Información del artículo
La aparición progresiva de cepas de microorganismos grampositivos resistentes a los antibacterianos de primera línea ha motivado la búsqueda de nuevas moléculas (quinolonas, estreptograminas, oxazolidinonas, cetólidos, glucopéptidos, daptomicina) que aumenten el arsenal terapéutico disponible. Linezolid es el primer representante comercializado de la familia de las oxazolidinonas, y se ha mostrado efectivo frente a cepas multirresistentes de microorganismos grampositivos (Staphylococcus aureus resistente a meticilina, S. aureus con sensibilidad disminuida a los glucopéptidos, Enterococcus spp. resistente a vancomicina, Streptococcus pneumoniae con sensibilidad disminuida a penicilina y cefalosporinas), por lo que se presenta como una nueva opción para el tratamiento de las infecciones por estos microorganismos. En este trabajo se revisan los aspectos microbiológicos y farmacológicos de este fármaco con el fin de ubicarlo en la terapéutica antimicrobiana.
Palabras clave:
Linezolid
Oxazolidinonas
Resistencia en grampositivos
Terapia antimicrobiana
The progressive emergence of multi-resistant gram-positive strains has prompted the search for new molecules (quinolones, streptogramins, oxazolidinones, ketolides, glycopeptides, daptomycin) to add to the current therapeutic arsenal. Linezolid, the first commercially available member of the oxazolidinone family, has evidenced activity against multi-resistant gram-positive strains (methicillin-resistant Staphylococcus aureus, S. aureus with decreased glycopeptide sensitivity, vancomycin-resistant Enterococcus spp., Streptococcus pneumoniae with decreased sensitivity to penicillin and cephalosporins), thereby providing a new option for treating infections by these microorganisms. This work reviews the microbiologic and pharmacologic aspects of this agent in order to establish its position among the available options for antimicrobial chemotherapy
Key words:
Linezolid
Oxazolidinones
Gram-positive resistance
Antimicrobial chemotherapy
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Bibliografía
[1.]
Grupo de trabajo EPINE, J. Vaqué, J. Roselló.
Sociedad Española de Medicina Preventiva, Salud Pública e Higiene, (2001),
[2.]
F.A. Waldogel.
Staphylococcus aureus (including toxic shock syndrome).
pp. 1755-1756
[3.]
J.A. García-Rodríguez, J.L. Muñoz Bellido.
Epidemiología de la resistencia de grampositivos en España.
Enferm Infecc Microbiol Clin, 1 (2002), pp. 1-7
[4.]
S. Grau, F. Álvarez-Lerma, M. Marín, J.L. Gimeno.
Problemática y soluciones actuales en el tratamiento de las infecciones por microorganismos grampositivos.
Enferm Infecc Microbiol Clin, 19 (2001), pp. 393-398
[5.]
K. Hiramatsu, N. Aritaka, H. Hanaki, S. Kawasaki, Y. Hosoda, S. Hori, et al.
Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneusly resistant to vancomycin.
Lancet, 350 (1997), pp. 1670-1673
[6.]
CDC Update.
Staphylococcus aureus with reduced susceptibility to vancomycin – United States 1997.
MMWR, 46 (1997), pp. 813-815
[7.]
M.J. Rybak, R.L. Akins.
Emergence of methicillin-resistant Staphylococcusaureus with intermediate glycopeptide resistance: Clinical significance and treatment options.
Drug, 61 (2001), pp. 1-7
[8.]
F.C. Tenover.
Implications of vancomycin-resistant Staphylococcus aureus.
J Hosp Infect, 43 (1999), pp. S3-S7
[9.]
Y. Cetinkaya, P. Falk, C. Glen.
Vancomycin-Resistant Enterococci.
Clin Microbiol Rev, 13 (2000), pp. 686-707
[10.]
D.L. Shinbarger, K.R. Marotti, R.W. Murray, A.H. Lin, E.P. Melchior, S.M. Swaney, et al.
Mechanism of Action of Oxazolidinones: Effects of Linezolid and Eperezolid on Translation Reactions.
