CARACTERISTICAS FARMACOLOGICAS DE UN NUEVO ANTIBIOTICO DE AMPLIO ESPECTRO





CARACTERISTICAS FARMACOLOGICAS DE UN NUEVO ANTIBIOTICO DE AMPLIO ESPECTRO

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La tigeciclina, el primer antibiótico perteneciente a la familia de las glicilciclinas, es un aporte significativo al arsenal de fármacos eficaces contra los gérmenes aerobios grampositivos resistentes a múltiples drogas.
guay9.jpg Autor:
David Guay
Columnista Experto de SIIC

Institución:
Department of Experimental & Clinical Pharmacology, College of Pharmacy, University of Minnesota


Artículos publicados por David Guay
Recepción del artículo
17 de Febrero, 2006
Aprobación
7 de Marzo, 2006
Primera edición
30 de Octubre, 2006
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
La tigeciclina es el derivado 9-t-butilciclamido de la tetraciclina minociclina. Es la primera glicilciclina en ser comercializada. Se piensa que la tigeciclina actúa a través de los mismos mecanismos que las tetraciclinas relacionadas estructuralmente, es decir la inhibición de la síntesis de proteínas al unirse a la subunidad 30S del ribosoma. Su actividad antibacteriana no está afectada por la presencia de los determinantes de resistencia a la tetraciclina, minociclina, penicilina, vancomicina, meticilina y los macrólidos, así como a las betalactamasas de amplio espectro. Su actividad es predominantemente bacteriostática y la resistencia está mediada por mecanismos que involucran las bombas de salida. A pesar de ser un antibiótico de amplio espectro, incluye en éste organismos de susceptibilidad intrínseca intermedia como Legionella, Ureaplasma, Proteus, Providencia, Morganella, Acinetobacter y especies de Bacteroides. Pseudomonas y las micobacterias atípicas son intrínsecamente resistentes. Disponible solamente para ser utilizada por vía intravenosa, la tigeciclina se concentra intracelularmente y penetra adecuadamente en varios compartimentos del tracto respiratorio y fluidos de las ampollas de la piel. El fármaco se elimina a través de un metabolismo hepático equilibrado, la secreción biliar y la excreción renal. El ajuste de dosis solamente es necesario en las alteraciones hepáticas graves (clase C de Child-Pugh; disminución de la dosis de mantenimiento del 50%). La tigeciclina demostró ser equivalente a los comparadores de referencia en el tratamiento de las infecciones intraabdominales complicadas, de la piel y sus anexos. Las náuseas y vómitos son los eventos adversos dependientes de la dosis más importantes, los cuales pueden disminuir parcialmente con las comidas. La única interacción farmacológica con importancia clínica potencial es con la warfarina, con la que la tigeciclina puede incrementar su respuesta hipoprotrombinémica al disminuir la depuración oral de la relación D-warfarina/L-warfarina en un 40%/23%. Si bien la introducción de la tigeciclina constituye un avance significativo en el tratamiento de las infecciones debidas a gérmenes aerobios grampositivos, se deben tener en cuenta dos aspectos importantes. Las náuseas y vómitos asociados a la dosis pueden comprometer seriamente la capacidad del médico para ajustar adecuadamente la posología del fármaco, lo cual, por otra parte, estimula la aparición y diseminación de los determinantes de resistencia vinculados a las bombas de salida hallados en varias especies (Salmonella, Proteus, Pseudomonas, etc.) y ser transferidos de un organismo a otro. Es esperable que estos factores no motiven que la tigeciclina muestre una breve vida como antimicrobiano en los humanos.

Palabras clave
tigeciclina, glicilciclina, minociclina


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Abstract
Tigecycline is the 9-t-butylglycylamido derivative of the tetracycline minocycline. It is the first glycylcycline to be marketed. Tigecycline is thought to act via the same mechanism as the structurally-related tetracyclines, i.e. inhibition of bacterial protein synthesis by binding to the 30S subunit of the ribosome. Its antibacterial activity is unaffected by the presence of resistance determinants to tetracycline, minocycline, penicillin, vancomycin, methicillin, and the macrolides as well as extended-spectrum beta-lactamases. Its activity is bacteriostatic in nature and resistance is mediated primarily by efflux pump mechanisms. Despite broad-spectrum activity, organisms commonly of intrinsic intermediate susceptibility include Legionella, Ureaplasma, Proteus, Providencia, Morganella, Acinetobacter, and Bacteroides species. Pseudomonas and atypical mycobacteria are usually intrinsically resistant. Available only for IV use, tigecycline concentrates intracellularly and penetrates well into various respiratory tract compartments and skin blister fluid. Elimination occurs via balanced hepatic metabolism, biliary secretion, and renal excretion. Dosage regimen adjustment is needed only in severe hepatic impairment (Child-Pugh class C; 50% decrease in maintenance dose). Tigecycline has proven equivalent to standard comparators in the treatment of complicated intra-abdominal and skin and skin structure infections. The major dose-limiting adverse events are nausea and vomiting, which may be somewhat ameliorated by dosing on a full stomach. The only drug-drug interaction of potential clinical importance occurs with warfarin, wherein tigecycline may potentiate its hypoprothrombinemic response by reducing the oral clearance of S-warfarin/R-warfarin by means of 40/23 percent. Although tigecycline is an important advance in the therapy to infections due to multi-resistant gram-positive aerobes, two findings are of concern. Dose-related nausea and vomiting may seriously compromise the clinician's ability to use adequate doses of the drug. This may, in turn, promote the development and dissemination of efflux pump resistance determinants, which have already been found in a variety of species (Salmonella, Proteus, Pseudomonas, etc.) and can be passed from one organism to another. It is hoped that these factors will not result in tigecycline having but a brief life span as a useful antimicrobial in humans.

Key words
tigecycline, glycylcycline, minocycline


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Especialidades
Principal: Farmacología
Relacionadas: Bioquímica, Infectología, Medicina Farmacéutica



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David Guay, Department of Experimental & Clinical Pharmacology, College of Pharmacy, University of Minnesota, MN 55455, Weaver-Densford Hall 7-115C, 308 Harvard St. SE, Minneapolis, EE.UU.
Bibliografía del artículo
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