Prognosis of Extended-Spectrum-Beta-Lactamase-Producing Agents in Emphysematous Pyelonephritis-Results from a Large, Multicenter Series.

BACKGROUND: Emphysematous pyelonephritis (EPN) is a necrotizing infection of the kidney and surrounding tissues with significant mortality. We aimed to assess the clinical factors and their influence on prognosis in patients being managed for EPN with and without ESBL-producing bacteria and to identify if those with EPN due to ESBL infections fared any different. METHODS: A retrospective analysis was performed on patients with EPN diagnosis from 22 centers across 11 countries (between 2013 and 2020). Demographics, clinical presentation, biochemical parameters, radiological features, microbiological characteristics, and therapeutic management were assessed. Univariable and multivariable analyses were performed to determine the independent variables associated with ESBL pathogens. A comparison of ESBL and non-ESBL mortality was performed evaluating treatment modality. RESULTS: A total of 570 patients were included. Median (IQR) age was 57 (47-65) years. Among urine cultures, the most common isolated pathogen was Escherichia coli (62.2%). ESBL-producing agents were present in 291/556 urine cultures (52.3%). In multivariable analysis, thrombocytopenia (OR 1.616 95% CI 1.081-2.413, p = 0.019), and Huang-Tseng type 4 (OR 1.948 95% CI 1.005-3.778, p= 0.048) were independent predictors of ESBL pathogens. Patients with Huang-Tseng Scale type 1 had 55% less chance of having ESBL-producing pathogens (OR 1.616 95% CI 1.081-2.413, p = 0.019). Early nephrectomy (OR 2.3, p = 0.029) and delayed nephrectomy (OR 2.4, p = 0.015) were associated with increased mortality in patients with ESBL infections. Conservative/minimally invasive management reported an inverse association with mortality (OR 0.314, p = 0.001). CONCLUSIONS: ESBL bacteria in EPN were not significantly associated with mortality in EPN. However, ESBL infections were associated with poor prognosis when patients underwent nephrectomy compared conservative/minimally invasive management.

Resistencia antibiótica de Escherichia coli, según producción de beta lactamasas de espectro extendido, en urocultivos. Hospital III-1. Chiclayo, Perú 2020

Objetivo: determinar la resistencia antibiótica de Echerichia coli, en urocultivos, según produccion de BLEE, en pacientes hospitalizados. El estudio: Diseño descriptivo - retrospectivo. La identificación bacteriana se hizo con VITEK XL, la susceptibilidad, con las pautas del CLSI M100. 30 edicion. Hallazgos. E. coli BLEE positivo, presento resistencia de 0% a: Meropenem, ertapenem, tigeciclina y colistina. Piperacilina/tazobactam, nitrofurantoina, imipenem, amicacina con 16.7%, 6.2%, 5% y 1% respectivamente. E. Coli BLEE negativo, presento resistencia de 0% a: cefotaxima, cefuroxime, tigeciclina y piperacilina/tazobactam. Ceftriaxona, cefepime, gentamicina, cefazolina, ceftazidima, nitrofurantoina, meropenem, amicacina, imipenem y ertapenem con 14.7%, 13%, 13%, 10.7%, 9.7%, 9.1%, 9.1%, 8%, 5%, 2.7%, respectivamente. Conclusion: Meropenen, ertapenem, tigeciclina, colestina, piperacilina/tazobactam, nitrofurantoina, amicacina y imipenem, con resistencia menor de 20%, fueron los mismos, para E. coli BLEE positivo, y E. coli, sin considerar la produccion de BLEE.

ABSTRAC Objective: to determine the antibiotic resistance of Echerichia coli, in urine cultures, according to ESBL production, in hospitalized patients. The study: Descriptive-retrospective design. Bacterial identification was done with VITEK XL, susceptibility, with the CLSI M100 guidelines. 30 edition. Findings: E. coli ESBL positive, presented 0% resistance to: Meropenem, ertapenem, tigecycline and colistin. Piperacillin/tazobactam, nitrofurantoin, imipenem, amikacin with 16.7%, 6.2%, 5% and 1% respectively. E. Coli ESBL negative, presented 0% resistance to: cefotaxime, cefuroxime, tigecycline and piperacillin/tazobactam. Ceftriaxone, cefepime, gentamicin, cefazolin, ceftazidime, nitrofurantoin, meropenem, amikacin, imipenem, and ertapenem with 14.7%, 13%, 13%, 10.7%, 9.7%, 9.1%, 9.1%, 8%, 5%, 2.7%, respectively. Conclusion: Meropenen, ertapenem, tigecycline, cholesterol, piperacillin/tazobactam, nitrofurantoin, amikacin and imipenem, with less than 20% resistance, were the same for ESBL-positive E. coli, and E. coli, without considering ESBL production.

