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Estudio de casos-controles de la infección por Clostridioides difficile en un área sanitaria rural
Case-control study of Clostridioides difficile in a rural health care area
Cristina Muñoz Cuevasa, María Ángeles Asencio Egeaa,
Autor para correspondencia
marian_asencio@yahoo.es

Autor para correspondencia.
, María Franco Huertab, María Huertas Vaqueroa, Ángel Arias Ariasc, Rafael Carranza Gonzáleza
a Laboratorio de Microbiología, Hospital General La Mancha Centro, Ciudad Real, España
b Servicio de Medicina Interna, Hospital General La Mancha Centro, Ciudad Real, España
c Unidad de Apoyo a la Investigación, Hospital General La Mancha Centro, Ciudad Real, España
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como &#237;leo paral&#237;tico y megacolon t&#243;xico&#46; La falta de sospecha cl&#237;nica&#44; sobre todo en aquellos pacientes que no presentan los factores de riesgo cl&#225;sicos &#40;edad avanzada&#44; hospitalizaci&#243;n prolongada&#44; consumo previo de antibi&#243;ticos&#41;&#44; ocasiona que la ICD sea todav&#237;a una enfermedad infradiagnosticada<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">3</span></a>&#46; Esto&#44; unido a su morbimortalidad&#44; plantea la necesidad de realizar estudios epidemiol&#243;gicos para establecer estrategias mejoradas de prevenci&#243;n y control de la infecci&#243;n&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">El objetivo del presente estudio fue determinar los factores de riesgo y los factores pron&#243;sticos de la ICD en un &#225;rea sanitaria rural&#44; as&#237; como establecer las principales diferencias entre los casos nosocomiales y los comunitarios&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Dise&#241;o</span><p id="par0015" class="elsevierStylePara elsevierViewall">Estudio observacional&#44; prospectivo&#44; de casos-controles&#44; de los pacientes de 2 o m&#225;s a&#241;os con diarrea &#40;&#8805;3 deposiciones no formes al d&#237;a&#41; atendidos en el &#193;rea Sanitaria La Mancha Centro&#44; que atiende a una poblaci&#243;n aproximada de 230&#46;000 habitantes&#44; desde el 1&#47;4&#47;2015 hasta el 30&#47;5&#47;2016&#46; El periodo de seguimiento de los pacientes se extendi&#243; 2 meses m&#225;s&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Selecci&#243;n de los pacientes</span><p id="par0020" class="elsevierStylePara elsevierViewall">Definici&#243;n de caso&#58; paciente con diagn&#243;stico cl&#237;nico y microbiol&#243;gico de ICD atendido en nuestra &#225;rea de salud&#46; Caso hospitalario&#58; paciente con ICD e ingreso hospitalario en las 4 semanas previas a la infecci&#243;n o cuya infecci&#243;n se desarrolla cuando lleva ingresado m&#225;s de 48 h&#46; Caso comunitario &#40;ICDC&#41;&#58; paciente con ICD sin ingreso hospitalario las 4 semanas previas o paciente cuya infecci&#243;n se desarrolla en las primeras 48 h del ingreso&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Definici&#243;n de control&#58; paciente atendido en nuestra &#225;rea de salud en el mismo periodo que el caso &#237;ndice en el que se solicit&#243; coprocultivo y el test de toxina result&#243; negativo&#46; Ser&#225; control hospitalario si adem&#225;s ha sido ingresado en las 4 semanas previas y control comunitario en el caso contrario&#46; Los controles elegidos fueron pacientes lo m&#225;s cercanos en tiempo y edad con el caso &#237;ndice&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Tama&#241;o muestral</span><p id="par0030" class="elsevierStylePara elsevierViewall">Se incluyeron de forma consecutiva todas las heces no formes de pacientes de 2 a&#241;os o mayores recibidas en el laboratorio de microbiolog&#237;a durante el periodo de estudio&#44; con independencia de la solicitud por parte del cl&#237;nico&#46; N&#250;mero de casos&#58; 61 &#40;hubo 3 casos que finalmente se excluyeron del estudio por ser recurrencias en lugar de casos nuevos&#41;&#46; N&#250;mero de controles&#58; 64&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Variables recogidas</span><p id="par0035" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0040" class="elsevierStylePara