Evaluación de la formación de biopelículas en aislamientos bacterianos y fúngicos por el método semicuantitativo de microtitulación con cristal violeta y el cualitativo de agar con rojo Congo / Assessment of biofilms formation of bacterial and fungal isolates using qualitative Congo red agar and semiquantitative crystal violet microtiter methods

Introducción. El 65 % de las infecciones humanas son producidas por bacterias o levaduras, cuya capacidad de formar biopelículas las hace más resistentes a los antimicrobianos y antifúngicos. Objetivo. Determinar la capacidad de formación de biopelículas en aislamientos bacterianos y fúngicos por medio de los métodos cuantitativo de microtitulación con cristal violeta y cualitativo de cultivo en agar con rojo Congo. Materiales y métodos. Con el método cuantitativo, se utilizaron los medios de cultivo infusión cerebro-corazón, tripticasa de soya y Müeller-Hinton para aislamientos bacterianos; para levaduras, se usaron caldo infusión cerebro-corazón y Sabouraud dextrosa. Para el método cualitativo de cultivo en agar, se utilizaron los mismos medios de cultivo más una solución con 3 % de rojo Congo y 10 % de dextrosa. Cómo método de referencia, se utilizó la propuesta de Stepanovic et al. Resultados. Se evaluaron 103 aislamientos bacterianos y 108 de levaduras. No es recomendable sustituir el caldo infusión cerebro-corazón por los caldos tripticasa de soya y Müeller-Hinton en el método cuantitativo, para evaluar la formación de biopelículas en los aislamientos bacterianos. El medio Sabouraud dextrosa, en caldo y agar, puede sustituir al de infusión de cerebro-corazón para evaluar la formación de biopelículas en levaduras, tanto por el método cuantitativo como por el cualitativo. Conclusión. El estudio de las biopelículas en el laboratorio de microbiología, a partir del método cualitativo de cultivo en agar con rojo Congo, es un procedimiento sencillo, rápido y de bajo costo, que proporciona información útil para el diagnóstico y la terapéutica de infecciones persistentes causadas por bacterias y levaduras.

Introduction. Sixty-five percent of human infections are caused by bacteria or yeasts able to form biofilms. This feature makes them more resistant to antimicrobials and antifungals. Objective. To determine biofilm formation capacity of bacterial and fungal isolates by quantitative crystal violet microtiter and qualitative Congo red agar methods. Materials and methods. Brain-heart infusion, trypticase soy broth and Müeller-Hinton culture media were used in bacterial isolates for the quantitative method; brain-heart infusion broth and Sabouraud dextrose were used for yeasts. The same culture media plus 3% Congo red and 10% dextrose were used to apply the qualitative method in agar. The proposal by Stepanovic, et al. was used as a reference method. Results. We evaluated 103 bacterial isolates and 108 yeasts isolates. We did not recommend substitute brain-heart infusion broth for trypticase soy and Müeller-Hinton broths for biofilm formation assessment in bacterial isolates using the quantitative method. Sabouraud dextrose medium, both broth and agar, can replace brain-heart infusion to assess biofilm formation in yeasts, quantitatively and qualitatively. Conclusion. The study of biofilms in the microbiology laboratory, using Congo red agar qualitative method, is a simple, fast, and inexpensive procedure that provides precise information for the diagnosis and treatment of persistent infections caused by bacteria and yeasts.

Executive summary of the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) on the diagnosis and antimicrobial treatment of infections due to carbapenem-resistant Gram-negative bacteria / Resumen ejecutivo del documento de consenso de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) sobre el diagnóstico y tratamiento antimicrobiano de las infecciones por bacterias gramnegativas resistentes a carbapenémicos

Infections caused by multidrug resistant Gram-negative bacteria are becoming a worldwide problem due to their increasing incidence and associated high mortality. Carbapenem-resistant bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii are the most important in clinical practice. The objective of these guidelines is to update the recommendations for the diagnosis and treatment of infections caused by these multidrug resistant bacteria. Although ‘old’ antibiotics such as aminoglycosides, colistin, or tigecycline are frequently used for therapy of these bacteria, the ‘new’ beta-lactams such as ceftazidime–avibactam, ceftolozane–tazobactam, meropenem–vaborbactam, imipenem–cilastatin–relebactam or cefiderocol are progressively becoming the first-line therapy for most of these microorganisms. The Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica) designated a panel of experts in the field to provide evidence-based recommendations in response to common clinical questions. This document is primarily focused on microbiological diagnosis, clinical management, and targeted antimicrobial therapy of these infections, with special attention to defining the role of the new antimicrobials in the treatment of these bacteria.(AU)

Las infecciones causadas por bacterias gramnegativas multirresistentes se han convertido en un problema mundial debido a su creciente incidencia y alta mortalidad asociada. Las bacterias resistentes a carbapenémicos como Klebsiella pneumoniae, Pseudomonas aeruginosa y Acinetobacter baumannii son las más importantes en la práctica clínica. El objetivo de este documento de consenso es actualizar las recomendaciones sobre diagnóstico y tratamiento de las infecciones causadas por estas bacterias multirresistentes. Aunque los antibióticos ‘antiguos’ como aminoglucósidos, colistina o tigeciclina se utilizan con frecuencia en el tratamiento de estas bacterias, los ‘nuevos’ betalactámicos como ceftazidima-avibactam, ceftolozano-tazobactam, meropenem-vaborbactam, imipenem-cilastatina-relebactam o cefiderocol se están convirtiendo de forma progresiva en el tratamiento de primera elección para la mayoría de estos microorganismos. La Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica ha designado un grupo de expertos en la materia para elaborar una guía de recomendaciones basadas en la evidencia sobre las cuestiones clínicas más habituales. Este documento está principalmente centrado en el diagnóstico microbiológico, el manejo clínico y el tratamiento dirigido de estas infecciones, con especial referencia a definir el papel de los nuevos antimicrobianos en el tratamiento de estas bacterias.(AU)

Frecuencia de Bacilos Gram Negativos en la cavidad bucal de estudiantes de una Universidad de Asunción