Caracterización clínica-microbiológica y factores de riesgo de las bacteriemias por enterobacterias productoras de betalactamasas de espectro extendido en el hospital universitario / Clinical-microbiological characterization and risk factors of bacteremia caused by extended-spectrum beta-lactamase-producing enterobacteria at the university hospital

INTRODUCCIÓN: Las infecciones del torrente sanguíneo se asocian con alta morbi- mortalidad, siendo frecuentemente causadas por enterobacterias, y cuando éstas producen ß-lactamasas de espectro extendido (BLEEs), la morbi-mortalidad, duración internación y costos sanitarios son aún mayores. OBJETIVO: Caracterizar los episodios de bacteriemia por enterobacterias en el Hospital Universitario en un período de 2 años. METODOLOGÍA: Estudio observacional, analítico, casos controles (1:1), con recolección de datos retrospectiva. Población: pacientes ≥18 años atendidos en el Hospital Universitario en período 01/01/2014 - 30/11/2015, con hemocultivo positivo por enterobacteria. Recolección datos clínicos-epidemiológicos: revisión registros médicos. Estudio microbiológico: Identificación y susceptibilidad - equipo automatizado Vitek® 2 system (bioMérieux, Marcy l'Etoile, France). Sensibilidad a fosfomicina: disco-difusión (E. coli) y dilución en agar (resto de las enterobacterias). Ceftazidime-avibactam: disco-difusión. Aislamientos BLEE+ según Vitek: confirmación y caracterización de BLEE: reacción en cadena de la polimerasa (PCR) y secuenciación. Investigación mecanismos transferibles de resistencia a quinolonas (TMQR) qnrB y aac(6')-Ib-cr: PCR. Caracterización molecular enterobacterias BLEE más prevalentes: MultiLocus Sequence Typing (MLST) y Pulsed Field Gel Electrophoresis (PFGE). Análisis casos y controles: I)Factores de riesgo bacteriemia BLEE: Casos - pacientes con bacteriemia por enterobacteria BLEE(+). Controles - pacientes con bacteriemia por enterobacteria BLEE (-) sensible a cefalosporinas tercera generación. II) Factores de riesgo mortalidad intrahospitalaria: Casos - pacientes con mortalidad hospitalaria por cualquier causa. Controles ­ pacientes egresados vivos. Análisis estadístico: paquete estadístico IBM SPSS Statistics 23. Análisis casos y controles: cálculo de odd ratios (OR) e intervalo de confianza al 95% (IC95%). Variables con p ≤0.05 en análisis univariado incluídas en análisis multivariado (regresión logística). Proyecto aprobado por Comité Ética del Hospital de Clínicas y financiado por ANII (FMV_3_2016_1_126580, Fondo María Viña ­ 2016). RESULTADOS: Principales resultados microbiológicos: 174 episodios de bacteriemia y 178 enterobacterias recuperadas, con confirmación molecular de producción BLEE en 41 enterobacterias (23%): 29 Klebsiella pneumoniae, 7 Escherichia coli, 2 Serratia marcescens, 1 Enterobacter cloacae, 1 Citrobacter freundii y 1 Morganella morganii. E. coli enterobacteria más recuperada (n=69), pero K. pneumoniae la enterobacteria BLEE más prevalente (56 aislamientos y 29/56 BLEE+), seguida de E. coli (7/69). Distribución de las enterobacterias BLEE+ según enzima detectada: CTX- M-15: 32 aislamientos, CTX-M-15 + CTX- M-14: 3 aislamientos, CTX-M-2: 3, CTX-M-8: 2, SHV-5: 1. Susceptibilidad enterobacterias BLEE: meropenem 100%, ceftazidime-avibactam 100%, fosfomicina 100%, imipenem 98%, ertapenem 97,6%, colistin 92,7%, amikacina 85,4%, gentamicina 36,6%, tigeciclina 29,3%, piperacilina-tazobactam 26,8%, trimetoprim-sulfametoxazol 19,5%, ciprofloxacina 12,2%. Detección de mecansimos transferibles de resistencia a quinolonas (TMQR) en 33/41 aislamientos (80,5%): aac(6')-Ib-cr: 22 aislamientos, qnrB: 2 aislamientos, y aac(6')-Ib-cr + qnrB: 9 aislamientos. Detección de secuenciotipos "exitosos" en principales enterobacterias BLEE: E. coli ST 73 (1), ST 95(1) y ST 38 (2) y ST 258 en K. pneumoniae (12/29=41,4%). También detección ST 258 en un aislamiento de K. pneumoniae BLEE (-). Principales resultados clínicos ­ epidemiológicos: Se revisaron 98 registros médicos; 60 bacteriemias nosocomiales, 29 comunitarias, 8 asociadas a los cuidados de la salud, 1 sin dato. 41 BLEE(+) y 57 BLEE(-). 80 pacientes vivos al egreso, 17 fallecidos y 1 sin dato. Factores de riesgo bacteriemia BLEE(+) (análisis multivariado) : presencia de dispositivo médico a permanencia previo (p 0,001, OR 55,2, IC 95%5,5-553) ) y bacteriemia no comunitaria (p 0,008 OR 17,4 IC95% 2,1-143). Factores de riesgo mortalidad intrahospitalaria (análisis multivariado): enfermedad hematooncológica o neoplásica (OR 4,687 IC95% 1,207-18,200) y score qPitt ≥2 (OR 10,332 IC95% 2,639-40,442). Antibioticoterapia empírica activa in vitro para la bacteriemia: 10/29(34,5%) en pacientes BLEE(+) y 36/40 BLEE(-) (90%). Se encontró asociación entre bacteriemia BLEE + y recibir antibioticoterapia empírica inactiva (p<0,0001) ; siendo el riesgo de recibir antibioticoterapia empírica inactiva 17 veces mayor en bacteriemias BLEE(+) respecto a BLEE(-). Se encontró que la mediana de la duración de la hospitalización a partir del episodio de bacteriemia es más prolongada en casos BLEE+ que en los controles BLEE- (22,5 versus 14 días, p=0,006). CONCLUSIONES: Enterobacteria BLEE más prevalente K. pneumoniae, y dentro de ella alta prevalencia del clon exitoso de alto riesgo ST 258. Predominio de CTX-M-15, y alta prevalencia (> 80%) de TMQR en aislamientos BLEE. Presencia de BLEE aumenta significativamente el riesgo de recibir antibioticoterapia empírica inactiva. Necesidad de mantener vigilancia de perfiles de susceptibilidad y clones circulantes y considerar posibles factores de riesgo al momento se seleccionar antibioticoterapia empírica.

