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.

Multidrug resistance and risk factors associated with community-acquired urinary tract infections caused by Escherichia coli in Venezuela / Multirresistencia a medicamentos y factores de riesgo asociados con infecciones urinarias por Escherichia coli adquiridas en la comunidad, Venezuela

Abstract Introduction: The treatment of urinary tract infections has become more challenging due to the increasing frequency of multidrug-resistant Escherichia coli in human populations. Objective: To characterize multidrug-resistant E. coli isolates causing community-acquired urinary tract infections in Cumaná, Venezuela, and associate possible risk factors for infection by extended-spectrum beta-lactamases (ESBL)-producing isolates. Materials and methods: We included all the patients with urinary tract infections attending the urology outpatient consultation and emergency unit in the Hospital de Cumaná, Estado Sucre, Venezuela, from January through June, 2014. blaTEM, blaSHV and blaCTX-M genes detection was carried out by PCR. Results: We found a high prevalence of multidrug-resistant E. coli (25.2%) with 20.4% of the isolates producing ESBL. The ESBL-producing isolates showed a high frequency (66.7%) of simultaneous resistance to trimethoprim-sulphamethoxazole, fluoroquinolones and aminoglycosides compared to non-producing isolates (2.4%). Of the resistant isolates, 65.4% carried the blaTEM gene, 34.6% the blaCTX-M and 23.1% the blaSHV. The blaCTX-M genes detected belonged to the CTX-M-1 and CTX-M-2 groups. Plasmid transfer was demonstrated by in vitro conjugation in 17 of the 26 ESBL-producing isolates. All three genes detected were transferred to the transconjugants. Age over 60 years, complicated urinary tract infections and previous use of a catheter predisposed patients to infection by ESBL-producing E. coli. Conclusions: The high frequency of multidrug-resistant ESBL-producing isolates should alert the regional health authorities to take measures to reduce the risk of outbreaks caused by these types of bacteria in the community.

Resumen Introducción. El tratamiento de las infecciones urinarias constituye un reto creciente por el aumento de Escherichia coli proveniente de la comunidad multirresistente a los medicamentos. Objetivo. Caracterizar aislamientos de E. coli multirresistente causantes de infecciones urinarias adquiridas en la comunidad en Cumaná, Venezuela, y detectar los posibles riesgos de infección por aislamientos productores de betalactamasas de espectro extendido (BLEE). Materiales y métodos. Se incluyeron todos los pacientes atendidos en la consulta externa de urología y en urgencias del Hospital de Cumaná entre enero y junio de 2014 y que evidenciaban infecciones urinarias. La detección de los genes blaTEM, blaSHV y blaCTX-M se hizo mediante la reacción en cadena de la polimerasa (PCR). Resultados. Se encontró una alta prevalencia de E. coli multirresistente a los medicamentos (25,2 %), con 20,4 % de aislamientos productores de BLEE y una gran frecuencia de resistencia simultánea a trimetoprim-sulfametoxazol, fluoroquinolonas y aminoglucósidos (66,7 %) comparados con los no productores (2,4 %). En el 65,4 % de los aislamientos resistentes, se encontró el gen blaTEM; en 34,6 %, el blaCTX-M, y en 23,1 %, el blaSHV. Los genes blaCTX-M detectados pertenecían a los grupos CTX-M-1 y CTX-M-2. Se demostró la transferencia in vitro de plásmidos por conjugación en 17 de los 26 aislamientos productores de BLEE. Los tres tipos de genes detectados se transfirieron a los transconjugantes. La edad mayor de 60 años, las infecciones urinarias con complicaciones y el uso previo de catéter, predispusieron a la infección por cepas de E. coli productoras de BLEE. Conclusiones. La gran frecuencia de aislamientos multirresistentes productores de BLEE debería alertar a las autoridades sanitarias para tomar medidas que reduzcan el riesgo de epidemias causadas por este tipo de bacterias en la comunidad.

