Resumen: Los pacientes cirróticos hospitalizados presentan una alta prevalencia de infecciones bacterianas. Entre ellas, las denominadas infecciones espontáneas del cirrótico, que incluyen la peritonitis bacteriana espontánea, la bacteriemia espontánea y el empiema bacteriano espontáneo, constituyen un grupo particular, con un elevado riesgo de complicaciones y mortalidad. El presente trabajo tiene como objetivo describir y caracterizar las infecciones espontáneas en el cirrótico, la microbiología prevalente y su perfil de resistencia antibiótica, en 2 centros asistenciales de Montevideo-Uruguay. Se realizó un estudio transversal, descriptivo y multicéntrico, que incluyó pacientes con cirrosis hepática hospitalizados, en el periodo marzo 2018-marzo 2019. Del total de pacientes ingresados con cirrosis (156), 25 (16%) desarrollaron una infección espontánea del cirrótico. En 24 de estos pacientes (96%) la cirrosis se encontraba en estadios avanzados (Child-Pugh B-C, MELD＞15). La forma de presentación más frecuente fue la peritonitis bacteriana espontánea (52%), seguida de la bacteriemia espontánea (40%) y del empiema bacteriano espontáneo (8%). El aislamiento microbiológico fue posible en 17 casos (68%). En 12 de ellos (70%) se aislaron bacilos Gram negativos, en 4 (24%) bacilos Gram positivos, y Candida en 1 solo caso. Se identificaron 3 cepas productoras de BLEE (2 K. pneumoniae y 1 E. coli), y 4 microorganismos con otros perfiles de resistencia antibiótica (2 E. faecalis, 1 K. oxytoca, 1 E. cloacae). La prevalencia de microorganismos multirresistentes fue del 41%, siendo todos los casos en el grupo de adquisición nosocomial. La realización de otros estudios en esta área podría aproximarnos al conocimiento de la epidemiología local, para la optimización de los tratamientos empíricos dirigidos a los microorganismos más prevalentes, con el objetivo de mejorar el abordaje de las infecciones en los pacientes con cirrosis.

Abstract: Hospitalized cirrhotic patients present with a high prevalence of bacterial infections. Among them, spontaneous cirrhotic infections include spontaneous bacterial peritonitis, spontaneous bacteremia and spontaneous bacterial empyema, which constitute a particular group, with a high risk of complications and mortality. The work above aims to describe and characterize the spontaneous infections in the cirrhotic, the prevalent microbiology and its resistance profile, in 2 healthcare centers in Montevideo-Uruguay. A multicenter, descriptive, cross-sectional study was held, including hospitalized patients with liver cirrhosis, between March 2018 - March 2019. 25 (16%) of the 156 patients admitted with cirrhosis developed a spontaneous cirrhotic infection. 24 (96%) of these patients were in an advanced stage of their disease, (Child-Pugh B-C, MELD＞15). The most frequent presentation was the spontaneous bacterial peritonitis (52%), followed by the spontaneous bacteremia (40%) and the spontaneous bacterial empyema (8%). Microbiological isolation was possible in 17 cases (68%), of which 12 (70%) developed gram negative bacilli, 4 (24%) gram positive bacilli and 1 case Candida. 3 ESBL producing strains were identified, (2 K. pneumoniae and 1 E. coli), and other 4 microorganisms with different antibiotic resistance profile (2 E. faecalis, 1 K. oxytoca, 1 E. cloacae). The prevalence of multiresistant microorganisms was 41%, all of nosocomial acquisition. Research on this topic may provide more knowledge about the local epidemiology, improving the empiric treatments, targeting the most prevalent microorganisms, in order to better approach the infections in cirrhotic patients.