BACKGROUND: Bloodstream infections are associated with high morbidity and mortality, being frequently caused by Enterobacteriaceae, and when they produce extended spectrum ß-lactamases (ESBL), morbidity, mortality and healthcare costs are even higher. OBJECTIVE: We aimed to characterize Enterobacteriaceae bacteremia episodes at the "Hospital de Clínicas", in a 2 years period. METHODS: Observational, analytical study, case-controls (1: 1), with retrospective data collection. Population: ≥18 years old patients attended at the "Hospital de Clínicas" between 01/01/2014 and 11/30/2015, with Enterobacteriaceae recovered from blood culture. Collection of clinical-epidemiological data: review of medical records. Microbiological study: identification and susceptibility: automated system Vitek® 2 (bioMérieux, Marcy l'Etoile, France). Susceptibility to fosfomycin: disc-diffusion (E. coli) and agar dilution (others Enterobacterales). Ceftazidime-avibactam: disc-diffusion. ESBL (+) isolates according to Vitek: ESBL confirmation and characterization by Polymerase Chain Reaction (PCR) and sequencing. Investigation of transferable mechanisms of quinolone resistance (TMQR) qnrB and aac (6 ')- Ib-cr: PCR. Molecular characterization of the most prevalent ESBL enterobacterales: MultiLocus Sequence Typing (MLST) and Pulsed Field Gel Electrophoresis (PFGE). Case-control analysis: I) ESBL bacteremia risk factors: Cases - patients with bacteremia by an ESBL-producing enterobacteria. Controls - patients with third generation cephalosporin susceptible enterobacteria, not ESBL-producing. II) In-hospital mortality risk factors: Cases - patients with in-hospital mortality from any cause. Controls - patients discharged alive. Statistical analysis: IBM SPSS Statistics 23 statistical package. Case-control analysis: calculation of odd ratios (OR) and 95% confidence interval (95% CI). Variables with p ≤0.05 in univariate analysis were included in multivariate analysis (logistic regression). Project approved by the Hospital de Clinicas Ethics Committee and financed by ANII (FMV_3_2016_1_126580, María Viña Fund - 2016). RESULTS: Main microbiological results: 174 bacteremia episodes and 178 enterobacterales recovered. ESBL production confirmated in 41 isolates (23%): 29 Klebsiella pneumoniae, 7 Escherichia coli, 2 Serratia marcescens, 1 Enterobacter cloacae, 1 Citrobacter freundii y 1 Morganella morganii.E. coli was the most recovered enterobacteria (n = 69), but K. pneumoniae was the most prevalent ESBL producing specie (56 isolates and 29/56 ESBL +), followed by E. coli (7/69). Distribution of ESBL producing enterobacterales according to enzyme detected: CTX- M-15: 32 isolates, CTX-M-15 + CTX-M-14: 3 isoaltes, CTX-M-2: 3, CTX-M-8: 2, SHV-5: 1. Antibiotic susceptibility in ESBL producers: meropenem 100%, ceftazidime-avibactam 100%, fosfomycin 100%, imipenem 98%, ertapenem 97,6%, colistin 92,7%, amikacin 85,4%, gentamicin 36,6%, tigecycline 29,3%, piperacillin-tazobactam 26,8%, trimethroprim sulfamethoxazole 19,5%, ciprofloxacin 12,2%. Detection of TMQR in 33/41 isolates (80.5%): aac(6')-Ib-cr: 22 isolates, qnrB: 2 isolates, and aac(6')Ib-cr + qnrb: 9 isolates. We detected "successful" sequence types within E. coli ESBL producing: ST 73 (1 isolate), ST 95 (1) and ST 38 (2) and a high prevalence of ST 258 among K. pneumoniae isolates (12/29 = 41.4%). ST 258 was also detected in one ESBL(-) K. pneumoniae isolate. Main clinical-epidemiological results: 98 medical records were reviewed; 60 bacteremia episodes were classified as nosomial, 29 as community acquired, 8 health care associated, and for one episode, data was insufficient for its classification. 41 were ESBL(+) and 57 ESBL(-). 80 patients alive at discharge, 17 deceased and 1 without data. Risk factors for ESBL bacteremia according to multivariate analysis were: use of medical device prior to hospitalization (OR = 50.226, 95% CI 4.367 - 577.721) and non-community bacteremia (OR 12.052, 95% CI 1.350-107.605). In-hospital mortality risk factors (multivariate analysis): hemato-oncological or neoplasic disease (OR 4,687 95% CI 1,207-18,200) and qPitt score ≥2 (OR 10,332 95% CI 2,639-40,442). The empirical antibiotic therapy was active according to the susceptibility test in 10/29 (34,5%) patients with ESBL (+) bacteremia and in 36/40 patients with ESBL (-) (90%). Presence of ESBL was found to be associated with inactive empirical antibiotic therapy (p<0.0001), and risk for receiving inactive empirical antibiotic therapy was 17 times higher in ESBL (+) compared to ESBL (-). The mean length of hospital stay after the onset of bacteraemia was longer in the cases of ESBL producers than in the cases of non-ESBL producers ( 22,5 vs. 14 days; P=0.006). CONCLUSIONS: K. pneumoniae was the most prevalent ESBL producing specie, and within it we found a high prevalence of the successful high-risk clone ST258. CTX-M-15 was the main ESBL detected and we found high prevalence (80%) of TMQR among ESBL(+). Presence of ESBL significantly increases the risk of receiving inactive empirical antibiotic therapy. Need to maintain surveillance of susceptibility profiles and circulating clones and to take into account possible risk factors when selecting empirical antibiotic therapy.

