Pandemia de COVID-19 y evolución de la resistencia a antimicrobianos en bacilos Gram negativos / COVID-19 pandemic and evolution of antimicrobial resistance in Gram negative bacilli

Introducción: La emergencia y diseminación de la re-sistencia a antimicrobianos está vinculada en parte al abuso y/o mal uso de los mismos. La propagación del SARS-CoV-2 implicó un mayor consumo de antibióticos. El objetivo de este trabajo fue analizar los mecanismos de resistencia a betalactámicos (MRB) en bacilos Gram negativos (BGN) y la resistencia a amikacina (R AKN) en Acinetobacter baumannii.Métodos: Se realizó un estudio retrospectivo descriptivo de 2863 muestras con aislamientos de BGN remitidas al sector de Bacteriología del hospital de mayo 2019 a abril 2022. Se definieron tres períodos: mayo 2019-abril 2020 (P0), mayo 2020-abril 2021 (P1) y mayo 2021-abril 2022 (P2).Resultados: En P0 se halló un 15% de MRB. En P1, un 17,7% y en P2, un 21%. La combinación de BLEE+MBL se encontró en un aislamiento de P0, en dos de P1 y en 13 de P2. KPC+MBL se halló en nueve aislamientos de P2. La R AKN en A. baumannii fue de 20,8% en P0, 29,8% en P1 y 42,7% en P2.Conclusiones: Hubo un aumento significativo de aisla-mientos de BGN con MRB. BLEE fue el MRB más frecuente y Klebsiella sp. el microorganismo con MRB aislado con mayor frecuencia. En P2 se observó un aumento de aisla-mientos con combinación de MRB. Se observó diferencia significativa en la R AKN en A. baumannii entre P0 y P2. Con la pandemia de COVID-19 aumentó la cantidad de BGN con MRB y la R AKN en A. baumannii

Introduction: emergency and disemination of antimicrobial resistance is partly linked to abusive or wrong usage of them. The spread of SARS-CoV-2 implied a rise in antibiotics consumption. The aim of this study was to analize the mechanisms of resistance to beta lactams (MRB) in Gram negative bacilli (BGN) and amikacin resistance (R AKN) in Acinetobacter baumannii.Methods: a retrospective, descriptive study was made on 2863 samples with BGN isolates which were remitted to the bacteriology laboratory from May 2019 to April 2022. 3 periods were defined: May 2019 - April 2020 (P0). May 2020 - April 2021 (P1) and May 2021 - April 2022 (P2).Results: in P0, 15% had MRB. In P1, 17,7% and in P2, 21%. Combination of BLEE+MBL was found in 1 isolate of P0, in 2 of P1 and in 13 of P2. KPC+MBL was found in 9 isolates of P2. R AKN in A. baumannii was 20.8% in P0, 29.8% in P1 and 42.7% in P2.Conclusion: there was a significant increase in BGN isolates with MRB. BLEE was the most frequent MRB and Klebsiella sp. the most frequently isolated microorganism with MRB. A significant difference was observed in R AKN in A. baumanii between P0 and P2. After COVID-19 pandemic, there was an increase in the number of BGN with MRB and in R AKN in A. baumannii

High-risk clones of ESBL-producing Klebsiella pneumoniae colonizing ICU patients in Natal, northeastern Brazil / Clones de alto risco de Klebsiella pneumoniae produtores de ESBL colonizando pacientes de UTI em Natal, Nordeste do Brasil / Clones de alto riesgo de Klebsiella pneumoniae productores de BLEE que colonizan pacientes de UCI en Natal, noreste de Brasil

Background and objectives: colonization by extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae in Intensive Care Unit (ICU) patients is considered a risk factor for infections, and poses as a source of spreading these strains in hospital facilities. This study aimed to perform the genetic characterization of ESBL-producing K. pneumoniae isolates recovered from surveillance swabs in an ICU in northeastern Brazil. Methods: the isolates were recovered between 2018-2019 from the nasal, axillary, and rectal sites of 24 patients admitted to the ICU. Bacterial identification was performed by traditional biochemical tests. Antimicrobial susceptibility was assessed by disk diffusion, and ESBL phenotype was detected by double-disc synergy test. Polymerase chain reaction (PCR) for blaCTX-M, blaSHV, and blaTEM genes, PFGE, and MLST were carried out in representative isolates. Results: a total of 27 isolates were recovered from 18 patients (75%). The ESBL production was detected in 85% of isolates. Resistance to ciprofloxacin, sulfamethoxazole/trimethoprim and most of the ß-lactams tested was recurrent, except for carbapenems. The blaSHV, blaTEM, and blaCTX-M genes were found in high frequency, and the CTX-M-(1, 2 and 9) groups were identified. Seven sequence types (ST11, ST14, ST17, ST395, ST709, ST855, and ST3827) were described, most of them considered high-risk. Conclusion: these findings emphasize the potential threat of well-established high-risk clones in an ICU, and highlight the importance of monitoring these clones to prevent infections.(AU)

Justificativa e objetivos: a colonização por Klebsiella pneumoniae produtora de ß-lactamase de espectro estendido (ESBL) em pacientes de Unidade de Terapia Intensiva (UTI) é considerada um fator de risco para infecções, e representa uma fonte de disseminação dessas cepas em instalações hospitalares. Este estudo objetivou realizar a caracterização genética de isolados de K. pneumoniae produtores de ESBL recuperados de swabs de vigilância em uma UTI no Nordeste do Brasil. Métodos: os isolados foram recuperados entre 2018-2019 dos sítios nasal, axilar e retal de 24 pacientes internados na UTI. A identificação bacteriana foi realizada por testes bioquímicos tradicionais. A suscetibilidade antimicrobiana foi avaliada por disco-difusão, e o fenótipo ESBL foi detectado pelo teste de sinergia de duplo-disco. Polymerase chain reaction (PCR) para os genes blaCTX-M, blaSHV e blaTEM, PFGE e MLST foram realizados em isolados representativos. Resultados: foram recuperados 27 isolados de 18 pacientes (75%). A produção de ESBL foi detectada em 85% dos isolados. A resistência à ciprofloxacina, sulfametoxazol/trimetoprima e à maioria dos ß-lactâmicos testados foi recorrente, exceto para os carbapenêmicos. Os genes blaSHV, blaTEM e blaCTX-M foram encontrados em alta frequência, e os grupos CTX-M-(1, 2 e 9) foram identificados. Sete sequence types (ST11, ST14, ST17, ST395, ST709, ST855 e ST3827) foram descritos, a maioria deles considerados de alto risco. Conclusão: esses achados enfatizam a ameaça potencial de clones de alto risco bem estabelecidos em uma UTI, e destacam a importância do monitoramento desses clones para prevenir infecções.(AU)

