Resistencia antimicrobiana, una pandemia silenciosa / Antimicrobial resistance, a silent pandemic / Resistência antimicrobiana, uma pandemia silenciosa

Introducción: la resistencia a los antimicrobianos ha sido una problemática creciente a nivel global, la problemática afecta no solo la salud de personas, animales y el ambiente en general, sino que ha generado impactos de índole productivo y comercial. Una de las estrategias para abordar esta problemática es el enfoque de una salud. Este enfoque destaca la participación multidisciplinaria para combatir la resistencia antimicrobiana; y es así que cada profesión o actividad laboral genera unas responsabilidades innatas para la profesión veterinaria. Los veterinarios tienen un rol fundamental para este propósito, ya que son ellos quienes integran la aplicabilidad de estrategias de promoción y prevención a nivel agropecuario, y de consolidación e interlocución entre los diferentes componentes del enfoque (animal, humano, ambiente) desde el ámbito de la salud pública veterinaria. Materiales y Método: se realizó una búsqueda de la literatura en diferentes bases de datos, con el objetivo de realizar una revisión actualizada sobre la resistencia antimicrobiana. Resultados: dentro de las principales estrategias se debería fomentar un uso adecuado y bajo prescripción de antimicrobianos en la producción animal. Promover buenas prácticas de higiene, bioseguridad y vacunación, facilitando un correcto diagnóstico de enfermedades infecciosas en animales. Discusión: la adopción de normas internacionales para el uso responsable de los antibióticos y las directrices establecidas por la Organización Mundial de la Salud y Organización de las Naciones Unidas para la Alimentación y la Agricultura, a través del Codex Alimentarius y la Organización Mundial de Sanidad Animal, son fundamentales para hacer frente al desafío que representa el problema de la resistencia a los antimicrobianos.

Introduction: Antimicrobial resistance has been a growing problem at a global level, affecting not only the health of people, animals and the environment in general, but it has also generated impacts of a productive and commercial nature. One of the strategies to address this problem is the one-health approach. This approach emphasizes multidisciplinary participation to combat antimicrobial resistance; and thus, each profession or work activity generates innate responsibilities for the veterinary profession. Veterinarians have a fundamental role for this purpose, since they are the ones who integrate the applicability of promotion and prevention strategies at the agricultural level, and of consolidation and interlocution between the different components of the approach (animal, human, environment) from the field of veterinary public health. Materials and Method: a literature search was carried out in different databases, with the aim of carrying out an updated review on antimicrobial resistance. Results: one of the main strategies should be to promote an adequate use and under prescription of antimicrobials in animal production. Promote good hygiene, biosecurity and vaccination practices, facilitating a correct diagnosis of infectious diseases in animals. Discussion: the adoption of international standards for the responsible use of antibiotics and the guidelines established by the World Health Organization and the Food and Agriculture Organization of the United Nations, through Codex Alimentarius and the World Organization for Animal Health, are fundamental to face the challenge posed by the problem of antimicrobial resistance.

Introdução: A resistência antimicrobiana tem sido um problema crescente em todo o mundo, afetando não apenas a saúde dos seres humanos, dos animais e do meio ambiente em geral, mas também causando impactos na produção e no comércio. Uma das estratégias para lidar com esse problema é a abordagem One Health. Essa abordagem enfatiza o envolvimento multidisciplinar no combate à resistência antimicrobiana, com cada profissão ou atividade de trabalho gerando responsabilidades inatas à profissão veterinária. Os veterinários têm um papel fundamental nesse sentido, pois são eles que integram a aplicabilidade das estratégias de promoção e prevenção em nível agropecuário e de consolidação e interlocução entre os diferentes componentes da abordagem (animal, humano, ambiental) do campo da saúde pública veterinária. Materiais e Métodos: foi realizada uma pesquisa bibliográfica em diferentes bases de dados, com o objetivo de realizar uma revisão atualizada sobre a resistência antimicrobiana. Resultados: uma das principais estratégias deve ser a promoção do uso adequado e com baixa prescrição de antimicrobianos na produção animal. Promover boas práticas de higiene, biossegurança e vacinação, facilitando o diagnóstico correto de doenças infecciosas em animais. Discussão: A adoção de padrões internacionais para o uso responsável de antibióticos e as diretrizes estabelecidas pela Organização Mundial da Saúde e pela Organização das Nações Unidas para Agricultura e Alimentação, por meio do Codex Alimentarius e da Organização Mundial de Saúde Animal, são essenciais para enfrentar o desafio representado pelo problema da resistência antimicrobiana.