Introducción: La cavidad bucal hospeda una gran cantidad de microorganismos, como los bacilos Gram negativos, y entre ellas, bacterias de gran importancia médica debido a su capacidad de producir enfermedades graves para el ser humano, especialmente en pacientes inmunodeprimidos. El objetivo de este trabajo fue determinar la presencia de Bacilos Gram Negativos y sus patrones de resistencia a antibióticos, en una población estudiantil de la ciudad de Asunción, en los años 2019 y 2020. Materiales y métodos: Se realizó un estudio observacional, descriptivo de corte transversal, donde se realizaron hisopados de la cavidad bucal a 35 alumnos de entre 18 a 24 años, de una universidad privada en la ciudad de Asunción. Se requirió consentimiento informado firmado por los participantes y fueron excluidos quienes tuvieron tratamientos antibióticos. Las muestras fueron obtenidas con un hisopo de algodón, posteriormente se colocaron en un medio de transporte para luego ser cultivadas en Agar MacConkey. El cultivo se realizó por 48 horas a 37° centígrados, luego se procedió a la identificación bacteriana. Por último, se realizó el antibiograma. Resultados: De los 35 alumnos se encontró una frecuencia de 48,57% de bacilos Gram negativos. Cepas de Klebsiella pneumoniae fueron las más frecuentes (35,29%). Se observó que las bacterias eran altamente resistentes a la Amoxicilina/Ácido Clavulánico. Conclusiones: La presencia de estos tipos de microorganismos puede ser peligrosa para la salud general de las personas, específicamente de los pacientes con algún tipo de inmunodepresión, debido a la gran la resistencia a antibióticos presentadas por algunas cepas.

Introduction: The oral cavity hosts a large number of microorganisms, such as Gram negative bacilli, and among them, bacteria of great medical importance due to their capacity to cause serious diseases for humans, especially in immunosuppressed patients. The objective of this work was to determine the presence of Gram Negative Bacilli and their patterns of resistance to antibiotics, in a student population of the city of Asunción, in the years 2019 and 2020. Materials and methods: An observational, descriptive cross-sectional study was carried out, where oral cavity swabs were made from 35 students between 18 and 24 years of age, from a private university in the city of Asunción. Informed consent signed by the participants was required and those who had antibiotic treatments were excluded. The samples were obtained with a cotton swab, later they were placed in a transport medium to later be cultured in MacConkey Agar. The culture was carried out for 48 hours at 37° Celsius, then the bacterial identification was carried out. Finally, the antibiogram was performed. Results: Of the 35 students, a frequency of 48,57% of Gram negative bacilli was found. Klebsiella pneumoniae strains were the most frequent (35.29%). The bacteria were found to be highly resistant to Amoxicillin/Clavulanic Acid. Conclusions: The presence of these types of microorganisms can be dangerous for the general health of people, specifically of patients with some type of immunosuppression, due to the great resistance to antibiotics presented by some strains.

Anti-endotoxin antibodies consumption in cardiovascular collapse: Pathophysiological concerns / Consumo de anticuerpos antiendotoxina en el shock: relación etiológica

Objective Abnormal endotoxin activity in critically ill patients has been described in the absence of Gram-negative bacterial (GNB) infection. As disease severity seems to be crucial in the detection of this phenomenon, we decided to assess and compare endotoxin exposure in those patients representing the critical situation: septic shock and cardiogenic shock. Design Prospective, observational non intervention study. Setting Critical Care Department of a University tertiary hospital. Patients Cardiogenic shock (CS) and septic shock (SS) patients. Interventions None. Measurements and main results Follow-up was performed for the first three days. Inflammatory biomarkers (C-reactive protein, procalcitonin and interleuquin-6) and IgM antiendotoxin-core antibodies titter (IgM EndoCAb) were daily analyzed. Sixty-two patients were included; twenty-five patients with SS and thirty-seven with CS. Microbial etiology was established in 23 SS patients (92%) and GNB were present in 13 cases (52%). Although infection was suspected and even treated in 30 CS patients (81%), any episode could be finally confirmed. EndoCAb consumption was more intense in SS patients, although twenty-two CS patients (59.5%) had IgM anti-endotoxin value below 10th percentile range for healthy people. No statistically significant difference in endotoxin exposure was detected between Gram-positive and Gram-negative infections in the SS group. Endotoxin exposure ability to distinguish between SS and CS was moderate (AUC 0.7892, 95% IC: 0.6564–0.9218).Conclusions In the severely ill patient some mechanisms take place allowing endotoxin incursion and therefore blurring the limits of diseases pathophysiology. Our work representatively shows how exposure to endotoxin was not fully capable of distinguishing between CS and SS. (AU)

Objetivo En el paciente crítico se ha descrito una actividad incrementada de la endotoxina no asociada a infección por bacterias gramnegativas (BGN). La gravedad de la enfermedad influye en este fenómeno, por ello realizamos este estudio en el paciente crítico por antonomasia: shock séptico y cardiogénico. Diseño Estudio prospectivo, observacional, sin intervención.Lugar de estudioUnidad de Cuidados Intensivos. Pacientes Pacientes en shock cardiogénico (SC) o séptico (SS).Intervención Ninguna. Determinaciones y principales resultados Seguimiento durante los 3 primeros días. Proteína C reactiva, procalcitonina e interleucina-6, y el título de anticuerpos IgM anti-edotoxina (IgM EndoCAb) se analizaron diariamente. Se incluyó a 62 pacientes; 25 con SS y 37 con SC. La etiología fue identificada en 23 pacientes con SS (92%), los BGN estuvieron presentes en 13 casos (52%). Se sospechó e incluso trató la infección en 30 pacientes con SC, pero en ningún caso se pudo confirmar. El consumo de EndoCAb fue más intenso en los pacientes con SS, pero 22 pacientes con SC (59,5%) tuvieron unos valores por debajo del percentil 10. Los niveles de EndoCAb no fueron significativamente diferentes entre las infecciones por BGN y cocos grampositivos. La capacidad de EndoCab para diferenciar entre SC y SS resultó ser moderada (AUC 0,7892; IC del 95%, 0,6564-0,9218).Conclusiones En el paciente crítico es frecuente que la endotoxina provoque una respuesta inflamatoria y la sumación de distintos mecanismos fisiopatológicos. En este sentido, nuestro trabajo pone de manifiesto que la determinación de exposición a endotoxina no es totalmente capaz de distinguir entre los pacientes con SC y SS. (AU)

Use of hospital resources in ICU inpatients with infections caused by carbapenem-resistant Gram-negative bacteria: A real clinical practice-based study in Spain / Uso de recursos hospitalarios en pacientes hospitalizados en UCI debido a infecciones causadas por bacterias gramnegativas resistentes a carbapenémicos: un estudio basado en la práctica clínica real en España

