Primeros aislados de Enterobacter cloacae complex co-productores de KPC y NDM en un hospital de segundo nivel en la Cuidad de Panamá / First isolates of Enterobacter cloacae complex co-producing KPC and NDM in a second level hospital in City of Panama

Resumen La aparición de Enterobacterales co-productores de dos o más carbapenemasas han despertado las alertas sanitarias en Latinoamérica. Las enterobacterias co-productoras de carbapenemasas KPC y NDM-1 son resistentes a casi todos los antibacterianos existentes. Panamá ha reportado la presencia de carbapenemasas KPC desde 2010 y NDM desde 2011; sin embargo, Enterobacterales con doble producción de carbapenemasas es un fenómeno reciente en nuestros hospitales. Presentamos los dos primeros aislados de Enterobacter cloacae complex co-productores de KPC y NDM, en un hospital de segundo nivel de la Ciudad de Panamá. El reforzamiento de los sistemas de vigilancia epidemiológica en los hospitales permite realizar una detección oportuna de estas nuevas combinaciones de mecanismos de resistencia; para así, implementar medidas de prevención y control de brotes.

Abstract Enterobacterales co-producing carbapenemases have awakened health alerts in Latin America. Carbapenemase-producing Enterobacterales harboring KPC and NDM-1 are resistant to almost all existing antibiotics. Panama reports KPC since 2010, and NDM since 2011, however, Enterobacterales with double carbapenemase production is new to our hospitals. We present the first two isolates of Enterobacter cloacae complex co-producing KPC and NDM, in a second level hospital in Panama City. Strengthening epidemiological surveillance systems in hospitals allows to carry out timely detection of these new combinations of resistance; to implement outbreak prevention and control measures.

Riesgo de infección en pacientes oncológicos colonizados por bacterias productoras de p-lactamasas de espectro extendido y enterobacterias productoras de carbapenemasas / Risk of infection in cancer patients colonized by extended expectrum p-lactamases and carbapenem producing Enterobacteriaceae

INTRODUCCIÓN: La prevalencia de microorganismos multirresistentes es un problema de salud pública que continúa creciendo a lo largo del mundo. Existe una población principalmente susceptible de ser colonizada y posteriormente infectarse, son los pacientes oncológicos. OBJETIVO: Identificar las características clínicas y patológicas de los pacientes oncológicos y su relación con la infección con microorganismos productores de BLEE y EPC. PACIENTES Y MÉTODOS: Se condujo un estudio retrospectivo y de carácter analítico entre el primero de enero de 2019 y el 30 de junio de 2020 en tres unidades hemato-oncológicas. RESULTADOS: Incluyó a 3.315 pacientes, de los cuales 217 (6,5%) se encontraban colonizados por microorganismos productores de BLEE y EPC; de éstos, 106/217 (48,8%) presentaron al menos un episodio de infección. El microorganismo más frecuentemente aislado fue Klebsiella pneumoniae, en 29/106 (27,4%). De los infectados, 18/106 (17%) presentaron infección por el mismo microorganismo colonizador. La mucositis (p = 0,002), edad mayor a 65 años (p = 0,041), hipoalbuminemia (p < 0,01), neutropenia (p < 0,01) y la presencia dispositivos invasivos (p < 0,01) demostraron una relación con el desarrollo de infección. CONCLUSIÓN: La presencia de hipoalbuminemia (OR 3,3, IC 1,5-7,1, p < 0,01), dispositivos invasivos (OR 5,8, IC 3.0-11,4, p < 0,01) y neutropenia (OR 4,1, IC 1,5-11,4, p < 0,01) predicen el desarrollo de infecciones.

BACKGROUND: The prevalence of multi-resistant microorganisms is a public health problem that continues to grow globally. There is a population that is mainly susceptible to being colonized and subsequently infected, and these are cancer patients. AIM: To identify the clinical and pathological characteristics of cancer patients and their relationship with infection with ESBL and CPE producing microorganisms. METHODS: A retrospective and analytical study was conducted between January 1, 2019 and June 30, 2020 in three hematooncological units. RESULTS: We included 3315 patients of which 217 (6.5%) were colonized by microorganisms producing ESBL and CPE. Of these, 106/217 (48.8%) had at least one episode of infection. The most frequently isolated microorganism was Klebsiella pneumoniae 29/106 (27.4%). Of those infected, 18/106 (17%) presented infection by the same colonizing microorganism. Mucositis (p = 0.002), age over 65 years (p = 0.041), hypoalbuminemia (p < 0.01), neutropenia (p < 0.01) and the presence of invasive devices (p < 0.01) demonstrated a relationship with development of infection. The presence of hypoalbuminemia (OR 3.3, CI 1.5-7.1, P < 0.01), invasive devices (OR 5.8, CI 3.0-11.4, p < 0.01) and neutropenia (OR 4.1, CI 1.5-11.4, p < 0.01) predict the development of infections.

Desarrollo y validación de un modelo diagnóstico de resistencia antimicrobiana por beta-lactamasas de espectro extendido en infecciones urinarias adquiridas en la comunidad. ¿Cómo ajustar la predicción en prevalencias variables del desenlace? La utilidad de la contracción de predictores con regresión LASSO / Development and validation of a diagnostic model of antimicrobial resistance by extended-spectrum beta-lactamases in community-acquired urinary tract infections. How to adjust the prediction in variable outcome prevalences? The usefulness of contracting predictors with LASSO regression