Perfil de resistencia del Mycobacterium tuberculosis a fármacos antituberculosos de primera línea y sus combinaciones / Resistance profile of Mycobacterium tuberculosis to first-line antituberculosis drugs and their combinations

Introducción: En Colombia el control de la tuberculosis se ha visto amenazado por la resistencia a los fármacos antituberculosos y especialmente la tuberculosis multidrogorresistente. Objetivo: Determinar la resistencia global y perfiles de resistencia del Mycobacterium tuberculosis a fármacos antituberculosos de primera línea y combinaciones. Métodos: Estudio descriptivo, transversal, en el que se evaluaron 2 701 pacientes con tuberculosis en el Departamento del Atlántico (Colombia), durante los años 2011 a 2016. Se valoraron aspectos sociodemográficos, clínicos y condiciones de riesgo. Se realizó análisis de frecuencias relativas y absolutas, diferencia de proporciones ((2) y razón de prevalencias. Resultados: El 66,5 por ciento de los pacientes eran hombres, el 53 por ciento tenían entre 15 y 44 años de edad. El 47,34 por ciento con pérdida en el seguimiento y el 11,62 por ciento monorresistentes a isoniacida. La resistencia en casos nuevos fue 7,30 por ciento (IC95 por ciento: 6,3-8,5), para este grupo la multidrogorresistencia fue de 1,1 por ciento; mientras que en los previamente tratados la resistencia fue de 18,27 por ciento (IC95 por ciento: 15,6- 22,4) y la multidrogorresistencia de 5,7 por ciento. Los factores asociados a resistencia fueron presencia de VIH/TB (RP= 2,6; p= 0,000), otros factores inmunosupresores (RP= 3,5; p= 0,009), contacto de paciente con tuberculosis multidrogorresistente (RP= 16; p= 0,000) y caso previamente tratado (RP= 2,24; p= 0,00). Conclusiones: Se evidencia un descenso en la resistencia global a rifampicina e isoniacida, así como en la prevalencia multidrogorresistente tanto en casos nuevos como en previamente tratados en la población estudiada; lo que genera una línea base para la toma de decisiones que permita continuar mejorando la vigilancia y control de la resistencia del M. tuberculosis a fármacos de primera línea, debido a los nuevos retos que este microorganismo representa para la salud pública(AU)

Introduction: Tuberculosis control in Colombia has been hampered by resistance to antituberculosis drugs and particularly by multi-drug resistant tuberculosis. Objective: Determine the overall resistance and resistance profiles of Mycobacterium tuberculosis to first-line antituberculosis drugs and their combinations. Methods: A descriptive cross-sectional study was conducted of 2 701 tuberculosis patients from Atlántico Department in Colombia in the period 2011-2016. The evaluation included sociodemographic aspects, clinical characteristics and risk conditions. Data analysis was based on relative and absolute frequencies, proportion difference (x2) and prevalence ratio. Results: Of the total sample, 66.5 percent were men and 53 percent were aged 15-44 years. 47.34 percent were lost to follow-up and 11.62 percent were monoresistant to isoniazid. In new cases resistance was 7.30 percent (CI 95 percent: 6.3-8.5) and multi-drug resistance was 1.1 percent, whereas in previously treated cases resistance was 18.27 percent (CI 95 percent: 15.6-22.4) and multi-drug resistance was 5.7 percent. The factors associated to resistance were the presence of HIV/TB (AR= 2.6; p= 0.000), other immunosuppressive factors (AR= 3.5; p= 0.009), contact with multi-drug resistant tuberculosis patient (AR= 16; p= 0.000) and previously treated case (AR= 2.24; p= 0.00). Conclusions: A reduction is observed in overall resistance to rifampicin and isoniazid, as well as in the prevalence of multi-drug resistance, both in new cases and in previously treated cases, which creates a baseline for the taking of decisions aimed at the continuing improvement of the surveillance and control of M. tuberculosis resistance to first-line drugs, due to the new challenges posed by this microorganism to public health(AU)