elsevierViewall">Edad&#44; sexo&#44; adquisici&#243;n &#40;comunitaria&#47;nosocomial&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0045" class="elsevierStylePara elsevierViewall">&#205;ndice de Charlson abreviado<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a>&#44; que engloba enfermedad cerebrovascular&#44; diabetes&#44; enfermedad pulmonar obstructiva cr&#243;nica&#44; insuficiencia card&#237;aca&#47;cardiopat&#237;a isqu&#233;mica&#44; demencia&#44; enfermedad arterial perif&#233;rica&#44; enfermedad renal cr&#243;nica y c&#225;ncer&#46; Adem&#225;s&#44; se recogieron las siguientes comorbilidades&#58; enfermedad inflamatoria intestinal&#44; inmunodepresi&#243;n&#44; quimioter&#225;picos&#44; trasplante de &#243;rgano s&#243;lido y&#47;o hematopoy&#233;tico e hipoalbuminemia&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0050" class="elsevierStylePara elsevierViewall">S&#237;ntomas&#58; fiebre asociada a diarrea &#40;FAD&#41;&#44; diarrea&#44; dolor abdominal y v&#243;mitos&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Tipo de antibi&#243;tico&#44; anti&#225;cido o inmunosupresor administrado previamente&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Tipo de ICD&#58;</p></li></ul></p><p id="par0065" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8728;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Infecci&#243;n grave&#44; si cumple uno o m&#225;s de los siguientes criterios&#58; signos sist&#233;micos de infecci&#243;n&#44; recuento leucocitario &#8805;15&#46;000&#47;&#956;l o incremento de creatinina<span class="elsevierStyleHsp" style=""></span>&#62;50&#37; del nivel basal&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8728;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Infecci&#243;n grave-complicada&#44; si cumple uno o m&#225;s de los siguientes criterios&#58; hipotensi&#243;n o sepsis&#44; &#237;leo paral&#237;tico&#44; megacolon t&#243;xico&#44; perforaci&#243;n intestinal&#44; ingreso en UCI por ICD&#44; cirug&#237;a por dicho motivo&#44; exitus atribuible&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8728;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Infecci&#243;n no grave&#44; si no cumple los criterios de infecci&#243;n grave o grave-complicada&#46;</p></li></ul></p><p id="par0085" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Recurrencia&#58; paciente que cumple de nuevo criterios de ICD en un periodo comprendido entre 3 y 60 d&#237;as de un episodio previo cl&#237;nicamente resuelto&#44; es decir&#44; durante las 8 semanas siguientes tras haber completado de forma correcta el tratamiento para la infecci&#243;n&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0095" class="elsevierStylePara elsevierViewall">Infecci&#243;n concomitante intestinal e infecci&#243;n en otras localizaciones&#46;</p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Diagn&#243;stico microbiol&#243;gico</span><p id="par0100" class="elsevierStylePara elsevierViewall">A todas las heces no formes recibidas durante el periodo de estudio&#44; con independencia de la solicitud por parte del cl&#237;nico&#44; se les realiz&#243; una prueba inmunocromatogr&#225;fica con detecci&#243;n simult&#225;nea del ant&#237;geno glutamato deshidrogenasa y las toxinas A&#47;B &#40;C&#46; Diff Quik-Check Complete&#174;&#44; Alere&#41;&#46; Los resultados discordantes se confirmaron mediante amplificaci&#243;n isot&#233;rmica mediada por bucle &#40;Illumigene&#174;&#44; Meridian Bioscience&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">An&#225;lisis bivariante</span><p id="par0105" class="elsevierStylePara elsevierViewall">La variable respuesta &#40;caso&#47;control&#41; se ha relacionado con cada una de las variables explicativas mediante la confecci&#243;n de tablas de contingencia para las variables cualitativas&#46; Para ello&#44; se ha estimado la significaci&#243;n estad&#237;stica &#40;pruebas de &#967;<span class="elsevierStyleSup">2</span> cuadrado o test exacto de Fisher si el n&#250;mero de efectivos esperados es inferior a 5&#41; y una medida de la magnitud de la asociaci&#243;n en forma de <span class="elsevierStyleItalic">odds ratio</span> y su correspondiente intervalo de confianza &#40;IC 