Evaluación de susceptibilidad y respuesta al tratamiento con piperacilina/tazobactam en pacientes con infecciones por Escherichia coli productoras de β -lactamasas de espectro extendido (BLEE) CTX-M / Evaluation of susceptibility and response to therapy with piperacillin-tazobactam in patients with infections caused by Escherichia coli with extended-spectrum β -lactamase (ESBL) CTX-M

Resumen Introducción: En las infecciones por enterobacterias productoras de β-lactamasas de espectro extendido (BLEE), los β-lactámicos preferidos para tratamiento son los carbapenémicos. Sin embargo, estudios clínicos muestran eficacia de piperacilina/tazobactam en ciertas infecciones por Escherichia coli productoras de BLEE. Objetivo: Determinar la cura clínica y microbiológica con piperacilina/tazobactam en pacientes con infecciones por E. coli productoras de BLEE, tipo CTX-M. Materiales/Métodos: Estudio descriptivo, retrospectivo, con adultos internados en un hospital universitario. Incluimos infecciones del tracto urinario (ITU), intra-abdominales (IIA) e infecciones de tejidos blandos (ITB). Resultados: Estudiamos 40 pacientes, donde 65% correspondían a ITU, 25% IIA y 10 % ITB. La cura clínica global se logró en 89,4%, con mejores resultados en las ITU (100%), seguidas de ITB (80%) e IIA (70%). El 85% de las cepas tenía concentraciones inhibitorias mínimas (CIM) ≤ 8 μg/mL y 70% con CIM ≤ 4 μg/mL. La tasa de fracaso fue mayor en las infecciones con inóculos altos intraabdominales. La BLEE del tipo CTX-M-15 se encontró en 62,5%. Conclusiones: Piperacilina/tazobactam logró cura clínica y microbiológica, en pacientes con infecciones por E. coli productoras de BLEE susceptibles, especialmente en ITU e IPB y en menor medida en IIA.

Background: Carbapenems are the preferred β-lactamics for treatment for infections caused by enterobacteria producing extended-spectrum β-lactamases (ESBL); however, clinical studies show effectiveness of piperacillin/tazobactam in certain infections by Escherichia coli ESBL producers. Aim: To determine the clinical and micro-biological cure with piperacillin/tazobactam in patients with infections caused by E. coli ESBL producers, CTXM type. Methods: Retrospective descriptive study with adults hospitalized in a university hospital. We included urinary tract infections (UTI), intra-abdominal infections (IAI), soft tissue infections (STI) and/or bacteremia. Results: We studied 40 patients, where 65% corresponded to UTI, 25% to IAI and 10% were STI. The overall clinical cure was achieved in 89.4%, with the best results in the ITU (100%), followed by STI (80%) and 70% in IAI. The 85% of the strains had minimum inhibitory concentrations (MIC) ≤8 μg/ml and 70% with MIC ≤4 μg/mL, however the rate of failure were high in intra-abdominal infections with high inocula or not controlled; CTX-M-15 was found in the 62.5%. Conclusions: Piperacillin/tazobactam was efficient to obtain clinical and microbiological cure in patients with infections caused by ESBL producers but susceptible E. coli, especially in UTI and STI and to a lesser extent in IAI.

Factores predictores de mortalidad intrahospitalaria en pacientes adultos con infecciones por Klebsiella pneumoniae resistente a carbapenémicos y colistín: un estudio de cohorte retrospectivo / Risk factors for in-hospital mortality among adult patients infected with colistin-resistant carbapenemase producing Klebsiella pneumoniae: a retrospective cohort study

Resumen Introducción: La emergencia de Klebsiella productora de carbapenemasas resistente a colistín representa un desafío clínico y un problema emergente. Objetivo: Evaluar la mortalidad intrahospitalaria y sus potenciales factores de riesgo en pacientes internados con infecciones clínicas por Klebsiella pneumoniae productora de carbapenemasas (KPC) resistente a colistín. Material y Método: Realizamos un estudio de cohorte retrospectivo, incluyendo pacientes adultos admitidos a un hospital universitario de tercer nivel en Buenos Aires, infectados por KPC resistente a colistín. El evento primario considerado fue la mortalidad intrahospitalaria. Se utilizaron modelos generalizados lineales para evaluar potenciales predictores de dicho evento. Resultados: En total, se identificaron 18 pacientes hospitalizados que presentaron una infección clínica por esta bacteria durante el año 2016 y que fueron incluidos en el análisis final. La mortalidad intrahospitalaria en esta cohorte fue de 38,9%. La presencia de bacteriemia, la injuria renal aguda al momento del diagnóstico y la presencia de shock séptico se asociaron a la ocurrencia del evento primario. Conclusión: El desarrollo de infecciones clínicamente relevantes por KPC resistente a colistín en pacientes internados es frecuente y presenta una elevada mortalidad. En nuestra cohorte, la presencia de shock e injuria renal aguda al momento del diagnóstico se asociaron a un incrementado riesgo de mortalidad intrahospitalaria. Futuras investigaciones deberían corroborar estos hallazgos e investigar factores adicionales que permitan identificar tempranamente a aquellos pacientes que presentarán eventos desfavorables.

