Meningitis neumocócica del adulto, 1977-1989: Impacto de la resistencia antibiótica. Estudio de los factores pronósticos y de nuevos aspectos terapéuticos

[spa] En 1977 iniciamos un proyecto de investigación clínica en torno a las infecciones del SNC, parte del cual consistió en la elaboración de un protocolo de estudio de las meningitis bacterianas. Trece años después, a finales de 1989, habían sido incluidos definitivamente en el protocolo 797 episodios de meningitis, entre los cuales se hallaban 132 episodios de meningitis neumocócica, objeto del presente estudio.La meningitis neumocócica del adulto despertó desde el principio nuestro interés debido a su especial gravedad y a las dificultades existentes en su tratamiento. Nos preocupó fundamentalmente que su pronóstico, en cuanto a mortalidad y desarrollo de secuelas neurológicas en los supervivientes, apenas hubiese mejorado en los últimos treinta años, a pesar de la introducción de nuevos antibióticos con gran actividad bactericida. La ulterior aparición y aumento progresivo del número de cepas de neumococo resistentes a la penicilina y a otros antibióticos supuso otra complicación adicional para el manejo adecuado de estos pacientes.Los objetivos concretos de nuestro estudio fueron:l. - Delimitar la situación actual de la meningitis neumocócica en el contexto de la meningitis bacteriana del adulto.2.- Conocer la actividad "in vitro" de los antimicrobianos frente a las cepas de "S. pneumoniae" causantes de meningitis.3. - Determinar la epidemiología y las características clínicas y evolutivas de la meningitis causada por neumococos resistentes a la penicilina en nuestro medio.4.- Establecer el papel de la penicilina G, cefalosporinas de tercera generación y vancomicina en el tratamiento de la meningitis causada por neumococos resistentes.5.- Determinar los factores pronósticos de la meningitis neumocócica.6. - Evaluar la influencia del tratamiento asociado en la evolución de la meningitis neumocócica.Los datos de los pacientes, tanto clínicos como de laboratorio, fueron recogidos en un protocolo informatizado de 115 variables, definidas previamente, rellenado una vez que el paciente era dado de alta y completado tras el seguimiento en consultas externas. Con posterioridad los datos se incluyeron en una base de datos (DBase III plus) y fueron explotados estadísticamente.Se realizó un análisis multivariado de la mortalidad global y de la atribuible directamente a la infección.Las intervenciones más importantes efectuadas fueron la introducción de las cefalosporinas de 3ª generación, como tratamiento antibiótico inicial en 1986 y la administración precoz y sistemática de manitol, dexametasona y difenilhidantoina, como tratamiento asociado a los antibióticos.Se realizó un estudio caso-control "matched" para analizar la influencia del tratamiento asociado a los antibióticos en la reducción de la mortalidad. Los cálculos estadísticos se realizaron en un microordenador mediante los paquetes SPSS y BMOP.Las principales conclusiones del estudio fueron:En nuestra comunidad, el neumococo es causa de una cuarta parte del total de casos de meningitis bacteriana, y de la mitad de aquellos casos que cursan sin púrpura. .En un 80-85% de pacientes con meningitis neumocócica puede detectarse el foco de origen de la infección, hecho que ocurre con mucha menor frecuencia en el resto de etiologías. En consecuencia, alrededor de las tres cuartas partes de casos de meningitis de la comunidad asociados a otitis media aguda, sinusitis, neumonía ó fístula de LCR, van a ser de etiología neumocócica.El neumococo es causa poco frecuente de meningitis nosocomial, habiendo originado un 7% de nuestros casos.La meningitis neumocócica sigue siendo una enfermedad muy grave, de peor pronóstico que la ocasionada por otros patógenos meníngeos clásicos como meningococo ó hemofilus. En nuestra serie, su tasa de mortalidad específica fue del 29%, sólo superada por la de los bacilos Gram negativos. Asimismo, en cifras absolutas, fue la etiología que ocasionó un mayor número de fallecimientos.La resistencia del neumococo a la penicilina ha aumentado de forma progresiva durante el período de estudio, tanto en frecuencia como en grado.El porcentaje global de resistencia en nuestra serie