Presencia de estafilococos coagulasa positiva ambientales, su relación clonal, factores de resistencia y habilidad para formar biopelícula / Presence of environmental coagulase-positive staphylococci, their clonal relationship, resistance factors and ability to form biofilm

Coagulase-positive staphylococci (CoPS) are opportunistic pathogens carrying various mechanisms of resistance that have a large number of virulence factors, and whose ability to induce illness is associated with the host. This study aimed to investigate the presence of environmental coagulase-positive staphylococci, their susceptibility profile, clonal relationship and ability to form biofilm. The 16S rRNA genes from CoPS isolates were analyzed, and their antibiotic susceptibility was evaluated using the agar dilution method in accordance with Clinical and Laboratory Standards Institute guidelines. The clonal profile was obtained by pulsed-field gel electrophoresis (PFGE) and biofilm formation was measured by a crystal violet retention assay. A total of 72 Staphylococcus spp. strains were isolated from air, metal surfaces, and nostrils from humans, dogs, cats, and birds. Three species were identified: Staphylococcus aureus (17%), Staphylococcus intermedius (63%), and Staphylococcus pseudintermedius (21%). Ninety three percent (93%) of the strains were resistant to at least one of 13 tested antibiotics. S. pseudintermedius strains were the only resistant ones to methicillin while most of these isolates were multidrug-resistant, had significantly higher ability to form biofilm and PFGE grouped into seven different patterns, without showing clonal dispersion among animals and environmental isolates. This study suggests that dogs, cat, and air are environmental sources potentially carrying multidrug-resistant S. pseudintermedius, which survives in different environments through biofilm formation and multidrug resistance, characteristics that can be transmitted horizontally to other bacteria and exacerbate the problem of antibiotic resistance in humans.

Los estafilococos coagulasa-positiva (CoPS) son patógenos oportunistas, portan varios mecanismos de resistencia, tienen un gran número de factores de virulencia y su capacidad para inducir la enfermedad está asociada con el hospedero. El objetivo de este estudio fue investigar la presencia de CoPS en el medio ambiente, su perfil de sensibilidad a los antibióticos, su relación clonal y su capacidad para formar biopelícula. De los aislamientos de CoPS se analizaron los genes 16S ARNr y se evaluó la sensibilidad a los antibióticos mediante el método de dilución en agar según el CLSI. El perfil clonal se obtuvo por electroforesis en gel de campo pulsado (PFGE) y la formación de biopelícula se analizó por retención de cristal violeta. Se aislaron 72 cepas de Staphylococcus spp. a partir de aire, superficies metálicas y narinas de humanos, perros, gatos y aves. Se identificaron tres especies: Staphylococcus aureus (17%), Staphylococcus intermedius (62%) y Staphylococcus pseudintermedius (21%). El 93% de las cepas fueron resistentes al menos a uno de 13 antibióticos probados. Los aislamientos de S. pseudintermedius fueron los únicos resistentes a meticilina y la mayoría fueron resistentes a múltiples fármcos, tuvieron una capacidad significativamente mayor para producir biopelícula y la PFGE los agrupó en 7 diferentes patrones, sin mostrar dispersión clonal entre los aislamientos de animales y de medio ambiente. Este estudio sugiere que los perros, los gatos y el aire son fuentes ambientales potencialmente portadoras de S. pseudintermedius resistente a múltiples antibióticos. Este agente sobrevive en diferentes entornos en virtud de la formación de biopelículas y la resistencia a múltiples antibióticos, características que pueden transmitirse horizontalmente a otras bacterias y, por ende, exacerbar el problema de la resistencia a los antibióticos en humanos.