INTRODUCCIÓN: Para el caso de infección urinaria adquirida en la comunidad la identificación de enterobacterias con beta-lactamasas de espectro extendido (BLEE) puede optimizar las estrategias de tratamiento, control y seguimiento; sin embargo, el efecto de prevalencias variables de este patrón de resistencia ha afectado la validez externa de este tipo de modelos. OBJETIVO: Desarrollar un modelo predictor diagnóstico que ajuste el error de predicción en prevalencias variables utilizando la regresión LASSO. MÉTODOS: Se diseñó un modelo predictor diagnóstico de infección urinaria adquirida en la comunidad por enterobacterias productoras de BLEE. Se empleó un estudio de corte transversal, tanto para la construcción como para la validación. Para evaluar el efecto de la prevalencia variable del desenlace, la validación se realizó con población en la que la proporción de aislados con este mecanismo de resistencia fue menor, los participantes fueron pacientes adultos que consultaron a servicios de urgencias de dos instituciones hospitalarias de mediano nivel de complejidad de la ciudad de Medellín. Para ajustar el efecto de un medio ambiente con menor proporción de resistencia antimicrobiana, utilizamos la contracción de predictores por regresión LASSO. RESULTADOS: Se incluyeron 303 pacientes para la construcción del modelo, se evaluaron seis predictores y la validación se realizó en 220 pacientes. CONCLUSIÓN: El modelo ajustado con regresión LASSO favoreció la validez externa del modelo en poblaciones con proporción de aislados productores de BLEE en urocultivo de pacientes ambulatorio entre 11 y 16%. Este estudio brinda criterios para un aislamiento temprano cuando los predictores están presentes en poblaciones con proporciones de resistencia en urocultivos ambulatorios cercanas a 15% y propone una metodología para ajuste de error en el diseño de modelos de predicción en resistencia antimicrobiana

BACKGROUND: In the case of community-acquired urinary tract infection, the identification of Enterobacteriaceae with extended spectrum beta-lactamases (ESBL) can optimize treatment, control and follow-up strategies, however the effect of variable prevalences of this resistance pattern has affected the external validity of this type of models. AIM: To develop a diagnostic predictive model that adjusts the prediction error in variable prevalences using the LASSO regression. METHODS: A diagnostic predictive model of community-acquired urinary tract infection by infection by ESBL producing Enterobacteriaceae was designed. A cross-sectional study was used for both construction and validation. To assess the effect of the variable prevalence of the outcome, the validation was performed with a population in which the proportion of isolates with this resistance mechanism was lower, the participants were adult patients who consulted the emergency services of two medium-level hospital institutions. complexity of the city of Medellin. To adjust for the effect of an environment with a lower proportion of antimicrobial resistance, we used the contraction of predictors by LASSO regression. RESULTS: 303 patients were included for the construction of the model, six predictors were evaluated and validation was carried out in 220 patients. CONCLUSION: The adjusted model with LASSO regression favored the external validity of the model in populations with a proportion of ESBL producing isolates in urine culture of outpatients between 11 and 16%. This study provides criteria for early isolation when predictors are present in populations with proportions of resistance in ambulatory urine cultures close to 15% and proposes a methodology for the adjustment of errors in the design of prediction models for antimicrobial resistance.

Prevalencia de infecciones osteoarticulares por enterobacterias productoras de ß-lactamasas de espectro extendido / Prevalence of osteoarticular infections by Enterobacteria producing extended-spectrum ß-lactamases

Resumen: Introducción: Las infecciones por enterobacterias productoras de β-lactamasas de espectro extendido (BLEEs) ocasionan una gran carga a los sistemas de salud. Poco se conoce de las infecciones osteoarticulares, por lo que este trabajo estudió la prevalencia de estas infecciones en un hospital de tercer nivel. Material y métodos: Estudio de prevalencia en pacientes de un servicio de traumatología durante 2016, con criterios de infección proporcionados por el CDC de Atlanta, Georgia. Se utilizó el sistema VITEK® 2 AST-N272 (bioMérieux) para la identificación bacteriana a nivel de especie y para las pruebas de susceptibilidad antimicrobiana. Resultados: Se reportaron 7.85% (n = 86) con infecciones osteoarticulares; 22.09% (n = 19) fueron por enterobacterias BLEEs. Con un promedio de 77.1 días de hospitalización (DE 37.7) (46-200 días); el aislamiento del microorganismo se produjo 15 días posteriores al ingreso; 16 (84.2%) pacientes presentaron osteomielitis, tres (15.8%) tuvieron infección protésica de rodilla o cadera. El promedio de días de tratamiento fue de 60 días (21-129 días); 18 pacientes (94.7%) fueron dados de alta con resolución de su cuadro infeccioso; un paciente falleció con infección sobreagregada por neumonía debida a K. pneumoniae resistente a carbapenémicos. Discusión: La prevalencia de infecciones osteoarticulares por enterobacterias BLEEs no se pudo calcular con precisión, pero consideramos que se encuentra dentro de lo esperado, las medidas de control de infecciones requieren tener estándares más elevados y falta desarrollar programas de uso racional de antimicrobianos para controlar la aparición de estas patologías.

Abstract: Introduction: Infections of enterobacteria producing extended-spectrum ß-lactamases place a heavy burden on health systems. Little is known in osteoarticular infections, so this work studied the prevalence of these infections in a third-level hospital. Material and methods: Prevalence study in patients of a Traumatology Service during 2016, with infection criteria provided by the CDC in Atlanta, Georgia. The VITEK® 2 AST-N272 (bioMérieux) system was used for bacterial identification at the species level and for antimicrobial susceptibility tests. Results: 7.85% (n = 86) were reported with osteoarticular infections; 22.09% (n = 19) were by enterobacteria BLEEs. An average of 77.1 days of hospitalization (SD 37.7) (46-200 days); isolation of the microorganism occurred 15 days after entry. Sixteen (84.2%) patients had osteomyelitis, three (15.8%) had a prosthetic knee or hip infection. The average number of treatment days was 60 days (21-129 days). Eighteen patients (94.7%) were discharged with resolution of their infectious picture; one patient died with infection over aggregated pneumonia due to carbapenem-resistant K. pneumoniae. Discussion: The prevalence of osteoarticular infections by enterobacteria BLEEs could not be accurately calculated, but we consider it to be within what is expected, infection control measures require higher standards and there is a lack of development programs to use antimicrobials rationally to control the emergence of these pathologies.