Justificación y objetivos: la colonización por Klebsiella pneumoniae productora de ß-lactamasas de espectro extendido (BLEE) en pacientes de Unidades de Cuidados Intensivos (UCI) se considera un factor de riesgo para infecciones, y se presenta como una fuente de propagación de estas cepas en instalaciones hospitalarias. Este estudio tuvo como objetivo realizar la caracterización genética de aislamientos de K. pneumoniae productores de BLEE recuperados de hisopos de vigilancia en una UCI en el noreste de Brasil. Métodos: los aislamientos se recuperaron entre 2018-2019 de sitios nasales, axilares y rectales de 24 pacientes ingresados en la UCI. La identificación bacteriana se realizó mediante pruebas bioquímicas tradicionales. La susceptibilidad antimicrobiana se evaluó mediante difusión en disco, y el fenotipo BLEE se detectó mediante la prueba de sinergia de doble-disco. La polymerase chain reaction (PCR) para los genes blaCTX-M, blaSHV y blaTEM, PFGE y MLST se llevaron a cabo en aislamientos representativos. Resultados: se recuperaron 27 aislamientos de 18 pacientes (75%). La producción de ESBL se detectó en 85% de los aislamientos. La resistencia a ciprofloxacino, sulfametoxazol/trimetoprima y a la mayoría de los ß-lactámicos evaluados fue recurrente, excepto a los carbapenémicos. Los genes blaSHV, blaTEM y blaCTX-M se encontraron en alta frecuencia, y se identificaron los grupos CTX-M-(1, 2 y 9). Se describieron siete sequence types (ST11, ST14, ST17, ST395, ST709, ST855 y ST3827), la mayoría consideradas de alto riesgo. Conclusión: estos hallazgos enfatizan la amenaza potencial de los clones de alto riesgo bien establecidos en una UCI, y resaltan la importancia de monitorear estos clones para prevenir infecciones.(AU)

Úlceras de pie diabético infectadas con bacterias multirresistentes a los antimicrobianos en pacientes venezolanos / Diabetic Foot Ulcers Infected with Bacteria Multiresistant to Antimicrobials in Venezuelan patients

Introducción: Las úlceras de pie diabético tienen una importante morbimortalidad, más aun, si están asociadas a bacterias multirresistentes a los antimicrobianos. Objetivo: Analizar las características de las úlceras de pie diabético infectadas con bacterias multirresistentes a los antimicrobianos. Métodos: Se realizó una investigación descriptiva, no experimental y transversal, en 87 pacientes con úlceras de pie diabético infectadas, atendidos en una consulta especializada del estado Zulia, Venezuela. Se realizó la anamnesis y exploración física, especialmente centrada en las características de las úlceras de pie diabético. Se obtuvieron muestras de tejido ulceroso para identificar las bacterias presentes y el antimicrobiano correspondiente. Resultados: Todos los pacientes tenían úlcera previa, con agudización de la infección (75,86 por ciento), rehospitalización (59,77 por ciento), amputación previa (36,78 por ciento), úlceras de pie diabético infectadas de larga duración (86,21 por ciento). El 95,40 por ciento recibieron antibióticos previos y 57,62 por ciento habían sido hospitalizados, la antigüedad de la enfermedad fue 16,17 ± 8,41 años y la HbA1c 8,87 ± 1,23. Las úlceras de pie diabético infectadas más frecuente fue neuroisquémica (71,26 por ciento). Predominó la flora monomicrobiana con un (62,07 por ciento) y bacterias gramnegativas (87,36 por ciento). El 79,3 por ciento presentaron bacterias multirresistentes a los antimicrobianos y el 20,69 por ciento panresistencia. Las bacterias multirresistentes fueron predominantemente gramnegativas, y para las grampositivas solo estuvo el Staphylococcus aureus. Conclusiones: Se presenció una alta frecuencia de úlceras de pie diabético infectadas con multirresistencia, predominantemente monomicrobianas y todas con resistencia a betalactámicos y fluoroquinolonas(AU)

Introduction: Diabetic foot ulcers have significant morbidity and mortality, even more so if they are associated with multi-resistant bacteria to antimicrobials. Objective: To analyze the characteristics of diabetic foot ulcers infected with bacteria multi-resistant to antimicrobials. Methods: A descriptive, non-experimental and cross-sectional investigation was carried out in 87 patients with infected diabetic foot ulcers. They were treated in a specialized clinic in Zulia state, Venezuela. Anamnesis and physical examination were performed, especially focused on the characteristics of diabetic foot ulcers. Ulcer tissue samples were obtained to identify the bacteria existing and the corresponding antimicrobial. Results: All the patients had previous ulcer, with exacerbation of the infection (75.86percent), rehospitalization (59.77percent), previous amputation (36.78percent), long-lasting infected diabetic foot ulcers (86.21percent). 95.40percent received previous antibiotics and 57.62percent had been hospitalized, the disease age was 16.17 ± 8.41 years and Hb A1c was 8.87 ± 1.23. The most frequent infected diabetic foot ulcers were neuroischemic (71.26percent). The monomicrobial flora (62.07percent) and gram-negative bacteria (87.36percent) predominated. 79.3percent had multi-resistant bacteria to antimicrobials and 20.69percent pan-resistance. Multi-resistant bacteria were predominantly gram-negative and for gram-positive only staphylococcus aureus. Conclusions: High frequency of multidrug-resistant infected diabetic foot ulcers was found, predominantly monomicrobial and all with resistance to beta-lactams and fluoroquinolones(AU)

Caracterización molecular del dominio de la hélice del gen k13 de Plasmodium falciparum en muestras de comunidades nativas de Condorcanqui, Amazonas, Perú / Molecular characterization of the Plasmodium falciparum k13 gene helix domain in samples from native communities of Condorcanqui, Amazonas, Perú

Introducción. La resistencia de Plasmodium falciparum a diferentes fármacos antipalúdicos es un obstáculo para eliminar la enfermedad. El genotipo resistente de P. falciparum a la artemisinina puede evaluarse examinando los polimorfismos en el dominio de la hélice del gen Pfk13. La Organización Mundial de la Salud recomienda utilizar estas mutaciones como marcadores moleculares para detectar la resistencia a la artemisinina en países donde la malaria por P. falciparum es endémica. Objetivo. Identificar mutaciones relacionadas con la resistencia a artemisinina presentes en el dominio de la hélice del gen k13 de P. falciparum. Materiales y métodos. Mediante la detección pasiva de casos, se recolectaron 51 muestras positivas por microscopía para Plasmodium, provenientes de seis comunidades del distrito de Río Santiago en Condorcanqui, Amazonas. Se realizó la confirmación molecular de la especie mediante PCR en tiempo real y el dominio de la hélice del gen Pfk13 se amplificó y secuenció por electroforesis capilar. Las secuencias obtenidas se compararon con la cepa de referencia 3D7 de fenotipo silvestre. Resultados. Se confirmó un total de 51 muestras positivas para P. falciparum, provenientes de las comunidades de Ayambis, Chapiza, Palometa, Muchinguis, Alianza Progreso y Caterpiza. Después del alineamiento de las secuencias de ADN, se determinó que las muestras no presentaron mutaciones asociadas con resistencia en el gen K13. Discusión. Los resultados obtenidos son coherentes con estudios similares realizados en otros países de Sudamérica, incluyendo Perú. Estos datos proporcionan una línea base para la vigilancia molecular de resistencia a artemisinina en la región Amazonas y refuerzan la eficacia de la terapia combinada con artemisinina en esta área.

Introduction. Resistance of Plasmodium falciparum to different antimalarial drugs is an obstacle to disease elimination. The artemisinin-resistant genotype of P. falciparum can be assessed by examining polymorphisms in the helix domain of the Pfk13 gene. The World Health Organization recommends these mutations as molecular markers to detect artemisinin-resistant in countries where P. falciparum malaria is endemic. Objective. To identify artemisinin resistance-related mutations present in the helix domain of the P. falciparum k13 gene. Materials and methods. We collected a total of 51 samples through passive case detection, positive for Plasmodium by microscopy, from six communities in the district of Río Santiago in Condorcanqui, Amazonas. Molecular species confirmation was performed by real-time PCR and Pfk13 helix domain was amplified and sequenced by capillary electrophoresis. The obtained sequences were compared with the wild type 3D7 reference strain. Results. A total of 51 positive samples were confirmed for P. falciparum from the communities of Ayambis, Chapiza, Palometa, Muchinguis, Alianza Progreso and Caterpiza. DNA sequences alignment showed the absence of resistance-associated mutations in the k13 gene of the collected samples. Discussion. The obtained results are consistent with similar studies conducted in other South American countries, including Perú, so these data provide a baseline for artemisinin- resistance molecular surveillance in the Amazon region and reinforce the efficacy of artemisinin-based combination therapy in this area.

