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Vol. 26. Núm. S2.
Infecciones por grampositivos: perspectivas terapéuticas actuales
Páginas 69-76 (enero 2008)
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Vol. 26. Núm. S2.
Infecciones por grampositivos: perspectivas terapéuticas actuales
Páginas 69-76 (enero 2008)
Infecciones por grampositivos: perspectivas terapéuticas actuales
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Efectos adversos e interacciones de los nuevos antibióticos activos frente a cocos grampositivos
Adverse effects and interactions of the new antibiotics active against Gram-positive cocci
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5171
José Ramón Azanza
Autor para correspondencia
jrazanza@unav.es

Correspondencia: Dr. J.R. Azanza. Servicio de Farmacología Clínica. Clínica Universitaria de Navarra. Avda. Pío XII s/n. 31008 Pamplona. España.
, Emilio García-Quetglas, Belén Sádaba
Servicio de Farmacología Clínica. Clínica Universitaria de Navarra. Facultad de Medicina. Universidad de Navarra. Pamplona. España
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Linezolid, tigeciclina, daptomicina y dalvabancina son nuevos antibacterianos con un perfil peculiar de efectos adversos (EA) y en algunos casos de interacciones. El primero de los citados destaca por la excelente tolerancia en tratamientos de corta duración, mientras que su utilización resulta más problemática cuando la duración se prolonga en el tiempo y parece que las 4 semanas pueden ser la barrera que marque, de algún modo, las diferencias. En cualquier caso, ninguno de los EA más problemáticos (neuritis, alteraciones de la médula ósea y acidosis láctica) parece presentarse bruscamente, por lo que la vigilancia de la presencia de síntomas precoces y/o alteraciones en el hemograma se convierte en relevante en este caso. En referencia a las interacciones, la peculiaridad parece ubicarse en su ligera capacidad de producir cierto efecto IMAO que conlleva un potencial de suma de efectos serotoninérgicos al asociarse con antidepresivos que elevan la actividad de este mismo neurotransmisor. De nuevo la precaución de reducir la dosis del antidepresivo y la de vigilar la presencia de síntomas precoces (digestivos, musculares y neurológicos) se convierte en la estrategia más acertada.

Tigeciclina muestra un perfil conocido porque lo comparte en su práctica totalidad con el de las tetraciclinas; las precauciones y las contraindicaciones de éstas se repiten en el caso de tigeciclina que, además, destaca por su potencial para producir náuseas y vómitos. Aparentemente parecen frecuentes, aunque el fármaco se administre cada 12h. La no asociación de estos efectos con concentraciones plasmáticas altas facilitaría su uso en una dosis única diaria más elevada que la actual, lo que además supondría conseguir concentraciones plasmáticas superiores. Daptomicina también presenta un perfil peculiar: la elevación en sangre de las enzimas musculares y, concretamente, de las cifras de creatincinasa, que parecen relacionarse muy directamente con la acumulación del fármaco en el músculo, por lo que resultan muy poco frecuentes si el intervalo de administración evita la mencionada acumulación. El uso de dosis adecuadas, pero en única administración diaria ajustada si hay disfunción renal, parece que es la solución definitiva de este problema, siempre que se tenga la precaución de vigilar posibles signos de miopatía, especialmente si el paciente está siendo tratado con otros fármacos que puedan producir este mismo problema.

Es todavía muy pronto para terminar de definir el perfil real de EA de dalvabancina, ya que la información de los ensayos clínicos es todavía escasa, pero aparentemente se trata de un fármaco con buen perfil de tolerancia.