Marcadores de resistencia plasmídica a quinolonas qnr en aislamientos clínicos de enterobacterias productoras de betalactamasas CTX-M en Lima, Perú / Markers of plasmid resistance to qnr quinolones in clinical isolates of CTX-M beta-lactamases-producing enterobacteria in Lima, Peru

RESUMEN Con el objetivo de reportar marcadores de resistencia plasmídica a quinolonas qnr en aislamientos clínicos de enterobacterias productoras de betalactamasas CTX-M, se realizó un estudio descriptivo, con aislamientos del cepario del proyecto TO-06/09 del Instituto Nacional de Salud del Niño. Se recuperaron 138 aislamientos. La susceptibilidad antimicrobiana se determinó por el método de disco difusión y la identificación de genes por reacción en cadena de la polimerasa. De los 138 aislados, 67 (48,5%) fueron positivos para proteínas qnr por el método genotípico. De los cuales 38 (56,7%) presentaron determinantes qnrB y 48 (71,6%) determinantes qnrS. Ningún aislado presentó determinantes qnrA. Se detectó determinantes qnr en aislamientos que presentaban betalactamasas CTX-M en una población no expuesta.

ABSTRACT Aimed at reporting markers of plasmid resistance to qnr quinolones in clinical isolates of CTX-M beta-lactamase-producing enterobacteria, a descriptive study was conducted with isolates from the strain repository of TO-06/09 project of the National Children´s Health Institute. 138 isolates were recovered. Antimicrobial susceptibility was determined by the diffusion disk method, and gene identification by polymerase chain reaction. Of the 138 isolates, 67 (48.5%) were genotypically positive for qnr proteins; of these, 38 (56.7%) had qnrB determinants and 48 (71.6%) had qnrS determinants. No isolate presented qnrA determinants. qnr determinants were detected in isolates containing CTX-M beta-lactamases in a non-exposed population.

High prevalence of CTX-M-1 group in ESBL-producing enterobacteriaceae infection in intensive care units in southern Chile

ABSTRACT Enterobacteria-producing extended-spectrum β-lactamases (ESBL) play an important role in healthcare infections, increasing hospitalization time, morbidity and mortality rates. Among several ESBLs that emerge from these pathogens, CTX-M-type enzymes had the most successful global spread in different epidemiological settings. Latin America presents high prevalence of CTX-M-2 in ESBL-producing enterobacterial infections with local emergence of the CTX-M-1 group. However, this high prevalence of the CTX-M-1 group has not yet been reported in Chile. The aim of this study was to identify ESBLs among enterobacteria isolated from clinical samples of critically ill patients from southern Chile. One-hundred thirty seven ESBL-producing bacteria were isolated from outpatients from all critical patient units from Hernán Henríquez Aravena Hospital. Phenotype characterization was performed by antibiogram, screening of ESBL, and determination of minimum inhibitory concentration (MIC). PCR was used for genetic confirmation of resistance. Molecular typing was performed by ERIC-PCR. ESBL-producing isolates were identified as Klebsiella pneumoniae (n = 115), Escherichia coli (n = 18), Proteus mirabilis (n = 3), and Enterobacter cloacae (n = 1), presenting multidrug resistance profiles. PCR amplification showed that the strains were positive for blaSHV (n = 111/81%), blaCTX-M-1 (n = 116/84.7%), blaTEM (n = 100/73%), blaCTX-M-2 (n = 28/20.4%), blaCTX-M-9 (0.7%), blaPER-1 (0.7%), and blaGES-10 (0.7%). The multiple production of ESBL was observed in 93% of isolates, suggesting high genetic mobility independent of the clonal relationship. The high frequency of the CTX-M-1 group and a high rate of ESBL co-production are changing the epidemiology of the ESBL profile in Chilean intensive care units. This epidemiology is a constant and increasing challenge, not only in Chile, but worldwide.

Frecuencia y factores de riesgo para bacteriemia por enterobacterias productoras de betalactamasa de espectro extendido en pacientes de un hospital público de Lima, Perú / Frequency and risk factors for bacteremia caused by extendedspectrum beta-lactamase-producing enterobacteriaceae in patients of a public hospital in Lima, Peru

RESUMEN Con el objetivo de determinar la frecuencia y factores de riesgo para bacteriemia por enterobacterias productoras de betalactamasa de espectro extendido (BLEE) en pacientes internados en un hospital público de Lima se realizó un estudio transversal. Fueron incluidos pacientes mayores de 14 años, con hemocultivos positivos durante su hospitalización en el Hospital Nacional Cayetano Heredia el 2016. Se clasificó a los pacientes según la bacteria aislada (productora o no de BLEE). El 50,6 % de las bacteriemias fueron causadas por enterobacterias productoras de BLEE, 55,8 % y 32,6 % por E. Coli y K. pneumoniae, respectivamente. No hallándose diferencias con relación a comorbilidades, ni uso previo de antibióticos (62,8 % de las bacteriemias por cepas productoras de BLEE y en 57 % en las no productoras (p=0,595)). La mitad de las bacteriemias por enterobacterias en pacientes hospitalizados son producidas por enterobacterias productoras de BLEE, y de estas, el 40 % son adquiridas en la comunidad.

ABSTRACT A cross-sectional study was conducted aimed at determining the frequency and the risk factors for bacteremia caused by extended-spectrum Beta-Lactamase (ESBL)-producing Enterobacteriaceae in patients hospitalized in a public hospital in Lima. The study included patients over 14 years of age, with positive blood cultures during their hospitalization in Hospital Nacional Cayetano Heredia in 2016. Patients were classified according to the isolated bacterium (ESBL-producing or not). Bacteremia was caused by ESBL-producing Enterobacteriacea in 50.6% of the cases; 55.8% and 32.6% by E. Coli and K. pneumoniae, respectively. No differences were found regarding co-morbidity, or prior antibiotic use (62.8% of bacteremia due to ESBLproducing strains and 57% in the non-producing strains [p=0.595]). Half of the bacteremia cases due to Enterobacteriaceae in hospitalized patients are produced by ESBL-producing Enterobacteriaceae and, of these, 40% are acquired in the community.