Artemisinin drug resistance and monitoring: a narrative review

Artemisinin drug resistance is one of the major reasons for malaria treatment failures in the sub-Saharan African countries where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria. The occurrence of single nucleotide polymorphisms (SNPs) is found to correlate with antimalarial drug resistance. With artemisinin, the SNPs occurs at the Kelch 13-propeller gene locus on chromosome 13. The artemisinin drug resistance surveillance strategy involves continuous monitoring of Kelch 13-propeller biomarker to detect emergence of mutations which could herald drug resistance in the region. In this narrative review paper, we examined existing literature to bridge the knowledge gap and accentuate the importance of routine surveillance for artemisinin resistance in sub-Saharan Africa. We conducted our search on PubMed database and Google Scholar to identify peer-reviewed articles, reports, and abstracts on artemisinin drug resistance using the following keywords; 'artemisinin drug resistance', 'antimalarial drug resistance', 'artemisinin-based combination therapy', 'Kelch 13-propeller', 'K13- propeller gene', and 'K13 molecular marker'. The review provided pertinent information on artemisinin derivatives, artemisinin-based combination therapy, molecular action of artemisinin, definition of artemisinin resistance, genetic basis of artemisinin drug resistance and discovery of Kelch 13, and the importance of artemisinin resistance surveillance. Molecular surveillance can provide healthcare policy makers a forecast of impending threats to malaria treatment. This is more so when drugs are in combination therapy, for instance, molecular surveillance can give a hint that one drug is failing despite the fact that in combination, it is still apparently clinically effective.

La résistance aux médicaments à base d'artémisinine est l'une des principales raisons des échecs du traitement du paludisme dans les pays d'Afrique subsaharienne où la polythérapie à base d'artémisinine (ACT) est le traitement de première intention du paludisme simple. L'apparition de polymorphismes mononucléotidiques (SNP) est corrélée à la résistance aux médicaments antipaludiques. Avec l'artémisinine, les SNP se produisent au locus du gène Kelch 13- propeller sur le chromosome 13. La stratégie de surveillance de la résistance aux médicaments à base d'artémisinine implique une surveillance continue du biomarqueur Kelch 13-propeller pour détecter l'émergence de mutations qui pourraient annoncer une résistance aux médicaments dans la région. Dans cet article de revue narrative, nous avons examiné la littérature existante pour combler le manque de connaissances et accentuer l'importance de la surveillance de routine de la résistance à l'artémisinine en Afrique subsaharienne. Nous avons effectué notre recherche sur la base de données PubMed et Google Scholar pour identifier des articles, des rapports et des résumés évalués par des pairs sur la résistance aux médicaments à base d'artémisinine en utilisant les mots-clés suivants; «résistance aux médicaments à base d'artémisinine¼, «résistance aux médicaments antipaludiques¼, «thérapie combinée à base d'artémisinine¼, «Kelch 13-propeller¼, «gène K13-propeller¼ et «marqueur moléculaire K13¼. L'examen a fourni des informations pertinentes sur les dérivés de l'artémisinine, la polythérapie à base d'artémisinine, l'action moléculaire de l'artémisinine, la définition de la résistance à l'artémisinine, la base génétique de la résistance aux médicaments à base d'artémisinine et la découverte de Kelch 13, ainsi que l'importance de la surveillance de la résistance à l'artémisinine. La surveillance moléculaire peut fournir aux responsables des politiques de santé une prévision des menaces imminentes pour le traitement du paludisme. C'est d'autant plus vrai lorsque les médicaments sont en thérapie combinée, par exemple, la surveillance moléculaire peut donner un indice qu'un médicament échoue malgré le fait qu'en combinaison, il est toujours apparemment cliniquement efficace.

Advances in Modeling of Multiple Myeloma in Mice / 中国医学科学院学报

Multiple myeloma(MM)is a systemic malignancy of plasma cells.Nowadays,the basic research on MM is flourishing with the continuous optimization and innovation of mouse models of MM.Heterologous mouse models of MM established with human-derived cells and immunodeficient mice have been applied in assessing drug efficacy,exploring drug resistance mechanisms,and observing tumor-bone marrow microenvironment interactions.In the last decades,the homologous mouse models of MM established with murine-derived cells or gene-editing technologies have been widely used in the research on the pathogenesis and drug development.Additionally,the stable modeling of targeted organ injury will be a key problem to be tackled in this field.This review summarizes the characteristics and application progress of mouse models of MM.

Fixation of pfcrt chloroquine resistance alleles in Plasmodium falciparum clinical isolates collected from unrest tribal agencies of Pakistan / Fixação de alelos de resistência à cloroquina pfcrt em isolados clínicos de Plasmodium falciparum coletados de agitações de agências tribais do Paquistão

Abstract Plasmodium falciparum resistance to Chloroquine (CQ) is a significant cause of mortality and morbidity worldwide. There is a paucity of documented data on the prevalence of CQ-resistant mutant haplotypes of Pfcrt and Pfmdr1 genes from malaria-endemic war effected Federally Administered Tribal Areas of Pakistan. The objective of this study was to investigate the prevalence of P. falciparum CQ-resistance in this area. Clinical isolates were collected between May 2017 and May 2018 from North Waziristan and South Waziristan agencies of Federally Administrated Trial Area. Subsequently, Giemsa-stained blood smears were examined to detect Plasmodium falciparum. Extraction of malarial DNA was done from microscopy positive P. falciparum samples, and P. falciparum infections were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes). All PCR confirmed P. falciparum samples were sequenced by pyrosequencing to find out mutation in Pfcrt gene at codon K76T and in pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y. Out of 121 microscopies positive P. falciparum cases, 109 samples were positive for P. falciparum by nested PCR. Pfcrt K76T mutation was found in 96% of isolates, Pfmdr1 N86Y mutation was observed in 20%, and 11% harboured Y184F mutation. All samples were wild type for Pfmdr1 codon N1042D and D1246Y. In the FATA, Pakistan, the frequency of resistant allele 76T remained high despite the removal of CQ. However, current findings of the study suggest complete fixation of P. falciparum CQ-resistant genotype in the study area.