Introduction: Carbapenem-resistant Gram-negative bacteria (CRGN) are an urgent public health threat because of the limited treatment options, its rapid spreading and high clinical impact and mortality rates. However, the burden and the use of resources of these infections have not been investigated. The aim of the current study is to understand the use of resources associated to the clinical management of CRGN infections in real clinical practice conditions. Methods: An observational retrospective chart review study was performed. Data regarding patient demographics, clinical management and use of resources associated to hospitalization were retrieved from clinical charts of ICU inpatients with a confirmed CRGN infection. Three reference Spanish hospitals were selected according to their patient volume and geographical coverage. Descriptive analyses of the clinical management and the use of resources and its cost were performed and then total costs by type of resource were calculated. Results: A total of 130 patients were included in the study. The higher number of patients (n=43; 33%) were between 61 and 70 years old. Ninety-four (72%) patients were male and 115 (88%) suffered from comorbidities. The mean total cost associated to the resources used in patients with CRGN infections hospitalized in ICU was 96,878€ per patient. These total costs included 84,140€ of total hospital stay, 11,021€ of treatments (558€ of antibiotics; 10,463€ of other treatments) and 1717€ costs of diagnostic tests. Conclusions: CRGN infection causes a high use of hospital resources, being the length of stay either in hospital wards or ICU the driver of the total costs. Diagnostic tests and treatments, including antibiotics, represent the lowest part of the use of resources and costs (13% of total costs).(AU)

Introducción: Las bacterias gramnegativas resistentes a carbapenémicos (CRGN) son una amenaza urgente de salud pública por las limitadas opciones de tratamiento, su rápida dispersión y el alto impacto clínico y tasas de mortalidad. Sin embargo, la carga y el uso de recursos de estas infecciones no han sido investigadas. El objetivo de este estudio es comprender el uso de recursos asociado al manejo clínico de las infecciones por CRGN en condiciones de práctica clínica real. Métodos: Se llevó a cabo un estudio observacional retrospectivo de revisión de historias clínicas. Se recogieron datos demográficos, del manejo clínico y del uso de recursos asociado a la hospitalización de historias clínicas de pacientes hospitalizados en UCI con una infección confirmada por CRGN. Se seleccionaron tres hospitales españoles de referencia por su cobertura geográfica. Se realizaron análisis descriptivos del manejo clínico y el uso de recursos y sus costes en episodios de infecciones por CRGN, y se calcularon los costes totales para cada tipo de recurso. Resultados: Se incluyeron en el estudio un total de 130 pacientes. La mayoría de los pacientes (n=43;33%) tenían entre 61-70 años. Noventa y cuatro pacientes (72%) eran hombres y 115 (88%) presentaron comorbilidades. El coste medio total asociado a los recursos usados durante el episodio de infección por CRGN por paciente fue de 96.878€. Este coste total incluye 84.140€ de la estancia en el hospital, 11.021€ de los tratamientos (558€ de antibióticos y 10.463€ de otros tratamientos) y 1.717€ del coste de test diagnósticos. Conclusiones: El episodio de infección por CRGN causa un alto uso de recursos hospitalarios, siendo la duración de la estancia tanto en planta hospitalaria como en UCI el factor con mayor peso de los costes totales. Los test diagnósticos clínicos y los tratamientos, incluyendo los antibióticos, representan la parte más pequeña del uso de recursos y sus costes (13% del coste total).(AU)

Use of hospital resources in ICU inpatients with infections caused by carbapenem-resistant Gram-negative bacteria: A real clinical practice-based study in Spain.

INTRODUCTION: Carbapenem-resistant Gram-negative bacteria (CRGN) are an urgent public health threat because of the limited treatment options, its rapid spreading and high clinical impact and mortality rates. However, the burden and the use of resources of these infections have not been investigated. The aim of the current study is to understand the use of resources associated to the clinical management of CRGN infections in real clinical practice conditions. METHODS: An observational retrospective chart review study was performed. Data regarding patient demographics, clinical management and use of resources associated to hospitalization were retrieved from clinical charts of ICU inpatients with a confirmed CRGN infection. Three reference Spanish hospitals were selected according to their patient volume and geographical coverage. Descriptive analyses of the clinical management and the use of resources and its cost were performed and then total costs by type of resource were calculated. RESULTS: A total of 130 patients were included in the study. The higher number of patients (n=43; 33%) were between 61 and 70 years old. Ninety-four (72%) patients were male and 115 (88%) suffered from comorbidities. The mean total cost associated to the resources used in patients with CRGN infections hospitalized in ICU was 96,878€ per patient. These total costs included 84,140€ of total hospital stay, 11,021€ of treatments (558€ of antibiotics; 10,463€ of other treatments) and 1717€ costs of diagnostic tests. CONCLUSIONS: CRGN infection causes a high use of hospital resources, being the length of stay either in hospital wards or ICU the driver of the total costs. Diagnostic tests and treatments, including antibiotics, represent the lowest part of the use of resources and costs (13% of total costs).

Anti-endotoxin antibodies consumption in cardiovascular collapse: Pathophysiological concerns.

OBJECTIVE: Abnormal endotoxin activity in critically ill patients has been described in the absence of Gram-negative bacterial (GNB) infection. As disease severity seems to be crucial in the detection of this phenomenon, we decided to assess and compare endotoxin exposure in those patients representing the critical situation: septic shock and cardiogenic shock. DESIGN: Prospective, observational non intervention study. SETTING: Critical Care Department of a University tertiary hospital. PATIENTS: Cardiogenic shock (CS) and septic shock (SS) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Follow-up was performed for the first three days. Inflammatory biomarkers (C-reactive protein, procalcitonin and interleuquin-6) and IgM antiendotoxin-core antibodies titter (IgM EndoCAb) were daily analyzed. Sixty-two patients were included; twenty-five patients with SS and thirty-seven with CS. Microbial etiology was established in 23 SS patients (92%) and GNB were present in 13 cases (52%). Although infection was suspected and even treated in 30 CS patients (81%), any episode could be finally confirmed. EndoCAb consumption was more intense in SS patients, although twenty-two CS patients (59.5%) had IgM anti-endotoxin value below 10th percentile range for healthy people. No statistically significant difference in endotoxin exposure was detected between Gram-positive and Gram-negative infections in the SS group. Endotoxin exposure ability to distinguish between SS and CS was moderate (AUC 0.7892, 95% IC: 0.6564-0.9218). CONCLUSIONS: In the severely ill patient some mechanisms take place allowing endotoxin incursion and therefore blurring the limits of diseases pathophysiology. Our work representatively shows how exposure to endotoxin was not fully capable of distinguishing between CS and SS.