ha sido del 27,5%.En la actualidad, estimamos que la probabilidad de que una meningitis neumocócica sea causada por una cepa con sensibilidad disminuida a la penicilina es el 50%, y que la mitad de las cepas con sensibilidad disminuida son altamente resistentes.Asimismo, la probabilidad de resistencia al cloramfenicol y al cotrimoxazol es de 35 % y 50 %, respectivamente.El 75 % de las cepas resistentes a penicilina muestran resistencia múltiple. La cefotaxima, la ceftriaxona y el imipeném son los antibióticos betalactámicos más activos frente a los neumococos resistentes a la penicilina. No hemos hallado cepas de neumococo resistentes a la vancomicina ni a la rifampicina.No observamos diferencias importantes (epidemiológicas, clínicas y evolutivas), entre los casos de meningitis causados por neumococos sensibles ó resistentes a la penicilina. Sin embargo, los casos resistentes con mayor frecuencia fueron ocasionados por el serotipo 23, eran de adquisición nosocomial, y habían recibido antibióticos previos.La penicilina debe reservarse exclusivamente para el tratamiento de las meningitis causadas por neumococos sensibles, puesto que ni con la utilización de dosis masivas puede garantizarse la curación bacteriológica de los casos con resistencia moderada.La cefotaxima y la ceftriaxona constituyen el tratamiento de elección de la meningitis neumocócica, antes de conocer la sensibilidad de la cepa causal. Ambas se han mostrado eficaces en los casos causados por neumococos con CBMs a la penicilina de hasta 4 mcg/ml.La vancomicina no debe ser utilizada como tratamiento de rutina de la meningitis causada por neumococos resistentes r debido a su alto índice de recaídas.Debe reservarse para casos de alta resistencia que no hayan respondido a la cefotaxima y para casos seleccionados de alergia a betalactámicos, siempre que sean resistentes al cloramfenicol.Los factores que se asociaron de forma independiente con una mayor mortalidad global fueron: la presencia de shock al ingreso (RR 8.1), la edad superior a 65 años (RR 4.6), el desarrollo de complicaciones pulmonares durante el ingreso (RR 4.6) y el que la infección hubiese tenido un foco de origen distante del SNC (RR 3.3).Los factores que se asociaron de forma independiente con una mayor mortalidad por la propia infección fueron: la presencia de shock al ingreso (RR 4.73) y el que la infección hubiese tenido un foco de origen distante del SNC (RR 4.4).En el subgrupo de pacientes con meningitis de foco de origen contiguo al SNC, sólo el desarrollo de convulsiones tras el ingreso (RR 4.9) se asoció de forma independiente con una mayor mortalidad por la propia infección.Mediante la administración sistemática y precoz de manital, dexametasona y difenilhidantoina, como tratamiento asociado a los antibióticos, conseguimos reducir muy significativamente la mortalidad de nuestros pacientes.Así pues, concluimos que la utilización de dicho tratamiento asociado parece constituir un gran avance en el manejo de los pacientes con meningitis neumocócica.[eng] We studied 132 episodes of adult pneumococcal meningitis (PM) as a part of a prospective study involving 797 cases of' bacterial meningitis observed from 1977 to 1989. The main objectives were: l) to know the "in vitro" activity of' different antimicrobial agents against the strains of pneumococci in our area, 2) to know the epidemiology, characteristics and outcome of the PM due to resistant strains, 3) to determine the best therapy for such infections, 4): to determine the prognostic factors of PM, and 5) to evaluate the effects of an adjunctive therapy on the outcome.We observed a sustained tendency towards increasing resistance of pneumococci to peniciline, cloramphenicol and cotrimoxazol. The current penicillin and cloranphenicol resistances approach 50%. The recommended initial therapy for a PM in our area is Cefrotaxime in doses of 300 mg/Kg/day. The major independent factors influencing mortality are the age of patients, the presence of shock on admission and the source of the infection. The early administration of manitol, dexamethasone and phenytoin as an adjunctive therapy to antibiotics, reduced significantly the mortality (from 30 to 5%) and thus appears to be a major advance in the therapy of PM

