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Farmacodivulgación CEFALOSPORINAS Rev Cubana Farm 2001;35(3):219-24 Farmacodivulgación Hospital Municipal Docente Alberto Fernández. Santa Cruz del Norte, La Habana CEFALOSPORINAS José Raúl Andraca Perera,1 Enrique Rodríguez Gil2 y Alexander Fundora Santana3 RESUMEN Se realiza una revisión y síntesis de información sobre un grupo importante de antibióticos: las cefalosporinas. Se señalan aspectos tan diversos como su origen, mecanismo de acción, farmacocinética, clasificación, actividad in vitro, así como sus dosificaciones e indicaciones, con el propósito de lograr en nuestros médicos generales integrales un perfeccionamiento y actualización en el uso clínico de estos agentes antimicrobianos. DeCS: CEFALOSPORINA/administración & dosificación; CEFALOSPORINA/ /farmacocinética; CEFALOSPORINA/uso terapéutico; ANTIBIOTICOS LACTAMICOS. Es un hecho conocido por todos que lactámicos, hasta hace muy poco no se el uso de los antibióticos en la práctica conocía resistencia a este antibiótico en clínica constituye “una batalla entre los patógenos humanos; en la actualidad, investigadores de la industria farmacéutica, existen enterococos con distintos que diseñan y buscan antibióticos y las fenotipos de resistencia.2 bacterias que desarrollan los mecanismos − En EE.UU. ha aumentado el número de para adaptarse a la introducción de estos casos de tuberculosis producida por fármacos”.1 Bastarían solo 2 ejemplos para cepas multirresistentes, cuyo trata- comprender esto: miento es siempre más largo y con frecuencia ineficaz.3,4 − la vancomicina empleada en el − En Cuba, el acceso directo de los tratamiento de infecciones por gérmenes médicos generales integrales a los grampositivos resistentes a beta servicios hospitalarios (rotaciones 1 Especialista de I Grado en Medicina General Integral. 2 Licenciado en Ciencias Farmacéuticas. 3 Licenciado en Enfermería. Instructor. 219 docente-asistenciales, guardias médi- 15 % (cefalexina y cefradina). En cuanto al cas, visitas a pacientes ingresados en nivel de distribución, cruzan fácilmente la hospitales, etc.) además del cumpli- placenta, alcanzan altas concetraciones en miento de misiones de colaboración en líquido sinovial, bilis y pericardio; su otros países del mundo, nos impone un distribución es relativamente baja en el perfeccionamiento y actualización en el humor acuoso y vítreo del ojo, siendo uso clínico de los agentes antimicro- además variable en los fluidos cerebro- espinales. En general, las cefalosporinas se bianos. Con el fin de ayudar en el excretan por el riñón; el probenecid cumplimiento de este objetivo comen- enlentece su eliminación y en presencia de zaremos con un grupo de fármacos que insuficiencia renal crónica se deben ajustar han ascendido a una posición privile- las dosis.5-9 giada en el mundo de los antibióticos: Clasificación de las cefalosporinas.7,8,10 las cefalosporinas. Se basa en la similitud de su actividad antimicrobiana y su introducción en el Historia y origen. El hongo Cephalos- mercado; de acuerdo con lo anterior se han porium acremonium que inició la primera definido en 1ra., 2da., 3ra. y 4ta. generación fuente de cefalosporinas fue aislado por (anexo). Brotzu en el mar, cerca de aguas servidas en la costa de Cerdeña. Se verificó que el 1ra. generación: hongo de Cerdeña contenía 3 antibióticos − definidos: cefalosporina P (activa contra Cefazolina − Cefalotina grampositivo), cefalosporina N (activa − contra grampositivo y gramnegativo) y Cefaloridina − Cefapirina cefalosporina C (menos potente que la − anterior, pero con la misma actividad Cefadroxil, oral − Cefalexina, oral antimicrobiana). − Las cefamicinas son similares a las Cefadrina − Cefatrizina cefalosporinas, pero derivan de especies de Streptomyces.5 2da. generación: Mecanismo de acción. Las cefalos- porinas y las cefamicinas inhiben la − Cefuroxima biosíntesis de peptidoglicanos, unidad − Cefamandol estructural esencial en la formación de la − Cefonicid pared celular bacteriana. − Ceforamida Este mecanismo es similar al de las − Moxalactan 5,6 penicilinas. − Cefuroxima, oral Absorción distribución y excreción de − Cefaclor, oral las cefalosporinas. Las cefalosporinas − Cefprozil, oral difieren individualmente en cuanto al grado − Cefotiam de absorción después de la administración − Cefamicinas: por vía oral, o la severidad del dolor • Cefoxitina producido por la inyección intramuscular. • Cefmetazol Después de la absorción el grado de unión • Cefminox a las proteínas plasmáticas varía • Cefotetan específicamente del 80 (cefazolina) hasta el • Cefbuperazona 220 3ra. generación: sensible a la cefuroxima, cefamandol y las cefalosporinas de 3ra. generación. − Cefotaxima − La Neisseria gonorrheae, incluyendo − Ceftazidime las cepas productoras de penicilinasas, − Ceftizoxime se mueren frente a las cefalosporinas