[Etiological profile and antimicrobial sensitivity in 1740 urinary infections of the community in the city of Córdoba, Argentina.] / Perfil etiológico y sensibilidad antimicrobiana en 1740 infecciones urinarias de la comunidad en la ciudad de Córdoba, Argentina.

INTRODUCTION: Urinary tract infections (Uti) are one of the most common infections that affec thumans throughout their lives and are a common healthproblem both at the community and at the nosocomial level. Knowing microbiological characteristics, sensitivity profile and risk factors allow to optimize the management of Utis minimizing the increase of antibiotic resistance (AR) and establishing early treatments to reduce the morbidity and severity of infection. This study aims to establish which microorganisms are responsible for urinary tract infections in our community and determine their AR. PATIENTS AND METHODS: An observational, descriptive, cross-sectional, retrospective study of all patients with the first episode of UTI recorded at the Sanatorio Allende in the city of Cordoba, Argentina, who were requested to under go urine culture (URC), from January 2016 to December 2017. RESULTS: 3636 positive URC were analyzed, of which1740 met the inclusion criteria. Of the total analyzed 90.2 % (n=1570) were female. The average age was 37.8 years (SD=15.2). Escherichia coli was the microorganism most frequently isolated in 80.3% followed by S. saprophyticus in 8.0%. The age group of 18-30 years (40.1%) showed the highest proportion of microorganisms, where we observed the highest prevalence of E. coli and S. saprophyticus. The following acquired resistances were obtained from the total isolations: 47.6% of the microorganisms were resistant to ampicillin, 29.6% to cotrimoxazole, 15.2% to ciprofloxacin, 4.6% to first generation of cephalosporins, 3.4% to cefixime, 2.3% to amoxicillin-clavulanic, 1,2% to gentamicin and 1% to nitrofurantoin. CONCLUSION: E. Coli was the most prevalent pathogenin our environment, with high rates of resistance to ampicillin, fluoroquinolones and trimethoprim-sulfamethoxazole, confirming the need for periodic studiesto determine the most optimal empirical antibiotic treatment.

INTRODUCCIÓN: Las infecciones del tracto urinario (ITU) son una de las infecciones más comunes que afectan al ser humano a lo largo de su vida y constituyen un problema de salud frecuente tanto en el ámbito comunitario como nosocomial. El conocimiento de las características microbiológicas, perfil de sensibilidad y factores de riesgo permiten optimizar el manejo de las ITU minimizando el incremento de resistencia antibiótica (RA), estableciendo tratamientos precoces para reducir la morbilidad y la gravedad de la infección. Este estudio tiene como objetivo establecer cuáles son los microorganismos responsables de las infecciones urinarias de la comunidad en nuestro medio y determinar su RA.PACIENTES Y MÉTODOS: Estudio observacional, descriptivo, transversal, retrospectivo de todos los pacientes con primer episodio de ITU registrado en el Sanatorio Allende de la ciudad de Córdoba, Argentina a los cuales se les solicitó urocultivo (URC), desde enero de 2016 a diciembre 2017.RESULTADOS: Se analizaron 3636 URC positivos de los cuales 1740 cumplieron con los criterios de inclusión. Del total analizado 90,2% (n=1570) fueron de sexo femenino. El promedio de edad fue 37,8 años (DE=15,2).Escherichia coli fue el microorganismo aislado en mayor frecuencia en un 80,3% seguido de S. saprophyticus en un 8,0 %. El grupo etario de 18-30 años (40,1%) demostró la mayor proporción de microorganismos, en donde observamos mayor prevalencia de E. coli y S. saprophyticus. Del total de aislamientos se obtuvieron las siguientes resistencias adquiridas: 47,6% de los microorganismos fueron resistentes a ampicilina, 29,6% a cotrimoxazol, 15,2% a ciprofloxacina, 4,6% a cefalosporinas de 1° generación, 3,4% a cefixima, 2,3% a amoxicilina-clavulánico, 1,2% a gentamicina y 1% anitrofurantoína.CONCLUSIÓN: E. Coli fue el patógeno más frecuente en nuestro entorno, con altas tasas de resistencia a ampicilina, fluoroquinolonas y TMS, confirmando la necesidad de estudios periódicos para determinar el tratamiento antibiótico empírico más óptimo.

Occurrence and Molecular Characteristics of Extended-Spectrum Beta-Lactamase-Producing Enterobacterales Recovered From Chicken, Chicken Meat, and Human Infections in Sao Paulo State, Brazil.

