1508-13.

  8. Zurenko GE, et al. In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents. Antimicrob Agents Chemother 1996;40(4):839-45.

  9. Noskin GA, et al. In vitro activities of linezolid against important Gram-positive bacterial pathogens including vancomycin-resistant enterococci. Antimicrob Agents Chemother 1999;43(8): 2059-62.

  10. Jones ME, et al. Comparative activities of clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, ofloxacin, sparfloxacin, and trovafloxacin and nonquinolones linozelid, quinupristin-dalfopristin, gentamicin, and vancomycin against clinical isolates of ciprofloxacin-resistant and -susceptible Staphylococcus aureus strains. Antimicrob Agents Chemother 1999;43(2): 421-3.

  11. Rybak MJ, et al. In vitro activities of daptomycin, vancomycin, linezolid, and quinupristin-dafflopristin against Staphylococci and Enterococci, including vancomycin-intermediate and-resistant strains. Antimicrob Agents Chemother 2000;44(4):1062-6.

  12. Betriu C, et al. Comparative in vitro activities of linezolid, quinupristin-dalfopristin, moxifloxacin, and trovafloxacin against erythromycin-susceptible and -resistant Streptococci. Antimicrob Agents Chemother 2000;44(7):1838-41.

  13. Betriu C, et al. Comparative activity of linezolid and other new agents against methicillin-resistant Staphylococcus aureus and teicoplanin-intermediate coagulase-negative Staphylococci. J Antimicrob Chemother 2001;48(6):911-3.

  14. Zaoutis T, et al. In vitro activities of linezolid, meropenem, and quinupristin-dalfopristin against group C and G streptococci, including vancomycin-tolerant isolates. Antimicrob Agents Chemother 2001;45(7):1952-4.

  15. Henwood CJ, et al. Susceptibility of Gram-positive coccifrom 25 UK hospitals to antimicrobial agents including linezolid. The Linezolid Study Group. J Antimicrob Chemother 2000; 46(6):931-40.

  16. Jones RN, Ballow CH, Biedenbach DJ. Multi-laboratory assessment of the linezolid spectrum of activity using the Kirby-Bauer disk diffusion method: Report of the Zyvox Antimicrobial Potenc Study (Z4PS) in the United States. Diagn Microbiol Infect Dis 2001;40(1-2):59-66.

  17. Cercenado E, Garcia-Garrote F, Bouza E. In vitro activity of linezolid against multiply resistant Gram-positive clinical isolates. J Antimicrob Chemother 2001;47(1):77-81.

  18. Ballow CH, et al. Multicenter Assessment of the Linezolid Spectrum and Activity Using the Disk Diffusion and Etest Methods: Report of the Zyvox (R) Antimicrobial Potency Study in Latin America (LA-Z4PS). Braz J Infect Dis, 2002.6(3):100-109.

  19. Gee T, et al. Pharmacokinetics and tissue penetration of linezolid following multiple oral doses. Antimicrob Agents Chemother 2001;45(6):1843-6.

  20. Perry CM, Jarvis B. Linezolid: a review of its use in the management of serious Gram-positive infections. Drugs 2001;61(4): 525-51.

  21. Kaye KS, Frairnow HS, Abrutyn E. Pathogens resistant to antimicrobial agents. Epidemiology, molecular mechanisms, and clinical management. Infect Dis Clin North Am 2000;14(2): 293-319.

  22. Chadwick PR, Wooster SL, Glycopeptide resistance in Staphylococcus aureus. J Infect 2000;40(3):211-7.

  23. Lundstrom TS, Sobel JD. Antibiotics for gram-positive bacterial infections. Vancomycin, teicoplanin, quinupristin/dalfopristin, and linezolid. Infect Dis Clin North Am 2000;14(2):463-74.

  24. Paradisi F, Corti G, Messeri D. Antistaphylococcal (MSSA, MRSA, MSSE, MRSE) antibiotics. Med Clin North Am 2001;85(1):1-17.

  25. Kaplan SL. Use of linezolid in children. Pediatr Infect Dis J 2002;1(9):870-2.

  26. Kaplan SL, et al. Linezolid for the treatment of community-acquired pneumonia in hospitalized children. Linezolid Pediatric Pneumonia Study Group. Pediatr Infect Dis J 2001; 20(5): 488-94.

  27. Graham PL, Ampofo K, Saiman L. Linezolid treatment of vancomycin-resistant Enterococcus faecium ventriculitis. Pediatr Infect Dis J 2002;21(8):798-800.