de − 2da., 3ra., y 4ta. generación. Cefoperazona − − Ceftriaxone La mayor actividad antibacteriana contra − Cefpirome el Proteus mirabilis, la Klebsiella, la E. − Cefixime, oral coli se logra con la cefuroxima, cefoxitina, cefotetan y las de 3ra. − Cefetamet, oral generación. − Proxetil-cefpodoxima, oral − Gérmenes gramnegativos (Serratia, − Ceftibuten, oral − Citrobacter, Enterobacter, Morganella, Cefdinir, oral Proteus vulgaris) son totalmente − Latamoxef, oral − resistentes a la 1ra. y 2da. generación; Cefodizima pero son sensibles a la cefotaxima, − Cefmenoxima − ceftizoxima, ceftadima y ceftriaxone a Cefsulodina elevadas concentraciones. − La Pseudomona aeruginosa solo es 4ta. generación: sensible en grado significativo a la ceftazidima, cefoperazona y específica- − Cefepime mente a la cefsulodina. − Cefaclidina − La cefoxitina y el cefotetan (cefamicinas) − Cefoselis muestran una actividad excelente contra − Cefelidina el Bacteroides fragilis y contra gérmenes anaerobios de la cavidad Espectro de actividad antibacteriana in bucal. vitro. Consideraciones generales.8,9,11 Uso clínico.6-8,11-15 − Las cefalosporinas de 1ra. generación tienen una excelente actividad frente a 1ra. generación: los grampositivos. − − Todas las cefalosporinas probadas en Infecciones cutáneas y de tejidos blandos (en escaras o “pie” de diabético la actualidad presentan fuerte actividad asociarlo con otro antibiótico). frente a los Estreptococos; pero no es − Colecistitis no complicadas. así contra enterococos. − − Infecciones urinarias. Los Estafilococos sensibles a la − Neumonía bacteriana adquirida en la meticilina, lo son igualmente a las comunidad o cuando se sospecha la cefalosporinas; los Estafilococos presencia de estafilococos. meticilina-resistentes son por lo general − Endocarditis estafilocócicas. resistentes a todas las cefalosporinas − Profilaxis quirúrgica (tórax, abdomen, (con excepción del cefprozil). ortopedia). − La 2da. generación es más estable frente − Infecciones del tracto respiratorio a las β-lactamasas. superior. − El Haemophilus influenzae es resistente − No usar en infecciones del sistema a las de 1ra. generación y es muy nervioso central. 221 2da. generación: − Infecciones agudas óseas y de articulaciones. − Sinusitis, epiglotitis, otitis media. − Profilaxis quirúrgicas (tórax gastroen- − Bronquitis aguda, neumonia (Klebsiella testinal y genitourinaria) o Haemophilus influenzae). − Blenorragia e infecciones urinarias. 4ta. generación: − Infecciones estreptocócicas. − Gangrena gaseosa (posterior a − Neumonias adquiridas en la comunidad penicilina y cloranfenicol). y nosocomiales. − Meningitis causadas por estafilococos − Exacerbaciones agudas de la bronquitis (cefuroxima) crónica. − Infecciones complicadas y no compli- Cefamicinas: cadas del tracto urinario. − Infecciones de piel y partes blandas − Infecciones intrabdominales. causadas por Estafilococos, Estrepto- − Enfermedad inflamatoria pélvica aguda cocos y Pseudomona aeruginosa. y endometritis. − Peritonitis y septicemias. − Infecciones de la cavidad bucal y − Infecciones anaerobias (combinada con neumonias por “aspiración”. metronidazol o clindamicina) − Infecciones crónicas de tejidos blandos (escaras y en diabéticos). Efectos adversos.6,-8,11,14,15 Con el uso − Profilaxis quirúrgica colorrectal. por vía intravenosa de las cefalosporinas, se ha reportado flebitis y significativamente 3ra. generación: dolorosa su administración por vía intramuscular. Entre el 5 y el 10 % de los − Infecciones por gramnegativas en pacientes alérgicos a las penicilinas lo son pacientes hospitalizados: a las cefalosporinas. Se han descrito • Neumonias nosocomiales y absceso reacciones similares al “antabus”, con el uso pulmonar. de cefamandol, cefoperazona, moxalactan • Infecciones posoperatorias de heridas. y la ingestión de alcohol. • Infecciones urinarias por catéteres. El moxalactan se ha asociado con − Blenorragia e infecciones de la piel. hemorragias por obstaculización de la agregación plaquetaria. Se ha informado − Infecciones intrabdominales y pélvicas sobre síndrome diarreico por supresión de (asociarlas con metronidazol) la flora intestinal más frecuentemente con − Neumonias adquiridas en la comunidad. − el uso de la ceftriaxona y cefoperazona. Infecciones por Pseudomonas, La toxicidad renal de las cefalosporinas Enterobacter, Serratia y Citrobacter. − está íntimamente relacionada con la dosis Meningoencefalitis bacteriana. administrada y la asociación con otros − Huésped neutropénico con fiebre, medicamentos nefrotóxicos (ej. amino- bacteriemia/septicemia. glucósidos). 222 ANEXO. Dosificación de cefalosporinas de uso comun7,8,14,16,17 Generación Medicamento Vía-Adm Dosis adultos Dosis pediátrica 1ra. Cefazolina (Ketzol-Ancef) i.m.-i.v. 500 mg c/ 8 h 25 - 100 mg x kg/d
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