Resumo A resistência do Plasmodium falciparum à cloroquina (CQ) é uma causa significativa de mortalidade e morbidade em todo o mundo. Há uma escassez de dados documentados sobre a prevalência de haplótipos mutantes CQ-resistentes dos genes Pfcrt e Pfmdr1 da guerra endêmica da malária em áreas tribais administradas pelo governo federal do Paquistão. O objetivo deste estudo foi investigar a prevalência de resistência a CQ de P. falciparum nesta área. Isolados clínicos foram coletados entre maio de 2017 e maio de 2018 nas agências do Waziristão do Norte e do Waziristão do Sul da Área de Ensaio Administrada Federalmente. Posteriormente, esfregaços de sangue corados com Giemsa foram examinados para detectar Plasmodium falciparum. A extração do DNA da malária foi feita a partir de amostras de P. falciparum positivas para microscopia, e as infecções por P. falciparum foram confirmadas por nested PCR (visando genes de ácido ribonucleico ribossômico de subunidade pequena de Plasmodium (ssrRNA)). Todas as amostras de P. falciparum confirmadas por PCR foram sequenciadas por pirosequenciamento para descobrir a mutação no gene Pfcrt no códon K76T e em pfmdr1 nos códons N86Y, Y184F, N1042D e D1246Y. De 121 microscopias de casos positivos de P. falciparum, 109 amostras foram positivas para P. falciparum por nested PCR. A mutação Pfcrt K76T foi encontrada em 96% dos isolados, a mutação Pfmdr1 N86Y foi observada em 20% e 11% abrigou a mutação Y184F. Todas as amostras eram do tipo selvagem para o códon N1042D e D1246Y de Pfmdr1. No FATA, Paquistão, a frequência do alelo resistente 76T permaneceu alta apesar da remoção de CQ. No entanto, as descobertas atuais do estudo sugerem a fixação completa do genótipo resistente a CQ de P. falciparum na área de estudo.

Drug resistance and genomic characteristics of Salmonella enterica serovar London from clinical and food sources in Hangzhou City from 2017 to 2021 / 中华预防医学杂志

Objective: To analyze the drug resistance and genomic characteristics of Salmonella enterica serovar London isolated from clinical and food sources in Hangzhou City from 2017 to 2021. Methods: A total of 91 Salmonella enterica serovar London strains isolated from Hangzhou City from 2017 to 2021 were analyzed for drug susceptibility, pulsed field gel electrophoresis (PFGE) typing and whole genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and detection of drug resistance genes were performed by using the sequencing data. Phylogenetic analysis was conducted to compare the 91 genomes from Hangzhou City with 347 genomes from public databases. Results: No significant difference in the drug resistance rate was observed between clinical strains and food strains to 18 drugs in Hangzhou City(all P>0.05), and the multidrug resistance (MDR) rate was 75.8% (69/91). Most strains were resistant to 7 drug classes simultaneously. One strain was resistant to Polymyxin E as well as positive for mcr-1.1, and 50.5% (46/91) of the strains were resistant to Azithromycin and were positive for mph(A). All 91 Salmonella enterica serovar London strains were ST155, which were subdivided into 44 molecular types by PFGE and 82 types by cgMLST. Phylogenetic analysis showed that most strains from Hangzhou City (83/91) were clustered together, and a small number of human isolates from Europe, North America and pork isolates from Hubei and Shenzhen were mixed in the cluster. Other strains from Hangzhou City (8/91) were closely related to strains from Europe, America and Southeast Asia. Strains isolated from pork were the most closely related to clinical strains. Conclusion: The epidemic of Salmonella enterica serovar London in Hangzhou City is mainly caused by the spread of ST155 strains, which is mainly transmitted locally. At the same time, cross-region transmission to Europe, North America, Southeast Asia, and other provinces and cities in China may also occur. There is no significant difference in the drug resistance rate between clinical strains and food strains, and a high level of MDR is found in the strains. Clinical infection of Salmonella enterica serovar London may be closely related to pork consumption in Hangzhou City.

Fixation of pfcrt chloroquine resistance alleles in Plasmodium falciparum clinical isolates collected from unrest tribal agencies of Pakistan / Fixação de alelos de resistência à cloroquina pfcrt em isolados clínicos de Plasmodium falciparum coletados de agitações de agências tribais do Paquistão

Plasmodium falciparum resistance to Chloroquine (CQ) is a significant cause of mortality and morbidity worldwide. There is a paucity of documented data on the prevalence of CQ-resistant mutant haplotypes of Pfcrt and Pfmdr1 genes from malaria-endemic war effected Federally Administered Tribal Areas of Pakistan. The objective of this study was to investigate the prevalence of P. falciparum CQ-resistance in this area. Clinical isolates were collected between May 2017 and May 2018 from North Waziristan and South Waziristan agencies of Federally Administrated Trial Area. Subsequently, Giemsa-stained blood smears were examined to detect Plasmodium falciparum. Extraction of malarial DNA was done from microscopy positive P. falciparum samples, and P. falciparum infections were confirmed by nested PCR (targeting Plasmodium small subunit ribosomal ribonucleic acid (ssrRNA) genes). All PCR confirmed P. falciparum samples were sequenced by pyrosequencing to find out mutation in Pfcrt gene at codon K76T and in pfmdr1 at codons N86Y, Y184F, N1042D, and D1246Y. Out of 121 microscopies positive P. falciparum cases, 109 samples were positive for P. falciparum by nested PCR. Pfcrt K76T mutation was found in 96% of isolates, Pfmdr1 N86Y mutation was observed in 20%, and 11% harboured Y184F mutation. All samples were wild type for Pfmdr1 codon N1042D and D1246Y. In the FATA, Pakistan, the frequency of resistant allele 76T remained high despite the removal of CQ. However, current findings of the study suggest complete fixation of P. falciparum CQ‑resistant genotype in the study area.

A resistência do Plasmodium falciparum à cloroquina (CQ) é uma causa significativa de mortalidade e morbidade em todo o mundo. Há uma escassez de dados documentados sobre a prevalência de haplótipos mutantes CQ-resistentes dos genes Pfcrt e Pfmdr1 da guerra endêmica da malária em áreas tribais administradas pelo governo federal do Paquistão. O objetivo deste estudo foi investigar a prevalência de resistência a CQ de P. falciparum nesta área. Isolados clínicos foram coletados entre maio de 2017 e maio de 2018 nas agências do Waziristão do Norte e do Waziristão do Sul da Área de Ensaio Administrada Federalmente. Posteriormente, esfregaços de sangue corados com Giemsa foram examinados para detectar Plasmodium falciparum. A extração do DNA da malária foi feita a partir de amostras de P. falciparum positivas para microscopia, e as infecções por P. falciparum foram confirmadas por nested PCR (visando genes de ácido ribonucleico ribossômico de subunidade pequena de Plasmodium (ssrRNA)). Todas as amostras de P. falciparum confirmadas por PCR foram sequenciadas por pirosequenciamento para descobrir a mutação no gene Pfcrt no códon K76T e em pfmdr1 nos códons N86Y, Y184F, N1042D e D1246Y. De 121 microscopias de casos positivos de P. falciparum, 109 amostras foram positivas para P. falciparum por nested PCR. A mutação Pfcrt K76T foi encontrada em 96% dos isolados, a mutação Pfmdr1 N86Y foi observada em 20% e 11% abrigou a mutação Y184F. Todas as amostras eram do tipo selvagem para o códon N1042D e D1246Y de Pfmdr1. No FATA, Paquistão, a frequência do alelo resistente 76T permaneceu alta apesar da remoção de CQ. No entanto, as descobertas atuais do estudo sugerem a fixação completa do genótipo resistente a CQ de P. falciparum na área de estudo.