Antimicrob Agents Chemother, 41 (1997), pp. 2132-2136
[11.]
S.M. Swaney, H. Aoki, M.C. Ganoza, D.L. Shinabarger.
The Oxazolidinone Linezolid Inhibits Initiation of Protein Synthesis in Bacteria.
Antimicrob Agents Chemother, 42 (1998), pp. 3251-3255
[13.]
M.J. Rybak, D.M. Cappelletty, T. Moldovan, J.R. Aeschlimann, G.W. Kaatz.
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, and Enterococcus faecium.
Antimicrob Agents Chemother, 42 (1998), pp. 721-724
[14.]
G.E. Zurenko, B.H. Yagi, R.D. Schaadt, J.W. Allison, J.O. Kilburn, S.E. Glickman, et al.
In vitro activities of U-100592 and U-100766, Novel Oxazolidinone Antibacterial Agents.
Antimicrob Agents Chemother, 40 (1996), pp. 839-845
[15.]
J.H. Jorgensen, M.L. Mcelmeel, C.W. Trippy.
In vitro activities of the oxazolidinone antibiotics U-100592 and U-100766 against Staphylococcus aureus and coagulase negative Staphylococcus species.
Antimicrob Agents Chemother, 41 (1997), pp. 465-467
[16.]
C.J. Henwood, D.M. Livermore, A.P. Johnson, D. James, M. Warner, A. Gardiner, et al.
Susceptibility of Gram-positive cocci from 25 UK hospitals to antimicrobial agents including linezolid.
J Antimicrob Chemother, 46 (2000), pp. 931-940
[17.]
C.G. Gemmell.
Susceptibility of a variety of clinical isolates to linezolid: A European inter-country comparison.
J Antimicrob Chemother, 48 (2001), pp. 47-52
[18.]
A.P. Johnson, M. Warner, D.M. Livermore.
Activity of linezolid against multi-resistant Gram-positive bacteria from diverse hospitals in the United Kingdom.
J Antimicrob Chemother, 45 (2000), pp. 225-230
[19.]
F. Tubau, R. Fernández-Roblas, J. Liñares, R. Martín, F. Soriano.
In vitro activity of linezolid and 11 other antimicrobials against 566 isolates and comparison between NCCLS microdilution and Etest methods.
J Antimicrob Chemother, 47 (2001), pp. 675-680
[20.]
C. Von Eiff, G. Peters.
Comparative in vitro activities of moxifloxacin, trovafloxacin, quinupristin/dalfopristin and linezolid against staphylococci.
J Antimicrob Chemother, 43 (1999), pp. 569-573
[21.]
M.E. Jones, M.R. Visser, M. Klootwijk, P. Heisig, J. Verhoef, F.J. Schmitz.
Comparative activities of clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, ofloxacin, saprfloxacin, and trovafloxacin and nonquinolones linezolid, quinupristin-dalfopristin, gentamicin, and vancomycin against clinical isolates of ciprofloxacin-resistant and susceptible Staphylococcus aureus strains.
Antimicrob Agents Chemother, 43 (1999), pp. 421-423
[22.]
E. Cercenado, F. García-Garrote, E. Bouza.
In vitro activity of Linezolid against multiply resistant Gram-positive clinical isolates.
J Antimicrob Chemother, 47 (2001), pp. 77-81
[23.]
G.A. Noskin, F. Siddiqui, V. Stosor, D. Hacek, L.R. Peterson.
In vitro activities of linezolid against important gram-positive bacterial patogens including vanxomycin-resistant enterococci.
Antimicrob Agents Chemother, 43 (1999), pp. 2059-2062
[24.]
Gobernado M, Santos M. Estudio comparative de Linezolid con otros antimicrobianos. Rev Esp Quimioterap 2001;14(Supl 1):En prensa.
[25.]
A. Hällgren, H. Abednazari, C. Ekdahl, H. Hanberger, M. Nilsson, A. Samuelsson, et al.
Antimicrobial susceptibility patterns of entercocci in intensive care units in Sweden evaluated by different MIC breakpoint systems.