ABSTRACT Background: The emergence of colistin resistant carbapenemase-producing Klebsiella represents a therapeutic challenge and a worldwide problem. Aim: To estimate the in-hospital mortality and identify the associated risk factors among patients with colistin-resistant carbapenemase-producing Klebsiella pneumoniae (KPC) that present with a clinical infection. Methods: We carried a retrospective cohort study, including adult patients infected with colistin-resistant KPC hospitalized at a tertiary teaching hospital in Buenos Aires, Argentina during the year 2016. The main outcome was in-hospital mortality. We used generalized lineal models to evaluate potential predictors of mortality. Results: 18 patients that developed a colistin-resistant KPC clinical infection were identified and included in the final analysis. In-hospital mortality in this cohort was 38.9%. The presence of bacteremia, acute renal injury at the time of diagnosis and septic shock were associated with the main outcome. Conclusions: Infections due to colistin-resistant KPC among in-hospital patients was frequent and was associated with high mortality rate. In our cohort, both shock and acute kidney injury were associated with a higher likelihood of poor outcomes. Further studies are warranted to evaluate the role of these and others risk factors so as to aid in the early detection of high risk patients.

Factores de riesgo para el desarrollo de infección de vías urinarias por microorganismos productores de betalactamasas de espectro extendido adquiridos en la comunidad, en dos hospitales de Bogotá D.C. Colombia / Risk factors for the development of community-acquired urinary tract infection, by extended-spectrum beta-lactamase producing microorganisms, at two hospitals in Bogotá, Colombia

Objetivo: Determinar factores de riesgo para infección urinaria por microorganismos productores de betalactamasas de espectro extendido (BLEE) adquirida en la comunidad en pacientes adultos. Material y método: Estudio de casos y controles, en el período comprendido entre enero de 2012 a mayo de 2015, en dos hospitales de Bogotá D.C., Colombia. Pareo por edad, año del aislamiento, microorganismo y género. Se excluyeron pacientes con antecedente de infección por un microorganismo productor de BLEE en el último mes e infección urinaria asociada al cuidado de la salud. Resultados: Se analizaron 555 pacientes: 185 casos y 370 controles. 462 pacientes (83,2%) de la Fundación Clínica Shaio y 93 (16,8%) del Hospital Santa Clara. Factores de riesgo identificados: Infección urinaria recurrente (OR 2,13 con IC de 1,48 a 3,07), enfermedad renal crónica (OR 1,56, IC del 95% de 1,07 a 2,27), uso previo de antibióticos (OR 3,46, IC del 95% de 2,48 a 5,35), hospitalización reciente (OR 3,0, IC del 95% de 1,96 a 2,45), diabetes mellitus (OR 1,61 con IC del 95% de 1,06 a 2,45) e infección urinaria alta (OR 2,64 con IC del 95% de 1,61 a 4,32). Conclusiones: Los factores de riesgo para microorganismos productores de BLEE adquiridos en la comunidad fueron en orden de frecuencia: antecedente de antibioticoterapia reciente, hospitalización previa, presencia de infección urinaria alta, así como los antecedentes de infección urinaria recurrente, enfermedad renal crónica y diabetes mellitus, lo que concuerda con los principales hallazgos descritos en la literatura mundial.

Aims: To determine risk factors for the development of community-acquired urinary tract infection, by extended-spectrum beta-lactamase producing microorganisms, in adult patients. Materials and methods: A case-control study in the period from January 2012 to May 2015, in two hospitals in Bogota, Colombia. Matching for age, year of isolation, microorganism and gender. We excluded patients with a history of infection with extended-spectrum beta-lactamase producing microorganisms in the last month and urinary infection associated with health care. Results: 555 patients were analyzed.185 cases and 370 controls. 462 patients (83.2%) from Fundación Clínica Shaio and 93 (16.8%) from Hospital Santa Clara. Identified risk factors: recurrent urinary tract infection (OR= 2.13, 95% CI= 1.48 - 3.07), chronic kidney disease (OR= 1.56, 95% CI= 1.07 - 2.27), previous use of antibiotics (OR= 3.46, 95% CI= 2.48 - 5.35), recent hospitalization (OR= 3.0, 95% CI= 1.96 to 2.45), diabetes mellitus (OR= 1.61, 95% CI= 1.06 - 2.45) and upper urinary tract infection (OR= 2.64, 95% CI= 1.61 - 4.32). Conclusions: The risk factors community-acquired urinary tract infection, by extended-spectrum beta-lactamase producing microorganisms, were in order of frequency: history of recent antibiotic therapy, prior hospitalization, the presence of high urinary infection, history of recurrent urinary tract infection, chronic kidney disease and diabetes mellitus. The described risk factors are consistent with the main findings described in the literature.