Analysis of tuberculosis epidemiological characteristics and drug resistance among the floating population in Beijing in 2019 / 中华流行病学杂志

Objective: To analyze the epidemic characteristics and drug resistance of pulmonary tuberculosis among the floating population in Beijing and to provide a scientific basis for formulating strategies for the prevention and control of tuberculosis among the floating population. Methods: Data of tuberculosis patients who were positive for Mycobacterium tuberculosis culture was collected from 16 districts and one municipal institution of tuberculosis control and prevention in Beijing in 2019. The strain samples were tested for drug sensitivity by the proportional method. According to household registration location, patients were divided into the floating population and Beijing registration. SPSS 19.0 software analyzed tuberculosis patients' epidemic characteristics and drug resistance in the floating population. Results: In 2019, there were 1 171 culture-positive tuberculosis patients in Beijing, among the floating population, 593 (50.64%) patients were identified, with a male-to-female sex ratio of 2.2∶1 (409∶184). Compared to patients under household registration as Beijing residents, a higher proportion of young adults aged 20-39 years (65.09%,386/593) were noticed, with 55.65% (330/593) reported from the urban areas and 96.80% (574/593) were reported the first time. The differences were statistically significant (all P<0.05). After completing the drug sensitivity test, 37 cases were with multiple drug-resistant tuberculosis, accounting for 6.24% (37/593). The rates of isoniazid resistance (42.11%,8/19) and multidrug resistance (21.05%,4/19) in floating population patients after retreatment were significantly higher than those in newly treated patients (11.67%, 67/574 and 5.75%, 33/574), and the differences were statistically significant (all P<0.05). Conclusions: Most patients with tuberculosis in the floating population in Beijing in 2019 were young males aged 20-39 years. The reporting areas were urban areas and the newly treated patients mainly. The patients with tuberculosis in the re-treated floating population were more likely to suffer from multidrug and drug resistance, which should be taken as the key population for prevention and control.

Effect of MiR-424-5p on the Drug Resistance of Diffuse Large B-Cell Lymphoma Cells by Regulating PD-1/PD-L1 Signaling Pathway / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of microRNA-424-5p (miR-424-5p) on the drug resistance of diffuse large B-cell lymphoma (DLBCL) cells by regulating the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling pathway.@*METHODS@#Human DLBCL cell line CRL2631 cells were induced to construct CRL2631-CHOP resistant cell line. RT-qPCR and Western blot were used to detect the expression levels of MiR-424-5p, PD-L1 mRNA and protein, and multidrug resistance gene-1 (MDR-1) protein in CRL2631 cells and CRL2631-CHOP cells, respectively. The target genes of MiR-424-5p was verified by dual luciferase reporter assay. The miRNA simulation/interference technology and thiazole blue (MTT) method were used to detect the resistance of CRL2631 cells and CRL2631-CHOP cells to CHOP.@*RESULTS@#Compared with CRL2631 cells, the drug resistance of CRL2631-CHOP cells to CHOP and the levels of MDR-1 protein (P<0.05), PD-L1 mRNA and protein in the cells were significantly increased (both P<0.001), while the relative level of MiR-424-5p was significantly reduced (P<0.001). The result of the dual luciferase reporter assay showed that PD-L1 was the direct downstream target gene of MiR-424-5p (P<0.001). After transfection of MiR-424-5p inhibitor, the resistance of CRL2631 cells to CHOP drugs increased, and the expression level of MDR-1 protein (P<0.01), PD-L1 mRNA and protein also increased significantly (both P<0.01). After transfection of MiR-424-5p mimics, the resistance of CRL2631-CHOP cells to CHOP drugs decreased, and the expression level of MDR-1 protein (P<0.001), PD-L1 mRNA and protein also decreased significantly (both P<0.001). Overexpression of PD-L1 could reverse the inhibitory effect of upregulating MiR-424-5p on PD-L1 (P<0.001).@*CONCLUSION@#Down-regulation of MiR-424-5p enhances the drug resistance of DLBCL cells by regulating the PD-1/PD-L1 signaling pathway.

An autophagy-related gene prognostic index predicting biochemical recurrence, metastasis, and drug resistance for prostate cancer / 亚洲男科学杂志(英文版)

Given the dual role of autophagy presenting in tumorigenesis and inhibition, we established an autophagy-related gene prognostic index (ARGPI) with validation to well predict the biochemical recurrence (BCR), metastasis, as well as chemoresistance for patients with prostate cancer (PCa) who underwent radical radiotherapy or prostatectomy. Then, Lasso and COX regression was used to develop the ARGPI. We performed the whole analyses through R packages (version 3.6.3). Secreted phosphoprotein 1 (SPP1), single-minded 2 (SIM2), serine protease inhibitor b5 (SERPINB5), aldehyde dehydrogenase 2 (ALDH2), and acyl-CoA synthetase long-chain 3 (ACSL3) were eventually used to establish the ARGPI score. Patients were divided into two different-risk groups based on the median ARGPI score, high-risk patients with a higher risk of BCR than low-risk patients (hazard ratio [HR]: 5.46, 95% confidence interval [CI]: 3.23-9.24). The risk of metastasis of high-risk patients was higher than low-risk patients (HR: 11.31, 95% CI: 4.89-26.12). In The Cancer Genome Atlas (TCGA) dataset, we observed similar prognostic value of ARGPI in terms of BCR-free survival (HR: 1.79, 95% CI: 1.07-2.99) and metastasis-free survival (HR: 1.80, 95% CI: 1.16-2.78). ARGPI score showed a diagnostic accuracy of 0.703 for drug resistance. Analysis of gene set enrichment analysis (GSEA) indicated that patients in the high-risk group were significantly positively related to interleukin (IL)-18 signaling pathway. Moreover, ARGPI score was significantly related to cancer-related fibroblasts (CAFs; r = 0.36), macrophages (r = 0.28), stromal score (r = 0.38), immune score (r = 0.35), estimate score (r = 0.39), as well as tumor purity (r = -0.39; all P < 0.05). Drug analysis showed that PI-103 was the common sensitive drug and cell line analysis indicated that PC3 was the common cell line of PI-103 and the definitive gene. In conclusion, we found that ARGPI could predict BCR, metastasis, and chemoresistance in PCa patients who underwent radical radiotherapy or prostatectomy.

Research progress on drug resistance of anti-varicella-zoster virus drugs / 中华预防医学杂志

Varicella-zoster virus (VZV) causes chickenpox when it first infects humans, and the virus may reactivate in adulthood and cause herpes zoster (HZ). Broad-spectrum antiviral drugs are one of the treatments for varicella and herpes zoster, but the emergence of drug resistance poses many challenges to this treatment and increases the burden of disease on patients. This paper discusses the resistance mechanisms, resistance sites and resistance detection methods of anti-VZV drugs in order to help further research on new anti-VZV targets, new drugs and monitoring of resistance to existing drugs.

Distribution and Drug Sensitivity Analysis of Pathogenic Bacteria Isolated from Patients in Hematology Department / 中国实验血液学杂志

OBJECTIVE@#To investigate the distribution and drug sensitivity of pathogenic bacteria isolated from patients in hematology department, in order to provide evidence for rational use of antibiotics in clinic.@*METHODS@#The distribution of pathogenic bacteria and drug sensitivity data of patients in the hematology department of The First Affiliated Hospital of Nanjing Medical University from 2015 to 2020 were retrospectively analyzed, and the pathogens isolated from different specimen types were compared.@*RESULTS@#A total of 2 029 strains of pathogenic bacteria were isolated from 1 501 patients in the hematology department from 2015 to 2020, and 62.2% of which were Gram-negative bacilli, mainly Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii. Gram-positive coccus accounted for 18.8%, mainly Coagulase-negative staphylococcus (CoNS) and Staphylococcus aureus. Fungi (17.4%) were mainly candida. The 2 029 strains were mainly isolated from respiratory tract (35.1%), blood (31.8%) and urine (19.2%) specimens. Gram-negative bacilli were the main pathogenic bacteria in different specimen types (>60%). K. pneumoniae, S. maltophilia and A. baumannii were the most common pathogens in respiratory specimens, E. coli, CoNS, K. pneumoniae and P. aeruginosa were common in blood samples, and E. coli and Enterococcus were most common in urine samples. Enterobacteriaceae had the highest susceptibility to amikacin and carbapenems (>90.0%), followed by piperacillin/tazobactam. P. aeruginosa strains had high sensitivity to antibiotics except aztreonam (<50.0%). The susceptibility of A. baumannii to multiple antibiotics was less than 70.0%. The antimicrobial resistance rates of E. coli and K. pneumoniae in respiratory tract specimens were higher than those in blood specimens and urine specimens.@*CONCLUSION@#Gram-negative bacilli are the main pathogenic bacteria isolated from patients in hematology department. The distribution of pathogens is different in different types of specimens, and the sensitivity of each strain to antibiotics is different. The rational use of antibiotics should be based on different parts of infection to prevent the occurrence of drug resistance.