Resultados de la vigilancia nacional de la resistencia antimicrobiana de enterobacterias y bacilos Gram negativos no fermentadores en infecciones asociadas a la atención de salud, Colombia, 2012-2014 / Results of the national surveillance of antimicrobial resistance of Enterobacteriaceae and Gram negative bacilli in health care-associated infections in Colombia, 2012-2014

Resumen Introducción. En el tercer trimestre de 2012, comenzó a operar el Sistema Nacional de Vigilancia de Resistencia Antimicrobiana en las infecciones asociadas a la atención en salud, con el fin de recabar y analizar la información referente al problema en Colombia. Objetivo. Describir los perfiles de resistencia y los resultados de la vigilancia por el laboratorio con base en los datos recolectados en el Sistema. Materiales y métodos. Se hizo un estudio descriptivo y retrospectivo con base en la información del Sistema Nacional de Vigilancia en Salud Pública, Sivigila, 1 de septiembre de 2012 a 31 de diciembre de 2014, así como de las bases de datos Whonet con los datos notificados por las unidades primarias generadoras de datos y los resultados de la confirmación por el laboratorio de la caracterización fenotípica y genotípica de la resistencia a carbapenemasas en 1.642 aislamientos (927 de enterobacterias, 614 de Pseudomonas spp. y 101 de Acinetobacter spp.). Resultados. La resistencia de Escherichia coli a las cefalosporinas de tercera generación presentó un incremento significativo, alcanzando 26,3 % en unidades de cuidados intensivos y 22,5 % en otras áreas de hospitalización. La resistencia a ertapenem de Klebsiella pneumoniae registró un incremento y alcanzó 14,6 % en unidades de cuidados intensivos. La resistencia de Acinetobacter baumannii a los carbapenémicos superó el 50 % en dichas unidades, en tanto que en Pseudomonas aeruginosa se presentaron porcentajes más bajos (38,8 %). Las carbapenemasas más frecuentes en enterobacterias fueron la KPC (n=574), seguida de la NDM (n=57); en P. aeruginosa, la VIM (n=229) y la KPC (n=114), y en A. baumannii, la OXA-23 (n=87). Se detectaron varias combinaciones de carbapenemasas, siendo la de KPC y VIM la más frecuente en Pseudomonas spp., y en enterobacterias. Conclusión. La información obtenida a partir del Sistema Nacional de Vigilancia ha permitido conocer los perfiles y los mecanismos de resistencia a carbapenémicos de las cepas que están circulando en las instituciones de salud del país.

Abstract Introduction: The Colombian National Antimicrobial Resistance Monitoring System for the surveillance of healthcare-associated infections was set up to meet this problem in the third quarter of 2012. Objective: To describe resistance profiles and laboratory-based surveillance based on the information collected by the System. Materials and methods: We conducted a retrospective and descriptive study of the information notified to the Colombian Public Health Surveillance System (Sivigila), and in the Whonet databases covering the period from July 2012 to December 2014 provided by the primary data-generating units in the country, as well as laboratory surveillance results from 1,642 phenotypic and genotypic tests on carbapenemase isolates (927 from Enterobacteriaceae, 614 from Pseudomonas spp. and 101 from Acinetobacter spp.). Results: There was a significant increase in Escherichia coli resistance to third-generation cephalosporins (reaching 26.3% in ICUs and 22.5% in other hospital wards), and Klebsiella pneumoniae resistance to ertapenem also increased (reaching 14.6% in ICUs). Acinetobacter baumannii carbapenem resistance exceeded 50% in ICUs whereas Pseudomonas aeruginosa had lower carbapenem resistance (38.8%). KPC (n = 574) and NDM (n=57) were the most frequently occurring carbapenemases in Enterobacteriaceae, VIM (n=229) and KPC (n=114) in P. aeruginosa, and OXA-23 in A. baumannii (n=87); several carbapenemase combinations were identified, KPC + VIM being the most common in Pseudomonas spp. and Enterobacteriaceae. Conclusion: The data from the surveillance of healthcare-associated infections revealed significant carbapenem resistance profiles and antimicrobial resistance mechanisms circulating in Colombian healthcare institutions.

Evaluation of carbapenem-resistant Enterobacteriaceae in a tertiary-level reference hospital in Rio Grande do Sul, Brazil

Abstract INTRODUCTION: The rapid global spread of carbapenem-resistant Enterobacteriaceae (CRE) is a threat to the health system. METHODS: We evaluated the antimicrobial susceptibility profiles of 70 CRE isolated in a tertiary hospital in Brazil between August and December 2015, and determined their resistance mechanisms. RESULTS: The most prevalent microorganism was Klebsiella pneumoniae (95.7%); it showed high-level resistance to carbapenems (>98%), with sensitivity to colistin (91.4%) and amikacin (98.6%). The bla KPC gene was detected in 80% of the CRE isolates. CONCLUSIONS: Evaluation of bacterial resistance contributes to an appropriate treatment, and the reduction of morbimortality and dissemination of resistance.

Infección del tracto urinario causada por Enterobacteriaceae y su relación con reflujo vésico-ureteral en recién nacidos / Urinary tract infection caused by Enterobacteriaceae and its relationship with vesicoureteral reflux

Resumen: Introducción: La primera infección del tracto urinario puede ser un marcador de una anomalía del tracto urinario, principalmente de reflujo vésico-ureteral. El objetivo de este trabajo fue determinar la asociación entre microorganismos de la familia Enterobacteriaceae con la presencia y grado de reflujo vésico-ureteral en pacientes neonatales quienes debutaron con infección del tracto urinario. Métodos: Se realizó un estudio retrospectivo, observacional y analítico de recién nacidos con infección del tracto urinario, quienes ingresaron en el Servicio de Neonatología del Hospital Pediátrico Universitario ''Juan Manuel Márquez'', La Habana, Cuba, desde 1992 hasta 2013, y en quienes el microorganismo causal era de la familia Enterobacteriaceae. Se realizaron estudios por imagen y se analizó la asociación entre la presencia y grado de reflujo vésico-ureteral con el microorganismo causal de la infección del tracto urinario. Resultados: Se estudiaron 450 recién nacidos. Los aislamientos bacterianos en los urocultivos correspondieron a E. coli en 316 casos (70.2%). La prevalencia de reflujo vésico-ureteral resultó del 18.2%. Se comprobó que el microorganismo causal -otras bacterias diferentes a E. coli correspondientes a la familia Enterobacteriaceae- se asoció significativamente con el riesgo (OR 2.02; p < 0.01) y el grado de reflujo vésico-ureteral (para los de más alto grado, p < 0.01). Conclusiones: E. coli es el agente causal más frecuente de la infección del tracto urinario neonatal. Sin embargo, existe una asociación entre la presencia de un microorganismo de la familia Enterobacteriaceae diferente a E. coli y el reflujo vésico-ureteral, principalmente los de mayor grado.