Carbapenem-resistant Pseudomonas aeruginosa: association with virulence genes and biofilm formation

Abstract Pseudomonas aeruginosa is an opportunistic pathogen that causes frequently nosocomial infections, currently becoming more difficult to treat due to the various resistance mechanisms and different virulence factors. The purpose of this study was to determine the risk factors independently associated with the development of bacteremia by carbapenem-resistant P. aeruginosa, the frequency of virulence genes in metallo-β-lactamases producers and to evaluate their ability to produce biofilm. We conducted a case–control study in the Uberlândia Federal University – Hospital Clinic, Brazil. Polymerase Chain Reaction was performed for metallo-β-lactamases and virulence genes. Adhesion and biofilm assays were done by quantitative tests. Among the 157 strains analyzed, 73.9% were multidrug-resistant, 43.9% were resistant to carbapenems, 16.1% were phenotypically positive for metallo-β-lactamases, and of these, 10.7% were positive for blaSPM gene and 5.3% positive for blaVIM. The multivariable analysis showed that mechanical ventilation, enteral/nasogastric tubes, primary bacteremia with unknown focus, and inappropriate therapy were independent risk factors associated with bacteremia. All tested strains were characterized as strongly biofilm producers. A higher mortality was found among patients with bacteremia by carbapenem-resistant P. aeruginosa strains, associated independently with extrinsic risk factors, however it was not evident the association with the presence of virulence and metallo-β-lactamases genes.

Caracterización clínica de infecciones de vías urinarias producidas por enterobacterias productoras de betalactamasas de espectro extendido en Duitama (Colombia), durante 2010-2015 / Clinical characterisation of urinary tract infections produced by extended-spectrum beta-lactamase-producing enterobacteria in Duitama (Colombia) from 2010-2015

Objetivo: Caracterizar las infecciones de vías urinarias (IVU) producidas por enterobacterias productoras de betalactamasas de espectro extendido (BLEE) en Duitama (Colombia) durante 2010-2015. Metodología: Se realizó un estudio descriptivo en 2 instituciones prestadoras de salud a partir de los aislamientos de patógenos BLEE asociados a IVU. Se tomaron variables sociodemográficas, comorbilidades, hospitalizaciones por IVU en el último año, agentes aislados, tratamiento empírico y dirigido, y respuesta clínica. Resultados: Se obtuvo un registro de 169 pacientes, con edad promedio de 66,01 ± 19,19; el 55,62% eran mayores de 65 años; el 59,2% eran de género femenino y el 73,6% provenían del área urbana. Las comorbilidades más frecuentes fueron enfermedad pulmonar obstructiva crónica (26%), diabetes (24,9%) y enfermedad renal crónica (16%), con un índice de Charlson de 4,43 ± 2,61. El 61,6% había sido hospitalizado en el último año a causa de IVU. Los agentes aislados más comunes fueron Escherichia coli (94,7%) y Klebsiella spp. (2,4%). Los tratamientos empíricos usados fueron ampicilina/sulbactam (15%), ciprofloxacino (29,6%) y nitrofurantoína (10,7%). Frente al tratamiento dirigido, el 36,7% no recibió ningún escalonamiento, el 32% fue tratado con ertapenem y el 8,9% con piperacilina/tazobactam. La mortalidad fue del 5,9% y la estancia hospitalaria fue en promedio de 7,24 ± 7,43 días. Conclusión: Los datos regionales son similares a los datos mundiales. Frente al tratamiento empírico se debe realizar una revaloración, ya que las guías actuales no recomiendan el uso de ciprofloxacino. También se debe hacer mejor seguimiento a las BLEE, ya que hay fallas en cuanto al tratamiento dirigido en gran porcentaje de las cepas.