Egr-1 Enhances Drug Resistance of Breast Cancer Cells by MDR1 Dependence

Abstract Paclitaxel (PTX) is one of the most effective drugs used in the treatment of breast cancer. Nonetheless, the appearance of MDR1 (multidrug resistance 1) in tumor cells has become a significant hindrance for efficacious chemotherapy. In this study, we show that the expression level of Egr-1 (early growth response gene-1) in cancer tissues (from paclitaxel chemotherapy failure patients) and MCF-7/PTX cells (the breast cancer cell line that was resistant to paclitaxel) was increased. Cell proliferation assay and apoptosis assay revealed that Egr-1 could promote cell growth and inhibit apoptosis in MCF-7/PTX. Mechanistic studies indicated that Egr-1 could bind to the proximal MDR1 promoter and enhance MDR1 transcription. These findings indicate that paclitaxel induced Egr-1 accumulation and upregulated the expression of MDR1, thereby inducing the drug resistance in MCF-7/PTX. Our results suggest a novel pathway by which paclitaxel induces MDR1 expression, possibly illuminating a potential target pathway for the prevention of MDR1-mediated drug resistance.

Mecanismos de expressão de resistência aos antibióticos e saúde pública / Mechanisms of expression of resistance to antibiotics and public health / Mecanismos de expresión de la resistencia a los antibióticos y salud pública

Com o avanço da medicina e o aumento do uso de antimicrobianos, a resistência microbiana vem se tornando um problema sério na saúde pública. Para que uma bactéria se torne resistente, são necessários vários fatores, entre eles, o uso indiscriminado e prolongado de antimicrobianos e as resistências intrínsecas e adquiridas. Nesse contexto, o objetivo do trabalho foi explorar os mecanismos de ação dos antimicrobianos, de resistência e a sua importância na saúde pública. Foram utilizadas para a presente pesquisa, as bases de dados Pubmed, Google acadêmico e Scielo. Segundo a Organização Mundial da Saúde define-se resistência ao antibiótico quando o mesmo não produz mais efeito. A inserção cada vez mais frequente de antimicrobianos favorece a resistência, onde provocam uma pressão seletiva sobre os microrganismos, tornando-os resistentes a diversas drogas. O uso indiscriminado de antimicrobianos é o principal fator de resistência microbiana, assim como o uso de antimicrobianos sem exame de cultura e teste de sensibilidade. Neste sentido, conclui-se que é de suma importância a atualização de protocolos que contenham os mecanismos de resistência bacteriana a fim de minimizar o uso indiscriminado de antimicrobianos, assim como capacitar os profissionais da saúde para este problema na saúde pública.

With the advance of medicine and the increase in the use of antimicrobials, microbial resistance has become a serious problem in public health. For a bacterium to become resistant, several factors are necessary, among them, the indiscriminate and prolonged use of antimicrobials and the intrinsic and acquired resistance. In this context, the objective of the work was to explore the mechanisms of action of antimicrobials, resistance and their importance in public health. Pubmed, Google academic and Scielo databases were used for this research. According to the World Health Organization, resistance to antibiotics is defined when it no longer has an effect. The increasingly frequent insertion of antimicrobials favors resistance, where they put selective pressure on microorganisms, making them resistant to various drugs. The indiscriminate use of antimicrobials is the main factor of microbial resistance, as well as the use of antimicrobials without culture examination and sensitivity test. In this sense, it is concluded that it is extremely important to update protocols that contain the mechanisms of bacterial resistance in order to minimize the indiscriminate use of antimicrobials, as well as to train health professionals for this problem in public health.

Con los avances de la medicina y el mayor uso de antimicrobianos, la resistencia microbiana se ha convertido en un grave problema de salud pública. Para que una bacteria se vuelva resistente son necesarios varios factores, entre ellos, el uso indiscriminado y prolongado de antimicrobianos y la resistencia intrínseca y adquirida. En este contexto, el objetivo de este trabajo fue explorar los mecanismos de acción de los antimicrobianos, la resistencia y su importancia en la salud pública. Para esta investigación se utilizaron las bases de datos Pubmed, Google Scholar y Scielo. Según la Organización Mundial de la Salud, la resistencia a un antibiótico se define cuando deja de producir efecto. El uso cada vez más frecuente de antimicrobianos favorece la resistencia, ya que provocan una presión selectiva sobre los microorganismos, haciéndolos resistentes a varios fármacos. El uso indiscriminado de antimicrobianos es el principal factor de resistencia microbiana, así como el uso de antimicrobianos sin pruebas de cultivo y sensibilidad. En este sentido, se concluye que es de suma importancia actualizar los protocolos que contienen los mecanismos de resistencia bacteriana para minimizar el uso indiscriminado de antimicrobianos, así como capacitar a los profesionales de la salud para este problema en la salud pública.

Identificación de enterobacterias multirresistentes a antibióticos en muestras de heces de lactantes residentes en Talara, Piura, Perú / Identification of multidrug-resistant enterobacteriaceae in fecal samples from infants residing in Talara, Piura, Peru Arturo

La colonización fecal en lactantes por bacterias resistentes a los antimicrobianos es un potencial riesgo para futuras terapias antibióticas. Nuestro objetivo fue determinar la frecuencia y características sociodemográficas de lactantes portadores fecales de enterobacterias resistentes a ciprofloxacina (PFRC) y sus genes de resistencia asociados. Analizamos muestras fecales de 41 niños lactantes residentes en el distrito de Talara-Piura, Perú, en 2019. Evaluamos la presencia de 3 genes de resistencia a quinolonas: aac(6')-Ib-cr, qnrB y oqxA y 2 de betalactamasas: bla CTX-M, bla PER-2.El 68% de lactantes fueron PFRC, Escherichia coli (83,3%) fue el más frecuente. El análisis genotípico detectó: oqxA (41,1%), qnrB (26,7%) y aac(6')-Ib-cr (20%) y al gen bla CTX-M en el 93,3% de los aislados con betalactamasas. La elevada frecuencia de PFRC nos alertan sobre el potencial riesgo en la pérdida de utilidad de esta familia antibiótica en el área de estudio.

Fecal colonization by antimicrobial-resistant bacteria in infants is a potential risk for future antibiotic therapy. We aimed to determine the sociodemographic characteristics and frequency of infants who were fecal carriers of ciprofloxacin-resistant enterobacteriaceae (FCCRE) and their associated resistance genes. We analyzed fecal samples from 41 infants from the district of Talara, Piura, Peru in 2019. The presence of 3 quinolone resistance genes was evaluated: aac(6')-Ib-cr, qnrB and oqxA as well as of 2 beta-lactamase genes: bla CTX-M,bla PER-2. We found that 68% of infants were FCCRE, Escherichia coli (83.3%) was the most frequent bacteria. The genotypic analysis detected: oqxA (41.1%), qnrB (26.7%), aac(6')-Ib-cr (20%) and the bla CTX-M gene (93.3%) of the isolates with beta-lactamases. The high frequency of FCCRE alerts us of the potential risk of this antibiotic family becoming less useful over time.