Abstract: Background: The first urinary tract infection can be a marker of a urinary tract anomaly, mainly vesicoureteral reflux. The aim of this work was to determine the association between isolated enterobacteria with the presence and grade of vesicoureteral reflux in neonatal patients with their first urinary tract infection. Methods: A retrospective, observational and analytic study of newborns, who were admitted to the Neonatal Department, University Pediatric Hospital ''Juan Manuel Márquez,'' in Havana, Cuba, from 1992 to 2013 was conducted. The causal microorganism of urinary tract infection was from the Enterobacteriaceae family. They were evaluated by radio imaging. The association between the presence and grade of vesicoureteral reflux with the causal microorganism of the urinary tract infection was analyzed. Results: Newborn infants with urinary tract infection (450) were studied. Bacterial isolations in the urine cultures corresponded to E. coli in 316 cases (70.2%). The prevalence of vesicoureteral reflux was 18.2%. The presence of bacteria corresponding to the Enterobacteriaceae family (other than E. coli) had significant risk association with vesicoureteral reflux (OR: 2.02; p < 0.01) and vesicoureteral reflux classification (for higher grades, p < 0.01). Conclusions: E. coli is the most frequent causal microorganism in neonatal urinary tract infection. However, an association between the isolation of a microorganism of the Enterobacteriaceae family different to E. coli with the presence of vesicoureteral reflux and mainly with higher grades of vesicoureteral reflux exists.

Factors associated with acquisition of carbapenem-resistant Enterobacteriaceae / Fatores associados à aquisição de Enterobactérias resistentes aos carbapenêmicos / Factores asociados con la contracción de enterobacterias resistentes al carbapenem

ABSTRACT Objective: to identify possible risk factors for acquisition of Enterobacterial strains with a marker for resistance to carbapenems. Methods: exploratory case-control study performed in hospital settings. The study sample consisted of patients with biological specimens that tested positive for carbapenem-resistant Enterobacteriaceae (cases), with the disk diffusion test and Etest, and controls with biological samples testing negative for carbapenem-resistant Enterobacteriaceae. In all, 65 patients were included: 13 (20%) cases and 52 (80%) controls. Results: the microorganisms isolated were Serratia marcescens (6), Klebsiella pneumoniae (4), and Enterobacter cloacae (3). Univariate analysis revealed that length of hospitalization prior to sample collection (p=0.002) and having a surgical procedure (p=0.006) were statistically significant. In the multivariable logistic regression model, both were still significant, with odds ratios of 0.93 (p = 0.009; 95% CI: 0.89 to 0.98) for length of hospitalization prior to sample collection, and 9.28 (p = 0.05; 95% CI: 1.01 to 85.14) for having a surgical procedure. Conclusion: shorter hospitalization times and increased surveillance of patients undergoing surgery could play a decisive role in reducing the spread of carbapenem-resistant microorganisms in hospital settings.

RESUMO Objetivo: identificar possíveis fatores de risco para a aquisição de cepas de Enterobactérias com marcador de resistência a carbapenem. Métodos: estudo caso-controle exploratório realizado em instituições hospitalares. A amostra do estudo consistiu de pacientes com espécimes biológicos positivos para Enterobactérias resistentes aos carbapenêmicos (casos) por teste de difusão em disco e Etest e controles com amostras biológicas negativas para Enterobactérias resistentes aos carbapenêmicos. No total, foram incluídos 65 pacientes: 13 (20%) casos e 52 (80%) controles. Resultados: os microrganismos isolados foram Serratia marcescens (6), Klebsiella pneumoniae (4) e Enterobacter cloacae (3). A análise univariada revelou que o tempo de internação antes da coleta da amostra (p=0,002) e o procedimento cirúrgico (p=0,006) foram estatisticamente significantes. No modelo de regressão logística multivariável, ambos foram ainda significativos, com odds ratios de 0,93 (p=0,009; IC 95%: 0,89 a 0,98) para o período de hospitalização antes da coleta da amostra e 9,28 (p=0,05; IC 95%: 1,01 a 85,14) para o procedimento cirúrgico. Conclusão: tempo de internação mais curto e maior vigilância de pacientes submetidos a cirurgia podem desempenhar um papel decisivo na redução da disseminação de microrganismos resistentes aos carbapenêmicos em instituições hospitalares.

RESUMEN Objetivo: identificar posibles factores de riesgo para la contracción de cepas de enterobacterias con marcador de resistencia a carbapenem. Métodos: estudio exploratorio de casos y controles realizado en entornos hospitalarios. La muestra del estudio consistió en pacientes con muestras biológicas que dieron positivo para enterobacterias resistentes a carbapenem (casos) con prueba de difusión en disco y Etest y controles con muestras biológicas negativas para enterobacterias resistentes a carbapenem. En total, se incluyeron 65 pacientes: 13 (20%) casos y 52 (80%) controles. Resultados: los microorganismos aislados fueron Serratia marcescens(6), Klebsiella pneumoniae(4) y Enterobacter cloacae(3). El análisis univariado reveló que la duración de la hospitalización antes de la recolección de la muestra (p = 0.002) y el Intervención quirúrgica (p = 0.006) fueron estadísticamente significativas. En el modelo de regresión logística multi variable, ambos fueron significativos, con razón de momios de 0.93 (p = 0.009; IC del 95%: 0.89 a 0.98) para la duración de la hospitalización antes de la recolección de la muestra y 9.28 (p = 0.05; IC del 95%: 1.01 a 85.14) por haberse sometido a un Intervención quirúrgica. Conclusión: tiempos de hospitalización más cortos y una mayor vigilancia de los pacientes sometidos a cirugía podrían desempeñar un papel decisivo en la reducción de la propagación de los microorganismos resistentes a los carbapenem en los hospitales.

