RESUMO
BACKGROUND: Neurons are an integral component of the immune system that functions to coordinate responses to bacterial pathogens. Sensory nociceptive neurons that can detect bacterial pathogens are found throughout the body with dense innervation of the intestinal tract. METHODS: In this study, we assessed the role of these nerves in the coordination of host defenses to Citrobacter rodentium. Selective ablation of nociceptive neurons significantly increased bacterial burden 10 days postinfection and delayed pathogen clearance. RESULTS: Because the sensory neuropeptide CGRP (calcitonin gene-related peptide) regulates host responses during infection of the skin, lung, and small intestine, we assessed the role of CGRP receptor signaling during C rodentium infection. Although CGRP receptor blockade reduced certain proinflammatory gene expression, bacterial burden and Il-22 expression was unaffected. CONCLUSIONS: Our data highlight that sensory nociceptive neurons exert a significant host protective role during C rodentium infection, independent of CGRP receptor signaling.
Assuntos
Citrobacter rodentium/imunologia , Sistema Nervoso Entérico/imunologia , Infecções por Enterobacteriaceae/imunologia , Interações Hospedeiro-Patógeno/imunologia , Nociceptores/imunologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/farmacologia , Modelos Animais de Doenças , Sistema Nervoso Entérico/citologia , Sistema Nervoso Entérico/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Mucosa Intestinal/inervação , Mucosa Intestinal/microbiologia , Intestino Delgado/inervação , Intestino Delgado/microbiologia , Camundongos , Camundongos Knockout , Nociceptores/efeitos dos fármacos , Nociceptores/metabolismo , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/metabolismo , Canais de Cátion TRPV/genéticaRESUMO
Continuous infusion of vancomycin may be a strategy for critically ill patients who do not achieve adequate plasma levels. There is few literature on this dosage regimen. We present six children (2 months to 7 years, 4 male and 2 female), admitted to the Intensive Care Unit of the "Prof. Dr. Garrahan Children Hospital", with methicillin-resistant Staphylococcus aureus sepsis, treated with vancomycin 40 and 60 mg/kg/day every 8-6 hrs. Continuous infusion at 50 mg/kg/day was implemented due to poor outcome, persistent fever, positive cultures and inadequate vancomycin plasma levels. All patients achieved levels between 10 and 25 ug/ml, their outcome was favorable and cultures became negative, with no signs of nephrotoxicity. Treatment duration of the continuous infusion was 9 to 18 days. Continuous infusion of vancomycin was effective in these patients without evidence of associated nephrotoxicity.
Assuntos
Antibacterianos/administração & dosagem , Vancomicina/administração & dosagem , Antibacterianos/sangue , Criança , Cuidados Críticos , Feminino , Humanos , Lactente , Infusões Intravenosas , Masculino , Vancomicina/sangueRESUMO
La administración de vancomicina en infusión continua es una estrategia de tratamiento posible en pacientes críticos que no alcancen niveles plasmáticos adecuados. Existe escasa bibliografía acerca de este tipo de administración. Se presentan 6 niños (2 meses a 7 años; 4 varones y 2 mujeres) que ingresaron en la unidad de cuidados intensivos del Hospital de Pediatría Garrahan con un cuadro clínico de sepsis por Staphylococcus aureus resistente a la meticilina, tratados con vancomicina, en dosis de entre 40 y 60 mg/kg/día cada 8-6 horas. Debido a la evolución clínica no favorable, la persistencia de la fiebre, los cultivos positivos y los niveles plasmáticos del antibiótico insuficientes, se implementó la infusión continua a 50 mg/kg/día. Todos los pacientes alcanzaron niveles entre 10 y 25 µg/ml, evolucionaron favorablemente y negativizaron los cultivos, sin signos de nefrotoxicidad. El tiempo de tratamiento en infusión continua fue entre 9 y 18 días. La infusión continua de vancomicina fue eficaz en estos pacientes, sin evidencias de nefrotoxicidad asociada.