This study aimed to investigate the phylogenetic diversity and epidemiology of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae from chicken, chicken meat, and human clinical isolates in Sao Paolo, Brazil, and characterize their respective ESBL-encoding plasmids. Three hundred samples from chicken cloaca, chicken meat, and clinical isolates were phenotypically and genotypically assessed for ESBL resistance. Isolates were identified by MALDI TOF-MS and further characterized by MLST analysis and phylogenetic grouping. ESBL genes were characterized and their location was determined by I-Ceu-I-PFGE and Southern blot, conjugation, transformation, and PCR-based replicon typing experiments. Thirty-seven ESBL-producing isolates (28 E. coli and 9 K. pneumoniae) that were positive for the bla CTX-M-1 or bla CTX-M-2 gene groups were obtained. Two isolates were negative in the transformation assay, and the chromosomal location of the genes was deduced by Southern blot. The bla CTX-M genes identified were carried on plasmid replicon-types X1, HI2, N, FII-variants, I1 and R. The E. coli isolates belonged to nine sequence types, while the K. pneumoniae isolates belonged to four sequence types. The E. coli isolates belonged to phylotype classification groups A, B1, D, and F. This study demonstrated that isolates from cloacal swabs, chicken meat, and human feces had genetic diversity, with a high frequency of bla CTX-M-15 among chickens, chicken meat, and human feces. Thus, this reinforces the hypothesis that chickens, as well as their by-products, could be an important source of transmission for ESBL-producing pathogens to humans in South America.

ESBL-Producing Escherichia coli Carrying CTX-M Genes Circulating among Livestock, Dogs, and Wild Mammals in Small-Scale Farms of Central Chile.

Antibiotic-resistant bacteria of critical importance for global health such as extended-spectrum beta-lactamases-producing (ESBL)-Escherichia coli have been detected in livestock, dogs, and wildlife worldwide. However, the dynamics of ESBL-E. coli between these animals remains poorly understood, particularly in small-scale farms of low and middle-income countries where contact between species can be frequent. We compared the prevalence of fecal carriage of ESBL-E. coli among 332 livestock (207 cows, 15 pigs, 60 horses, 40 sheep, 6 goats, 4 chickens), 82 dogs, and wildlife including 131 European rabbits, 30 rodents, and 12 Andean foxes sharing territory in peri-urban localities of central Chile. The prevalence was lower in livestock (3.0%) and wildlife (0.5%) compared to dogs (24%). Among 47 ESBL-E. coli isolates recovered, CTX-M-group 1 was the main ESBL genotype identified, followed by CTX-M-groups 2, 9, 8, and 25. ERIC-PCR showed no cluster of E. coli clones by either host species nor locality. To our knowledge, this is the first report of ESBL-E. coli among sheep, cattle, dogs, and rodents of Chile, confirming their fecal carriage among domestic and wild animals in small-scale farms. The high prevalence of ESBL-E. coli in dogs encourages further investigation on their role as potential reservoirs of this bacteria in agricultural settings.

Escherichia coli y Klebsiella pneumoniae productoras de betalactamasas de espectro extendido en un hospital de La Habana

RESUMEN Introducción: En microorganismos gramnegativos la producción de enzimas betalactamasas es el mecanismo más común de resistencia. Las de espectro extendido constituyen un grupo importante por su capacidad de inactivar las cefalosporinas de tercera y cuarta generación y el aztreonam. Su detección es vital para indicar el tratamiento óptimo y las medidas de aislamiento que eviten la dispersión de los microorganismos que las portan. Objetivos: Determinar la incidencia y principales características de los aislados de Escherichiacoli y Klebsiellapneumoniae productores de betalactamasas de espectro extendido en muestras no urogenitales. Métodos: Estudio transversal realizado en el hospital "Salvador Allende" durante el año 2017. Se determinó la frecuencia de Escherichia coli y Klebsiella pneumoniae productoras de betalactamasas de espectro extendido, su procedencia según servicio del hospital, tipo de muestra clínica, y su sensibilidad antimicrobiana. La identificación de betalactamasas de espectro extendido se hizo por el método de doble disco de Jarlier. Resultados: Fueron productores de betalactamasas de espectro extendido 46 y 50 % de aislados de Escherichia coli y Klebsiella pneumoniae, respectivamente. La mayoría provenían de muestras de las salas del Instituto de Angiología, el antimicrobiano con mayor efectividad fue el meropenem, la sensibilidad al resto de los antimicrobianos estuvo por debajo de 80 % y no hubo aislados sensibles a las cefalosporinas de tercera generación. Conclusiones: Se demuestra una alta incidencia de aislados de Escherichia coli y Klebsiella pneumoniae productores de betalactamasas de espectro extendido en el Hospital "Salvador Allende" de La Habana, más marcada en las salas del Instituto de Angiología y en muestras de piel.

ABSTRACT Introduction: Beta-lactamase production is the most common resistance mechanism in gram-negative microorganisms. Extended-spectrum beta-lactamases are an important group of enzymes capable of inactivating third- and fourth-generation cephalosporins and aztreonam. Their detection is important to indicate the optimum treatment as well as isolation measures aimed at preventing the spread of carrier microorganisms. Objectives: Determine the incidence and main characteristics of isolates of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae from non-urogenital samples. Methods: A cross-sectional study was conducted at Salvador Allende hospital during the year 2017. Determination was made of the frequency of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae, their origin by hospital service, the type of clinical sample and their antimicrobial sensitivity. Identification of extended-spectrum beta-lactamases was based on the Jarlier double disc method. Results: Of the total Escherichia coli and Klebsiella pneumoniae isolates studied, 46% and 50%, respectively, were extended-spectrum beta-lactamase producers. Most had been obtained from samples taken in wards of the Institute of Angiology; the most effective antimicrobial was meropenem; sensitivity to the remaining antimicrobials was below 80%; no isolates were sensitive to third-generation cephalosporins. Conclusions: A high incidence was found of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates at Salvador Allende Hospital in Havana, more noticeably in Institute of Angiology wards and skin samples.