Resistência antimicrobiana em uroculturas de moradores das Zonas Norte e Nordeste de Porto Alegre / Antimicrobial resistance in urine cultures of residents of North and Northeast Porto Alegre / Resistencia a los antimicrobianos en urocultivos de residentes de las Zonas Norte y Noreste de Porto Alegre

Introdução: Infecção urinária é motivo comum de consulta na Atenção Primária, requerendo tratamento empírico. Para a seleção do antimicrobiano, é necessário conhecer o perfil de resistência dos uropatógenos na comunidade. Objetivo: Analisar o perfil de resistência antimicrobiana em uroculturas realizadas em pacientes da Atenção Primária à Saúde do Serviço de Saúde Comunitária do Grupo Hospitalar Conceição, de julho de 2017 a junho de 2019. Métodos: Estudo transversal, observacional e descritivo com uroculturas de pacientes ambulatoriais das Unidades de Saúde do Serviço de Saúde Comunitária do Grupo Hospitalar Conceição, nas Zonas Norte e Nordeste de Porto Alegre, de julho de 2017 a junho de 2019. Os dados das uroculturas foram fornecidos pelo laboratório do Grupo Hospitalar e analisados por meio das proporções, por sexo, micro-organismo e resistência antimicrobiana. Resultados: Encontraram-se 2.000 uroculturas positivas no período, principalmente por Escherichia coli (75,50%), Klebsiella pneumoniae (7,80%), Staphylococcus saprophyticus (4,95%), Enterococcus specie (3,35%) e Proteus mirabilis (2,85%). Entre os antibióticos orais testados, a maior resistência foi para ampicilina (48,95%), seguida por sulfametoxazol+trimetoprima (25,85%), norfloxacino (18,05%), ciprofloxacino (18,00%), amoxicilina+clavulanato (11,05%) e nitrofurantoína (8,60%). Considerando-se apenas E. coli, as resistências foram 47,75% para ampicilina, 29,74% para sulfametoxazol+trimetoprima, 19,74% para norfloxacino e ciprofloxacino, 8,08% para amoxicilina+clavulanato e 1,99% para nitrofurantoína. Conclusões: O perfil de resistência antimicrobiana nas Zonas Norte e Nordeste de Porto Alegre sugere que sejam utilizados para tratamento empírico de infecção do trato urinário nessa localidade nitrofurantoína ou amoxicilina+clavulanato.

Introduction: Urinary tract infection is a common reason for consultation in primary care, requiring empirical treatment. For the selection of the antimicrobial, it is necessary to know the resistance profile of uropathogens in the community. Objective: To analyze the profile of antimicrobial resistance in urine cultures performed on primary health care patients from the Community Health Service of Grupo Hospitalar Conceição from July 2017 to June 2019. Methods: Cross-sectional, observational and descriptive study with urine cultures of outpatients from the Health Units from the Community Health Service of Grupo Hospitalar Conceição, in North and Northeast Porto Alegre, Brazil, from July 2017 to June 2019. The data on urine cultures were provided by the Grupo Hospitalar laboratory and analyzed through proportions, by sex, microorganism, and antimicrobial resistance. Results: Two thousand positive urine cultures were found in the period, mainly for Escherichia coli (75.50%), Klebsiella pneumoniae (7.80%), Staphylococcus saprophyticus (4.95%), Enterococcus specie (3.35%) and Proteus mirabilis (2.85%). Among the oral antibiotics tested, the most frequent resistance was to ampicillin (48.95%), followed by trimethoprim+sulfamethoxazole (25.85%), norfloxacin (18.05%), ciprofloxacin (18.00%), amoxicillin-clavulanate (11.05%) and nitrofurantoin (8.60%). Considering only E. coli, resistance was 47.75% to ampicillin, 29.74% to trimethoprim+sulfamethoxazole, 19.74% to norfloxacin and ciprofloxacin, 8.08% to amoxicillin-clavulanate and 1.99% to nitrofurantoin. Conclusions: The profile of antimicrobial resistance in the North and Northeast Zones of Porto Alegre suggests that nitrofurantoin or amoxicillin-clavulanate should be used for empirical treatment of urinary tract infection in this locality.

Introducción: La infección del tracto urinario es un motivo frecuente de consulta en atención primaria, requiriendo tratamiento empírico. Para la selección del antimicrobiano, es necesario conocer el perfil de resistencia de los uropatógenos en la comunidad. Objetivo: Analizar el perfil de resistencia antimicrobiana en urocultivos realizados en pacientes de atención primaria de salud de Serviço de Saúde Comunitária de Grupo Hospitalar Conceição de julio de 2017 a junio de 2019. Métodos: Estudio transversal, observacional y descriptivo con urocultivos de pacientes ambulatorios de las Unidades de Salud de Serviço de Saúde Comunitária de Grupo Hospitalar Conceição, en las Zonas Norte y Nordeste de Porto Alegre, de julio de 2017 a junio de 2019. Los datos de urocultivos fueron proporcionados por el laboratorio de Grupo Hospitalar y analizados a través de proporciones, por sexo, microorganismos y resistencia a los antimicrobianos. Resultados: En el período se encontraron 2.000 urocultivos positivos, principalmente por Escherichia coli (75,50%), Klebsiella pneumoniae (7,80%), Staphylococcus saprophyticus (4,95%), Enterococcus especie (3,35%) y Proteus mirabilis (2,85%). Entre los antibióticos orales probados, la mayor resistencia fue para la ampicilina (48,95%), seguida de sulfametoxazol+trimetoprima (25,85%), norfloxacina (18,05%), ciprofloxacina (18,00%), amoxicilina+clavulanato (11,05%) y nitrofurantoína (8,60%). %). Considerando solo a E. coli, la resistencia fue del 47,75% para ampicilina, 29,74% para sulfametoxazol + trimetoprima, 19,74% para norfloxacina y ciprofloxacina, 8,08% para amoxicilina + clavulanato y 1,99% para nitrofurantoína. Conclusiones: El perfil de resistencia a los antimicrobianos en las regiones Norte y Nordeste de Porto Alegre sugiere que se utilizan para el tratamiento empírico de la infección del tracto urinario en esta localidad nitrofurantoína o amoxicilina+clavulanato.

Praziquantel-encapsulated niosomes against Schistosoma mansoni with reduced sensitivity to praziquantel / Niosomas encapsulados en prazicuantel contra Schistosoma mansoni con sensibilidad reducida al prazicuantel

Introduction: Praziquantel (PZQ) is the only commercially available drug for schistosomiasis. The current shortage of alternative effective drugs and the lack of successful preventive measures enhance its value. The increase in the prevalence of PZQ resistance under sustained drug pressure is, therefore, an upcoming issue. Objective: To overcome the tolerance to PZQ using nanotechnology after laboratory induction of a Schistosoma mansoni isolate with reduced sensitivity to the drug during the intramolluscan phase. Materials and methods: Shedding snails were treated with PZQ doses of 200 mg/kg twice/ week followed by an interval of one week and then repeated twice in the same manner. The success of inducing reduced sensitivity was confirmed in vitro via the reduction of cercarial response to PZQ regarding their swimming activity and death percentage at different examination times. Results: Oral treatment with a single PZQ dose of 500 mg/kg in mice infected with cercariae with reduced sensitivity to PZQ revealed a non-significant reduction (35.1%) of total worm burden compared to non-treated control mice. Orally inoculated PZQ- encapsulated niosomes against S. mansoni with reduced sensitivity to PZQ successfully regained the pathogen's sensitivity to PZQ as evidenced by measuring different parameters in comparison to the non-treated infected animals with parasites with reduced sensitivity to PZQ. The mean total worm load was 1.33 ± 0.52 with a statistically significant reduction of 94.09% and complete eradication of male worms. We obtained a remarkable increase in the percentage reduction of tissue egg counts in the liver and intestine (97.68% and 98.56%, respectively) associated with a massive increase in dead eggs and the complete absence of immature stages. Conclusion: PZQ-encapsulated niosomes restored the drug sensitivity against laboratory- induced S. mansoni adult worms with reduced sensitivity to PZQ.