95&#37;&#41;&#46; Para las variables cuantitativas se ha utilizado el test t de Student o el de U de Mann-Whitney&#44; seg&#250;n la distribuci&#243;n de la variable&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Posteriormente&#44; los casos fueron comparados en funci&#243;n del tipo de adquisici&#243;n de la infecci&#243;n &#40;nosocomial versus comunitaria&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">An&#225;lisis multivariante</span><p id="par0115" class="elsevierStylePara elsevierViewall">Todas aquellas variables explicativas que han tenido una relaci&#243;n con la variable respuesta con una significaci&#243;n <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;20&#44; seg&#250;n el criterio de Maldonado y Greenland<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a>&#44; han formado parte de los modelos multivariantes de regresi&#243;n log&#237;stica&#46; Se ha utilizado la regresi&#243;n log&#237;stica condicional &#40;hacia delante&#41; debido a la naturaleza pareada de los controles&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Para determinar los factores de pron&#243;stico desfavorable de la ICD &#40;aparici&#243;n de complicaciones&#44; recurrencias o mortalidad atribuible&#41; se evaluaron las siguientes variables&#44; que incluyen sintomatolog&#237;a y posibles factores de riesgo&#58; edad avanzada &#40;mayores de 65 a&#241;os&#41;&#44; sexo&#44; tipo de adquisici&#243;n&#44; ingreso hospitalario previo&#44; sintomatolog&#237;a&#44; exposici&#243;n antibi&#243;tica previa&#44; uso de inhibidores de la bomba de protones&#44; inmunodepresi&#243;n&#44; alimentaci&#243;n enteral&#44; hipoalbuminemia e infecciones concomitantes&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Se ha utilizado como criterio de permanencia en el modelo final una significaci&#243;n estad&#237;stica &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Los c&#225;lculos se realizaron con el programa estad&#237;stico SPSS Statistics para Windows&#44; versi&#243;n 18&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; EE&#46;&#160;UU&#46;&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Aspectos &#233;ticos</span><p id="par0130" class="elsevierStylePara elsevierViewall">Este estudio fue aprobado por el Comit&#233; de &#201;tica del Hospital General La Mancha Centro&#46; Todos los datos recogidos durante el desarrollo del proyecto de investigaci&#243;n han sido tratados conforme a la Ley Org&#225;nica 3&#47;2018&#44; de 5 de diciembre&#44; de protecci&#243;n de datos personales y garant&#237;a de los derechos digitales&#46; La base de datos creada para el desarrollo de la presente investigaci&#243;n ha sido anonimizada mediante c&#243;digos y debidamente custodiada por el investigador principal&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Resultados</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">An&#225;lisis descriptivo</span><p id="par0135" class="elsevierStylePara elsevierViewall">Se analizaron 640 muestras de heces&#44; 61 de las cuales tuvieron un resultado de toxina A&#47;B positiva&#44; lo que supone un 9&#44;5&#37; de casos de ICD&#46; La incidencia fue de 4&#44;51 casos por 10&#46;000 pacientes-d&#237;as&#46; Se estudiaron 61 casos &#40;72&#44;1&#37; de adquisici&#243;n nosocomial y 27&#44;9&#37; comunitarios&#41; y 64 controles&#46; La distribuci&#243;n mensual de los casos de ICD fue heterog&#233;nea&#59; se observ&#243; estacionalidad &#40;mayor en oto&#241;o e invierno&#41; con un ac&#250;mulo de 26 casos &#40;42&#44;6&#37;&#41; en el &#250;ltimo trimestre de 2015&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">La mediana de edad de los casos fue de 80 a&#241;os &#40;RIQ 13 a&#241;os&#59; rango de 28 a 95&#41;&#44; con un ligero predominio del sexo femenino &#40;57&#44;4&#37;&#41;&#46; El histograma de edad muestra una distribuci&#243;n heterog&#233;nea&#44; con tendencia a aumentar en edades avanzadas &#40;70-90 a&#241;os&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">El 52&#37; de los casos procedi&#243; del Servicio de Medicina Interna&#44; el 80&#37; present&#243; alguna enfermedad de base y el 56&#37; alguna infecci&#243;n concomitante&#44; de las que la infecci&#243;n