Factores de riesgo para infección del tracto urinario por microorganismos productores de betalactamasas de espectro extendido en niños en Huancayo, Perú / Risk factors for urinary tract infection by microorganisms producing extended spectrum beta-lactamase in children of Huancayo, Peru

Introducción: La infección del tracto urinario en los niños es una de las infecciones bacterianas más frecuentes con una alta tasa de recurrencia. Objetivo: Determinar los factores de riesgo para infección del tracto urinario adquirida en la comunidad por microorganismos productores de betalactamasas de espectro extendido en niños en Huancayo, Perú. Métodos: Estudio de tipo analítico con diseño de casos y controles. Se estudiaron 220 niños entre el mes de nacido hasta 13 años de edad, ingresados en el hospital nacional Ramiro Priale Priale con el diagnóstico de infección del tracto urinario durante el año 2019. Se distribuyeron en dos grupos (40 casos y 80 controles). Para cada paciente se llenó un cuestionario con las variables de interés y se realizó la comparación entre los grupos. Se realizó el análisis multivariado considerando significativo un valor de p< 0,05. Resultados: La frecuencia de infección del tracto urinario causada por microorganismos productores de betalactamasas de espectro extendido es de 18,18 por ciento. En los casos la edad predominante está entre 1 y 3 años con 42,5 por ciento, sexo femenino con 62,5 por ciento, la bacteria predominante es: Escherichia coli en 85,0 por ciento. Durante el análisis multivariado la presencia de infección del tracto urinario complicada tuvo OR 18,62 y p= 0,000 y la recurrente OR 12,98 y p= 0,004, ambas estadísticamente significativas para el desenlace de esta infección en los niños. Conclusión: Los factores de riesgo para infección del tracto urinario adquirida en la comunidad por microorganismos productores de betalactamasas de espectro extendido en niños son: infección del tracto urinario complicada y la recurrente(AU)

Introduction: Urinary tract infection in children is one of the most frequent bacterial infections with a high rate of recurrence. Objective: Determine the risk factors for community-acquired urinary tract infection by microorganisms producing extended-spectrum beta-lactamases in children of Huancayo, Peru. Methods: Analytical study with case-control design. 220 children from one month to 13 years of age were studied, whom were admitted to Ramiro Priale Priale National Hospital with the diagnosis of urinary tract infection during the year 2019. They were distributed in two groups (40 cases and 80 controls). For each patient, a questionnaire was completed with the variables of interest, and the comparison between the groups was made. The multivariate analysis was performed considering significant a value of p< 0.05. Results: The frequency of urinary tract infection caused by microorganisms producing extended-spectrum beta-lactamases is 18.18 percent. In the cases, the predominant age is between 1 and 3 years with 42.5 percent, female sex with 62.5 percent, the predominant bacterium is: Escherichia coli in 85.0 percent. During the multivariate analysis, the presence of complicated urinary tract infection had OR 18.62 and p= 0.000 and recurrent OR 12.98 and p= 0.004, both statistically significant for the outcome of this infection in children. Conclusion: The risk factors for community-acquired urinary tract infection by microorganisms producing extended-spectrum beta-lactamases in children are complicated and recurrent urinary tract infections(AU)

Factores de riesgo asociados a infecciones del tracto urinario por gérmenes productores de betalactamasas de espectro extendido / Risk factors associated with urinary tract infections by spectrum betalactamase producing germs extended

El tratamiento de las infecciones del tracto urinario requiere la constante actualización de la susceptibilidad in vitro de los gérmenes de la zona o institución que permita orientar la elección apropiada del tratamiento empírico. Objetivo: Identificar los factores de riesgo asociados a infecciones del tracto urinario por gérmenes productores de BLEE en pacientes hospitalizados en el Hospital Militar "Dr. Carlos Arvelo" con diagnóstico de infección del tracto urinario durante el periodo enero de 2015 y diciembre de 2019. Método: estudio retrospectivo, corte transversal, casos y controles. Tratamiento estadístico: Se calculó la razón de probabilidades de los factores de riesgo previamente establecidos. Los factores que demuestren asociación significativa en el análisis univariable serán incluidos en el modelo de regresión logística a fin de determinar los predictores independientes de infección por gérmenes productores BLEE. Resultados: Se evaluaron 283 pacientes, 161 con fenotipo de BLEE y 122 no BLEE. La edad mayor a 65 años (p =0,001; OR 1,059), infección del tracto urinario recurrente (p <0,001; OR 3,689), uso de antibióticos en los último 3 meses (p <0,001; OR 6,921), y sondaje vesical permanente mayor a 30 días (p <0,001; OR 6,801) fueron predictores independientes de ITU por bacterias productoras de BLEE. Conclusiones: Los factores de riesgo identificados en nuestro estudio ayudarán a guiar el reconocimiento de pacientes con alto riesgo de infección por estos organismos. Estos resultados sugieren la necesidad de revisión de los esquemas terapéuticos empíricos locales en el tratamiento de infecciones del tracto urinario, basándose en el riesgo de cada paciente(AU)