Introducción. El prazicuantel es el único fármaco disponible comercialmente para la esquistosomiasis. La escasez actual de medicamentos alternativos y la falta de medidas preventivas eficaces aumentan su valor. La creciente prevalencia de la resistencia al prazicuantel bajo una presión prolongada del fármaco es, por tanto, un tema emergente. Objetivos. Superar la tolerancia al prazicuantel mediante nanotecnología después de la inducción en laboratorio de un aislamiento de Schistosoma mansoni con sensibilidad reducida al fármaco durante la fase intramolusco. Materiales y métodos. Los caracoles que liberaban cercarias se trataron con prazicuantel en dosis de 200 mg/kg dos veces por semana, seguidas de un intervalo de una semana, y luego se repitieron dos veces de la misma manera. La inducción exitosa de la sensibilidad reducida se confirmó in vitro mediante la reducción de la reacción de las cercarias al prazicuantel con respecto a su actividad de natación y el porcentaje de muerte en diferentes momentos de examen. El éxito en inducir una menor sensibilidad se confirmó in vitro mediante la reducción de la reacción de las cercarias al prazicuantel. Resultados. El tratamiento oral con una dosis única de prazicuantel de 500 mg/kg en ratones infectados con cercarias con sensibilidad reducida al prazicuantel, reveló una reducción no significativa (35,1 %) de la carga total de gusanos en comparación con los ratones de control no tratados. Los niosomas encapsulados en prazicuantel inoculados por vía oral contra S. mansoni con sensibilidad reducida al prazicuantel, permitieron reestablecer con éxito la sensibilidad del patógeno al medicamento, como lo demostró la medición de diferentes parámetros en comparación con los animales infectados no tratados con parásitos con sensibilidad reducida a prazicuantel. La carga media total de gusanos fue de 1,33 ± 0,52, con una reducción estadísticamente significativa del 94,09 %, y la erradicación completa de los gusanos machos adultos. Se obtuvo un aumento notable en el porcentaje de reducción del recuento de huevos en el tejido del hígado y el intestino (97,68 % y 98,56 %, respectivamente), asociado con un aumento masivo de huevos muertos y ausencia total de estadios inmaduros. Conclusión. Los niosomas encapsulados en prazicuantel restauraron la sensibilidad al fármaco contra gusanos adultos de S. mansoni con sensibilidad reducida al prazicuantel inducida en el laboratorio.

Helicobacter pylori: novedades, genes de virulencia y resistencia a los antibióticos en Colombia / Helicobacter pylori: novelties, virulence genes and antibiotic resistance in Colombia / Helicobacter pylori: novidades, genes de virulência e resistência aos antibióticos na Colômbia

Helicobacter pylori es un carcinógeno tipo I resistente a múltiples antibióticos y con alta prioridad en salud pública. La infección por este microorganismo está influenciada por una interacción compleja entre la genética del huésped, el entorno y múltiples factores de virulencia de la cepa infectante. Afecta al 50 % de la población mundial, provocando afecciones gastroduodenales graves, la mayoría de forma asintomática. El 20 % de los individuos con H. pylori pueden desarrollar a través del tiempo lesiones gástricas preneoplásicas y el 2 % de ellos un cáncer gástrico. Las manifestaciones clínicas gastrointestinales y extragastrointestinales están asociadas a su virulencia y a la respuesta del sistema inmunológico con la liberación de citosinas proinflamatorias, tales como TNF-alfa, IL-6, IL-10 e IL-8, causantes de inflamación aguda y crónica. Múltiples factores de virulencia han sido estudiados como el gen A asociado a la citotoxina (CagA) y la citotoxina vacuolante (VacA), los cuales juegan un rol importante en la aparición del cáncer gástrico. Dada la resistencia cada vez mayor a los antibióticos utilizados, las líneas de estudio en el futuro inmediato deben estar encaminadas en establecer la utilidad de los nuevos antibióticos y la determinación de profagos colombianos en todo el país. Esta revisión tiene como objetivo hacer una puesta al día sobre las características del H. pylori, los mecanismos patogénicos, genes de virulencia, su asociación con el mayor riesgo de cáncer gástrico, farmacorresistencia microbiana y su erradicación.

Helicobacter pylori is recognized as a class I carcinogen resistant to multiple antibiotics and with high priority in public health. The infection caused by this microorganism is influenced by a complex interaction between host genetics, environment, and multiple virulence factors of the infecting strain. It affects 50% of the world population, causing severe gastroduodenal conditions, most of them asymptomatic. Through time, 20% of individuals with H. pylori may develop preneoplastic gastric lesions and 2% of them develop gastric cancer. The gastrointestinal and extra-gastrointestinal clinical manifestations are associated with its virulence and the response of the immune system with the release of pro-inflammatory cytokines, such as TNF-alpha, IL-6, IL-10 and IL-8, which cause acute and chronic inflammation. Multiple virulence factors have been studied, such as cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA), which play an important role in the development of gastric cancer. Due to the increasing antibiotics resistance, the research in the immediate future should be aimed at establishing the usefulness of the new antibiotics and the determination of Colombian prophages throughout the country. This paper aims to update the characteristics of H. pylori, its pathogenic mechanisms, virulence genes, its association with the increased risk of gastric cancer, microbial drug resistance, and eradication.

Helicobacter pylorié um carcinógeno tipo I resistente a múltiplos antibióticos e com alta prioridade na saúde pública. A infecção por este microrganismo está influenciada por uma interação complexa entre a genética do hospede, o entorno e múltiplos fatores de virulência da cepa infectante. Afeta a 50% da população mundial, provocando afeções gastroduodenais graves, a maioria de forma assintomática. 20% dos indivíduos com H. pylori podem desenvolver através do tempo lesões gástricas pré-neoplásicas e 2% deles um câncer gástrico. As manifestações clínicas gastrointestinais e extragastrointestinais estão associadas à sua virulência e à resposta do sistema imunológico com a liberação de citocinas pró-inflamatórias, tais como TNF-alfa, IL-6, IL-10 e IL-8, causantes de inflamação aguda e crónica. Múltiplos fatores de virulência hão sido estudados como o gene. A associado à citotoxina (CagA) e a citotoxina vacuolante (VacA), os quais jogam um papel importante no aparecimento do câncer gástrico. Dada a resistência cada vez maior aos antibióticos utilizados, as linhas de estudo no futuro imediato devem estar encaminhadas em estabelecer a utilidade dos novos antibióticos e a determinaçãode profagos colombianos em todo o país. Esta revisão tem como objetivo fazer uma atualização sobre as características do H. pylori, os mecanismos patogénicos, genes de virulência, sua associação com o maior risco de câncer gástrico, farmacorresistência microbiana e sua erradicação.