Executive summary of the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) on the diagnosis and antimicrobial treatment of infections due to carbapenem-resistant Gram-negative bacteria.

Infections caused by multidrug resistant Gram-negative bacteria are becoming a worldwide problem due to their increasing incidence and associated high mortality. Carbapenem-resistant bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii are the most important in clinical practice. The objective of these guidelines is to update the recommendations for the diagnosis and treatment of infections caused by these multidrug resistant bacteria. Although 'old' antibiotics such as aminoglycosides, colistin, or tigecycline are frequently used for therapy of these bacteria, the 'new' beta-lactams such as ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam or cefiderocol are progressively becoming the first-line therapy for most of these microorganisms. The Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica) designated a panel of experts in the field to provide evidence-based recommendations in response to common clinical questions. This document is primarily focused on microbiological diagnosis, clinical management, and targeted antimicrobial therapy of these infections, with special attention to defining the role of the new antimicrobials in the treatment of these bacteria.

Temporal association between antibiotic use and resistance in Gram-negative bacteria / Associação temporal entre o uso de antibióticos e resistência em bactérias gram-negativas

Abstract The β-lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p<0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.

Resumo Os medicamentos combinados de β-lactâmicos / inibidores da lactamase (BLBLIs) são considerados uma alternativa eficaz aos carbapenêmicos. No entanto, existe uma preocupação crescente de que o aumento do uso de BLBLIs pode levar ao aumento da resistência. Este estudo determinou a associação temporal entre o consumo de BLBLI e a resistência antimicrobiana em bactérias gram-negativas. Neste estudo retrospectivo, os dados eletrônicos sobre as bactérias gram-negativas isoladas, incluindo A. baumannii, P. aeruginosa, E. coli e K. pneumoniae de pacientes internados e os resultados dos testes de suscetibilidade foram recuperados dos registros médicos do laboratório clínico. Uma regressão linear e análise de correlação cruzada foram realizadas nos dados adquiridos. Foram observadas tendências crescentes (p < 0,05) no consumo de BIBLI e carbapenem com uma mediana de uso de 27,68 e 34,46 DDD/1000 PD por trimestre, respectivamente. Foi observada uma tendência de diminuição (p = 0,023) no consumo de fluoroquinolonas com uma mediana de uso de 29,13 DDD/1000 PD por trimestre. A taxa de resistência de K. pneumoniae foi sincronizada com os consumos de BIBLI e carbapenem com coeficiente de correlação de 0,893 (p = 0,012) e 0,951 (p = 0,016), respectivamente. A análise de correlação cruzada contra o consumo de BIBLI e K. pneumoniae resistente ao meropenem atingiu o pico no intervalo de 0 quarto (r = 951, p = 0,016). Houve uma tendência de aumento no consumo de BLBLI e carbapenêmicos. A tendência crescente nas taxas de resistência a piperacilina/tazobactam, em linha com o consumo crescente de BLBLI, sugere que BLBLI deve ser usado com cautela e não pode ser considerado diretamente como alternativa de longo prazo aos carbapenêmicos.

Temporal association between antibiotic use and resistance in Gram-negative bacteria / Associação temporal entre o uso de antibióticos e resistência em bactérias gram-negativas

The β-lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p<0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.

Os medicamentos combinados de β-lactâmicos / inibidores da lactamase (BLBLIs) são considerados uma alternativa eficaz aos carbapenêmicos. No entanto, existe uma preocupação crescente de que o aumento do uso de BLBLIs pode levar ao aumento da resistência. Este estudo determinou a associação temporal entre o consumo de BLBLI e a resistência antimicrobiana em bactérias gram-negativas. Neste estudo retrospectivo, os dados eletrônicos sobre as bactérias gram-negativas isoladas, incluindo A. baumannii, P. aeruginosa, E. coli e K. pneumoniae de pacientes internados e os resultados dos testes de suscetibilidade foram recuperados dos registros médicos do laboratório clínico. Uma regressão linear e análise de correlação cruzada foram realizadas nos dados adquiridos. Foram observadas tendências crescentes (p < 0,05) no consumo de BIBLI e carbapenem com uma mediana de uso de 27,68 e 34,46 DDD/1000 PD por trimestre, respectivamente. Foi observada uma tendência de diminuição (p = 0,023) no consumo de fluoroquinolonas com uma mediana de uso de 29,13 DDD/1000 PD por trimestre. A taxa de resistência de K. pneumoniae foi sincronizada com os consumos de BIBLI e carbapenem com coeficiente de correlação de 0,893 (p = 0,012) e 0,951 (p = 0,016), respectivamente. A análise de correlação cruzada contra o consumo de BIBLI e K. pneumoniae resistente ao meropenem atingiu o pico no intervalo de 0 quarto (r = 951, p = 0,016). Houve uma tendência de aumento no consumo de BLBLI e carbapenêmicos. A tendência crescente nas taxas de resistência a piperacilina/tazobactam, em linha com o consumo crescente de BLBLI, sugere que BLBLI deve ser usado com cautela e não pode ser considerado diretamente como alternativa de longo prazo aos carbapenêmicos.

Temporal association between antibiotic use and resistance in Gram-negative bacteria

Abstract The -lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p 0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.