Resumo: Pacientes cirróticos hospitalizados presentam alta prevalência de infecções bacterianas. Dentre elas, as chamadas infecções cirróticas espontâneas, que incluem a peritonite bacteriana espontânea, a bacteremia espontânea e o empiema bacteriano espontâneo, constituem um grupo particular, com alto risco de complicações e mortalidade. O presente trabalho tem como objetivo descrever e caracterizar as infecções espontâneas em pacientes cirróticos, a microbiologia prevalente e seu perfil de resistência aos antibióticos, em 2 centros de saúde em Montevidéu-Uruguai. Foi realizado um estudo transversal, descritivo e multicêntrico, que incluiu pacientes hospitalizados com cirrose hepática, no período de março de 2018 a março de 2019. Do total de pacientes internados com cirrose (156), 25 (16%) desenvolveram infecção cirrótica espontânea. A cirrose estava em estágios avançados, em 24 desses pacientes (96%) (Child-Pugh B-C, MELD ＞ 15). A forma de apresentação mais frequente foi peritonite bacteriana espontânea (52%), seguida de bacteremia espontânea (40%) e empiema bacteriano espontâneo (8%). O isolamento microbiológico foi possível em 17 casos (68%). Em 12 deles (70%) foram isolados bacilos Gram negativos, em 4 (24%) bacilos Gram positivos e Candida em apenas 1 caso. Foram identificadas 3 cepas produtoras de ESBL (2 K. pneumoniae e 1 E. coli) e 4 microrganismos com outros perfis de resistência a antibióticos (2 E. faecalis, 1 K. oxytoca, 1 E. cloacae). A prevalência de microrganismos multirresistentes foi de 41%, todos no grupo de aquisição nosocomial. A realização de outros estudos nesta área poderá nos aproximar do conhecimento da epidemiologia local, para a otimização de tratamentos empíricos direcionados aos microrganismos mais prevalentes, com o objetivo de melhorar o manejo de infecções em pacientes com cirrose.

Introduction: the Klebsiella genus gives rise to many hospital outbreaks due to multi-drug-resistant strains on different continents and leads to increased morbidity and mortality. Objectives: to identify the Klebsiella species causing infections in Cuban hospitals, to determine the origin of isolates per service, their antimicrobial susceptibility and, to determine the production and type of extended-spectrum ß-lactamases (ESBLs) and the susceptibility of these isolations to several antimicrobials of therapeutic interest. Methods: a descriptive study was conducted on 448 Klebsiella spp. Isolates that were received in the national reference microbiology laboratory of "Pedro Kouri" Institute of Tropical Medicine from 40 hospitals located in 12 Cuban provinces during the 2010-2012 period. Species identification was based on conventional biochemical tests and mass spectrometry technique called MS MALDI-TOF. The susceptibility to 15 antimicrobials and the extended spectrum ß-lactamase production were determined by the E-test method and by the combined disks method, respectively, according to recommendations of the Institute of Clinical and Laboratory Standards. The polymerase chain reaction made it possible the detection of BlaESBL genes as indicated in the previously described protocol. Results: Klebsiella pneumoniae (95.4 %) was the prevalent species, followed by K. oxytoca (4.1%), and K. ozaenae (0.5 %). The isolates were mainly from the intensive care units (26.3 %), surgery (22 %), and neonatology (13%) services. The highest resistance rate was observed for cephalosporins (48-52 %), trimethoprim-sulfamethoxazole (49 %), gentamicin (43 %), nalidixic acid (38 %), and tetracycline (34 %). Fifty-two percent of the isolates were extended spectrum ß-lactamase producers, with CTX-M (82 %) and TEM (70 %) enzymes prevailing. Conclusions: This study shows the clinical impact of Klebsiella spp in Cuban hospitals, which is highly resistant to different antimicrobials. The production of extended spectrum ß-lactamases provides a significant resistance mechanism in Klebsiella in which carbapenems, piperacillin-tazobactam, cholistin and tigecycline play an important therapeutic role.