Objective: To characterise epidemiologically urinary tract infections (UTI) caused by extended-spectrum betalactamase producing (ESBL)-producing Enterobacteriaceae in Duitama (Colombia) from 2010-2015. Methodology: A descriptive study was conducted on ESBL isolates of pathogens associated with UTI in 2 health institutions. Sociodemographic variables, comorbidities, hospitalisations in the last year for UTI, isolated agents, empirical and directed treatment, and clinical response were recorded. Results: A total of 169 patients were included, with an average age of 66.01 ± 19.19; 55.62% were over 65; 59.2% were female and 73.6% were from an urban area. The most frequent comorbidities were chronic obstructive pulmonary disease in 26%; 24.9% had diabetes and 16% had chronic kidney disease, with a Charlson index of 4.43 ± 2.61. Some 61.6% had been hospitalised in the last year due to UTIs. The most common isolated agents were Escherichia coli in 94.7% and Klebsiella spp. in 2.4%. The empirical treatments used were ampicillin/sulbactam in 15%, ciprofloxacin in 29.6% and nitrofurantoin in 10.7%. Regarding directed treatment, 36.7% do not have des-escalation, 32% of patients were treated with ertapenem and 8.9% were treated with piperacillin/tazobactam. Mortality was 5.9% and the average hospital stay was 7.24 ± 7.43 days. Conclusion: Regional data are similar to global data. Empirical treatment should be revaluated, since current guidelines do not recommend the use of ciprofloxacin. In addition, better tracking of ESLB is needed due to flaws in empirical treatment for a large percentage of the strains.

Factores asociados a infecciones urinarias producidas por enterobacterias productoras de β -lactamasas de espectro extendido: una cohorte prospectiva / Factors associated with extended-spectrum betalactamases-producing organisms among patients with urinary tract infections: a prospective cohort study

Background: Urinary tract infections (UTIs) caused by extended-spectrum betalactamases (ESBL) are an increasingly common problem. Aim: To develop an association model to allow an early detection of ESBL-producing microorganisms. Methods: A prospective observational cohort study was undertaken among patients admitted with a diagnosis of culture-proven UTI to the Internal Medicine Ward of the Hospital Naval Almirante Nef between February and November, 2011. Patients with polimicrobial cultures were excluded from analyses, which was undertaken using multiple logistic regression. Results: Two-hundred and forty-nine patients were analysed and 35 (14%) presented an ESBL-producing microorganism. Seventy-one percent were female and the mean age was 70,7 ± 16,9 years. A history of a recent hospitalization (< 3 months) or institutionalization (p = 0.027), previous infections by an ESBL-producing bacteria (p < 0.001), recent antimicrobial use (p = 0.013) and metastatic cancer (p = 0.007) were independently associated with a current UTI with an ESBL-producing pathogen. Discussion: Our findings are similar to those found in other populations. This tool offers assistance to clinicians who need to choose an appropriate antimicrobial therapy. This model needs to be validated prior to implementation.

Introducción: La infección del tracto urinario (ITU) por microorganismos productores de β-lactamasas de espectro extendido (BLEE) es un problema infectológico creciente. Objetivo: Determinar factores de riesgo predisponentes a infecciones por microorganismos productores de BLEE. Pacientes y Método: Cohorte prospectiva de pacientes > 18 años ingresados al Servicio de Medicina Interna del Hospital Naval Almirante Nef de Viña del Mar desde febrero a noviembre de 2011 con diagnóstico de ITU confirmado en un urocultivo. Se excluyeron pacientes con urocultivos polimicrobianos. El análisis se hizo mediante una regresión logística múltiple. Resultados: Se analizaron 249 pacientes, 35 (14%) presentaron un microorganismo productor de BLEE. El 71% fueron mujeres y la edad promedio 70,7 ± 16,9 años. El antecedente de hospitalización en los últimos tres meses o el vivir institucionalizado (p = 0,027), la infección por bacteria productora de BLEE previa (p < 0,001), el uso de antimicrobianos recientes (p = 0,013) y el antecedente de cáncer metastásico (p = 0,007) se asociaron a la producción de BLEE. Discusión: Los factores encontrados en la presente cohorte están de acuerdo a lo descrito en otras poblaciones. Esta herramienta ofrece asistencia para el médico clínico en la selección de la antibioterapia más apropiada. Es necesario validar este modelo previo a su implementación.

Successful treatment of lower urinary tract infections with oral fosfomycin: a report of three cases

Infections due to multidrug-resistant organisms continue to increase, and therapeutic options remain scarce. Given this challenge, it has become necessary to use older antimicrobials for treatment of these pathogens. We report three patients with lower urinary tract infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae who were successfully treated with a seven-day course of oral fosfomycin monotherapy.

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.

