Publication: Evaluación de moxifloxacino como tratamiento alternativo en las infecciones por "Stenotrophomonas maltophilia": optimización de dosis empleando sistemas farmacodinámicos
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2016-08-10
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Universidad Complutense de Madrid
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Abstract
Stenotrophomonas maltophilia es un patógeno nosocomial, emergente, cuya incidencia en procesos severos esta aumentado de manera análoga al incremento de las poblaciones de pacientes con factores predisponentes. S. maltophilia es un microorganismo ubicuo y adaptado a múltiples ambientes, lo que explica la elevada diversidad genética y el resistoma característico de esta especie que le confiere resistencia a la mayoría de clases de antimicrobianos. Se sugiere que el paciente porta al microorganismo en el momento del ingreso y que la combinación entre la presión antibiótica, especialmente aminoglucósidos y carbapenemas, y el profundo y prolongado estado de inmunosupresión favorecen el desarrollo de la infección. El tratamiento de las infecciones severas, bacteriemias y neumonías, es empírico, y relacionado con una elevada mortalidad, 36-67%, que es atribuida a que la mayoría de pacientes recibe una terapia inapropiada. La carencia de antimicrobianos con suficiente actividad, la rápida aparición de resistencias en los pacientes bajo tratamiento y la ausencia de ensayos clínicos que discriminen tratamientos efectivos, condicionan el complicado manejo de los pacientes infectados por S. maltophilia . En la actualidad solo seis antimicrobianos, cotrimoxazol, ticarcilina-ácido clavulánico, de elección y ceftazidima, levofloxacino, minociclina y cloranfenicol, son considerados tratamientos apropiados para este microorganismo por el CLSI o el EUCAST. La probabilidad de supervivencia aumenta con la rápida administración de agentes sensibles in vitro , pero la mortalidad continúa siendo extraordinariamente alta, 14 y el 45%, lo que demuestra la urgente necesidad de alternativas terapéuticas y de la revaloración de los actuales puntos de corte microbiológicos empleados en el pronóstico de eficacia clínica para esta especie...
Stenotrophomonas maltophilia is an emerging nosocomial pathogen which has been increasingly reported as a cause of life-threatening infections, in particular in populations of patients with predisposing factors, such as immunosuppression, neutropenia or antimicrobial pressure. S. maltophilia is a ubiquitous gram-negative bacillus that has been isolated from humans, animals, soil, food, and pharmaceuticals. Because of this adaptation to different habitats, S. maltophilia shows great genetic diversity and a particular resistome which confer resistance to virtually all classes of antimicrobial agents. It has been suggested that patients might carry a strain at the time of admission to the hospital and the combined action of antibiotic pressure plus profound and prolonged immunodepression may favour the development of infection. Treatment of severe infections, bacteraemia and pneumonia is often empiric and it is associated to high mortality rates (36-67%) as a consequence that the majority of patient did not receive adequate empiric antibiotic therapy. The lack of agents that have significant activity against S. maltophilia , the rapid emergence of resistance in patients under therapy and the absence of clinical trial to select reasonable therapies determine the managing of infected patients. Currently, cotrimoxazole and ticarcillin-clavulanic acid, as drugs of choice, and ceftazidime, levofloxacin, and chloramphenicol are the only agents recommended as appropriate treatments for this microorganism by CLSI or EUCAST. Although patient survival increases with the rapid administration of an antimicrobial agent to which the strain is in vitro susceptible, the mortality remains too high (14-45%), indicating that therapeutic options are urgently required and an assessment of current accepted breakpoint to predict clinical success against this microorganism...
Stenotrophomonas maltophilia is an emerging nosocomial pathogen which has been increasingly reported as a cause of life-threatening infections, in particular in populations of patients with predisposing factors, such as immunosuppression, neutropenia or antimicrobial pressure. S. maltophilia is a ubiquitous gram-negative bacillus that has been isolated from humans, animals, soil, food, and pharmaceuticals. Because of this adaptation to different habitats, S. maltophilia shows great genetic diversity and a particular resistome which confer resistance to virtually all classes of antimicrobial agents. It has been suggested that patients might carry a strain at the time of admission to the hospital and the combined action of antibiotic pressure plus profound and prolonged immunodepression may favour the development of infection. Treatment of severe infections, bacteraemia and pneumonia is often empiric and it is associated to high mortality rates (36-67%) as a consequence that the majority of patient did not receive adequate empiric antibiotic therapy. The lack of agents that have significant activity against S. maltophilia , the rapid emergence of resistance in patients under therapy and the absence of clinical trial to select reasonable therapies determine the managing of infected patients. Currently, cotrimoxazole and ticarcillin-clavulanic acid, as drugs of choice, and ceftazidime, levofloxacin, and chloramphenicol are the only agents recommended as appropriate treatments for this microorganism by CLSI or EUCAST. Although patient survival increases with the rapid administration of an antimicrobial agent to which the strain is in vitro susceptible, the mortality remains too high (14-45%), indicating that therapeutic options are urgently required and an assessment of current accepted breakpoint to predict clinical success against this microorganism...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, leída el 22-01-2016