Introducción: el género Klebsiella causa brotes hospitalarios, por cepas multidrogorresistentes en diferentes continentes y conlleva a un aumento en la morbimortalidad. Objetivos: identificar las especies de Klebsiella causantes de infecciones en hospitales cubanos, determinar la procedencia de los aislamientos según el servicio, y la susceptibilidad antimicrobiana, conocer la prevalencia de aislamientos productores de ß-lactamasas de espectro extendido (BLEE), y tipos, así como la susceptibilidad de los mismos a diferentes antimicrobianos de interés terapéutico. Métodos: se realizó un estudio descriptivo en 448 aislamientos de Klebsiella spp. recibidos en el Laboratorio Nacional de Referencia de Microbiología del IPK (LRNM/IPK) procedentes de 40 hospitales de 12 provincias del país durante el período de 2010 a 2012. La identificación de las especies se realizó mediante pruebas bioquímicas convencionales y por la técnica de Espectrometría de masas MS MALDI-TOF. Se determinó la susceptibilidad a 15 antimicrobianos mediante el método E-test y la producción de BLEE mediante el método de discos combinados según las recomendaciones del Instituto de Estándares Clínicos y de Laboratorio. Los genes blaESBL se determinaron mediante la reacción en cadena de la polimerasa según protocolo descrito previamente. Resultados: la especie prevalente fue Klebsiella pneumoniae (95,1 %), seguida por K. oxytoca (4,5 %) y K. ozaenae (0,4 %). Los aislamientos procedieron, principalmente, de los servicios de Unidades de Cuidados Intensivos (26,3 %), cirugía (22 %) y neonatología (13 %). La mayor resistencia se observó para las cefalosporinas (48-52 %), trimetoprim-sulfametoxazol (49 %), gentamicina (43 %), ácido nalidíxico (38 %) y tetraciclina (34 %). El 52 % de los aislamientos fueron productores de BLEE y prevaleció la enzima CTX-M (82 %) y la TEM (70 %). Conclusiones: se evidencia la repercusión clínica de Klebsiella spp. en hospitales cubanos con elevada resistencia a diferentes antimicrobianos. La producción de BLEE es un mecanismo de resistencia importante en esta bacteria en las que los carbapenémicos, la piperacilina-tazobactam, la colistina, y la tigeciclina juegan un rol terapéutico importante.

In this work was synthesized a pregnenolone derivative; the route involved preparation of pregnenolone hemisuccinate (2) by esterification of pregnenolone (1) with succinic anhydride followed by formation of the hemisuccinate of pregnenolone-vitamin B1 conjugate (3). The antibacterial activity of compound 3, as well as 2 and vitamin B1, was evaluated in vitro on S. aureus, K. pneumoniae and E. coli using dilution method and the minimum inhibitory concentration (MIC). The structure of 3 was confirmed by spectroscopy and spectrometry data. The ¹H NMR spectrum showed, up field shifts at 2.52 and 2.58 ppm for methyls present in the heterocyles rings; at 2.90 and 3.77 methylenes of the hydroxietilen moiety bonded to thiazol ring, in addition the hydrogens of the methylene between the pyrimidine and thiazol ring appears at 4.39 ppm. At down field there are two chemical shifts (7.54, 8.33) corresponding to protons in the heterocyles. The results of the biological activity indicate that the bacterial growth of the microorganisms studied was inhibited by 3, and 2 in a manner dose-dependent, but not by vitamin B1. These data suggest that quaternary amine group involved in the HPVB1 conjugate requires the hydrophobic region of the steroid in order to interact with some components of bacterial cell, disturbing the bacterial growth and to cause cell death.

En este trabajo fue sintetizado un derivado de pregnenolona, la ruta involucra la preparación de hemisuccinato de pregnenolona (2) por esterificación de pregnenolona (1) con anhídrido succínico, seguido por formación del conjugado hemisuccinato de pregnenolona-vitamina B1 (3). La actividad antibacterial del compuesto 3, así como la de 2 y de la vitamina B1 fue evaluada en vitro sobre S. aureus, K. pneumoniae and E. coli usando el método de dilución y la concentración mínima inhibitoria (CMI). La estructura 3 fue confirmada por datos espectroscópicos y espectrométricos. El espectro de ¹H NMR mostró cambios a 2.52 y 2.58 ppm para metilos presentes en los anillos heterocíclicos; a 2.90 y 3.77 para metilenos del hidroxietilén enlazado al anillo de tiazol; además, los hidrógenos del metileno entre la piridina y el anillo de tiazol aparecen a 4.39 ppm. A campos bajos hay dos cambios químicos (7.54, 8.33) correspondientes a protones en los heterociclicos. Los resultados de la actividad biológica indican que el crecimiento bacterial de los microorganismos estudiados fue inhibido por 3 y 2 en una manera dosis-dependiente pero no por la vitamina B1 . Esos datos sugieren que el grupo amino cuaternario envuelto en el conjugado hemisuccinato de pregnenolona-vitamina B1 posiblemente requiere la región hidrófobica del esteroide para interactuar con algunos componentes de la célula bacterial perturbando el crecimiento bacterial y causar muerte celular.

