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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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5191
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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