Palabras clave:
Antibióticos
Cocos grampositivos
Efectos adversos
Interacciones

Linezolid, tigecycline, daptomycin and dalbavancin are new antibacterial agents with a peculiar adverse event and, in some cases, interactions profile. Linezolid is notable for its excellent tolerance in short-lasting treatments; however the use of this drug for more than 4 weeks seems to be more problematic. None of the most problematic adverse events (neuritis, bone marrow alterations and lactic acidosis) seem to be of brusque onset and consequently close monitoring for the presence of early symptoms and/or hemogram abnormalities is important. The peculiarity of interactions with linezolid seems to lie in this drug's relatively weak monoamine oxidase inhibitor (MAOI) effect, which may enhance serotoninergic effects when combined with antidepressants, increasing the activity of serotonin. The most appropriate strategy is to reduce the dose of the antidepressant and remain vigilant for the presence of early symptoms (gastrointestinal, muscular neurological). Tigecycline has a well-known profile because it is shared by almost all tetracyclines and the precautions and contraindications of these drugs are repeated in the case of tigecycline which, moreover, is notable for its potential to produce nausea and vomiting. These adverse effects seem to be frequent, even when the drug is administered every 12hours. The fact that these effects do not seem to be associated with high plasma concentrations would facilitate use of this drug in a higher single daily dose than that currently used, which would also achieve higher plasma concentrations. Daptomycin also has a peculiar profile, consisting of elevation in blood of muscular enzymes and specifically of CPK counts, which seem to be directly related to accumulation of the drug in muscle; consequently these effects are infrequent if the interval of administration avoids this accumulation. The use of appropriate doses, but in an adjusted single daily dose if there is renal dysfunction, seems to be the definitive solution to this problem, as long as possible signs of myopathy are monitored, especially if the patient is also under treatment with other drugs that could produce the same problem. It is still too soon to define the definitive adverse event profile of dalbavancin, since data from clinical trials is scarce; however, the drug seems to be well tolerated.

Key words:
Antibiotics
Gram-positive cocci
Adverse effects
Interactions
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Bibliografía
[1.]
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
[2.]
D.L. Stevens, L.G. Smith, J.B. Bruss, M.A. McConnell-Martin, 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
[3.]
E. Rubinstein, R. Isturiz, H.C. Standiford, L.G. Smith, T.H. Oliphant, S. Cammarata, et al.
Worldwide assessment of linezolid's clinical safety and tolerability: comparator-controlled phase III studies.
Antimicrob Agents Chemother, 47 (2003), pp. 1824-1831
[4.]
D.J. Kuter, D. Phil, G.S. Tillotson.
Hematologic effects of antimicrobials: focus on the oxazolidinone linezolid.
Pharmacotherapy, 21 (2001), pp. 1010-1013
[5.]
B. Jaksic, G. Martinelli, J. Pérez-Oteyza, C.S. Hartman, L.B. Leonard, K.J. Tack.
Efficacy and safety of linezolid compared with vancomycin in a randomized, double-blind study of febrile neutropenic patients with cancer.
Clin Infect Dis, 42 (2006), pp. 597-607
[6.]
C.R. Rayner, L.M. Baddour, M.C. Birmingham, C. Norden, A.K. Meagher, J.J. Schentag.
Linezolid in the treatment of osteomyelitis: results of compassionate use experience.
Infection, 32 (2004), pp. 8-14
[7.]
E. Senneville, L. Legout, M. Valette, Y. Yazdanpanah, F. Giraud, E. Beltrand, et al.
Risk factors for anaemia in patients on prolonged linezolid therapy for chronic osteomyelitis: a case-control study.
J Antimicrob Chemother, 54 (2004), pp. 798-802
[8.]
A. Herruzo, C. Pigrau, D. Rodríguez, B. Almiorante, M. Villar, A. Pahissa, et al.
Effectiveness and tolerability of prolonged linezolid therapy for chronic osteomyelitis.
26th Annual Meeting European Bone and Joint Infection Society,
[9.]
A. Soriano, J. Gómez, L. Gómez, J.R. Azanza, R. Pérez, F. Romero, et al.
Efficacy and tolerability of prolonged linezolid therapy in the treatment of orthopedic implant infections.