Fatores de risco para infecções relacionadas à assistência à saúde causadas por enterobactérias produtoras de carbapenemase portadoras de gene blakKPC / Risk factors for health care-related infections caused by carbapenemase-producing enterobacteria carrying blakKPC gene

As enterobactérias produtoras de carbapenemase portadoras do gene blaKPC (EPC-KPC) se disseminam de forma rápida e, por limitarem as opções terapêuticas para os pacientes infectados, acabam se associando a uma alta taxa de mortalidade. No ambiente hospitalar, a identificação precoce de fatores de risco para Infecções relacionadas à Assistência à Saúde (IRAS) causadas por esses microrganismos específicos são importantes para o controle da disseminação entre pacientes, profissionais e/ou ambientes. No entanto, ainda não há um consenso na literatura sobre quais fatores de risco estão diretamente associados às IRAS causadas por EPC-KPC. Por este motivo, a pesquisa teve por objetivo avaliar os fatores de risco associados às infecções relacionadas à assistência à saúde causadas por EPC-KPC no ambiente hospitalar. Tratou-se de um estudo de caso-controle que constituiu uma amostra de 82 pacientes casos e 164 controles, totalizando 246 pacientes. Os pacientes do grupo controle foram sorteados aleatoriamente e pareados por sexo e idade proporcional. Os dados foram coletados pelo Sistema Automatizado de Controle de Infecção Hospitalar (SACIH) e prontuário eletrônico do paciente. Os resultados mostraram que os pacientes colonizados previamente por microrganismos gram-negativos (OR: 10,7, IC95%: 2-60, p=0,007), os com câncer (OR:20,8, IC95%:4-120, p...

Enterobacteria producing carbapenemase carrying the blaKPC gene (EPC-KPC) spread rapidly and, by limiting the therapeutic options for infected patients, end up associated with a high mortality rate. In the hospital environment, the early identification of risk factors for Healthcare associated Infections (HAI) caused by the blaKPC gene are important for the control of dissemination among patients, professionals and/or environment. However, there is still no consensus in the literature on which risk factors are directly associated with HAI caused by EPC-KPC. This study aimed to evaluate the risk factors associated with Healthcare associated Infections caused by EPC-KPC in the hospital environment. It was a case-control study that consisted of a sample of 82 infected patients and 164 controls, totaling 246 patients. Patients in the control group were randomly selected and matched by sex and proportional age. The data were collected by the Automated System of Control of Hospital Infection and electronic patient record. The results showed that patients previously colonized by gramnegative microorganisms (OR: 10.7, 95% CI: 2-60, p = 0.007), those with cancer (OR: 20.8, 95% CI: 4-120, p...

Antimicrobial resistance in Enterobacteriaceae in Brazil: focus on ß-lactams and polymyxins

ABSTRACT During the last 30 years there has been a dissemination of plasmid-mediated β-lactamases in Enterobacteriaceae in Brazil. Extended spectrum β-lactamases (ESBL) are widely disseminated in the hospital setting and are detected in a lower frequency in the community setting. Cefotaximases are the most frequently detected ESBL type and Klebsiella pneumoniae is the predominant species among ESBL producers. Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae became widely disseminated in Brazil during the last decade and KPC production is currently the most frequent resistance mechanism (96.2%) in carbapenem resistant K. pneumoniae. To date KPC-2 is the only variant reported in Brazil. Polymyxin B resistance in KPC-2-producing K. pneumoniae has come to an alarming rate of 27.1% in 2015 in São Paulo, the largest city in Brazil. New Delhi metallo-β-lactamase was detected in Brazil in 2013, has been reported in different Brazilian states but are not widely disseminated. Antimicrobial resistance in Enterobacteriaceae in Brazil is a very serious problem that needs urgent actions which includes both more strict adherence to infection control measures and more judicious use of antimicrobials.

CTX-M extended-spectrum ß-lactamase-producing Klebsiella spp, Salmonella spp, Shigella spp and Escherichia coli isolates in Iranian hospitals

Abstract This study was conducted in Iran in order to assess the distribution of CTX-M type ESBLs producing Enterobacteriaceae. From January 2012 to December 2013, totally 198 E. coli, 139 Klebsiella spp, 54 Salmonella spp and 52 Shigella spp from seven hospitals of six provinces in Iran were screened for resistance to extended-spectrum cephalosporins. After identification and susceptibility testing, isolates presenting multiple-drug resistance (MDR) were evaluated for ESBL production by the disk combination method and by Etest using (cefotaxime and cefotaxime plus clavulanic acid). All isolates were also screened for bla CTX-M using conventional PCR. A total of 42.92%, 33.81%, 14.81% and 7.69% of the E. coli, Klebsiella spp, Salmonella spp and Shigella spp isolates were MDR, respectively. The presence of CTX-M enzyme among ESBL-producing isolates was 85.18%, 77.7%, 50%, and 66.7%, in E. coli, Klebsiella spp, Salmonella spp and Shigella spp respectively. The overall presence of CTX-M genes in Enterobacteriaceae was 15.4% and among the resistant isolates was 47.6%. This study indicated that resistance to β-lactams mediated by CTX-M enzymes in Iran had similar pattern as in other parts of the world. In order to control the spread of resistance, comprehensive studies and programs are needed.