Tumor size and prognosis in patients with Wilms tumor / Tamanho tumoral e prognóstico em pacientes portadores de tumor de Wilms

OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ) and before preoperative chemotherapy (TVBPQ) with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ>500mL and the difference between the TVBPQ and TVAPQ (p=0.015) and histologic types of risk (p=0.008). It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037). When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013), i.e., for each increase of 10mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable. .

OBJETIVO: Investigar a relação entre o volume do tumor após a quimioterapia pré-operatória (VTPOS) e antes da quimioterapia pré-operatória (VTPRE) com sobrevida geral aos dois e cinco anos e tempo de vida. MÉTODOS: A amostra foi composta por pacientes consecutivos avaliados de 1989 a 2009, em um serviço de onco-hematologia. Os dados clínicos, histológicos e volumétricos foram coletados a partir dos registros médicos. Para análise, usaram-se os testes qui-quadrado, Kaplan-Meier, log-rank e regressão de Cox. RESULTADOS: A amostra foi composta de 32 pacientes, 53,1% do sexo masculino, com mediana de idade ao diagnóstico de 43 meses. Houve associação significativa entre VTPOS >500 mL e a diferença entre o VTPRE e VTPOS (p=0,015) e os tipos histológicos de risco (p=0,008). Verificou-se também uma associação entre a diferença entre o VTPRE e VTPOS e o tumor de predomínio estromal (p=0,037). Quando se avaliou o VTPOS de todos os pacientes, sem um ponto de corte definido, observou-se associação dessa variável com o tempo de vida (p=0,013), isto é, para cada aumento de 10 mL no VTPOS houve um aumento médio de 2% no risco de morte. CONCLUSÕES: Embora os resultados indiquem que o VTPOS poderia ser considerado um preditor isolado de mau prognóstico, independentemente do ponto de corte sugerido na literatura, mais estudos são necessários para substituir a histologia e estadiamento pelo tamanho do tumor como melhor variável prognóstica. .

Análise molecular da expressão do fenótipo multi-droga resistente (MDR) em enterobactérias isoladas de amostras clínicas após exposição in vitro ao Imipenem / Molecular analysis of multi-drug resistant phenotype expression (MDR) in enterobacteria isolated from clinical specimens after exposure in vitro to imipenem

Após o surgimento e disseminação das ß-lactamases de amplo espectro em membros da família Enterobacteriaceae, os antibióticos carbapenêmicos (imipenem, meropenemeertapenem) têm sido considerados a terapia de escolha devido à estabilidade apresentada contra estas enzimas. A desvantagem destes antibióticos é a sua capacidade de induzir resistência aos ß-lactâmicos e a outros antibióticos quimicamente não relacionados. O imipenem tem favorecido a indução de cefalosporinases cromossômicas (AmpC) e também tem sido relacionado, in vivo, com a seleção de mecanismos intrínsecos de resistência, contribuindo com o perfil multi -droga resistente (MDR). Esse perfil é freqüentemente associado à diminuição da permeabilidade por alteração na síntese de porinas em conjunto com um aumento da atividade de bombas de efluxo, as quais não permitem o estabelecimento de uma concentração ativa do antibiótico no interior da célula bacteriana. O presente trabalho teve como objetivo avaliar o estabelecimento do perfil MDR em enterobactérias provenientes de isolados clínicos em função da exposição a diferentes concentrações de imipenemin vitro. A seleção do grupo das amostras estudadas foi feito por meio da determinação do perfil de sensibilidade dos isolados, tipagem molecular e ensaio de hidrólise de Imipenem. Nos isolados selecionados para a indução foi realizada numa etapa inicial (etapa basal) a análise de porinas de membrana externa por SDS-PAGE e o estudo de genes codificadores de ß-lactamases pela técnica de PCR. O estudo do estabelecimento do perfil MDR foi feito por meio de passagens sucessivas das amostras em meio contendo concentrações sub-inibitórias de imipenem seguido de análise fenotípica (CIM e acúmulo do antibiótico intracelular e SDS-PAGE), e a análise da expressão gênica de genes associados a permeabilidade de membrana (ompC, ompF eAcrA) e genes reguladores(marA e ompR). Após a indução com o imipenem, 77% dos isolados induzidos aumentaram a CIM para os carbapenêmicos, mudando assim o perfil de resistência observado na etapa basal Também foi afetado o perfil de resistência para outros antibióticos não relacionados a ß-lactámicos, porém numa percentagem menor. Com relação à alteração da permeabilidade, a perda de porina foi observada apenas para um isolado, no entanto a diminuição na expressão gênica de Omp36 foi significativa desde o começo da indução. A expressão da bomba de efluxoAcrAB foi afetada pela indução com imipenem, aumentando significativamente a expressão de AcrA, enquanto os reguladores estudados, MarA e OmpR tiveram a sua expressão induzida pelo imipenem. Foi possível observar também associação do nível de expressão gênica do regulador MarA com a expressão de AcrA,porém não foi possível observar uma associação estatisticamente significativa deste regulador com o perfil de expressão de OMPs. A indução de OmpR foi associado com um aumento da expressão de RNAm de Omp35, já para Omp36 foi possível observar apenas uma tendência na repressão deste gene. O estudo da resposta destes genes reguladores e determinantes de resistência, em resposta à exposição ao com o imipenem in vitro, permitiu reportar o comportamento molecular da bactéria numa resposta adaptativa no estagio inicial do estabelecimento do fenótipo MDR. A utilização de isolados clínicos com diversos determinantes de resistência permitiu observar a variabilidade nas respostas adaptativas das enterobacterias, o que é fundamental para a compreensão dos mecanismos de adaptação da bactéria e sua contribuição na falha terapêutica