Eur J Clin Microbiol Infect Dis, 26 (2007), pp. 353-356
[10.]
V.C. Wu, Y.T. Wang, C.Y. Wang, I.J. Tsai, K.D. Wu, J.J. Hwang, et al.
High frequency of linezolid-associated thrombocytopenia and anemia among patients with end-stage renal disease.
Clin Infect Dis, 42 (2006), pp. 66-72
[11.]
S. Grau, J.A. Morales-Molina, J. Mateu-de Antonio, M. Marín-Casino, F. Álvarez-Lerma.
Linezolid: low pre-treatment platelet values could increase the risk of thrombocytopenia.
J Antimicrob Chemother, 56 (2005), pp. 440-441
[12.]
D. Plachouras, E. Giannitsioti, S. Athanassia, F. Kontopidou, A. Papadopoulos, K. Kanellakopoulou, et al.
No effect of pyridoxine on the incidence of myelosuppression during prolonged linezolid treatment.
Clin Infect Dis, 43 (2006), pp. e89-e91
[13.]
Y.H. Lin, V.C. Wu, I.J. Tsai, Y.L. Ho, J.J. Hwang, Y.K. Tsau, et al.
High frequency of linezolid-associated thrombocytopenia among patients with renal insufficiency.
Int J Antimicrob Agents, 28 (2006), pp. 345-351
[14.]
M. Javaheri, R.N. Khurana, T.M. O’Hearn, M.M. Lai, A.A. Sadun.
Linezolid-induced optic neuropathy: a mitochondrial disorder?.
Br J Ophthalmol, 91 (2007), pp. 111-115
[15.]
L. Azamfirei, S.M. Copotoiu, K. Branzaniuc, J. Szederjesi, R. Copotoiu, C. Berteanu.
Complete blindness after optic neuropathy induced by short-term linezolid treatment in a patient suffering from muscle dystrophy.
Pharmacoepidemiol Drug Saf, 16 (2007), pp. 402
[16.]
J.C. Rucker, S.R. Hamilton, D. Bardenstein, C.M. Isada, M.S. Lee.
Linezolid-associated toxic optic neuropathy.
[17.]
K. Kulkarni, L.V. del Priore.
Linezolid induced toxic optic neuropathy.
Br J Ophthalmol, 89 (2005), pp. 1664-1665
[18.]
T. Saijo, K. Hayashi, H. Yamada, M. Wakakura.
Linezolid-induced optic neuropathy.
Am J Ophthalmol, 139 (2005), pp. 1114-1116
[19.]
A.A. Apodaca, R.M. Rakita.
Linezolid-induced lactic acidosis.
N Engl J Med, 348 (2003), pp. 86-87
[20.]
A.S. De Vriese, R.V. Coster, J. Smet, S. Seneca, A. Lovering, L.L. van Haute, et al.
Linezolid-induced inhibition of mitochondrial protein synthesis.
Clin Infect Dis, 42 (2006), pp. 1111-1117
[21.]
D.L. Blazes, C.F. Decker.
Symptomatic hyperlactataemia precipitated by the addition of tetracycline to combination antiretroviral therapy.
Lancet Infect Dis, 4 (2006), pp. 249-252
[22.]
L. Palenzuela, N.M. Hahn, R.P. Nelson Jr, J.N. Arno, C. Schobert, R. Bethel, et al.
Does linezolid cause lactic acidosis by inhibiting mitochondrial protein synthesis?.
Clin Infect Dis, 40 (2005), pp. e113-e116
[23.]
P. Kopterides, E. Papadomichelakis, A. Armaganidis.
Linezolid use associated with lactic acidosis.
Scand J Infect Dis, 37 (2005), pp. 153-154
[24.]
P.E. Hendershot, E.J. Antal, I.R. Welshman, D.H. Batts, N.K. Hopkins.
Linezolid: pharmacokinetic and pharmacodynamic evaluation of coadministration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorphan HBr.