  28. Kearns GL, et al. Single dose pharmacokinetics of linezolid in infants and children. Pediatr Infect Dis J 2000;19(12):1178-84.

  29. Conte JE Jr, et al. Intrapulmonary pharmacokinetics of linezolid. Antimicrob Agents Chemother2002;46(5):1475-80.

  30. Gentry-Nielsen MJ, Olsen KM, Preheim LC. Pharmacodynamic activity and efficacy of linezolid in a rat model of pneumococcal pneumonia. Antimicrob Agents Chemother 2002;46(5): 1345-51.

  31. Yanagihara K, et al. Efficacy of linezolid against methicillin-resistant or vancomycin-insensitive Staphylococcus aureus in a model of hematogenous pulmonary infection. Antimicrob Agents Chemother 2002;46(10):3288-91.

  32. Zeana C, et al. Vancomycin-resistant Enterococcus faecium meningitis successfully managed with linezolid: case report and review of the literature. Clin Infect Dis 2001;33(4):477-82.

  33. Hachem R, et al. Successful treatment of vancomycin-resistant Enterococcus meningitis with linezolid. Eur J Clin Microbiol Infect Dis 2001;20(6):432-4.

  34. Shaikh ZH, Peloquin CA, Ericsson CD. Successful treatment of vancomycin-resistant Enterococcus faecium meningitis with linezolid: case report and literature review. Scand J Infect Dis 2001;33(5):375-9.

  35. Villani P, et al. Cerebrospinal fluid linezolid concentrations in postneurosurgical central nervous system infections. Antimicrob Agents Chemother 2002;46(3):936-7.

  36. Pelton SI, et al. Efficacy of linezolid in experimental otitis media. Antimicrob Agents Chemother 2000;44(3):654-7.

  37. McNeil SA, et al. Successful treatment of vancomycin-resistant Enterococcus faecium bacteremia with linezolid afterfailure of treatment with synercid (quinupristin/dalfopristin). Clin Infect Dis 2000;30(2):403-4.

  38. Babcock HM, et al. Successful treatment of vancomycin-resistant Enterococcus endocarditis with oral linezolid. Clin Infect Dis 2001;32(9):1373-5.

  39. Patel R, et al. Linezolid therapy of vancomycin-resistant Enterococcus faecium experimental endocarditis. Antimicrob Agents Chemother 2001;45(2):621-3.

  40. Dailey CF, et al. Efficacy of linezolid in treatment of experimental endocarditis caused by methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2001;45(8): 2304-8.

  41. Melzer M, Goldsmith D, Gransden W. Successful treatment of vertebral osteomyelitis with linezolid in a patient receiving hemodialysis and with persistent methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus bacteremias. Clin Infect Dis 2000;31(1):208-9.

  42. Till M, Wixson RL, Pertel PE, Linezolid treatment for osteomyelitis due to vancomycin-resistant Enterococcus faecium. Clin Infect Dis 2002;34(10):1412-4.

  43. Bassetti M, et al. Linezolid treatment of prosthetic hip Infections due to methicillin-resistant Staphylococcus aureus (MRSA). J Infect 2001;43(2):148-9.

  44. Drago L, et al. Effect of linezolid in comparison with that of vancomycin on glycocalix production: in vitro study. Antimicrob Agents Chemother 2002;46(2):598-9.

  45. Gerson SL, et al. Hematologic effects of linezolid: summary of clinical experience. Antimicrob Agents Chemother 2002;46(8):2723-6.

  46. Attassi K, et al. Thrombocytopenia associated with linezolid therapy. Clin Infect Dis 2002;34(5):695-8.

  47. Kuter DJ, Tillotson GS, Hematologic effects of antimicrobials: focus on the oxazolidinone linezolid. Pharmacotherapy 2001;21(8):1010-3.

  48. Lawyer MC, Lawyer EZ. Linezolid and reversible myelosuppression. Jama 2001;286(16):1974.

  49. Li Z, et al. Comparison of length of hospital stay for patients with known or suspected methicillin-resistant Staphylococcus species infections treated with linezolid or vancomycin: a randomized, multicenter trial. Phannacotherapy 2001;21(3):263-74.

  50. Li JZ, et al. Approaches to analysis of length of hospital stay related to antibiotic therapy in a randomized clinical trial: linezolid versus vancomycin for treatment of known or suspected methicillin-resistant Staphylococcus species infections. Pharmacotherapy 2002;22(2 Pt 2):45S-54S.




2020     |     www.medigraphic.com