J Antimicrob Chemother, 48 (2001), pp. 53-62
[26.]
G. Doern, K.P. Heilmann, H.K. Huynh, P.R. Rhomberg, S.L. Coffman, A.B. Brueggemann.
Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in the United States during 1999-2000, including a comparison of resistance rates since 1994-1995.
Antimicrob Agents Chemother, 45 (2001), pp. 1721-1729
[27.]
C. Betriu, M. Redondo, M.L. Palau, A. Sánchez, M. Gómez, E. Culebras, et al.
Comparative in vitro activities of linezolid, quinupristin-dalfopristin, moxifloxacin and trovafloxacin against erytromycin-susceptible and resistant streptococci.
Antimicrob Agents Chemother, 44 (2000), pp. 1838-1841
[28.]
T. Zaoutis, L.S. Moore, K. Furness, J.D. Klein.
In vitro activities of linezolid, meropenem, and quinupristin-dalfopristin against group C and G streptococci, including vancomycin-tolerant isolates.
Antimicrob Agents Chemother, 45 (2001), pp. 1952-1954
[29.]
B.A. Brown-Elliot, S.C. Ward, C.J. Crist, L.B. Mann, R.W. Wilson, R.J. Wallace.
In vitro activities of linezolid against multiple Nocardia species.
Antimicrob Agents Chemother, 45 (2001), pp. 1295-1297
[30.]
C.M. Perry, B. Jarvis.
Linezolid: revisión de su uso en el tratamiento de las infecciones graves por grampositivos.
Drugs, 61 (2001), pp. 525-552
[31.]
E.J.C. Goldstein, D.M. Citron, C.V. Merina.
Linezolid activity compared to those of selected macrolides and other agents against aerobic and anaerobic pathogens isolated from sofa tissue bite infections in humans.
Antimicrob Agents Chemother, 43 (1999), pp. 1469-1474
[32.]
D.M. Livermore, S. Mushtaq, M. Warner.
Susceptibility testing with linezolid by different methods, in relation to published ‘general breakpoints’.
J Antimicrob Chemother, 48 (2001), pp. 452-454
[33.]
W.J. Munckhof, C. Giles, J.D. Turnidge.
Post-antibiotic growth suppression of linezolid against Gram-positive bacteria.
J Antimicrob Chemother, 47 (2001), pp. 879-883
[34]
G.W. Kaatz, S.M. Seo.
In vitro activities or oxazolidinone compounds U100592 and U100766 against Staphylococcus aureus and Staphylococcus epidermidis.
Antimicrob Agents Chemother, 40 (1996), pp. 799-801
[35]
L. Mulazimoglu, S.D. Drenning, V.L. Yu.
In vitro activities of two novel oxazolidinones (U100592 and U100766), a new fluorquinolone (trovafloxacin), and dalfopristin-quinupristin against Staphylococcus aureus and Staphylococcus epidermidis.
Antimicrob Agents Chemother, 40 (1996), pp. 2428-2430
[36]
M. Fines, R. Leclercq.
Activity of linezolid against Gram-positive cocci possessing genes conferring resistance to protein synthesis inhibitors.
J Antimicrob Chemother, 47 (2000), pp. 797-802
[37]
Zyvoxid Ficha Técnica para Europa. Pharmacia Spain 2001.
[38]
Base de Datos del Medicamento. Consejo General de Colegios Oficiales de Farmacéuticos. Madrid 2002. Consulta febrero 2002. Disponible enhttp://www.portalfarma.com/home.nsf
[39]
Linezolid. Drug Evaluation Monographs. DRUGDEX33System. Drug Information. Micromedex Computerized Clinical Information System. Englewood, Colorado 2002; Vol 111. Consultada febrero 2002. Disponible en:http://www.sefh.es/micromedex.htm.
[40]
T. Gee, R. Ellis, G. Marshall, J. Andrews, J. Ashby, R. Wise.
Pharmacokinetics and Tissue Penetration of Linezolid following Multiple Oral Doses.