After emergence and broad dissemination of extended spectrum ß-lactamases into the Enterobacteriaceae family, the carbapenemic antibiotics (imipenem, meropenem and ertapenem) have been considered the chosen therapy in the treatment of nosocomial infections by the stability that these antibiotics show to these enzymes. The disadvantage of carbapenems is theirs capacity to induce resistance against ß-lactamics and to other chemically unrelated antibiotics. The imipenem has been shown to induce chromosomal cephalosporinases (AmpC) and it was also related, in vivo, with the selection of intrinsic mechanism leading to multi-drug resistance profile (MDR). This profile is usually associated with membrane impermeability due to reduced outer membrane porin synthesis with an incremented activity of efflux pumps, which results in a reduced concentration of antibiotics inside the bacteria. This study aimed to evaluate the establishment of the MDR profile in Enterobacteriaceae from clinical isolates by exposure to different concentrations of imipenem in vitro. The selection of the study group was performed by determination of antibiotic susceptibility profile,molecular typing and hydrolysis assay of imipenem. In the selected isolates submitted to induction, in an initial step (baseline), was performed the outer membrane porin analysis by SDS-PAGE and the gene-specific amplification of B-lactamase enzymes by PCR. The study of the establishment of MDR was performed by progressive passages with subclinical concentrations of imipenem, followed each one by the evaluation of phenotypic profile (MIC, accumulation antibiotic in celland SDS-PAGE) and gene expression analysisof genes related to membrane permeability (ompC, ompF and acrA) and regulatory genes(MarA and ompR). After induction with imipenem, 77 % of the isolates increased the MIC for the carbapenems, changing the resistance profile at the baseline. In a lesser percentage, the resistance profile to other ß-lactams-unrelated antibiotics was also affected. Loss of porin was observed only for an isolated, however a significantly decreased Omp36 mRNA expression was observed from the start of induction. The expression of the efflux pump AcrAB ,was also affected by the imipenem induction, significantly increasing the AcrA gene expression, whereas the studied regulatory genes,MarA and OmpR,were induced by the imipenem. It was also possible to observe an association between the expression of the regulator MarA and the expression of AcrA, nevertheless no association was observed between this regulator and OMPs . OmpR induction was associated with an increased Omp35mRNA expression, however only a trend for the repression of Omp36was observed. The study of the response of these regulatory genes and genetic determinants of resistance, in response to the imipenem exposure in vitro, allowed to report the molecular behavior of the bacteria in an adaptive response in the initial stage of the establishment of a MDR phenotype. The use of clinical isolates with diverse resistance determinants allowed observing the variability in adaptive responses in enterobacteria, which is important to understand the adaptive mechanisms of bacteria to this antibiotic, the involvement in the emergence of the MDR profile and its contribution to the treatment failure

