ABSTRACT
La selección de microorganismos multirresistentes, como efecto indeseable de la utilización de los antimicrobianos, y la escasez de novedades terapéuticas que se prevé para los próximos años obligan a una utilización racional de los antimicrobianos de uso habitual. La optimización de los regímenes terapéuticos mediante la utilización del análisis farmacocinético/farmacodinámico (PK/PD) sin duda contribuirá a alargar la vida útil de los antimicrobianos y a la contención de la resistencia bacteriana. Se revisa la importancia de la adecuada selección del régimen de dosificación de los antimicrobianos, la aplicación del análisis PK/PD en antibioterapia, la simulación de Montecarlo, los índices de eficacia y los puntos de corte PK/PD.El análisis PK/PD también se puede aplicar para la prevención de resistencias. Para estudiar los principios que predicen su aparición y difusión se pueden utilizar diferentes métodos: modelos in vitro, modelos animales y métodos para la evaluación de la prevención de resistencias (ventanas de selección de mutantes).Aunque el análisis PK/PD en antibioterapia es una herramienta muy útil que facilita la selección del tratamiento antimicrobiano más adecuado, presenta una serie de limitaciones para su aplicación en la práctica clínica
The selection of multiresistant microorganisms, as a side-effect of the use of antimicrobials, together with the lack of new therapeutic drugs expected in the near future, forces to a rational use of antibiotics. The optimisation of antibacterial treatments based on pharmacokinetic/pharmacodynamic analysis (PK/PD) may contribute to prolong the life of antibiotics and to contain the bacterial resistance to them. A review is made of the importance of the appropriateness of the dose regimen selected, the application of PK/PD analysis of antimicrobials, the Monte Carlo simulation, PK/PD indices for efficacy, and PK/PD cut-off points.PK/PD analysis is also applicable to the prevention of bacterial resistance. Different methods have been used to study the factors that lead to its emergence and spread, such as in vitro and animal models, and resistance prevention studies (mutant selection window).Although the PK/PD analysis is a very useful tool for the selection of the most appropriate dose regimen of antibiotics, several problems limit its use in clinical practice
Subject(s)
Humans , Animals , Anti-Infective Agents/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Infections/drug therapy , Drug Resistance, Multiple , Drug-Related Side Effects and Adverse Reactions , Treatment Outcome , Disease Models, AnimalABSTRACT
The selection of multiresistant microorganisms, as a side-effect of the use of antimicrobials, together with the lack of new therapeutic drugs expected in the near future, forces to a rational use of antibiotics. The optimisation of antibacterial treatments based on pharmacokinetic/pharmacodynamic analysis (PK/PD) may contribute to prolong the life of antibiotics and to contain the bacterial resistance to them. A review is made of the importance of the appropriateness of the dose regimen selected, the application of PK/PD analysis of antimicrobials, the Monte Carlo simulation, PK/PD indices for efficacy, and PK/PD cut-off points. PK/PD analysis is also applicable to the prevention of bacterial resistance. Different methods have been used to study the factors that lead to its emergence and spread, such as in vitro and animal models, and resistance prevention studies (mutant selection window). Although the PK/PD analysis is a very useful tool for the selection of the most appropriate dose regimen of antibiotics, several problems limit its use in clinical practice.
Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial , Microbial Sensitivity Tests/methods , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Bacteria/drug effects , Bacteria/genetics , Clinical Trials as Topic , Computer Simulation , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Drug Resistance, Microbial/genetics , Drug Resistance, Multiple, Bacterial/genetics , Humans , Models, Animal , Models, Biological , Monte Carlo Method , Observational Studies as Topic , Selection, GeneticABSTRACT
Antecedentes: Los cistoadenocarcinomas mucinososretroperitoneales primarios son neoplasias muy poco frecuentes.Hay 34 casos descritos en la literatura inglesa y continúasiendo controvertida su patogénesis. Métodos: Presentamosel caso de una mujer de 47 años con una lesión quísticaasintomática de 8 cm de longitud diagnosticada dequiste cortical renal, en otro centro. En revisiones posterioresla lesión alcanza 23 cm de diámetro. Es remitida al Hospitalde Móstoles donde se realiza un TAC que es informadocomo quiste mesotelial o linfangioma retroperitoneal. Losniveles de alfa-fetoproteína estaban dentro de la normalidad.Se realiza su resección quirúrgica. El Servicio de AnatomíaPatológica recibe una tumoración quística unilocular, quepesa 4.300 gramos y mide 24 × 18 × 15 cm, cuyos cortes histológicosmuestran un epitelio mucosecretor con áreas sólidaspapilares y focos infiltrativos pobremente diferenciados.Seis meses después de la cirugía no hay evidencia de recidivaneoplásica. Resultados y conclusiones: Los cistoadenocarcinomasmucinosos retroperitoneales primarios presentanun curso clínico agresivo, cuyo tratamiento de elección esquirúrgico y en ocasiones quimioterápico. Respecto a supatogenia existen diversas teorías: unas postulan su origen entejido ovárico heterotópico, otras en un teratoma retroperitonealo duplicación intestinal. La hipótesis mas aceptadaactualmente es el desarrollo a partir de metaplasia mucinosadel mesotelio celómico. Es importante tener presente al cistoadenocarcinomamucinoso retroperitoneal en el diagnósticodiferencial de otros tumores quísticos retroperitoneales(AU)
Introduction: Retroperitoneal mucinous cystadenocarcinomais extremely rare, with only 34 cases published todate. The pathogenesis of this tumour remains controversial.Materials and methods: This case report presents a 47 yearold woman who was being investigated for a renal cyst. An8cm retroperitoneal cystic mass was seen initially but, onsubsequent examination, it had increased to 23 cm in diameter.A CT scan rendered a diagnosis of mesothelial cystor retroperitoneal lymphangioma. á-fetoprotein levels werenormal. The tumour was surgically excised. Macroscopicallyit was a 24 × 18 × 15 cm, unilocular, cystic tumourwith solid areas. Microscopically, it was seen to be lined bymucinous epithelial cells with poorly differentiated areas. 6months post-operatively, she is alive and well and withoutevidence of recurrence. Results and conclusions: Retroperitonealmucinous cystadenocarcinoma has an aggressiveclinical course, and surgical excision is the treatment ofchoice, followed by chemotherapy on some occasions. Thereare various hypotheses for the pathogenesis of thistumour, including an origin from heterotopic ovarian tissue,retroperitoneal teratoma or intestinal duplication. However,the most widely accepted theory is that of coelomic metaplasia.Although rare, these tumours should be included inthe differential diagnosis of retroperitoneal cystic tumours(AU)
Subject(s)
Humans , Female , Middle Aged , Cystadenocarcinoma, Mucinous/complications , Cystadenocarcinoma, Mucinous/diagnosis , Cystadenocarcinoma, Mucinous/pathology , Retroperitoneal Neoplasms/complications , Retroperitoneal Neoplasms/diagnosis , Lymphangioma/complications , Lymphangioma/pathology , Lymphangioma, Cystic/pathology , Cystadenocarcinoma, Mucinous/surgery , Cystadenocarcinoma, Mucinous , Retroperitoneal Neoplasms/pathology , Retroperitoneal Space/pathology , Retroperitoneal Space/surgery , Retroperitoneal SpaceABSTRACT
Se presenta un caso de epitelioma cuniculatum de localización plantar. Se hacen revisiones bibliográficas de esta tumoración. Se exponen conclusiones sobre el lugar de esta tumoración dentro del grupo de las carcinomas verrucosos y su interés para aclarar las carcinogénesis experimental de los tumores cutáneas.