Abundant immunohistochemical expression of dopamine D2 receptor and p53 protein in meningiomas: follow-up, relation to gender, age, tumor grade, and recurrence

Meningiomas are common, usually benign tumors, with a high postoperative recurrence rate. However, the genesis and development of these tumors remain controversial. We aimed to investigate the presence and implications of a mutated p53 protein and dopamine D2 receptor in a representative series of meningiomas and to correlate these findings with age, gender, tumor grade, and recurrence. Tumor tissue samples of 157 patients diagnosed with meningioma (37 males and 120 females, mean age 53.6±14.3 years) who underwent surgical resection between 2003 and 2012 at our institution were immunohistochemically evaluated for the presence of p53 protein and dopamine D2 receptor and were followed-up to analyze tumor recurrence or regrowth. Tumors were classified as grades I (n=141, 89.8%), II (n=13, 8.3%), or grade III (n=3, 1.9%). Dopamine D2 receptor and p53 protein expression were positive in 93.6% and 49.7% of the cases, respectively. Neither of the markers showed significant expression differences among different tumor grades or recurrence or regrowth statuses. Our findings highlight the potential role of p53 protein in meningioma development and/or progression. The high positivity of dopamine D2 receptor observed in this study warrants further investigation of the therapeutic potential of dopamine agonists in the evolution of meningiomas.

ß-lactamases produced by amoxicillin-clavulanate-resistant enterobacteria isolated in Buenos Aires, Argentina: A new blaTEMgene / ß-lactamasas producidas por enterobacterias resistentes a amoxicilina-ácido clavulánico aisladas en Buenos Aires, Argentina: un nuevo gen blaTEM

La resistencia a la combinación de ß-lactámico/inhibidor de ß-lactamasa en enterobacterias es un problema creciente que no ha sido estudiado intensamente en Argentina. En el presente trabajo, 54/843 enterobacterias recolectadas en un hospital universitario de la ciudad de Buenos Aires fueron resistentes a ampicilina-sulbactama, pero se mantuvieron sensibles a las cefalosporinas de segunda y tercera generación. Se analizaron los mecanismos enzimáticos presentes en los aislamientos que también fueron resistentes a amoxicilina-ácido clavulánico (AMC) (18/54). La secuenciación reveló dos variantes diferentes de blaTEM-1, donde blaTEM-1b es el alelo más frecuentemente detectado (10 Escherichia coli, 3 Klebsiella pneumoniae, 2 Proteus mirabilis y 1 Raoultella terrigena), seguidos por blaTEM-1a(1 K. pneumoniae). La resistencia a AMC parece estar asociada principalmente con la hiperproducción de TEM-1 (sobre todo en E. coli) o con la coexpresión con ß-lactamasas tipo OXA-2 y/o SHV (K. pneumoniae y P. mirabilis). Se describió una nueva variante de blaTEM(TEM-163) en un aislamiento de E. coli que presentó una CIM frente a AMC de 16/8 µg/ml. La enzima TEM-163 contiene dos sustituciones de aminoácidos respecto de TEM-1, Arg275Gln y His289Leu. Teniendo en cuenta la alta actividad específica observada y la baja IC50 para el ácido clavulánico, el patrón de resistencia de este aislamiento parece obedecer a la hiperproducción de la nueva variante de la ß-lactamasa de amplio espectro, en lugar de vincularse con un comportamiento similar al de una TEM resistente a inhibidores (IRT).

Resistance to ß-lactam/ß-lactamase inhibitors in enterobacteria is a growing problem that has not been intensively studied in Argentina. In the present work, 54/843 enterobacteria collected in a teaching hospital of Buenos Aires city were ampicillin-sulbactam-resistant isolates remaining susceptible to second-and third-generation cephalosporins. The enzymatic mechanisms present in the isolates, which were also amoxicillin-clavulanic acid (AMC)-resistant (18/54) were herein analyzed. Sequencing revealed two different variants of blaTEM-1, being blaTEM-1b the most frequently detected allelle (10 Escherichia coli, 3 Klebsiella pneumoniae, 2 Proteus mirabilis and 1 Raoultella terrigena) followed by blaTEM-1a(1 K. pneumoniae). Amoxicillin-clavulanate resistance seems to be mainly associated with TEM-1 overproduction (mostly in E. coli) or co-expressed with OXA-2-like and/or SHV ß-lactamases (K. pneumoniae and P. mirabilis). A new blaTEMvariant (TEM-163) was described in an E. coli strain having an AMC MIC value of 16/8 µg/ml. TEM-163 contains Arg275Gln and His289Leu amino acid substitutions. On the basis of the high specific activity and low IC50 for clavulanic acid observed, the resistance pattern seems to be due to overproduction of the new variant of broad spectrumß-lactamase rather than to an inhibitor-resistant TEM (IRT)-like behavior.

Revisión sistemática de la farmacorresistencia en enterobacterias de aislamientos hospitalarios en Colombia / Systematic review of antimicrobial resistance in Enterobacteriaceae isolates from Colombian hospitals

Introducción. La resistencia bacteriana es un problema de salud pública a nivel mundial que compromete seriamente la capacidad de tratar las infecciones. Objetivo. Describir el perfil de resistencia a los antimicrobianos marcadores en enterobacterias identificadas en hospitales colombianos. Materiales y métodos. Se hizo una revisión bibliográfica sistemática de las publicaciones indexadas en Medline, Embase y Lilacs, además de la búsqueda manual de todos los números de revistas colombianas reconocidas en el campo de la infectología y otros afines para identificar referencias no disponibles electrónicamente. Resultados. Se identificaron 43 estudios y reportes de vigilancia epidemiológica con información sobre la resistencia de las enterobacterias en hospitales, principalmente de Bogotá, Cali y Medellín. La tasa de resistencia en Escherchia coli oscila entre 3 y 11 %, 5 y 20 % y 0,2 a 0,8 % para piperacilina-tazobactam, cefalosporinas de tercera generación y carbapenémicos, respectivamente. En aislamientos de Klebsiella pneumoniae , la resistencia oscila entre 21,8 y 48,1 % frente a piperacilina-tazobactam, 20 y 35 % frente a cefalosporinas de amplio espectro y 3 y 8 % frente a carbapenémicos, con variaciones importantes por ciudades, niveles de atención y circunstancias clínicas. Conclusiones. La diseminación de la resistencia bacteriana en enterobacterias aisladas en hospitales colombianos es un problema creciente que requiere medidas prontas para cortar las cadenas de transmisión.