del tracto urinario y las infecciones respiratorias fueron las m&#225;s frecuentes&#46; El 52&#37; de los casos se asoci&#243; con al menos un proceso gastrointestinal&#58; la alimentaci&#243;n enteral y el c&#225;ncer gastrointestinal fueron los m&#225;s frecuentes&#46; El 26&#37; de los pacientes present&#243; un proceso tumoral&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">El s&#237;ntoma m&#225;s frecuente fue la diarrea&#44; que estuvo presente en todos los pacientes excepto uno &#40;98&#44;4&#37;&#41;&#44; seguido de la fiebre &#40;42&#44;6&#37;&#41;&#44; dolor abdominal &#40;24&#44;6&#37;&#41; y v&#243;mitos &#40;6&#44;5&#37;&#41;&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Se administr&#243; un total de 129 antibi&#243;ticos&#46; Solo 3<span class="elsevierStyleHsp" style=""></span>pacientes &#40;5&#37;&#41; no recibieron ning&#250;n antibi&#243;tico antes del desarrollo de la infecci&#243;n&#46; La familia de antibi&#243;ticos m&#225;s usada fue la de los betalact&#225;micos &#40;56&#44;5&#37;&#41;&#44; seguida por las fluorquinolonas &#40;20&#44;1&#37;&#41;&#46; Los antibi&#243;ticos que se administraron con mayor frecuencia fueron&#58; amoxicilina-clavul&#225;nico &#40;20&#37;&#41;&#44; levofloxacino &#40;13&#37;&#41; e imipenem &#40;10&#37;&#41;&#46; El 94&#44;4&#37; consum&#237;a anti&#225;cidos de manera continua&#44; de los que el omeprazol era el m&#225;s utilizado &#40;74&#37;&#41; <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0160" class="elsevierStylePara elsevierViewall">El 34&#44;4&#37; de los casos tuvo una evoluci&#243;n grave y&#44; de ellos&#44; el 11&#44;5&#37; desarroll&#243; adem&#225;s alg&#250;n tipo de complicaci&#243;n&#59; 5 pacientes &#40;8&#44;5&#37;&#41; requirieron ingreso en UCI&#46; La mortalidad global fue del 18&#37;&#44; mientras que la mortalidad atribuible a la ICD fue del 6&#44;6&#37;&#46; Doce pacientes &#40;19&#44;7&#37;&#41; tuvieron una primera recurrencia&#44; y de ellos&#44; 3<span class="elsevierStyleHsp" style=""></span>sufrieron una segunda reca&#237;da &#40;5&#37;&#41;&#46; Solo un paciente tuvo una tercera recurrencia &#40;1&#44;6&#37;&#41;&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Factores de riesgo</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">An&#225;lisis bivariante</span><p id="par0165" class="elsevierStylePara elsevierViewall">La diarrea fue el s&#237;ntoma m&#225;s com&#250;n en ambos grupos&#44; aunque la FAD fue el &#250;nico s&#237;ntoma estad&#237;sticamente significativo&#59; fue m&#225;s frecuente en los casos que en los controles &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; Los factores de riesgo asociados a la ICD fueron la adquisici&#243;n nosocomial&#44; la hospitalizaci&#243;n previa 4 semanas antes&#44; el consumo previo de antimicrobianos y de anti&#225;cidos&#44; la hipoalbuminemia y las infecciones concomitantes &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">An&#225;lisis multivariante</span><p id="par0170" class="elsevierStylePara elsevierViewall">Mediante el an&#225;lisis por regresi&#243;n log&#237;stica se han identificado como factores de riesgo independientes de ICD el ingreso hospitalario las 4 semanas previas a la infecci&#243;n&#44; la hipoalbuminemia y la administraci&#243;n previa de antibi&#243;ticos &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; La probabilidad de desarrollar una ICD cuando un paciente presenta uno o ninguno de estos factores de riesgo es del 30&#37;&#44; asciende al 70&#37; cuando presenta 2<span class="elsevierStyleHsp" style=""></span>factores y&#44; por &#250;ltimo&#44; al 78&#37; sumando los 3<span class="elsevierStyleHsp" style=""></span>factores&#44; lo que constituye un riesgo casi 3 veces mayor de adquirir la infecci&#243;n&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Factores pron&#243;sticos de evoluci&#243;n de la infecci&#243;n por <span class="elsevierStyleItalic">Clostridioides difficile</span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">An&#225;lisis bivariante</span><p id="par0175" class="elsevierStylePara elsevierViewall">Hemos encontrado como factores de pron&#243;stico desfavorable la FAD&#44; el ingreso hospitalario durante