Effect of curcumin on human colon cancer multidrug resistance in vitro and in vivo

OBJECTIVE: To determine whether curcumin reverses the multidrug resistance of human colon cancer cells in vitro and in vivo. METHODS: In a vincristine-resistant cell line of human colon cancer, the cell viability of curcumin-treated cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Rhodamine123 efflux was evaluated to detect P-glycoprotein transporter activity, and expression of the multidrug resistance protein 1 and survivin genes was analyzed by reverse transcription polymerase chain reaction and western blotting. In addition, xenograft mouse tumors were grown and treated with curcumin. The morphology of the xenografts was investigated by hematoxylin-eosin staining. The in vivo expression of the multidrug resistance gene and P-glycoprotein and survivin genes and proteins was observed using reverse transcription-polymerase chain reaction and western blotting, respectively. RESULTS: Curcumin was not obviously toxic to the vincristine-resistant human colon cancer cells at concentrations less than 25 μM, but the growth of cells was significantly inhibited. At concentrations greater than 25 μM, curcumin was toxic in a concentration-dependent manner. The sensitivity of cells to vincristine, cisplatin, fluorouracil, and hydroxycamptothecin was enhanced, intracellular Rhodamine123 accumulation was increased (p<0.05), and the expression of the multidrug resistance gene and P-glycoprotein were significantly suppressed (p<0.05). The combination of curcumin and vincristine significantly inhibited xenograft growth. The expression of the multidrug resistance protein 1 and survivin genes was significantly reduced in xenografts of curcumin-treated mice and mice treated with both curcumin and vincristine relative to control mice. CONCLUSION: Curcumin has strong reversal effects on the multidrug resistance of human colon carcinoma in vitro and in vivo. .

High level of gentamicin resistance [HLGR] among enterococcus strains isolated from clinical specimens

Enterococci are pathogens that can cause nosocomial infections and acquire resistance properties via several molecular mechanisms. The aac [6']Ie-aph[2"]Ia gene plays a significant role in the emergence of high-level gentamicin-resistant [HLGR] strains. The screening of resistant strains and the provision of appropriate antibiotic therapy can decide the outcome of serious nosocomial infections. In the present study, 142 enterococci were isolated from patients, and the species were identified using standard methods. An antimicrobial susceptibility test was performed using the disc diffusion method, and the minimum inhibition concentration [MIC] of gentamicin was determined according to the broth micro-dilution method. Additionally, PCR was utilized to detect the aac[6']Ie-aph[2"]Ia gene, the presence of which was confirmed by digestion with Sca1 and sequencing. Of the 142 isolates, 62 [43.7%] were found to exhibit the HLGR phenotype. All except one of the HLGR isolates contained the aac[6']Ie-aph[2"]Ia gene. The prevalence of resistance to other antibiotics and multi-drug resistance [MDR] was higher among the HLGR isolates compared to the non-HLGR isolates. Our results indicate that high prevalence rates of MDR and HLGR enterococci are an important problem associated with medical treatment. Furthermore, the presence of the aacaacaac[6']Ie-aph[2"]Ia gene was shown to correspond to the presence of the HLGR phenotype among enterococci

Cost of antimicrobial treatment in patients infected with multidrug-resistant organisms in the Intensive Care Unit / Costo de la terapia antimicrobiana en pacientes infectados con microorganismos multirresistentes en la Unidad de Cuidados Intensivos