Introduction: Bacterial resistance is a public health problem worldwide that seriously compromises the possibility to treat infections. Objective: To identify levels of resistance to antibiotic markers in Enterobacteriaceae isolates from Colombian hospitals. Materials and methods: A systematic literature survey was done including articles indexed in Medline, Embase and LILACS. A manual search was made of Colombian scientific journals and other publications on infectious disease that were not available electronically. Results: In total, 43 observational studies and epidemiological reports were identified with information about resistance among Enterobacteriaceae isolates in Colombian hospitals, mainly from Bogotá, Cali and Medellín. The resistance rate of Escherichia coli ranges from 3 to 11%, 5 to 20% and from 0.2 to 0.8% for piperacillin-tazobactam, third generation cephalosporins and carbapenems, respectively. For Klebsiella pneumoniae resistance rates ranges from 21.8 to 48.1% to piperacillin-tazobactam, 20 to 35% to broad-spectrum cephalosporins and 3 to 8% to carbapenems, with significant variations by cities, levels of care and clinical settings. Conclusions: The spread of bacterial resistance in Enterobacteriaceae isolated in Colombian hospitals is a growing problem that calls for priority action to cut the chains of transmission.

Rates of Fecal Transmission of Extended-Spectrum beta-Lactamase-Producing and Carbapenem-Resistant Enterobacteriaceae Among Patients in Intensive Care Units in Korea

BACKGROUND: We investigated the rates of fecal transmission of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) and carbapenem-resistant Enterobacteriaceae (CRE) among patients admitted to intensive care units (ICUs). METHODS: From June to August 2012, rectal cultures were acquired from all patients at ICU admission. For patients not carrying ESBL-E or CRE at admission, follow-up cultures were performed to detect acquisition. A chromogenic assay was used to screen for ESBL-E and CRE. Bacterial species identification and antibiotic susceptibility tests were performed using the Vitek 2 system (bioMerieux, France). ESBL genotypes were determined by PCR, and clonal relatedness of the isolates was assessed by pulsed-field gel electrophoresis. RESULTS: Out of 347 ICU admissions, 98 patients were found to be carriers of ESBL-E (28.2%, 98/347). Follow-up cultures were acquired from 91 of the patients who tested negative for ESBL-E at admission; the acquisition rate in this group was 12.1% (11/91), although none was a nosocomial transmission. For CRE, the prevalence of fecal carriage was 0.3% (1/347), and the acquisition rate was 2.9% (4/140). None of the CRE isolates were carbapenemase-producers. CONCLUSIONS: The high prevalence of ESBL-E carriage on admission (28.2%), coupled with rare nosocomial transmission and the very low carriage rate of CRE (0.3%), challenge the routine use of active surveillance in non-epidemic settings. Nevertheless, passive surveillance measures, such as rapid and accurate screening of clinical specimens, will be critical for controlling the spread of CRE.

Prevalence and risk factors of carbapenem-resistant gram negative bacilli in Assiut University Hospital

Carbapenem-resistant Gram negative bacilli [CRGNB] resulting from carbapenemase enzyme production have been reported to be an important cause of nosocomial infection and are a critical therapeutic problem worldwide. This study was conducted to determine the prevalence of carbapenem-resistant Gram negative bacilli in Asiut University Hospital and relevant risk factors associated with its occurrence. The study was conducted over a period of 12 month from January 2011 to January 2012 on 355 specimen of 134 nosocomialy infected patients, aged two month to 82 years, admitted to the ICUs at Assiut University Hospital. Patient demographics, comorbidities, antibiotics, invasive devices were determined to identify risk factors associated with CRGNB infections. Three hundred and fifty five Gram negative bacilli isolates [47.92%] were isolated from patients. Ninety seven [27.17%] of Gram negative bacilli isolates were carbapenem-resistant. Patients aged above 40 years, male sex, prior antibiotic treatment, the presence of a urinary catheter, mechanical ventilation and central line in ICU were the most prevalent risk factors associated with the accurence of nosocomial CRGNB infections. The prevalence of CRGNB was 27.17% among GNB isolates. Patients aged above 40 years, male sex, prior antibiotic treatment, the presence of a urinary catheter, mechanical ventilation and central line in ICU were the most prevalent risk factors Interventions aimed reducing initial broad spectrum antibiotics are clearly needed to help control the spread in of these difficult to treat infections

Molecular epidemiology of CTX-M producing Enterobacteriaceae isolated from bloodstream infections in Rio de Janeiro, Brazil: emergence of CTX-M-15

OBJECTIVE: The present studywas designed to evaluate the molecular epidemiology of CTX-M producing Klebsiella pneumoniae, Enterobacter cloacae and Escherichia coli isolated from bloodstream infections at tertiary care hospitals in the State of Rio de Janeiro, Brazil. MATERIAL AND METHODS: A total of 231 nonduplicate Enterobacteriaceae were isolated from five Brazilian hospitals between September 2007 and September 2008. The antimicrobial susceptibility testing was performed by disk diffusion method according to the Clinical Laboratory Standard Institute. Isolates showing resistance to third-generation cephalosporins were screened for ESBL activity by the double-disk synergy test. The presence of blaCTX-M , blaCTX-M-15 and blaKPC genes was determined by Polymerase Chain Reaction (PCR) amplification andDNA sequencing. The molecular typing of CTX-M producing isolateswas performed by pulsed-field gel electrophoresis (PFGE). RESULTS AND DISCUSSION: Ninety-three isolates were screened as ESBL positive and 85 (91%) were found to carry CTX-M-type, as follows: K. pneumoniae 59 (49%), E. cloacae 15 (42%), and E. coli 11 (15%). Ten isolates resistant for carbapenems in K. pneumoniae were blaKPC-2 gene positive. Among CTX-M type isolates, CTX-M-15 was predominant in more than 50% of isolates for K. pneumoniae, E. coli, and E. cloacae. PFGE analysis of CTX-M producing isolates showed the predominance of CTX-M-15 in 10 of 24 pulsotypes in K. pneumoniae, 6 of 13 in E. cloacae and 3 of 6 in E. coli. CTX-M-15 was also predominant among KPC producing isolates. In conclusion, this study showed that CTX-M-15 was circulating in Rio de Janeiro state in 2007-2008. This data reinforce the need for continuing surveillance because this scenario may have changed over the years.