Drug-resistant Streptococcus pneumoniae

To the Editor: since the first description of infection caused by β-lactam-resistant Streptococcus pneumoniae, the optimal empirical antibiotic therapy for patients with suspected meningitis caused by this microorganism has remained unknown. Hofmann et al. (Aug. 24 issue)1 reported a 25 percent prevalence of penicillin-resistant S. pneumoniae isolates and a 9 percent prevalence of cephalosporin-resistant isolates among 431 patients with invasive pneumococcal infections in Atlanta. The authors recommended adding vancomycin to the initial therapeutic regimen of patients with suspected pneumococcal meningitis

Rainfall is a risk factor for sporadic cases of Legionella pneumophila Pneumonia

It is not known whether rainfall increases the risk of sporadic cases of Legionella pneumonia. We sought to test this hypothesis in a prospective observational cohort study of non-immunosuppressed adults hospitalized for community-acquired pneumonia (1995-2011). Cases with Legionella pneumonia were compared with those with non-Legionella pneumonia. Using daily rainfall data obtained from the regional meteorological service we examined patterns of rainfall over the days prior to admission in each study group. Of 4168 patients, 231 (5.5%) had Legionella pneumonia. The diagnosis was based on one or more of the following: sputum (41 cases), antigenuria (206) and serology (98). Daily rainfall average was 0.556 liters/m2 in the Legionella pneumonia group vs. 0.328 liters/m2 for non-Legionella pneumonia cases (p = 0.04). A ROC curve was plotted to compare the incidence of Legionella pneumonia and the weighted median rainfall. The cut-off point was 0.42 (AUC 0.54). Patients who were admitted to hospital with a prior weighted median rainfall higher than 0.42 were more likely to have Legionella pneumonia (OR 1.35; 95% CI 1.02-1.78; p = .03). Spearman Rho correlations revealed a relationship between Legionella pneumonia and rainfall average during each two-week reporting period (0.14; p = 0.003). No relationship was found between rainfall average and non-Legionella pneumonia cases (−0.06; p = 0.24). As a conclusion, rainfall is a significant risk factor for sporadic Legionella pneumonia. Physicians should carefully consider Legionella pneumonia when selecting diagnostic tests and antimicrobial therapy for patients presenting with CAP after periods of rainfall

El portafoli electrònic com a complement docent d'habilitats clíniques en ciències de la salut

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/66524[cast] Introducción: El portafolio es una herramienta docente útil para la enseñanza y evaluación, de amplia difusión en los últimos años. Su objetivo es mejorar el aprendizaje mediante la reflexión del alumno y el feed-back continuado de las evaluaciones. En Ciencias de la Salud ha de mostrado ser útil para la evaluación de competencias trasversales y técnicas realizadas mediante prácticas clínicas y talleres. La implantación de la informática ha facilitado la introducción del portafolio electrónico (e-portafolio). Nuestra experiencia previa en portafolio en papel, nos decidió a implantarlo en alguna asignatura de nuestro Departamento. Objetivos: 1. Valorar la realización del e-portafolio. 2. Evaluar la satisfacción del alumnado. 3 Determinar la carga del proceso en el profesorado..

Treball de Fi de Grau: punts forts i punts febles

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/6652

Invasive meningococcal disease: what we should know, before it comes back

Background: invasive meningococcal disease (IMD), sepsis and/or meningitis continues to be a public health problem, with mortality rates ranging from 5% to 16%. The aim of our study was to further knowledge about IMD with a large series of cases occurring over a long period of time, in a cohort with a high percentage of adult patients. Methods: observational cohort study of patients with IMD between 1977 hand 2013 at our hospital, comparing patients with only sepsis and those with meningitis and several degrees of sepsis. The impact of dexamethasone and prophylactic phenytoin was determined, and an analysis of cutaneous and neurological sequelae was performed. Results: a total of 527 episodes of IMD were recorded, comprising 57 cases of sepsis (11%) and 470 of meningitis with or without sepsis (89%). The number of episodes of IMD decreased from 352 of 527 (67%) in the first to 20 of 527 (4%) in the last quarter (P < .001). Thirty-three patients died (6%): 8 with sepsis (14%) and 25 with meningitis (5%) (P = .02). Cutaneous and neurological sequelae were present in 3% and 5% of survivors of sepsis and meningitis, respectively. The use of dexamethasone was safe and resulted in less arthritis, and patients given prophylactic phenytoin avoided seizures. Conclusions: the frequency of IMD has decreased sharply since 1977. Patients with sepsis only have the highest mortality and complication rates, dexamethasone use is safe and can prevent some arthritis episodes, and prophylactic phenytoin might be useful in a selected population. A rapid response and antibiotic therapy may help improve the prognosis

Impact of a training program on the surveillance of Clostridioiaes difficile infection

A high degree of vigilance and appropriate diagnostic methods are required to detect Clostridioides difficile infection (CDI). We studied the effectiveness of a multimodal training program for improving CDI surveillance and prevention. Between 2011 and 2016, this program was made available to healthcare staff of acute care hospitals in Catalonia. The program included an online course, two face-to-face workshops and dissemination of recommendations on prevention and diagnosis. Adherence to the recommendations was evaluated through surveys administered to the infection control teams at the 38 participating hospitals. The incidence of CDI increased from 2.20 cases/10 000 patient-days in 2011 to 3.41 in 2016 (P < 0.001). The number of hospitals that applied an optimal diagnostic algorithm rose from 32.0% to 71.1% (P = 0.002). Hospitals that applied an optimal diagnostic algorithm reported a higher overall incidence of CDI (3.62 vs. 1.92, P < 0.001), and hospitals that were more active in searching for cases reported higher rates of hospital-acquired CDI (1.76 vs. 0.84, P < 0.001). The results suggest that the application of a multimodal training strategy was associated with a significant rise in the reporting of CDI, as well as with an increase in the application of the optimal diagnostic algorithm