Resumo Os medicamentos combinados de -lactâmicos / inibidores da lactamase (BLBLIs) são considerados uma alternativa eficaz aos carbapenêmicos. No entanto, existe uma preocupação crescente de que o aumento do uso de BLBLIs pode levar ao aumento da resistência. Este estudo determinou a associação temporal entre o consumo de BLBLI e a resistência antimicrobiana em bactérias gram-negativas. Neste estudo retrospectivo, os dados eletrônicos sobre as bactérias gram-negativas isoladas, incluindo A. baumannii, P. aeruginosa, E. coli e K. pneumoniae de pacientes internados e os resultados dos testes de suscetibilidade foram recuperados dos registros médicos do laboratório clínico. Uma regressão linear e análise de correlação cruzada foram realizadas nos dados adquiridos. Foram observadas tendências crescentes (p 0,05) no consumo de BIBLI e carbapenem com uma mediana de uso de 27,68 e 34,46 DDD/1000 PD por trimestre, respectivamente. Foi observada uma tendência de diminuição (p = 0,023) no consumo de fluoroquinolonas com uma mediana de uso de 29,13 DDD/1000 PD por trimestre. A taxa de resistência de K. pneumoniae foi sincronizada com os consumos de BIBLI e carbapenem com coeficiente de correlação de 0,893 (p = 0,012) e 0,951 (p = 0,016), respectivamente. A análise de correlação cruzada contra o consumo de BIBLI e K. pneumoniae resistente ao meropenem atingiu o pico no intervalo de 0 quarto (r = 951, p = 0,016). Houve uma tendência de aumento no consumo de BLBLI e carbapenêmicos. A tendência crescente nas taxas de resistência a piperacilina/tazobactam, em linha com o consumo crescente de BLBLI, sugere que BLBLI deve ser usado com cautela e não pode ser considerado diretamente como alternativa de longo prazo aos carbapenêmicos.

A systematic literature review and expert consensus on risk factors associated to infection progression in adult patients with respiratory tract or rectal colonisation by carbapenem-resistant Gram-negative bacteria / Revisión sistemática de la literatura y consenso de expertos sobre los factores de riesgo asociados a la progresión de la infección en pacientes adultos con colonización del tracto respiratorio o rectal por bacterias gramnegativas resistentes a carbapenémicos

Objective. Risk factors (RFs) associated with infection progression in patients already colonised by carbapenem-resistant Gram-negative bacteria (CRGNB) have been addressed in few and disperse works. The aim of this study is to identify the relevant RFs associated to infection progression in patients with respiratory tract or rectal colonisation.Material and methods. A systematic literature review was developed to identify RFs associated with infectionprogression in patients with CRGNB respiratory tract or rectal colonisation. Identified RFs were then evaluated and discussed by the expert panel to identify those that are relevant according to the evidence and expert’s experience.Results. A total of 8 articles were included for the CRGNB respiratory tract colonisation and 21 for CRGNB rectal colonisation, identifying 19 RFs associated with pneumonia development and 44 RFs associated with infection progression, respectively. After discussion, the experts agreed on 13 RFs to be associated with pneumonia development after respiratory tract CRGNB colonisation and 33 RFs to be associated with infection progression after rectal CRGNB colonisation. Respiratory tract and rectal colonisation, previous stay in the ICU and longer stay in the ICU were classified as relevant RF independently of the pathogen and site of colonisation. Previous exposure to antibiotic therapy or previous carbapenem use were also common relevant RF for patients with CRGNB respiratory tract and rectal colonisation. (AU)

Objetivo. Los factores de riesgo (FR) asociados a la progresión de la infección en pacientes ya colonizados por bacterias gramnegativas resistentes a carbapenémicos (BGNRC) han sido abordados en pocos y dispersos trabajos. El objetivo de este estudio es identificar los factores de riesgo relevantes asociados a la progresión de la infección en pacientes con colonización del tracto respiratorio o rectal.Material y métodos. Se realizó una revisión sistemática de la literatura para identificar los FR asociados a la progresión de la infección en pacientes con colonización del tracto respiratorio o rectal por BGNRC. Los FR identificados fueron luego evaluados y discutidos por el panel de expertos para identificar aquellos que son relevantes según la evidencia disponible y la experiencia de los expertos.Resultados. Un total de 8 artículos fueron incluidos en el análisis de los FR en la colonización del tracto respiratorio y 21 para la colonización rectal, identificándose 19 FR asociados al desarrollo de neumonía y 44 FR asociados a la progresión de la infección respectivamente. Tras la sesión de discusión, los expertos acordaron que 13 FR se asociaban al desarrollo de neumonía tras la colonización del tracto respiratorio por BGNRC y 33 FR a la progresión de la infección tras la colonización rectal por BGNRC. La colonización del tracto respiratorio y rectal, la estancia previa en la UCI y una estancia prolongada en la UCI se clasificaron como FR relevantes independientemente del patógeno y del lugar de colonización. La exposición previa a antibióticos o el uso previo de carbapenémicos se clasificaron como FR relevantes para varios de los patógenos tanto en pacientes con colonización del tracto respiratorio como rectal. (AU)

Comparação do mecanismo de heterorresistência em Serratia marcescens por time kill curve frente ao meropeném / Comparison of heteroresistance mechanism in Serratia marcescens by time kill curve against meropenem

Serratia marcescens pertence à Família Enterobacteriaceae, é Gram-negativa e anaeróbica facultativa, sendo bem distribuída na natureza; pode ser isolada como saprófita do solo e da água. Possui um significado clínico relevante, pois acarreta infecções nosocomiais e pulmonares em determinados setores da saúde, como unidades neonatais, maternidades e UTIs, além de sepse, meningite, choque endotóxico e infecções do trato urinário. O intuito desse estudo foi analisar o mecanismo de heterorresistência em linhagens sensíveis de Serratia marcescens diante das concentrações testadas de meropeném. As linhagens SR1 e SR2 apresentaram perfil heterorresistente, ao passo que a SR6 demonstrou ser não heterorresistente, com CIM elevado (32µg/mL). Os isolados de Serratia marcescens são suscetíveis ao meropenem, por testes de sensibilidade padrão, mas contêm subpopulações resistentes ao mesmo.

Serratia marcescens belongs to the Enterobacteriaceae family, it is optional anaerobic gram-negative, being well distributed in nature and it might be isolated as saprophytic from soil and water. It has a meaningful clinical significance, because it causes nosocomial and lung infections in certain healthcare sectors, such as neonatal units, maternity units and UTIs; septicemia, meningitis, endotoxin shock and urinary tract infections. The aim of this study was to analyze the mechanism of heteroresistance in susceptible strains of Serratia marcescens in the presence of the tested concentration of meropenem. The lineages SR1 and SR2 presented heteroresistant profile, while the SR6 showed to be nonheterorresistente, with CIM (32 µg/mL). The Isolates of Serratia marcescens are susceptible to meropenem, by standard sensitivity testing, but there are subpopulations resistant to it.