Klebsiella ESBL bacteremia-mortality and risk factors

Background: Extended spectrum β-lactamase (ESBL)-producing bacteria have become recognized as a problem in South America. The aim of this study was to evaluate risk factors and mortality rate in bacteremia caused by ESBL-producing Klebsiella pneumoniae in a Brazilian hospital. Methods: A three-year retrospective cohort study with 104 cases of K. pneumoniae bacteremia (61 ESBL and 43 non-ESBL). Several clinical and laboratory variables were evaluated. The outcome of interest was 30-day mortality. The adequate treatment was evaluated according to antibiotic susceptibility. Results: Multivariable analysis showed that central venous catheter and mechanical ventilation were independent risk factors for ESBL. The duration of hospitalization before the bacteremia was not a risk factor. Mortality was similar in ESBL and non-ESBL and inadequate therapy was not shown to be a risk factor. Conclusion: ESBL-producing Klebsiella bacteremia can occur early, suggesting that a carbapenem should be included in the initial empirical therapy for bacteremia in patients under mechanical ventilation and/or central venous catheter in our institution.

Epidemiology of extended spectrum β-lactamase producing Enterobacter bacteremia in a brazilian hospital / Epidemiologia de bacteremia causadas por Enterobacter produtores de β-lactamases de espectro estendido em um hospital brasileiro

INTRODUCTION: Enterobacter can be included in the group of extended spectrum β-lactamases (EBSL)-producing bacteria, though few studies exist evaluating risk factors associated with this microorganism. A retrospective cohort study was conducted to determine risk factors associated with ESBL-producing-Enterobacter and mortality METHODS: A retrospective cohort study with 58 bacteremia caused by ESBL-producing-Enterobacter (28 cases) and non-ESBL (30 cases) RESULTS: Risk factors associated with ESBL-Enterobacter were trauma, length of hospitalization, admission to the intensive care unit, urinary catheter and elective surgery (p< 0.05). The survival curves were similar for ESBL and non-ESBL CONCLUSIONS: ESBL-producing-Enterobacter bacteremia is prevalent and the survival curve was similar to non-ESBL-producing strains.

INTRODUÇÃO: Enterobacter pode ser incluído no grupo de bactérias produtoras de β-lactamases de espectro estendido (ESBL), mas existem poucos estudos avaliando fatores de risco para ESBL. Nós realizamos uma coorte retrospective para determiner fatores de risco associados com Enterobacter produtores de ESBL MÉTODOS: Uma coorte retrospectiva com 58 bacteremias por Enterobacter ESBL (28 casos) e não-ESBL (30 casos) RESULTADOS: Fatores de risco para ESBL-Enterobacter foram trauma, tempo de internação, admissão em UTI, sonda vesical e cirurgia eletiva (p<0.05). A mortalidade foi similar entre ESBL e não-ESBL CONCLUSÕES: Enterobacter produtor de ESBL é prevalente e a curva de mortalidade foi semelhante com o grupo não-ESBL.

Bloodstream infections caused by ESBL-producing E. Coli and K. pneumoniae: risk factors for multidrug-resistance

This prospective case-control study was conducted from October 2003 to June 2007 to evaluate risk factors for multidrug resistance among extended-spectrum-b-lactamase-producing Escherichia coli and Klebsiella spp. (ESBL-EK) isolates in blood cultures. All adult patients (>18 years old) whose blood cultures grew ESBL-EK during the study period were included. An ESBL-EK isolate was defined as MDR if it was resistant to at least one member of following two classes of antibiotics: aminoglycosides (amikacin, gentamicin, or netilmycin) and fluoroquinolones (ofloxacin, or ciprofloxacin). Case patients were those with a MDR ESBL-EK isolate, and control patients were those with a non-MDR ESBL-EK isolate. A total of 94 bloodstream infections, including 37 (39,4 percent) bloodstream infections with ESBL-producing E. coli and 57 (60,6 percent) with ESBL-producing K. pneumoniae,in 86 patients were enrolled. Thirty episodes (31.9 percent) were due to MDR ESBL-EK. The only independent risk factor for MDR ESBL-EK was duration of hospitalization before bacteraemia (OR 3.88; 95 percent CI 1.55-9.71; p=0.004). The rate of multidrug resistance among ESBL-EK bloodstream isolates was high, and duration of hospitalization before bacteraemia was the only indeepended risk factor for the MDR ESBL-EK bloodstream infections.