Incidence and molecular typing of Mycobacterium kansasii in a defined geographical area in Catalonia, Spain

A retrospective population-based study was conducted between January 1990 and December 1998 to investigate the incidence of Mycobacterium kansasii disease and the heterogeneity of the isolates in a well-defined geographical area in Catalonia, Spain. A total of 136 patients were identified. Overall incidence and incidence in AIDS patients was 1. 5 (95% CI 1.2-1.8) and 1089.6 (95% CI 689-1330) cases/100 000 persons per year respectively, which is comparable to that reported from most of other geographical areas. Surprisingly, although 7 subtypes of M. kansasii have been consistently reported, in the present study 91 of the 93 isolates (97.8%) tested for genotype were subtype I, regardless of HIV status of the patients. In conclusion, the high rate of infection observed in the AIDS population contributes significantly to the burden of the M. kansasii disease in our area. M. kansasii disease in our geographical area was almost exclusively caused by subtype I regardless of HIV status

Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain

Background: Penicillin-resistant strains of Streptococcus pneumoniae are now found worldwide, and strains with resistance to cephalosporin are being reported. The appropriate antibiotic therapy for pneumococcal pneumonia due to resistant strains remains controversial. Methods: To examine the effect of resistance to penicillin and cephalosporin on mortality, we conducted a 10-year, prospective study in Barcelona of 504 adults with culture-proved pneumococcal pneumonia. Results: Among the 504 patients, 145 (29 percent) had penicillin-resistant strains of S. pneumoniae (minimal inhibitory concentration [MIC] of penicillin G, 0.12 to 4.0 μg per milliliter), and 31 patients (6 percent) had cephalosporin-resistant strains (MIC of ceftriaxone or cefotaxime, 1.0 to 4.0 μg per milliliter). Mortality was 38 percent in patients with penicillin-resistant strains, as compared with 24 percent in patients with penicillin-sensitive strains (P = 0.001). However, after the exclusion of patients with polymicrobial pneumonia and adjustment for other predictors of mortality, the odds ratio for mortality in patients with penicillin-resistant strains was 1.0 (95 percent confidence interval, 0.5 to 1.9; P = 0.84). Among patients treated with penicillin G or ampicillin, the mortality was 25 percent in the 24 with penicillin-resistant strains and 19 percent in the 126 with penicillin-sensitive strains (P = 0.51). Among patients treated with ceftriaxone or cefotaxime, the mortality was 22 percent in the 59 with penicillin-resistant strains and 25 percent in the 127 with penicillin-sensitive strains (P = 0.64). The frequency of resistance to cephalosporin increased from 2 percent in 1984-1988 to 9 percent in 1989-1993 (P = 0.002). Mortality was 26 percent in patients with cephalosporin-resistant S. pneumoniae and 28 percent in patients with susceptible organisms (P = 0.89). Among patients treated with ceftriaxone or cefotaxime, mortality was 22 percent in the 18 with cephalosporin-resistant strains and 24 percent in the 168 with cephalosporin-sensitive organisms (P = 0.64). Conclusions: Current levels of resistance to penicillin and cephalosporin by S. pneumoniae are not associated with increased mortality in patients with pneumococcal pneumonia. Hence, these antibiotics remain the therapy of choice for this disease

Impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia

The aim of this study was to compare the evolution of systemic cytokine levels over time in patients with pneumococal pneumonia treated either with β-lactam monotherapy or with combination therapy (β-lactam plus fluoroquinolone). Prospective observational study of hospitalized non-immunocompromised adults with PP. Concentrations of IL-6, IL-8, IL-10, and TNF-α were determined on days 0, 1, 2, 3, 5, and 7. Patients on β-lactam monotherapy were compared with those receiving combination therapy. Fifty-two patients were enrolled in the study. Concentrations of IL-6, IL-8, and IL-10 decreased rapidly in the first days after admission, in accordance with the mean time to defervescence. High levels of IL-6 were found in patients with the worst outcomes, measured by the need for intensive care unit admission and mortality. No major differences in demographic or clinical characteristics or severity of disease were found between patients treated with β-lactam monotherapy and those treated with combination therapy. IL-6 levels fell more rapidly in patients with combination therapy in the first 48 h (p = 0.016). Our data suggest that systemic expression of IL-6 production in patients with PP correlates with prognosis. Initial combination antibiotic therapy produces a faster decrease in this cytokine in the first 48 h