las 4 semanas previas a la infecci&#243;n&#44; la hipoalbuminemia y la presencia de infecciones concomitantes &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">An&#225;lisis multivariante</span><p id="par0180" class="elsevierStylePara elsevierViewall">Encontramos como factores pron&#243;sticos independientes de evoluci&#243;n desfavorable la FAD y el ingreso hospitalario las 4 semanas previas a la infecci&#243;n &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Comparaci&#243;n entre casos hospitalarios y comunitarios</span><p id="par0185" class="elsevierStylePara elsevierViewall">Encontramos que el 40&#37; de los menores de 65 a&#241;os fueron de adquisici&#243;n comunitaria frente al 25&#37; de los pacientes con 65 a&#241;os o m&#225;s&#46; El 82&#44;3&#37; de los casos comunitarios fueron hospitalizados&#46; En el grupo de adquisici&#243;n nosocomial encontramos mayor n&#250;mero de ingresos hospitalarios las 4-12 semanas previas a la ICD&#44; diferencia que era estad&#237;sticamente significativa &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46; La alimentaci&#243;n enteral estuvo cerca de la significaci&#243;n&#46; Sin embargo&#44; aunque observamos mayor gravedad y&#44; en general&#44; peor pron&#243;stico entre los casos intrahospitalarios&#44; las diferencias no alcanzaron la significaci&#243;n estad&#237;stica &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">tabla 6</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Discusi&#243;n</span><p id="par0190" class="elsevierStylePara elsevierViewall">Para conocer el papel de <span class="elsevierStyleItalic">C&#46; difficile</span> en nuestra &#225;rea de salud hemos llevado a cabo este trabajo de investigaci&#243;n con 61 casos de ICD y 64 controles en un periodo de 14 meses&#46; El ingreso hospitalario las 4 semanas previas a la infecci&#243;n&#44; la hipoalbuminemia y la administraci&#243;n previa de antibi&#243;ticos resultaron factores de riesgo para desarrollar ICD&#46; Sin embargo&#44; otros factores de riesgo cl&#225;sicos como la hospitalizaci&#243;n las 4-12 semanas previas o el consumo de anti&#225;cidos e inmunosupresores&#44; aunque fueron m&#225;s frecuentes en los casos que en los controles&#44; no se han asociado de forma significativa con un mayor riesgo de infecci&#243;n&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Espa&#241;a es uno de los pa&#237;ses europeos con mayor consumo de antibi&#243;ticos<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">6</span></a>&#44; lo cual&#44; unido al envejecimiento de la poblaci&#243;n&#44; con numerosas comorbilidades y continuas hospitalizaciones&#44; genera el caldo de cultivo id&#243;neo para adquirir la ICD&#46; En nuestro estudio observamos una incidencia de 4&#44;51 casos por 10&#46;000 pacientes-d&#237;as&#44; inferior a la encontrada en Espa&#241;a &#40;6&#44;5 episodios por cada 10&#46;000 pacientes-d&#237;as&#41;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a>&#46; Hallamos un mayor n&#250;mero de casos durante los meses de oto&#241;o-invierno&#44; momento en que aumentan las infecciones respiratorias y&#44; por tanto&#44; el consumo de antibi&#243;ticos&#44; muchas veces de forma innecesaria por tratarse de infecciones virales&#44; como la gripe&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">La ICD de adquisici&#243;n comunitaria ha aumentado en la pasada d&#233;cada<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">8</span></a>&#44; que ha llegado a representar hasta un tercio de los casos nuevos<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">9&#44;10</span></a> y afecta a grupos de poblaci&#243;n antes considerados de bajo riesgo<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">11</span></a>&#46; Este incremento en los casos comunitarios podr&#237;a explicarse&#44; en parte&#44; por el hecho de haber estado infradiagnosticados por tratarse de casos leves y autolimitados&#46; Nuestros resultados son consistentes con estos hallazgos&#44; ya que el 28&#37; de los casos fueron comunitarios&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Nuestros resultados mostraron que el grupo de ICDC eran pacientes m&#225;s j&#243;venes&#44; con menos d&#237;as