Evaluación y manejo del adulto inmunocompetente hospitalizado por neumonía adquirida en la comunidad, en un hospital de baja complejidad, basado en la Guía Clínica Chilena / Management of community acquired pneumonia in adults following clinical guidelines at a rural hospital

Background: A National Consensus Guideline published in 2005 established the basis for the diagnostic, severity assessment and treatment of community acquired pneumonia (CAP) in the adult population. The compliance with pneumonia clinical guidelines has been associated to a reduction in hospital stay healthcare-related costs, morbidity and mortality. Aim To describe the management and outcome of non-severe CAP in hospitalized adult patients treated in a rural hospital, based on the national clinical guidelines. Patients and methods: Ninety six patients aged 74 ± 13 years (50 males) hospitalized with non-severe pneumonia (group 3) at a community-based primary care center between January 1, 2006, and March 31, 2007, were evaluated. Results: Eighty percent of patients had concomitant diseases such as hypertension in 49 percent, diabetes in 23 percent and chronic obstructive pulmonary disease in 18 percent. All were treated with a third generation cephalosporin (ceftriaxone 1-2 g/day TV) as empirical therapy. Only 9 percent of patients also received a macrolide. Early switch to oral antimicrobial therapy was successful in two third of cases. Mean hospital length of stay was 5.0 ± 2.5 days, and 30-day mortality was 6.3 percent. Conclusions: Following the recommendations of the national clinical guidelines, most of these patients had a favorable response to monotherapy with a B-lactam antimicrobial. Early switch therapy to oral antibiotic was effective and safe, reducing significantly hospital length of stay as compared to previous national clinical studies.

Betalactámicos con inhibidores de betalactamasas: Amoxicilina-sulbactam / Betalactam antibiotics combined with bectalactamases inhibitors: Amoxicillin-sulbactam

La producción de betalactamasas constituye uno de los principales mecanismos de resistencia bacteriana a los antibióticos betalactámicos. La utilización de inhibidores de betalactamasas en combinación con antibióticos betalactámicos permite la inactivación de determinadas betalactamasas producidas por gérmenes Gram positivos, Gram negativos, anaerobios, y aun por micobacterias. Los inhibidores de betalactamasas representan una alternativa terapéutica mejorada respecto del resto de los betalactámicos al asegurar, en la mayoría de los casos, un mayor espectro antimicrobiano comparado con el de sus análogos. La actividad enzimática de las betalactamasas está dirigida específicamente a la hidrólisis del anillo betalactámico, con producción de un compuesto sin actividad antibacteriana. De acuerdo con su posición genómica dentro de los microorganismos, las betalactamasas pueden ser cromosómicas o plasmídicas. Actualmente existen tres inhibidores de betalactamasas localmente disponibles: ácido clavulánico, sulbactam y tazobactam. De ellos, sólo el sulbactam posee actividad antimicrobiana intrínseca sobre las proteínas ligadoras de penicilina. La experiencia clínica acumulada durante más de 20 años confirma que las combinaciones de betalactámicos-inhibidores de betalactamasas son efectivas en el tratamiento empírico inicial de infecciones respiratorias, intraabdominales, urinarias y ginecológicas, incluidas las de origen polimicrobiano. En el caso particular de amoxicilina-sulbactam, la evidencia citada indica que esta combinación es efectiva para el tratamiento de absceso periamigdalino, otitis media, sinusitis, neumonía extrahospitalaria, exacerbación aguda de enfermedad pulmonar obstructiva crónica (EPOC), infección del tracto urinario e infecciones ginecoobstétricas. Por su espectro y propiedades farmacológicas, la combinación amoxicilina-sulbactam constituye una excelente opción también para el tratamiento de infecciones de piel y partes blandas e infecciones intraabdominales.

Betalactamases production is one of the main bacterial resistance mechanisms to betalactam antibiotics. The use of bectalactamases inhibitors combined with betalactam antibiotics allows the inactivation of certain betalactamases produced by Gram positive, Gram negative and anaerobic organisms, and even by mycobacteria. Betalactamases inhibitors are an improved therapeutic alternative compared with the other betalactam since, in most cases, they cover a wider antimicrobial spectrum than their analogues. Betalactamases enzimatic activity is specifically directed to the betalactam ring hydrolisis, producing a compound without antibacterial activity. According to their genomic position within microorganisms, betalactamases can be either chromosomic or plasmidic. Currently there are three betalactamases inhibitors locally available: clavulanic acid, sulbactam and tazobactam. Of them, only sulbactam has an intrinsic antimicrobial activity against penicillin binding proteins. The clinical experience from over 20 years confirms that the combination of betalactam antibiotics is effective in the empirical initial treatment of respiratory, intraabdominal, urinary tract and gynecologic infections, including those of polymicrobial origin. In the specific case of amoxicillin-sulbactam, experiences have shown the effectiveness of the combination in the treatment of peritonsillar abscess, otitis media, sinusitis, community acquired pneumonia, acute exacerbation of chronic obstructive pulmonar disease (COPD), urinary tract infection and obstetric/ gynecologic infections. The spectrum and pharmacologic properties of this combination makes it also an excellent option for the treatment of skin/soft tissue and intraabdominal infections.