Urinary tract infections are an important cause of disease, its treatment requires the permanent update of in vitro antimicrobial susceptibility of the major germs of the institution to allow the appropriate choice of empirical treatment; Objective: To identify the risk factors associated with urinary tract infections caused by extended-spectrum beta-lactamases-producing germs in patients admitted at the Hospital Militar "Dr. Carlos Arvelo" with urinary tract infections between the january 2015 and december 2019. Methods: this is a retrospective study of a crosssectional cohort of cases and controls. Statistical Analysis: We also calculated adjusted odds ratios and 95% confidence intervals for target risk factors. Risk factors with significant association to ESBLs in the univariate analysis were included in a logistic regression model in order to determine independent forecasters of infections by ESBL-producing organisms. Results: Two hundred and eighty three patients were assessed: 161 with a phenotype of ESBL and 122 without ESBL. Ages over 65 years old (p =0,001; OR 1,059), regular urinary tract infection (p <0,001; OR 3,689), use of antibiotics in the last 3 months (p <0,001; OR 6,921), and permanent bladder catheterization for more than 30 days (p <0,001; OR 6,801) were independent forecasters of UTIs by ESBL-producing bacteria. Conclusions: the risk factors identified in our study will help guide the recognition of patients at high risk of infection by these organisms. These results suggest the need to review local empirical therapeutic schemes in the management of urinary tract infections, based on the odds of each patient of acquiring these bacteria(AU)

Epidemiology and antimicrobial susceptibility profiles of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichiacoli in China.

OBJECTS: The retrospective study aimed to determine the prevalence rate and antimicrobial susceptibility of extended-spectrum beta-lactamases (ESBLs)-producing Klebsiella pneumoniae and Escherichia coli in 2013-2017 at a single center in China. METHODS: Klebsiella pneumoniae and Escherichia coli data were collected from the microbiological laboratory. VITEK 2 compact system was used for the identification and antimicrobial susceptibility testing. ESBL status was determined as per the Clinical and Laboratory Standards Institute (CLSI) protocols microdilution method. RESULTS: Among a total of 2774 strains of Klebsiella pneumoniae and 2154 strains of Escherichia coli, 15.79% and 36.86% were found to be ESBL producers, respectively. In all patients infected by ESBLs-producing strains, those over 60 years accounted for the largest proportion. Infection by ESBLs-producing Klebsiella pneumoniae was more common in male, while that by ESBLs-producing Escherichia coli was more common in female. Urine and respiratory secretions were the most common sources of ESBLs-producing strains; however, ESBLs-producing strains from urine had been significantly declined. No carbapenem-resistant isolate was found, and all ESBLs-producing strains were resistant to ceftriaxone, aztreonam, and piperacillin. There were no differences in resistance rates between ESBLs-producing Escherichia coli and Klebsiella pneumoniae to ceftazidime and cefepime; however, ESBLs-producing Klebsiella pneumoniae showed higher resistance rates to piperacillin/tazobactam, amikacin, gentamicin, and co-trimoxazole compared with ESBLs-producing Escherichia coli. CONCLUSION: Different ESBLs-producing organisms have their own epidemiological characteristics, and the resistance of ESBLs-producing Klebsiella pneumoniae and Escherichia coli is different even to the same antibiotics. Therefore, it is important to continuously monitor the status of ESBLs-producing organisms, and an improved antimicrobial stewardship and infection control are much required.

Estudio teórico de compuestos derivados de cefalosporinas con potencial actividad inhibitoria frente a proteína de unión a penicilina (PBP) y resistencia a enzimas betalactamasa de espectro extendido (BLEE) producidas por Escherichia coli / Theoretical study of compounds derived from cephalosporins with inhibitory activity potential front to penicillin binding proteins (PBP) and resistance to Extended spectrum Beta-lactamase (ESBL) produced by Escherichia coli

RESUMEN Se han utilizado herramientas computacionales para proponer moléculas derivadas de cefalosporinas con potencial actividad antibacteriana, frente a cepas de Escherichia Coli, con mayor afinidad como inhibidores de enzimas de unión a penicilinas y que a su vez disminuyan o no tengan afinidad por betalactamasas de espectro extendido. Se diseñaron 20 moléculas con base en la estructura molecular de la cefalosporina, las estructuras fueron optimizadas utilizando la teoría del funcional de la densidad, se calcularon descriptores moleculares de reactividad, de forma paralela se sometieron a acoplamiento molecular con las enzimas antes mencionadas. Las moléculas presentaron valores de energía de unión negativos, doce moléculas mostraron una orientación e interacciones favorables en el sitio activo de la enzima de unión a penicilinas y trece moléculas presentaron menor afinidad que el ligando nativo (cefotaxima) por la betalactamasa. Tres moléculas pueden considerarse como potenciales inhibidores de enzimas de unión a penicilinas resistentes y betalactamasas.

SUMMARY Computational tools have been used to propose molecules derived from cephalosporins with potential antibacterial activity, against strains of Escherichia Coli, with higher affinity as inhibitors of penicillin-binding enzymes and which in turn decrease or do not have affinity for extended-spectrum beta-lactamases. 20 molecules were designed based on the molecular structure of the cephalosporin, the structures were optimized using the density functional theory, molecular descriptors of reactivity were calculated, and in parallel form they were subjected to molecular docking with the enzymes mentioned above. The molecules showed negative binding energy values, 12 molecules showed an orientation and favorable interactions in the active site of the penicillin binding enzyme and thirteen molecules had lower affinity than the native ligand (Cefotaxime) for betalactamase. Three molecules can be considered as potential inhibitors of binding enzymes to resistant penicillins and betalactamases.