de estancia hospitalaria y menor riesgo de tener una infecci&#243;n grave&#44; hallazgos estos consistentes con otros estudios publicados<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">9-11</span></a>&#46; Por tanto&#44; estos datos acent&#250;an la necesidad de encontrar otras posibles fuentes de infecci&#243;n que justifiquen el incremento en el n&#250;mero de casos en la comunidad&#44; como la transmisi&#243;n de la enfermedad a partir del contacto con animales y de los alimentos<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">El uso de antibi&#243;ticos modifica la microbiota intestinal normal&#44; lo que proporciona un &#171;nicho&#187; para el sobrecrecimiento de <span class="elsevierStyleItalic">C&#46; difficile</span><a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a>&#46; Hay que tener en cuenta que tanto la exposici&#243;n prolongada a antibi&#243;ticos como la exposici&#243;n a m&#250;ltiples antibi&#243;ticos aumentan el riesgo de ICD<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">14</span></a>&#46; El 95&#37; de nuestros pacientes hab&#237;a recibido antibi&#243;ticos en los 3 meses anteriores&#46; Dado que la exposici&#243;n previa a antibi&#243;ticos es el factor de riesgo modificable m&#225;s importante para el desarrollo de ICD&#44; enfatizamos la importancia del desarrollo de programas de optimizaci&#243;n de antibi&#243;ticos tanto en el &#225;mbito hospitalario como en el comunitario&#46; Otro factor de riesgo de ICD modificable es la hipoalbuminemia&#44; que puede constituir un punto clave para prevenir la infecci&#243;n&#46; Varios estudios muestran que la hipoalbuminemia es&#44; adem&#225;s&#44; una variable predictora de infecci&#243;n recurrente y con mayor mortalidad<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a>&#46; Seg&#250;n nuestros datos&#44; los pacientes con hipoalbuminemia presentan m&#225;s del doble de riesgo de adquirir una ICD&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">La incidencia de colonizaci&#243;n por <span class="elsevierStyleItalic">C&#46; difficile</span> durante la hospitalizaci&#243;n var&#237;a entre el 2 y el 20&#37;&#44; que llega hasta al 50&#37; tras un mes de estancia hospitalaria&#46; En nuestro estudio&#44; el ingreso de los pacientes las 4 semanas previas supuso un riesgo de infectarse casi 4 veces mayor&#46; Adem&#225;s&#44; el 35&#37; de los casos comunitarios hab&#237;a tenido un ingreso hospitalario anterior&#46; Estos datos confirman la importancia de los centros sanitarios como reservorios de esporas de <span class="elsevierStyleItalic">C&#46; difficile</span>&#44; sobre todo en las urgencias&#44; ya que el volumen elevado de pacientes que son atendidos en cada turno y el recambio continuo de enfermos limitan la capacidad de desinfecci&#243;n adecuada entre uno y otro<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">16</span></a>&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">No hemos podido identificar la edad como factor de riesgo independiente de ICD&#44; puesto que&#44; dado el dise&#241;o de nuestro estudio&#44; los controles han sido apareados por edad y sexo con los casos&#46; El hecho de que la mediana de edad de los casos fuera de 80 a&#241;os indica que&#44; efectivamente&#44; la edad es un factor de riesgo potencial de ICD&#46; Debido a que es frecuente que varios de los factores de riesgo reconocidos de ICD est&#233;n presentes en los ancianos<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a>&#44; la l&#237;nea que separa un factor de riesgo y un factor de confusi&#243;n puede difuminarse&#44; creando cierto grado de controversia en los resultados&#46; As&#237;&#44; por ejemplo&#44; autores como Khanafer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">18</span></a> no asocian la edad con la infecci&#243;n&#44; mientras que otros autores&#44; al igual que nosotros&#44; no encuentran una relaci&#243;n estad&#237;sticamente significativa con la administraci&#243;n de anti&#225;cidos<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">19</span></a>&#59; sin embargo&#44; observamos un elevado consumo continuado en nuestros pacientes&#44; por lo que ser&#237;a recomendable reevaluar la