Risk factors for infection by extended-spectrum beta-lactamase producing Klebsiella pneumoniae in a tertiary hospital in Salvador, Brazil

Nosocomial infection caused by extended-spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-Kp) have been frequently reported worldwide. We have no information on such problems in Bahia, Brazil. OBJECTIVES: Evaluate the risk factors for nosocomial infections caused by ESBL-Kp, in a tertiary hospital, in Bahia, Brazil. MATERIAL AND METHODS: We evaluated all reported cases of nosocomial infections caused by ESBL-Kp in a private, tertiary hospital, in Salvador, Brazil, from 2000 through 2004. We compared patients with a diagnosis of ESBL-Kp (cases) and patients infected by non-ESBL producing K. pneumoniae (controls). Mean age, underlying disease, and frequency of invasive procedures were compared between the two groups. History of previous use of antibiotics was also analyzed. RESULTS: Based on multivariate analysis, previous use of antibiotics, diagnosis of malignant diseases, and diabetes mellitus were independent risk factors for acquisition of ESBL-Kp infection. No correlation was found for age, use of corticosteroids, diagnosis of chronic renal failure or AIDS, and infection by ESBL-Kp. CONCLUSION: Our findings suggest that the use of antibiotics or underlying disease that increases the chance of antibiotic are the main risk factors for ESBL-Kp infections. Programs focusing on rational use of antibiotics are mandatory for prevention and control of such infections.

Correlaçäo epidemiológica, microbiológica e clínicas das infecçöes hospitalares em unidades de terapia intensiva causadas por Klebsiella pneumoniae / Epidemiological, microbiological and clinical correlation of the nosocomial infections caused by Klebsiella pneumoniae in the intensive care units

Klebsiella pneumoniae é um importante patógeno freqüentemente relacionado como agente etiológico das infecções hospitalares. O estudo foi realizado nas UTIs geral adulto e neonatal no período de janeiro de 1998 a julho de 2001. Foram identificados 29 pacientes com infecção por K. pneumoniae na LITIGA e 26 pacientes com infecção pelo mesmo microorganismo na UTIN. Um estudo caso-controle foi realizado para identificar os fatores de risco para infecção por K. pneumoniae. O estudo da disseminação da K pneumoniae nas duas UTIs utilizou duas técnicas moleculares: Ribotipagem Automatizada e Eletroforese em Campo Elétrico Pulsado e para detectar o gene produtor de b-lactamase CTX-M foram usadas as técnicas da Reação da Polimerase em Cadeia e Southern-blot. Neste estudo a prevalência das infecções causadas por Klebsiella pneumoniae produtora de ESBL foi elevada (69,0 por cento na LITIGA e 53,8 por cento na UTIN). O uso de antimicrobianos antecedendo ao diagnóstico de infecção causada por este microorganismo foi feito pela maioria dos pacientes envolvidos deste estudo, porém não foi encontrada correlação entre o consumo de cefalosporina de espectro ampliado e o surgimento de infecção causada por K. pneumoniae produtora de ESBL. Vários fatores de risco para aquisição de infecções causadas por K. pneumoniae foram relacionados. Pela análise multivariada foi demonstrado que a ventilação mecânica e a transfusão de sangue e/ou hemoderivados para os pacientes hospitalizados na LITIGA e o uso de nutrição parenteral total, o tamanho pequeno para idade gestacional, a transfusão de sangue e/ou hemoderivados bem como o uso de bloqueador de receptor de H2 foram as variáveis independentes para os pacientes hospitalizados na UTIN. Foi observado ainda que o modo de disseminação destas infecções foi clonal e multiclonal. O uso de antimicrobianos específicos para o tratamento adequado das infecções causadas por K pneumoniae entre os pacientes hospitalizados nas duas UTIs, não alterou a elevada taxa de mortalidade, sobretudo para aqueles pacientes cuja infecção foi causada por K pneumoniae produtora de ESBL,...(au)