Justificación: La resistencia a antibióticos por parte de bacterias patógenas es un grave problema mundial. Su control ha sido difícil pero deben hacerse todos los esfuerzos por realizarlo. Conocer la epidemiología en las diferentes regiones y países se constituye en parte importante de este control. Este estudio se llevóa cabo con el fin de analizar el comportamiento de la resistencia en el hospital San Juan de Dios, centro de atención nacional de adultos de aproximadamente 700 camas. Materiales y métodos: El estudio se basóen los datos obtenidos en los años 1995-1999 ya que en 1995 se inició el empleo de equipo automatizado VITEK® en este hospital. Se analizaron 2817 aislamientos de cocos Gram positivos (CGP) y 7626 de bacilos Gram negativos (BGN) obtenidos de todos los sitios anatómicos y fluidos corporales. Por ser un estudio retrospectivo, no se pudo definir cuáles aislamientos provenían de infecciones intra o extrahospitalarias. Resultados: Staphylococcus aureus fue el CGP más frecuentemente aislado, mientras que el BGN más frecuente fue Escherichia coli. En más de 90% de los estafilococos aislados se demostróresistencia a la penicilina. La resistencia a la oxacilina en S.aureus se incrementóde 35% en 1995 a 52% en 1999 mientras que en los estafilococos coagulasa negativa, pasóde 70 a 77% en el mismo periodo. La resistencia a la cefalotina en S.aureus pasóde 35 a 50% mientras que en los estafilococos coagulasa negativa pasóde 65 a 76%. La resistencia a la clindamicina en ambos grupos bacterianos se mantuvo relativamente estable. No se demostróresistencia a la vancomicina. La mayoría de los enterococos aislados correspondieron a E. faecalis, 75% de ellos fueron sensibles a la penicilina y 50% no mostraron sinergismo de la gentamicina con los antibióticos que actúan sobre la pared. No se encontraron enterococos vancomicina resistentes. En las enterobacterias se observó un aumento importante de la resistencia a cefalosporinas de tercera generación. E. colimostró un aumento de la resistencia a ceftazidima de 10% en 1995 a 35% en 1999, mientras que Klebsiella pmeumoniae pasó de 0% a 52% para el mismo antibiótico en ese periodo. Con respecto a cefotaxima, mientras que en E.coli se incrementó la resistencia de 5 a 12%, en K. pneumoniae se modificó de 5 a 24%. Esto podría deberse a la presencia de ß-lactamasas de espectro ampliado. La sensibilidad a ciprofloxacina en E. colial igual que en K. pneumoniae se mantuvo estable. En cuanto a amicacina, E.coli pasó de 0% de resistencia en 1995 a 15% en 1999 y K. pneumoniae de 20 a 32%. En Enterobacter cloacae se demostróaumento importante de la resistencia a cefalosporinas de tercera generación y a amicacina no asía la ciprofloxacina. En todas las enterobacterias se mantuvo una baja resistencia al imipenem. En cuanto a BGN no fermentadores, se demostró en Pseudomonas aeruginosa un aumento de la resistencia a la mayoría de los antibióticos con excepción del imipenem y ceftazidima. No obstante Acinetobacter calcoaceticus presentóun incremento importante de la resistencia a amicacina (de 20 a 72%), a cefalosporinas de tercera generación (de 0 a 61%) y ciprofloxacina (57%), manteniendo alta sensibilidad sólo a imipenem (95%).