J Clin Pharmacol, 41 (2001), pp. 563-572
[25.]
S. Packer, S.A. Berman.
Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid.
Am J Psychiatry, 164 (2007), pp. 346-347
[26.]
M. Steinberg, A.K. Morin.
Mild serotonin syndrome associated with concurrent linezolid and fluoxetine.
Am J Health Syst Pharm, 64 (2007), pp. 59-62
[27.]
T.B. Strouse, T.N. Kerrihard, C.A. Forscher, P. Zakowski.
Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine.
J Clin Psychopharmacol, 26 (2006), pp. 681-683
[28.]
D.B. Clark, M.R. Andrus, D.C. Byrd.
Drug interactions between linezolid and selective serotonin reuptake inhibitors: case report involving sertraline and review of the literature.
Pharmacotherapy, 26 (2006), pp. 269-276
[29.]
R.J. DeBellis, O.P. Schaefer, M. Liquori, G.A. Volturo.
Linezolid-associated serotonin syndrome after concomitant treatment with citalopram and mirtazepine in a critically ill bone marrow transplant recipient.
J Intensive Care Med, 20 (2005), pp. 351-353
[30.]
J.A. Morales-Molina, J. Mateu-de Antonio, S. Grau Cerrato, M. Marín Casino.
Likely serotoninergic syndrome from an interaction between amitryptiline, paroxetine, and linezolid.
Farm Hosp, 29 (2005), pp. 292-293
[31.]
C.R. Thomas, M. Rosenberg, V. Blythe, W.J. Meyer 3rd.
Serotonin syndrome and linezolid.
J Am Acad Child Adolesc Psychiatry, 43 (2004), pp. 790
[32.]
S.L. Jones, E. Athan, D. O’Brien.
Serotonin syndrome due to co-administration of linezolid and venlafaxine.
J Antimicrob Chemother, 54 (2004), pp. 289-290
[33.]
N. Tahir.
Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram.
J Am Med Dir Assoc, 5 (2004), pp. 111-113
[34.]
J. Breedt, J. Teras, J. Gardovskis, F.J. Maritz, T. Vaasna, D.P. Ross, Tigecycline 305 cSSSI Study Group, et al.
Safety and efficacy of tigecycline in treatment of skin and skin structure infections: results of a double-blind phase 3 comparison study with vancomycin-aztreonam.
Antimicrob Agents Chemother, 49 (2005), pp. 4658-4666
[35.]
S. Sacchidanand, R.L. Penn, J.M. Embil, M.E. Campos, D. Curcio, E. Ellis-Grosse, et al.
Efficacy and safety of tigecycline monotherapy compared with vancomycin plus aztreonam in patients with complicated skin and skin structure infections: Results from a phase 3, randomized, double-blind trial.
Int J Infect Dis, 5 (2005), pp. 251-261
[36.]
M.E. Oliva, A. Rekha, A. Yellin, J. Pasternak, M. Campos, G.M. Rose, 301 Study Group, et al.
A multicenter trial of the efficacy and safety of tigecycline versus imipenem/cilastatin in patients with complicated intra-abdominal infections.
BMC Infect Dis, 5 (2005), pp. 88
[37.]
K.A. Rodvold, M.H. Gotfried, M. Cwik, J.M. Korth-Bradley, G. Dukart, E.J. Ellis-Grosse.
Serum, tissue and body fluid concentrations of tigecycline after a single 100 mg dose.
J Antimicrob Chemother, 58 (2006), pp. 1221-1229
[38.]
P.J. Petersen, P. Labthavikul, C.H. Jones, P.A. Bradford.
In vitro antibacterial activities of tigecycline in combination with other antimicrobial agents determined by chequerboard and time-kill kinetic analysis.
J Antimicrob Chemother, 57 (2006), pp. 573-576
[39.]
R.D. Arbeit, D. Maki, F.P. Tally, E. Campanaro, B.I. Eisenstein.