necesidad de su administraci&#243;n&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">La selecci&#243;n de los controles adecuados es uno de los puntos que m&#225;s puede influir en los resultados de un dise&#241;o de casos y controles&#46; Por ello&#44; para evitar posibles sesgos&#44; se han escogido los controles lo m&#225;s cercanos en tiempo y edad a los casos&#46; La informaci&#243;n recogida en las historias cl&#237;nicas puede no reflejar los datos fielmente&#44; puede estar incompleta o incluso contener datos contradictorios&#46; No obstante&#44; creemos que este sesgo de informaci&#243;n no afecta de forma diferencial a los casos y a los controles&#44; por lo que suponemos que no invalidar&#237;a las asociaciones encontradas&#46; Adem&#225;s&#44; hemos tratado de controlar los posibles factores de confusi&#243;n en las estimaciones de las asociaciones&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Para proporcionar un mayor entendimiento sobre las lagunas existentes con relaci&#243;n a la transmisi&#243;n de <span class="elsevierStyleItalic">C&#46; difficile</span>&#44; creemos necesarios m&#225;s estudios para determinar si los animales son un reservorio importante para la ICDC<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">20</span></a> y si <span class="elsevierStyleItalic">C&#46; difficile</span> puede transmitirse tras la exposici&#243;n a ciertos alimentos&#44; como carnes rojas&#44; aves o verduras frescas<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a>&#46; De esta manera&#44; el estilo de vida o la profesi&#243;n del paciente podr&#237;an influir en el riesgo de adquirir la infecci&#243;n&#44; ya sea por los h&#225;bitos alimenticios o por el contacto con animales dom&#233;sticos en el hogar o en el &#225;mbito profesional en el caso de veterinarios o granjeros&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conclusiones</span><p id="par0235" class="elsevierStylePara elsevierViewall">Los factores de riesgo independientes para adquirir una ICD en nuestra &#225;rea de salud son el ingreso hospitalario las 4 semanas anteriores&#44; la administraci&#243;n previa de antibi&#243;ticos y la hipoalbuminemia&#46; La identificaci&#243;n de estos factores favorece la sospecha de la infecci&#243;n&#46; Adem&#225;s&#44; identificamos fiebre y hospitalizaci&#243;n previa como factores de pron&#243;stico desfavorable&#46; Modificando o suspendiendo el tratamiento antibi&#243;tico siempre que sea posible&#44; ajustando los niveles de alb&#250;mina y pautando precozmente una terapia espec&#237;fica podremos mejorar el pron&#243;stico de la infecci&#243;n&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Financiaci&#243;n</span><p id="par0240" class="elsevierStylePara elsevierViewall">La presente investigaci&#243;n no ha recibido ayudas espec&#237;ficas provenientes de agencias del sector p&#250;blico&#44; sector comercial o entidades sin &#225;nimo de lucro&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Conflicto de intereses</span><p id="par0245" class="elsevierStylePara elsevierViewall">Ninguno&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Determinar los factores de riesgo y factores pron&#243;sticos de la infecci&#243;n por <span class="elsevierStyleItalic">Clostridioides difficile</span> &#40;ICD&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Pacientes y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo de casos-controles &#40;61 casos y 64 controles&#41; de 2 a&#241;os o m&#225;s con diarrea&#44; atendidos en un &#225;rea sanitaria manchega durante 14 meses&#46; El diagn&#243;stico se realiz&#243; mediante inmunocromatograf&#237;a &#40;glutamato deshidrogenasa y toxina A&#47;B&#41;&#44; realizando amplificaci&#243;n isot&#233;rmica en los casos discordantes&#46; Se recogieron variables demogr&#225;ficas&#44; comorbilidades&#44; tipo de adquisici&#243;n&#44; administraci&#243;n previa de antibi&#243;ticos&#44; anti&#225;cidos e inmunosupresores y evoluci&#243;n&#46; Los datos se analizaron mediante la prueba de &#967;<span class="elsevierStyleSup">2</span> y el efecto de los factores de riesgo y pron&#243;sticos se cuantific&#243; mediante <span class="elsevierStyleItalic">odds