Administración previa de antibiótico como factor asociado con infección urinaria por E. coli productora de BLEE de origen comunitario en pacientes diabéticos / Previous administration of antibiotic as factor related to urinary infection due to E. coli producers of ESBL of community origin in diabetic patients

Resumen ANTECEDENTES: las infecciones urinarias causadas por bacilos gramnegativos productores de betalactamasas de espectro extendido (BLEE) constituyen un problema mundial de salud pública. OBJETIVO: determinar si existe relación entre el tratamiento antibiótico previo y el desarrollo de E. coli BLEE al ingreso en pacientes con diabetes mellitus tipo 2. MATERIAL Y MÉTODO: estudio piloto de tipo transversal, analítico, en el que se revisaron los casos de infección de vías urinarias en pacientes diabéticos atendidos en el Nuevo Sanatorio Durango. Se compararon dos grupos según el resultado del urocultivo de ingreso. Se recolectaron datos tomando en cuenta el antecedente de tratamiento antibiótico, cifra de hemoglobina glucosilada (Hb1Ac), antecedente de hospitalización, si había antecedente de catéter urinario (sonda Foley) y diagnóstico de enfermedad renal crónica. RESULTADOS: se incluyeron 103 pacientes: 49 con E. coli y 54 con E. coli BLEE. Se encontró mayor asociación con infecciones urinarias productoras de BLEE en individuos de 68 ± 14.04 años en comparación con la edad de 49 ± 12 años en los sujetos con infecciones urinarias no productoras de BLEE. Se calculó razón de momios para cada uno de los rubros, se encontró asociación estadísticamente significativa por medio de X2 (p<0.05) calculando una razón de momios de 10.2 para el antecedente de administración de antibiótico y de 2.97 para el diagnóstico de enfermedad renal crónica y para el aislamiento de E. coli productora de BLEE. CONCLUSIÓN: existe asociación de la administración previa de tratamiento antibiótico y la existencia de enfermedad renal crónica con el aislamiento E. coli BLEE en infecciones adquiridas en la comunidad en pacientes diabéticos.

Abstract BACKGROUND: Urinary tract infections caused by gram-negative bacilli producers of extended-spectrum beta-lactamases (ESBL) are a global public health problem. MATERIAL AND METHOD: An analytical, cross-sectional, pilot study was carried out in Nuevo Sanatorio Durango, Mexico City, in which the cases of urinary tract infection in diabetic patients were reviewed. Two groups were compared depending on the result of the urinary culture. Data were collected taking into account the antecedent of antibiotic treatment, glycosylated hemoglobin (Hb1Ac), history of hospitalization, history of urinary catheter (Foley catheter) and diagnosis of chronic kidney disease. RESULTS: There were included 103 patients, divided according to the result of the urinary culture: E. coli (n = 49) and E. coli ESBL (n = 54). We found a greater association with ESBL-producing urinary tract infections in individuals aged 68 ± 14.04 years. We calculated odds ratios for each of the items, finding a statistically significant association by means of X2 test (p < 0.05), calculating an OR of 10.2 with the antecedent of antibiotic use and a OR of 2.97 with the diagnosis of chronic kidney disease, when there was isolation of E. coli producing ESBL. CONCLUSION: There is an association between the use of antibiotic treatment and the presence of chronic kidney disease with E. coli ESBL isolation in community-acquired infections in diabetic patients.

First report of TEM-104-, SHV-99-, SHV-108-, and SHV-110-producing Klebsiella pneumoniae from Iran

Abstract: INTRODUCTION: Extended-spectrum beta-lactamases (ESBLs) are bacterial enzymes capable of hydrolyzing beta-lactams. The aim of this study was to describe the prevalence of TEM- and SHV-type ESBL-producing Klebsiella pneumoniae strains in Zahedan, Southeast Iran. METHODS: A total of 170 non-repetitive K. pneumoniae strains were collected from patients referred to three teaching hospitals of Zahedan. Antibiotic susceptibility testing was determined for 17 antibiotics using the Kirby-Bauer disc diffusion method. The frequency of ESBL-producing strains was calculated, and minimum inhibitory concentrations of ESBL-producing strains were determined for cefotaxime, ceftazidime, ceftriaxone, and cefpodoxime. The presence of bla TEM and bla SHV genes was tested in all ESBL-producing strains using polymerase chain reaction and DNA sequencing. RESULTS: Among the 170 K. pneumoniae clinical isolates, 55 (32.4%) were ESBL producers; 92.7% (n=51) and 72.7% (n=40) of the isolates carried the bla SHV and bla TEM genes, respectively, and 67.3% (n=37) carried both genes. The sequencing results showed that all bla TEM types were bla TEM-1, except for two isolates that were bla TEM-104. The bla SHV types were bla SHV-1, bla SHV-11, bla SHV-12, bla SHV-99, bla SHV-108, and bla SHV-110. CONCLUSIONS: The percentage of bla TEM and bla SHV among ESBL-producing K. pneumoniae isolates from Zahedan is relatively high, indicating the need for further surveillance and consideration in antibiotic use. To the best of our knowledge, this is the first report of TEM-104-, SHV-99-, SHV-108-, and SHV-110-type ESBLs among clinical isolates of K. pneumoniae from Iran, and TEM-1, SHV-1, SHV-11, and SHV-12 appear to be the dominant ESBLs in this region.