This study aims to compare the costs of antimicrobial drugs used in the treatment of patients infected with multidrug-resistant organisms (MDRO) or those not infected with this type of organisms in an intensive care unit (ICU). It is a retrospective comparative case-control study, performed in a public hospital in the capital city of Brazil, comprising the years 2007, 2008 and 2009. Information on age, sex, length of hospitalization, clinical outcome, antimicrobial drugs, microorganisms and microbial sensitivity to antibiotics was collected. Spearman and Mann-Whitney tests were used for statistical analysis. The level of significance was set at p < 0.05. The sample consisted of 401 patients with a mean age of 51.36 years (± 19.68) being 226 (56.4%) male. As for the length of stay, 32.9% of the patients remained more than 20 days, with 195 discharged and 206 deaths. Global cost of antimicrobial treatment was US$ 1113 221.55 during the three year period. Treatment cost for patients with MDRO was higher than for those without (p = 0.010). At least one MDR strain was isolated in 54.6% of the patients. According to these results, nosocomial infections due to MDRO and the high costs involved may endanger the effectiveness of antimicrobial therapy in ICU and Health Centers.

El presente estudio tuvo como objetivo comparar los costos del tratamiento con fármacos antimicrobianos para las infecciones debidas a organismos multirresistentes (OMDR) versus aquellas debidas a gérmenes no multirresistentes, en la Unidad de Cuidados Intensivos (UCI) de un hospital público de Brasilia, Distrito Federal. Fue un estudio retrospectivo, de casos y controles y abarcó un período de tres años (2007, 2008, 2009). Se recolectó información sobre edad, sexo, tiempo de internación, resultados clínicos, antimicrobianos usados, microorganismos aislados y su sensibilidad a los antibióticos. Se utilizaron en el análisis estadístico las pruebas de Spearman y de Mann-Whitney, con p < 0.05. La muestra consistió en 401 pacientes con media de edad de 51.36 años (± 19.68), siendo 226 varones (56.4%). En cuanto al tiempo de internación, un 32.9% de los pacientes permanecieron más de 20 días, con 195 altas y 206 óbitos. El tratamiento antimicrobiano costó US$ 1113 221.55 en los tres años, siendo éste mayor para los que presentaron OMDR que para los que no los presentaron (p = 0.01). Se comprobó la presencia de, por lo menos, un microorganismo multirresistente en el 54.6% de los pacientes. La infección intrahospitalaria con OMDR y el elevado costo del tratamiento de los pacientes infectados con estos microorganismos puede comprometer la efectividad de la terapia antimicrobiana en estas Unidades y Centros de Salud.

Occurrence & antibiogram of Salmonella Typhi & S. Paratyphi A isolated from Rourkela, Orissa.

Background & objectives: Almost round-the-year occurrence of Salmonella Typhi and Salmonella Paratyphi A has been noticed in Rourkela since last 13 and five years respectively. The incidence of infection along with the antibiogram of these two serotypes in this area were carried out. Methods: The study was carried out at Ispat General Hospital, Rourkela, India, between January 2005 and December 2008 with 5340 blood samples collected from patients with suspected enteric fever and pyrexia of unknown origin. Isolation, identification and antibiogram of the causative organisms were performed according to standard bacteriological procedures. Results: A total of 298 Salmonella isolates showed an overall per cent positivity of 5.58. Multidrug resistance was found in 11.96 per cent and 15.62 per cent isolates of S. Typhi and S. Paratyphi A respectively. Less than 2 per cent isolates of Salmonella showed resistance to ciprofloxacin. A resistance of 3.0 to 6.25 per cent against third generation cephalosporins was observed among the salmonella isolates. Interpretation & conclusion: A round-the-year occurrence of Salmonella spp. in Rourkela might have been due to the presence of a considerable number of carriers in the locality, poor sanitation in nearby slum areas, and inadequate and contaminated community water supply at times. Higher degree of susceptibility among S. Typhi isolates against various antibiotics was encouraging, but increasing trend of resistance observed among S. Paratyphi A isolates was a matter of concern.