ratio</span> con intervalos de confianza del 95&#37;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Como factores de riesgo independientes de ICD encontramos el ingreso hospitalario las 4 semanas previas a la infecci&#243;n&#44; la hipoalbuminemia y la administraci&#243;n previa de antibi&#243;ticos&#46; Presentar estos 3 factores supuso un riesgo casi 3 veces mayor de infectarse&#46; En el grupo de adquisici&#243;n nosocomial se encontr&#243; mayor n&#250;mero de ingresos hospitalarios las 4-12 semanas previas a la ICD y&#44; aunque hubo mayor tendencia a las recurrencias y al pron&#243;stico desfavorable entre los casos intrahospitalarios&#44; estas diferencias no fueron significativas&#46; Identificamos como factores de pron&#243;stico desfavorable la fiebre y el ingreso hospitalario las 4 semanas previas a la infecci&#243;n&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Los factores de riesgo independientes de ICD fueron&#58; ingreso hospitalario las 4 semanas previas a la infecci&#243;n&#44; hipoalbuminemia y administraci&#243;n previa de antibi&#243;ticos&#46; La fiebre y la hospitalizaci&#243;n las 4 semanas anteriores se identificaron adem&#225;s como factores pron&#243;sticos de evoluci&#243;n desfavorable&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To determine the risk and prognostic factors for <span class="elsevierStyleItalic">Clostridioides difficile</span> infection &#40;CDI&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Prospective&#44; case-control study with 61 cases and 64 controls&#44; aged &#8805;2 years with diarrhoea&#44; carried out in Castilla-La Mancha Health Care Area for 14 months&#46; The diagnosis was made by immunochromatography technics &#40;glutamate dehydrogenase and toxin A&#47;B&#41;&#44; confirming discordant cases by isothermal amplification&#46; Demographic variables&#44; comorbidities&#44; type of acquisition&#44; previous administration of antibiotics&#44; antacids and immunosuppressants&#44; and evolution were collected&#46; The data were analysed using the chi-square test and the effect of risk and prognostic factors was quantified using an odds ratio with 95&#37; confidence intervals&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Hospital admission 4 weeks prior to infection&#44; hypoalbuminemia&#44; and previous administration of antibiotics were identified as independent risk factors for CDI&#46; Presenting these 3 factors constitutes nearly 3-fold increase in the risk of becoming infected&#46; A greater number of hospital admissions in the 4-12 weeks prior to CDI were found in the group of nosocomial acquisition&#46; Although there was a greater tendency to recurrence and an unfavourable prognosis among nosocomial cases&#44; these differences were not significant&#46; We found that fever and hospital admission in the 4 weeks prior to infection were unfavourable prognostic factors of CDI&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The independent risk factors for CDI were&#58; Hospital admission in the 4 weeks prior to infection&#44; hypoalbuminemia&#44; and previous administration of antibiotics&#46; Fever and hospitalisation in the previous 4 weeks were also identified as prognostic factors of unfavourable evolution&#46;</p></span>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hombre&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mujer&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hospitalario&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Comunitario&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Ingreso hospitalario previo</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Ingreso en 4 semanas previas</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3 &#40;4&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  """
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">7 &#40;33&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Ingreso en 4 semanas previas</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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Información del artículo
ISSN: 02105705
Idioma original: Español
DOI:10.1016/j.gastrohep.2022.01.006
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