Antimicrob Agents Chemother, 45 (2001), pp. 1843-1846
[41]
D.L. Stevens, L.G. Smith, J.B. Bruss, A. McConnell-Martín, S.E. Duvall, W.M. Todd, et al.
Randomized Comparison of Linezolid (PNU-100766) versus oxacillin-dicloxacillin for treatment of complicated skin and soft tissue infections.
Antimicrob Agents Chemother, 44 (2000), pp. 3408-3413
[42]
E. Rubinstein, S.K. Cammarata, T.H. Oliphant, R.G. Wunderink.
Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: A randomized, double-blind, multicenter study.
Clin Infect Dis, 32 (2001), pp. 402-412
[43]
P. Cottagnoud, C.M. Gerber, F. Acosta, M. Cottagnoud, K. Neftel, M.G. Tauber.
Linezolid against penicillin-sensitive and –resistant pneumococci in the rabbit meningitis model.
J Antimicrob Chemother, 46 (2000), pp. 981-985
[44]
P. Villani, M.B. Villani, F. Regazzi, P. Marubbi, P. Viale, L. Pagani, F. Cristini, et al.
Cerebrospinal fluid linezolid concentrations in postneurosurgical central nervous system infections.
Antimicrob Agents Chemother, 46 (2002), pp. 936-937
[45]
Z.H. Shaikh, C.A. Peloquin, C.D. Ericsson.
Successful treatment of vancomycin-resistant Enterococcus faecium meningitis with linezolid: Case report and literature review.
Scand J Infect Dis, 33 (2001), pp. 375-379
[46]
C. Zeana, C.J. Kubin, P. Della-Latta, S.M. Hammer.
Vancomycin-resistant Enterococcus faecium meningitis successfully managed with linezolid: Case report and review of the literature.
Clin Infect Dis, 33 (2001), pp. :477-482
[47.]
R. Patel, K.E. Piper, M.S. Rouse, J.M. Steckelberg.
Linezolid therapy of Staphylococcus aureus experimental osteomyelitis.
Antimicrob Agents Chemother, 44 (2000), pp. 3438-3440
[48]
M. Melzer, D. Goldsmith, W. Gransden.
Successful treatment of vertebral osteomyelitis with linezolid in a patient receiving hemodyalisis and with persistent methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus bacteremias.
Clin Infect Dis, 31 (2000), pp. 208-209
[49]
C.F. Dailey, C.L. Dileto-Fang, L.V. Buchanan, M.P. Oramas-Shirey, D.H. Batts, C.W. Ford, et al.
Efficacy of linezolid in treatment of experimental endocarditis caused by methicillin-resistant Staphylococcus aureus.
Antimicrob Agents Chemother, 45 (2001), pp. 2304-2308
[50]
M.P. Oramas-Shirey, L.V. Buchanan, C.L. Dileto-Fang, C.W. Ford, D.H. Batts, et al.
Efficacy of linezolid in a staphylococcal endocarditis rabbit model.
J Antimicrob Chemother, 47 (2001), pp. 349-352
[51.]
R. Patel, M.S. Rouse, K.E. Piper, J.M. Steckelberg.
Linezolid therapy of vancomycin resistant Enterococcus faecium experimental endocarditis.
Antimicrob Agents Chemother, 45 (2001), pp. 621-623
[52.]
J.W. Chien, M.L. Kucia, R.A. Salata.
Use of linezolid, an oxazolidinone, in the treatment of multidrug-resistant gram-positive bacterial infections.
Clin Infect Dis, 30 (2000), pp. 146-151
[53.]
H.M. Babcock, D.J. Ritchie, E. Christiansen, R. Starlin, R. Little, S. Stanley.
Successful treatment of vancomycin-resistant Enterococcus endocarditis with oral linezolid.
Clin Infect Dis, 32 (2001), pp. 1373-1375
[54.]
M.E. Valencia, V. Moreno, F. Laguna, J.M. González-Lahoz.
Tuberculosis multirresistente por Mycobacterium bovis e infección por el virus de la inmunodeficiencia humana ¿Existen nuevas posibilidades terapéuticas?.