Background and aim: Antimicrobial resistance results in increased morbidity, mortality and costs of health care. Therefore, surveillance of antimicrobial resistance in hospitals must be part of infection control programs. The Hospital San Juan de Dios is a tertiary health care center in Costa Rica with 700 beds for adults. Since 1995, an automatized system (VITEK®) is used in our bacteriology laboratory allowing an adequate control of the resistance patterns of bacterias isolated from different sites. The aim of this report is to describe the susceptibility to some antibiotics found in bacterias isolated from different sites from 1995 to 1999 and to determine their changes in resistance. Materials and Methods: Were reviewed. The files of the bacteriology laboratory of the hospital was done. We analized bacterial strains from 1995 to 1999. Data from 1996 were incomplete and were not studied. All isolates were analized in the automatized system VITEK®. Streptococcus pneumoniae strains from blood or sputum were studied by the E-test method and their sensitivity ranges met the NCCLS criteria. Results: We studied 2817 Gram positive cocci (GPC) strains and 7626 isolates of Gram negative bacteria (GNB). Staphylococcus aureus was the most frequently GPC specie found and Escherichia coliwas the most common GNB. More than 90% of staphylococcal species produced ß-lactamase and were resistant to penicillin. Resistance to oxacillin (methicillin) in Staphylococcus aureus increased from 35% to 52% in this period. In coagulase negative staphylococci the resistance to this antibiotic was very high (70-77%). Susceptibility to cephalotin and clindamycin in Staphylococcus aureus was similarly high (50-60%) in the years studied and in coagulase negative staphylococci (Staphylococcus epidermidis) the resistance stayed in high levels (65-70%). There were not resistance to vancomycin in the staphylococci analyzed. Ninety eight per cent of the 61 isolates of Streptococcus pneumoniae were susceptible to penicillin. Susceptibility to penicillin was observed in 80% of 483 isolates of Enterococcus faecalis. Fifty percent of the enterococci showed synergism between gentamicin and cell-wall active agents. Only a few isolates of Enterococcus faecuim were analized and no resistance to vancomycin was found. Resistance to aminoglycosides was demonstrated in 50% of enterococci isolates. Regarding enterobacterias, Escherichia colistrains presented high resistance to ampicillin (60%), sulfa trimetoprin (60%) and a decrease in the susceptibility to ceftazidime from 90% in 1995 to 65% in 1999, to cefotaxime from 95% to 88%, from 67% to 57% to cephalotin and from 100% to 85% to amikacin in the same period. Resistance to ciprofloxacin was 10% in 1995 and 20% in 1999. Regarding Klebsiella pneumoniae, resistance to amikacin increase from 20% to 32%, to ceftazidime from 0% to 52%, to cefotaxime from 5% to 24% but susceptibility to ciprofloxacin was high in the period (80-90%). Resistance to ampicillin was present in more than 90% of the K.pneumoniaeisolates and to cephalotin in more than 50% of this bacteria. Enterobacter cloacae showed high resistance patterns to ampicillin (>95%),cephalotin (> 90%) and ceftazidime (2550%). In non-fermenting Gram negative bacilli, resistance to amikacin (20%-72%) ceftazidime (42%-61%) and ciprofloxacin(58%) was documented in Acinetobacter calcoaceticus. In Pseudomonas aeruginosa an increase in the resistance to amikacin (15%-30%) and ciprofloxacin(20%-37%) were noted. In all BGN strains studied, a high susceptibility pattern to imipenem (from 88% in Ps. aeruginosa and 95% in Ac. calcoaceticus to 100% in enterobacterias) were observed. Discussion: We analized these findings and compared them with those found in the medical literature. High resistance patterns to penicillin and oxacillin in staphylococci strains were documented. High resistance in GNB to ampicillin, cephalotin, ceftazidime and ciprofloxacin was observed. High susceptibility patterns to imipenem in GNB were found. Key words: antibiotics, antibiotic resistance, bacterial infections, beta-lactam resistance, vancomycin resistance, pneumococcus drug resistance, broad spectrum ß-lactamases.

Snakebite envenomation is a worldwide problem and in Costa Rica. The following is a retrospective review of 79 patients admitted to the Hospital Nacional de Niños (HNN) from January 1985 to September 1996. Child's age ranged from 9 months to 14 years. The M: F ratio was 1.5:1. Sixty percent of the patients lived in remote rural areas. The most common clinical signs at the time of hospitalization were pain and edema. Fifty patients (63,29%) showed moderate to severe envenomation grades. Fifty-one (64,55%) was caused by Bothrops asper. Complications during hospitalization were compartment syndrome and secondary infection. Three children died, one from disseminated intravascular coagulation, another from renal insufficiency, and the third from a perforated duodenal ulcer. Patients who underwent early fasciotomy had significantly less hospitalization and fewer infectious complications, (p < 0.001). There was no relationship between the envenomation grade and length of hospitalization (p = 0.4). The most common pathogen isolated was S. aureus. Early fasciotomy seemed to reduce the complications seen in these patients. Further studies are necessary to identify the factors that may help clinicians to decide those who should undergo fasciotomy, as well as the best moment to perform it.