Tolerancia al triclosán en cepas de Klebsiella pneumoniae y Escherichia coli de origen clínico / Triclosan tolerance in Klebsiella pneumoniae and Escherichia coli strains of clinical origin / Tolerância a Triclosan em cepas de Klebsiella pneumoniae e Escherichia coli de origem clínica

Introducción: Los biocidas son compuestos químicos que se emplean comúnmente para inhibir o eliminar el crecimiento microbiano. El triclosán es un agente biocida que afecta la estructura y función microbiana. Es am-pliamente utilizando como desinfectante y antiséptico en suturas quirúrgicas, exfoliantes, implantes y dispositivos médicos, pero se ha observado el desarrollo de múltiples mecanismos de tolerancia bacteriana a este agente. Objetivo: Determinar la tolerancia al triclosán en cepas de Escherichia coli y Klebsiella pneumoniae. Materiales y métodos: Se llevó a cabo un estudio descriptivo de corte transversal, de tipo observacional, a partir de cepas de origen clínico que presentaran algunos genotipos de resistencia a los antibióticos como blaTEM, blaCTXM1 y blaSHV. Se determinó la concentración mínima inhibitoria (C1, C2, C3, C4 y C5) al triclosán. Resultados: De los 32 aislamientos recuperados, 17 fueron de E. coli y 15 de K. pneumoniae. Se evidenció que el 25 % de los aislamientos evaluados presentó tolerancia a concentraciones más bajas C1 (0,00025 %) de triclosán y que el 12 % fue tolerante a la concentración más alta C1 (1 %). Adicionalmente, un mayor número de cepas de E. coli presentó mayor tolerancia al triclosán que las cepas de K. pneumoniae. Así mismo, se evidenció que la mayoría de las cepas fueron tolerantes a las concentraciones evaluadas más bajas. Conclusiones: El 37 % de los aislados presentaron tolerancia al triclosán, con predominio de la E. coli. Palabras clave: triclosán; tolerancia; bacterias; gramnegativas

Introduction: Biocides are chemical compounds that are commonly used to inhibit or eliminate mi-crobial growth. Triclosan is a biocidal agent that affects microbial structure and function. It is widely used as a disinfectant and antiseptic in surgical sutures, exfoliants, implants and medical devices. The development of multiple mechanisms of bacterial tolerance to this agent has been observed. Target. To determine the tolerance to triclosan in strains of Escherichia coli and Klebsiella pneumoniae. Materials and methods: A descriptive, cross-sectional, observational study was carried out using strains of clinical origin, which presented some genotypes of resistance to antibiotics such as blaTEM, blaCTXM1, and blaSHV. The Minimum Inhibitory Concentration (C1, C2, C3, C4, and C5) to triclosan was determined. Results: Of the 32 isolates recovered, 17 were E. coli and 15 were K. pneumoniae. It was evidenced that 25% of the evaluated isolates presented tolerance to lower concentrations C1 (0.00025%) of triclosan and 12% were tolerant to the highest concentration C1 (1%). Additionally, a greater number of E. coli strains presented greater tolerance to triclosan than the K. pneumoniae strains, likewise, it was evidenced that most of the strains were tolerant to the lowest concentrations evaluated.

Introdução: Os biocidas são compostos químicos comumente usados para inibir ou eliminar o cres-cimento microbiano. O Triclosan é um agente biocida que afeta a estrutura e função microbiana. É amplamente utilizado como desinfetante e anti-séptico em suturas cirúrgicas, esfoliantes, implantes e dispositivos médicos, mas foram observados múltiplos mecanismos de tolerância bacteriana a este agente. Objetivo: Determinar a tolerância ao Triclosan nas cepas Escherichia coli e Klebsiella pneumoniae. Materiais e métodos: Foi realizado um estudo descritivo, transversal, observacional, em cepas de origem clínica com alguns genótipos de resistência a antibióticos como blaTEM, blaCTXM1 e blaSHV. A concentração inibitória mínima (C1, C2, C3, C4 e C5) de Triclosan foi determinada. Resultado: Dos 32 isolados recuperados, 17 eram E. coli e 15 eram K. pneumoniae. Verificou-se que 25% dos isolados testados eram tolerantes a menores concentrações de C1 (0,00025%) de Triclosan e 12% eram tolerantes à maior concentração C1 (1%). Além disso, um maior número de cepas de E. coli foram tolerantes a Triclosan, do que às cepas de K. pneumoniae. Foi também evidente que a maioria das cepas foi tolerante às menores concentrações testadas

Prevalência de bastonetes Gram-negativos não fermentadores isolados em amostras de hemoculturas / Prevalence of non-fermenter Gram-negative bacilli isolated in blood culture samples

Objetivos: Avaliar a prevalência de bactérias não fermentadoras em amostras de hemoculturas provenientes das Unidades de Terapia Intensiva (UTI's) adulto e neonatal e da Unidade Coronariana (UC); definir o perfil de suscetibilidade aos antimicrobianos das cepas bacterianas prevalentes. Métodos: Foram coletados dados de todas as hemoculturas positivas das UTIs Adulto, Neonatal e UC de um hospital privado, em Juiz de Fora, Minas Gerais, Brasil, de janeiro de 2017 a janeiro de 2019. Resultados: Foram analisados 3.535 resultados de amostras de hemoculturas onde 2.464 (69,7%) foram negativas e 1.071 (30,3%) positivas para algum microrganismo. Dentre as amostras positivas foram encontrados 77 bastonetes Gram-negativos não fermentadores (6,9%), com a prevalência de Acinetobacter baumannii (51,9%) seguido de Pseudomonas aeruginosa (32,5%). As cepas de A. baumannii foram resistentes aos carbapenêmicos e às quinolonas. Quanto às cepas de P. aeruginosa, as drogas testadas que apresentaram maior resistência foram a ampicilina, ampicilina com tazobactam, as cefalosporinas de segunda e terceira geração, exceto ceftazidima; e a tigeciclina. As drogas que apresentaram boa atividade na inibição do crescimento das cepas analisadas foram tigeciclina para A. baumannii e colistina para ambas as cepas. Conclusão: o presente estudo alerta para a resistência a múltiplas classes de antimicrobianos das cepas advindas das UTIs e UC, demonstrando um cenário preocupante e a necessidade de desenvolvimento de novas drogas e novas medidas de controle.