Enferm Infecc Microbiol Clin, 19 (2001), pp. 37-39
[55.]
B. Brown-Elliott, R.J. Wallace, R. Blinkhorn, C.J. Crist, L.B. Mann.
Successful treatment of disseminated Mycobacterium chelonae infection with linezolid.
Clin Infect Dis, 33 (2001), pp. 1433-1434
[56.]
D.J. Cada, D.E. Baker, T. Levien.
Linezolid.
Hosp Pharm, 35 (2000), pp. 980-993
[57.]
Linezolid USP DI55Drug Information for the Health Care Professional. Micromedex Computerized Clinical Information System. Englewood, Colorado 2002; Vol 111. Consultada febrero 2002. Disponible en: http://www.sefh.es/micromedex.htm.
[58.]
J.E. García Sánchez, M.J. Fresnadillo Martínez.
Nuevos antibióticos activos frente a grampositivos.
Rev Esp Quimioter, 13 (2000), pp. 344-351
[59.]
Anon.
Linezolid (Zyvox).
Med Lett Drug Ther, 42 (2000), pp. 45-46
[60.]
Medical Economics Company, (2001),
[61.]
J. Cupo-Abbott.
Linezolid: A synthetic oxazolidinone antimicrobial for treatment of serious Gram-positive infections.
Formulary, 35 (2000), pp. 483-497
[62.]
H.B. Fung, H.L. Kirschenbaum, B.O. Ojofeitimi.
Linezolid: An oxazolidinone antimicrobial agent.
Clin Ther, 23 (2001), pp. 356-391
[63.]
American Health-System Pharmacists Society.
Drug Information ASHP.
Bethesda, (2001),
[64.]
D.J. Diekema, R.N. Jones.
Oxazolidinones A review.
Drug, 59 (2000), pp. 7-16
[65.]
Y.Q. Xiong, M.R. Yeaman, A.S. Bayer.
Linezolid: A new antibiotic.
Drug of Today, 36 (2000), pp. 631-639
[66.]
K.T. Bain, E.T. Wittbrodt.
Linezolid for the treatment of resistant gram-positive cocci.
Ann Pharmacother, 35 (2001), pp. 566-575
[67.]
D.J. Kuter, G.S. Tillotson.
Hematologic effects of antimicrobials: Focus on the oxazolidinone linezolid.
Pharmacotherapy, 21 (2001), pp. 1010-1013
[68.]
K. Attassi, E. Hershberger, R. Alam, M.J. Zervos.
Thrombocytopenia associated with linezolid therapy.
Clin Infect Dis, 34 (2002), pp. 695-698
[69.]
T.W. Waldrep, D.J. Skies.
Linezolid-Induced anemia and thrombocytopenia.
Pharmacotherapy, 22 (2002), pp. 109-112
[70.]
R. Norrby.
Linezolid-A review of the first oxazolidinone.
Expert Opin Pharmacother, 2 (2001), pp. 293-302
[71.]
UK Medicines Information Pharmacists Group. Linezolid. Evaluated information for the NHS, june 2001. Disponible en: http://www.ukdipg.org.uk/docs/linezolid.pdf.
[72.]
J.F. Plouffe.
Emerging Therapies for Serious Gram-positive Bacterial Infections: A Focus on Linezolid.
Clin Infect Dis, 31 (2000), pp. S144-S149
[73.]
S.L. Green, J.C. Maddox, E.D. Huttenbach.
Linezolid and reversible myelosupression.
JAMA, 285 (2001), pp. 1291
[74.]
D.M. Livermore.
Quinupristin-dalfopristin and linezolid: Where, when, which and whether to use?.
J Antimicrob Chemother, 46 (2000), pp. 347-350
[75.]
J.Y. Fagon, H. Patrick, D.W. Haas, A. Torres, C. Gibert, W.G. Cheadle, et al.
Treatment of gram-positive nosocomial pneumonia. Prospective randomized comparison of quinupristin/dalfopristin versus vancomycin.
Am J Respir Crit Care Med, 161 (2000), pp. 753-762
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