Daptomycin 98-01 and 99-01 Investigators. The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections.
Clin Infect Dis, 38 (2004), pp. 1673-1681
[40.]
V.G. Fowler Jr, H.W. Boucher, G.R. Corey, E. Abrutyn, A.W. Karchmer, M.E. Rupp, S. aureus Endocarditis and Bacteremia Study Group, et al.
Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus.
N Engl J Med, 355 (2006), pp. 653-665
[41.]
A. Kazory, K. Dibadj, I.D. Weiner.
Rhabdomyolysis and acute renal failure in a patient treated with daptomycin.
J Antimicrob Chemother, 57 (2006), pp. 578-579
[42.]
S. Papadopoulos, A.M. Ball, S.E. Liewer, C.A. Martin, P.S. Winstead, B.S. Murphy.
Rhabdomyolysis during therapy with daptomycin.
Clin Infect Dis, 42 (2006), pp. e108-e110
[43.]
F.B. Oleson Jr, C.L. Berman, J.B. Kirkpatrick, K.S. Regan, J.J. Lai, F.P. Tally.
Once-daily dosing in dogs optimizes daptomycin safety.
Antimicrob Agents Chemother, 44 (2000), pp. 2948-2953
[44.]
S.M. Bhavnani, P.G. Ambrose, F.B. Oleson, G.L. Drusano.
Toxicodynamics of Daptomycin in patients wtih bacteriemia and/or endocarditis. (A655).
46th ICAAC, (2006),
[45.]
M. Benvenuto, D.P. Benziger, S. Yankelev, G. Vigliani.
Pharmacokinetics and tolerability of daptomycin at doses up to 12 milligrams per kilogram of body weight once daily in healthy volunteers.
Antimicrob Agents Chemother, 50 (2006), pp. 3245-3249
[46.]
F. Soriano.
Nuevos antibióticos frente a grampositivos: linezolid, tigeciclina, daptomicina, dalbavancina, telavancina, ceftobiprole.
Enferm Infecc Microbiol Clin, 25 (2007), pp. 13-20
[47.]
D. Hayes, M.I. Anstead, R.J. Kuhn.
Eosinophilic pneumonia induced by daptomycin.
J Infect, 5 (2007), pp. e211-e213
[48.]
F. Cilli, S. Aydemir, A. Tunger.
In vitro activity of daptomycin alone and in combination with various antimicrobials against Gram-positive cocci.
J Chemother, 18 (2006), pp. 27-32
[49.]
A. Leighton, A.B. Gottlieb, M.B. Dorr, D. Jabes, G. Mosconi, C. VanSaders, et al.
Tolerability, pharmacokinetics, and serum bactericidal activity of intravenous dalbavancin in healthy volunteers.
Antimicrob Agents Chemother, 48 (2004), pp. 940-945
[50.]
I. Raad, R. Darouiche, J. Vázquez, A. Lentnek, R. Hachem, H. Hanna, et al.
Efficacy and safety of weekly dalbavancin therapy for catheter-related bloodstream infection caused by gram-positive pathogens.
Clin Infect Dis, 40 (2005), pp. 374-380
[51.]
L.E. Jauregui, S. Babazadeh, E. Seltzer, L. Goldberg, D. Krievins, M. Frederick, et al.
Randomized, double-blind comparison of once-weekly dalbavancin versu s twice-daily linezolid therapy for the treatment of complicated skin and skin structure infections.
Clin Infect Dis, 4 (2005), pp. 1407-1415
[52.]
E. Seltzer, M.B. Dorr, B.P. Goldstein, M. Perry, J.A. Dowell, T. Henkel, Dalbavancin Skin and Soft-Tissue Infection Study Group.
Once-weekly dalbavancin versus standard-of-care antimicrobial regimens for treatment of skin and soft-tissue infections.
Clin Infect Dis, 37 (2003), pp. 1298-1303
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