Continuous infusion of vancomycin may be a strategy for critically ill patients who do not achieve adequate plasma levels. There is few literature on this dosage regimen. We present six children (2 months to 7 years, 4 male and 2 female), admitted to the Intensive Care Unit of the "Prof. Dr. Garrahan Children Hospital", with methicillin-resistant Staphylococcus aureus sepsis, treated with vancomycin 40 and 60 mg/kg/day every 8-6 hrs. Continuous infusion at 50 mg/kg/day was implemented due to poor outcome, persistent fever, positive cultures and inadequate vancomycin plasma levels. All patients achieved levels between 10 and 25 ug/ml, their outcome was favorable and cultures became negative, with no signs of nephrotoxicity. Treatment duration of the continuous infusion was 9 to 18 days. Continuous infusion of vancomycin was effective in these patients without evidence of associated nephrotoxicity.
Assuntos
Criança , Feminino , Humanos , Lactente , Masculino , Antibacterianos/administração & dosagem , Vancomicina/administração & dosagem , Antibacterianos/sangue , Cuidados Críticos , Infusões Intravenosas , Vancomicina/sangueRESUMO
La administración de vancomicina en infusión continua es una estrategia de tratamiento posible en pacientes críticos que no alcancen niveles plasmáticos adecuados. Existe escasa bibliografía acerca de este tipo de administración. Se presentan 6 niños (2 meses a 7 años; 4 varones y 2 mujeres) que ingresaron en la unidad de cuidados intensivos del Hospital de Pediatría Garrahan con un cuadro clínico de sepsis por Staphylococcus aureus resistente a la meticilina, tratados con vancomicina, en dosis de entre 40 y 60 mg/kg/día cada 8-6 horas. Debido a la evolución clínica no favorable, la persistencia de la fiebre, los cultivos positivos y los niveles plasmáticos del antibiótico insuficientes, se implementó la infusión continua a 50 mg/kg/día. Todos los pacientes alcanzaron niveles entre 10 y 25 Ag/ml, evolucionaron favorablemente y negativizaron los cultivos, sin signos de nefrotoxicidad. El tiempo de tratamiento en infusión continua fue entre 9 y 18 días. La infusión continua de vancomicina fue eficaz en estos pacientes, sin evidencias de nefrotoxicidad asociada.(AU)
Continuous infusion of vancomycin may be a strategy for critically ill patients who do not achieve adequate plasma levels. There is few literature on this dosage regimen. We present six children (2 months to 7 years, 4 male and 2 female), admitted to the Intensive Care Unit of the "Prof. Dr. Garrahan Children Hospital", with methicillin-resistant Staphylococcus aureus sepsis, treated with vancomycin 40 and 60 mg/kg/day every 8-6 hrs. Continuous infusion at 50 mg/kg/day was implemented due to poor outcome, persistent fever, positive cultures and inadequate vancomycin plasma levels. All patients achieved levels between 10 and 25 ug/ml, their outcome was favorable and cultures became negative, with no signs of nephrotoxicity. Treatment duration of the continuous infusion was 9 to 18 days. Continuous infusion of vancomycin was effective in these patients without evidence of associated nephrotoxicity.(AU)
Assuntos
Criança , Feminino , Humanos , Lactente , Masculino , Antibacterianos/administração & dosagem , Vancomicina/administração & dosagem , Antibacterianos/sangue , Cuidados Críticos , Infusões Intravenosas , Vancomicina/sangueRESUMO
Continuous infusion of vancomycin may be a strategy for critically ill patients who do not achieve adequate plasma levels. There is few literature on this dosage regimen. We present six children (2 months to 7 years, 4 male and 2 female), admitted to the Intensive Care Unit of the "Prof. Dr. Garrahan Children Hospital", with methicillin-resistant Staphylococcus aureus sepsis, treated with vancomycin 40 and 60 mg/kg/day every 8-6 hrs. Continuous infusion at 50 mg/kg/day was implemented due to poor outcome, persistent fever, positive cultures and inadequate vancomycin plasma levels. All patients achieved levels between 10 and 25 ug/ml, their outcome was favorable and cultures became negative, with no signs of nephrotoxicity. Treatment duration of the continuous infusion was 9 to 18 days. Continuous infusion of vancomycin was effective in these patients without evidence of associated nephrotoxicity.