Objectives: To evaluate the prevalence of non-fermenting bacteria in blood culture samples from the adult and neonatal intensive care units (ICUs) and the Coronary Care Unit (UC); define the antimicrobial susceptibility profile of prevalent bacterial strains. Methods: Data were collected on all positive blood cultures from the Adult, Neonatal and UC ICUs of a private hospital in Juiz de Fora, Minas Gerais, Brazil, from January 2017 to January 2019. Results: 3535 results of blood culture samples were analyzed, where 2464 (69.7%) were negative and 1071 (30.3%) positive for some microorganism. Among the positive samples, 77 non-fermenting Gram negative rods (6.9%) were found, with the prevalence of Acinetobacter baumannii (51.9%) followed by Pseudomonas aeruginosa (32.5%). A. baumannii strains were resistant to carbapenems and quinolones. As for strains of P. aeruginosa, the drugs tested that showed greater resistance were ampicillin, ampicillin with tazobactam, second and third generation of cephalosporins, except ceftazidime; and tigecycline. The drugs that showed good activity in inhibiting the growth of the strains analyzed were tigecycline for A. baumannii and colistin for both strains. Conclusion: the present study warns of resistance to multiple classes of antimicrobial strains from the ICUs and UC, demonstrating a worrying scenario and the need to develop new drugs and new control measures.

What's new in mechanisms of antibiotic resistance in bacteria of clinical origin?

The discovery, commercialization and administration of antibiotics revolutionized the world of medicine in the middle of the last century, generating a significant change in the therapeutic paradigm of the infectious diseases. Nevertheless, this great breakthrough was soon threatened due to the enormous adaptive ability that bacteria have, through which they are able to develop or acquire different mechanisms that allow them to survive the exposure to antibiotics. We are faced with a complex, multifactorial and inevitable but potentially manageable threat. To fight against it, a global and multidisciplinary approach is necessary, based on the support, guidance and training of the next generation of professionals. Nevertheless, the information published regarding the resistance mechanisms to antibiotics are abundant, varied and, unfortunately, not always well structured. The objective of this review is to structure the, in our opinion, most relevant and novel information regarding the mechanisms of resistance to antibiotics that has been published from January 2014 to September 2019, analysing their possible clinical and epidemiological impact.

Factores pronósticos de mortalidad por agente infeccioso en un hospital de alta complejidad de Cartagena-Colombia / Prognostic factors for mortality caused by an infectious agent in a high complexity hospital in Cartagena-Colombia

Introducción: La identificación de los principales factores clínico-epidemiológicos que determinan causas de mortalidad en pacientes hospitalizados es una necesidad apremiante, principalmente cuando los esfuerzos realizados en la actualidad no permiten asumir acciones fundamentadas en la identificación de las causas de dicho evento. Objetivo: Establecer cuáles son los factores pronósticos de mortalidad por agente infeccioso en un hospital de alta complejidad de la ciudad de Cartagena- Colombia. Material y Métodos: Se realizó un estudio de casos y controles retrospectivo, con muestra proyectada de 86 casos y 258 controles, en una relación 1:3, que cumplieron con los criterios de elegibilidad respectivos y en los que realizaron análisis bivariados y posteriormente un análisis multivariado que incluyó métodos de regresión logística binaria. Resultados: El riesgo de mortalidad en el análisis multivariado está determinado por variables como sexo masculino (ORa 1,695 IC 95 por ciento: 1,005-2,856); Cáncer (ORa 2,389 IC 95 por ciento 1,230-4,642); inmunosupresión (ORa 3,211 IC 95 por ciento 1,004-10,26); Ventilación mecánica (ORa 2,541 IC 95 por ciento 1,128-5,722); Estancia en la UCI (ORa 2,331 IC 95 por ciento1,227-4,425) e Infección por bacterias productoras de carbapenemasas (ORa 4,778 IC95 por ciento 1,313-17,38). Conclusiones: En pacientes masculinos con cáncer o cualquier otra forma de inmunosupresión, en los que se requiera el uso del ventilador mecánico o estancia en la unidad de cuidado intensivo y que además desarrollen infecciones por bacterias productoras de carbapenemasas existe mayor riesgo de muerte por agente infeccioso(AU)

Introduction: The identification of the main epidemiological clinical factors that determine the causes of mortality in hospitalized patients is a pressing need, mainly when the efforts made at present do not allow us to take actions based on the identification of the causes of the aforementioned event. Objective: To identify the prognostic factors for mortality caused by infectious agents in a high complexity hospital in the city of Cartagena, Colombia. Material and Methods: A retrospective case-control study was conducted in 86 cases and 258 control samples that met the eligibility criteria, at the 1: 3 ratio. Bivariate analyses and a subsequent multivariate analysis that included binary logistic regression methods were also performed. Results: In the multivariate analysis, the risk of mortality is determined by variables such as male sex (ORa 1,695 95 percent CI: 1.005-2.856); cancer (ORa 2,389 95 percent CI 1,230-4,642); immunosuppression (ORa 3.211 95 percent CI 1.004-10.26); mechanical ventilation (ORa 2.541 95 percent CI 1.128-5.722); stay in the ICU (ORa 2,331 95 percent CI 1,227-4,425) and infection caused by carbapenemase-producing bacteria (ORa 4,778 95 percent CI 1,313-17.38). Conclusions: Male patients with cancer or any other form of immunosuppression who require the use of a mechanical ventilator or admission to the intensive care unit who also develop infections caused by carbapenemase-producing bacteria, are at greater risk of death from an infectious agent(AU)

What's new in mechanisms of antibiotic resistance in bacteria of clinical origin? / ¿Qué novedades hay en los mecanismos de resistencia a antimicrobianos en bacterias de origen clínico?