Betamethasone inhibits tumor development, microvessel density and prolongs survival in mice with a multiresistant adenocarcinoma TA3

Tumor resistance to traditional cancer treatments poses an important challenge to modern science. Thus, angiogenesis inhibition is an important emerging cancer treatment. Many drugs are tested and corticosteroids have shown interesting results. Herein we investigate the effect on microvessel density, survival time and tumoral volume of mice with TA3-MTX-R tumors. Twenty six mice were inoculated with lxlO6 tumor cells, 4-5 days after injection, six mice were injected with PBS (group A) and twenty mice were treated with p-met (group B). All animals from Group A died on day 22. Group B was divided into Bl (treated discontinued) and B2 (treated daily) and observed until day 88. All mice were processed for histo-immunohistochemical analysis and the blood vessels were counted. A decrease in microvessel density and tumoral volume and longer survival times were observed in the treated group. We propose that the antiangiogenic p-met effect explains, at least partially, its tumor inhibitory properties. As an important perspective, we will experimentally combine these strategies with those recently described by us with regard to the important antiangiogenic-antitumor effects of Trypanosoma cruzi calreticulin. Since the molecular targets of these strategies are most likely different, additive or synergic effects are envisaged.

Characterization of methicillin resistant staphylococcal aureus [MRSA] isolates from mansoura university hospitals

Hospital-acquired infections due to MRSA are associated with considerable morbidity, mortality, and excess costs. Our work aimed to study the prevalence, risk factors and genotypic characteristics of MRSA isolates from patients admitted at Mansoura University Hospitals [muhs]. A total 184 of Staphylococcal aureus [SA] clinical specimens were collected from our in-patients between June 2009 to June 2010. Isolated colonies were identified in a systematic manner for selection of MRSA. Oxacillin and cefoxitin resistance tests identified MRSA that were subjected to antibiogram and resistogram. MRSA amplified genes, visualized by agarose gel electrophoresis, were analyzed by Sanger sequencing. Only 49 isolates out of the isolated strains of SA were identified as MRSA strains by cefoxitin disc diffusion test. All strains are resistant to cefoxitin, ceftriaxon, cloxacillin and ampicillin while most strains were susceptible to vancomycin. Sanger sequencing of meca gene showed 3 monographs. MRSA isolates were more from blood samples [F< 0.001] of patients above 60 years [P< 0.001], of low socioeconomic status [P< 0.001], and of >2wks duration hospital stay [P< 0.05], in icus [P< 0.001], with a previous history of hospital admission within the past year [P< 0.001] and a positive history of antibiotic use in the last 6 months [P< 0.001]. Positive family history of chronic disease [P< 0.001] or hospitalization within the last year [P< 0.05] and the presence of family member working in a clinic or a hospital [P< 0.05] were noted in MRSA-positive patients. Our data revealed an increased prevalence of multi-drug resistant MRSA isolates where PCR was of the best choice for their rapid and accurate detection. An effective infection control program should be implemented for appropriate MRSA management

A possible mechanism of macrolide resistance among multiple resistant Campylobacter jejuni and Campylobacter coli isolated from Thai children during 1991-2000.

A total of 495 Campylobacterjejuni and 122 C. coli isolated from Thai children were screened for macrolide (erythromycin and azithromycin) resistance by disk diffusion assay. Minimum inhibitory concentrations for erythromycin, azithromycin, nalidixic acid, ciprofloxacin, tetracycline, streptomycin, gentamicin and chloramphenicol were further determined for these macrolide-resistant Campylobacter isolates. Presence of known point mutations resulting in reduced susceptibility to macrolides was investigated by PCR and DNA sequencing. Seventeen percent (23/122) of C. coli and 2.4% (12/495) of C. jejuni isolates were resistant to macrolides. By sequencing domain V of the 23S ribosomal DNA from all 35 macrolide-resistant isolates, a known point mutation of 23S rRNA associated with reduced susceptibility to macrolides was detected in all isolates except one. Among the macrolide-resistant isolates, all were multiply resistant to nalidixic acid and ciprofloxacin, of which the latter is the preferred antimicrobial used for diarrheal treatment in Thailand. Furthermore, most macrolide-resistant isolates were also resistant to tetracycline and streptomycin. The spread of macrolide and quinolone resistant Campylobacter should be monitored closely in Thailand and elsewhere as these antimicrobials are preferred drugs for treatment of diarrhea.