The discovery, commercialization and administration of antibiotics revolutionized the world of medicine in the middle of the last century, generating a significant change in the therapeutic paradigm of the infectious diseases. Nevertheless, this great breakthrough was soon threatened due to the enormous adaptive ability that bacteria have, through which they are able to develop or acquire different mechanisms that allow them to survive the exposure to antibiotics. We are faced with a complex, multifactorial and inevitable but potentially manageable threat. To fight against it, a global and multidisciplinary approach is necessary, based on the support, guidance and training of the next generation of professionals. Nevertheless, the information published regarding the resistance mechanisms to antibiotics are abundant, varied and, unfortunately, not always well structured. The objective of this review is to structure the, in our opinion, most relevant and novel information regarding the mechanisms of resistance to antibiotics that has been published from January 2014 to September 2019, analysing their possible clinical and epidemiological impact.(AU)

El descubrimiento, la comercialización y la administración de antibióticos revolucionó la medicina a mediados del siglo pasado, generando un cambio significativo en el paradigma terapéutico de las enfermedades infecciosas. Sin embargo, este avance no tardó en verse amenazado debido a la enorme capacidad que tienen las bacterias para desarrollar o adquirir distintos mecanismos que les permiten sobrevivir a los antibióticos. Nos encontramos frente a una amenaza compleja, multifactorial e inevitable, pero potencialmente manejable. Para luchar contra ella es necesario un abordaje multidisciplinar basado en el apoyo, la orientación y el entrenamiento de la próxima generación de profesionales. No obstante, la información publicada referente a nuevos mecanismos de resistencia a antibióticos es abundante, variada y, desgraciadamente, no siempre bien estructurada. El objetivo de esta revisión es ordenar la información, a nuestro juicio más relevante y novedosa, que se ha publicado en referencia los nuevos mecanismos de resistencia a los antibióticos desde enero de 2014 hasta septiembre de 2019, analizando su posible impacto clínico y epidemiológico.(AU)

Determining the burden of infectious diseases caused by carbapenem-resistant gram-negative bacteria in Spain / Determinación de la carga de las infecciones causadas por bacterias gramnegativas resistentes a carbapenemas en España

Objective: To estimate the burden of nosocomial infections induced by carbapenem resistant Gram-negative (CRGN) pathogens in Spain, focusing on both the clinical and economic impact. Methods: The burden of disease was estimated using data from 2017 according to the availability of data sources. The impact, both clinical and economic, of the most frequent CRGN nosocomial infections (those produced by Klebsiella pneumoniae, Pseudomonasaeruginosa and Acinetobacter baumannii) was analysed. Incidence and mortality of CRGN nosocomial infections were estimated, as well as the direct and indirect costs produced by this health problem. Results: Approximately 376,346 patients are believed to have suffered a nosocomial infection in Spain in 2017; 3.2% of them due to CRGN bacilli. Infections by carbapenem-resistant P. aeruginosa produced the highest mortality rates (2578 deaths) when compared with A. baumannii (1571) and K. pneumoniae (415). Total economic costs of CRGN nosocomial infections in Spain were estimated to be €472 million in 2017, with 83% of the total cost caused by direct costs. Conclusion: CRGN nosocomial infections have a high clinical impact on patients’ lives, high mortality rates, and represent one of the hospitalisation episodes with the most associated costs. Efforts should be focussed to implement preventive policies in order to avoid infections due to CRGN pathogens and the resulting burden, and to reduce direct costs due to morbimortality, specifically in those infections produced by P. aeruginosa.(AU)

Objetivo: Estimar la carga de las infecciones nosocomiales inducidas por patógenos gramnegativos resistentes a carbapenemas (GNRC) en España, focalizada tanto en el impacto clínico como en el económico. Métodos: La carga de la enfermedad se estimó utilizando datos del año 2017, de acuerdo con la disponibilidad de los mismos en bases de datos. Se analizó el impacto, tanto clínico como económico, de las infecciones nosocomiales GNRC más habituales (causadas por Klebsiella pneumoniae, Pseudomonas aeruginosa y Acinetobacter baumannii). Se estimaron la incidencia y la mortalidad de las infecciones nosocomiales GNRC, así como los costes directos e indirectos derivados de este problema de salud. Resultados: Aproximadamente 376.346 pacientes podrían haber sufrido una infección nosocomial en España durante el año 2017; siendo el 3,2% de ellas producidas por bacilos GNRC. Las infecciones causadas por P. aeruginosa resistente a carbapenemas produjeron las mayores tasas de mortalidad (2.578 muertes) en comparación con A. baumannii (1.571) y K. pneumoniae (415). Los costes económicos totales de las infecciones nosocomiales producidas por GNRC en España se estimaron en 472 M€ en 2017, siendo el 83% del coste total representado por los costes directos. Conclusión: Las infecciones nosocomiales producidas por GNRC tienen un gran impacto en la vida de los pacientes, altas tasas de mortalidad y representan uno de los episodios de hospitalización con más costes hospitalarios asociados. Se deben focalizar los esfuerzos en políticas de prevención para evitar las infecciones por patógenos GNRC y su carga, así como para reducir los costes directos producidos por la morbimortalidad, concretamente en aquellas infecciones producidas por P. aeruginosa.(AU)

Tratamiento exitoso de la ventriculitis por Acinetobacter baumanii multidrogo resistente con colistina intravenosa e intraventricular / Successful treatment of ventriculitis due to multidrug resistant Acinetobacter baumanii with intravenous and intraventricular colistin

RESUMEN Las infecciones del sistema nervioso central asociadas a dispositivos como el drenaje ventricular externo son frecuentes. Sin embargo, la ventriculitis por bacterias Gram negativas y resistentes a antibióticos genera un reto para el tratamiento médico y quirúrgico. Se presenta el caso de un paciente con diagnóstico de malformación arteriovenosa rota con hemorragia intraventricular que requirió la colocación de un dren ventricular externo. En la evolución posterior, desarrolló ventriculitis por Acinetobacter baumanii multidrogo resistente (MDR) confirmada por cultivos de líquido cefalorraquídeo y se procedió a tratamiento antibiótico dirigido por antibiograma, usando colistina endovenosa e intraventricular asociando meropenem, logrando la normalización de los valores de LCR. Además describimos la evolución clínica, tratamiento médico-quirúrgico y complicaciones asociadas durante su estancia en la unidad de cuidados intensivos.

SUMMARY Central nervous system infections associated with devices such as external ventricular drains are frequent. Ventriculitis due to multi drug resistant (MDR) Gram-negative bacteria represent a surgical and medical challenge. We present the case of a patient who presented with intraventricular hemorrhage due to a rupture of an arteriovenous malformation that needed the insertion of an external ventricular drainage. The patient subsequently developed ventriculitis due to a MDR Acinetobacter baumanii confirmed by isolation from the cerebral spinal fluid (CSF) hat was treated based on the drug susceptibility test with intravenous and intraventricular colistin plus meropenem achieving normalization of the CSF parameters. We report the clinical evolution, complications and medical-surgical treatment in the intensive care unit.