Frecuencia de E. coli y Klebsiella spp productoras de betalactamasas en cultivos procesados en un laboratorio clínico / Frequency of E. coli and betalactamase-producing Klebsiella spp in cultures processed in a clinical laboratory / Frequência de E. coli e Klebsiella spp produtoras de betalactamase em culturas processadas em laboratório clínico

Introducción: la resistencia antibiótica en bacterias patógenas como Escherichia coli y Klebsiella spp. productoras de betalactamasas, han surgido como un problema global de salud pública. Su presencia, se asocia con infecciones intrahospitalarias y comunitarias, aumentando la morbilidad y la mortalidad de los pacientes. Objetivo: determinar la frecuencia de E.coli y Klebsiella spp productoras de betalactamasas en cultivos procesados en un laboratorio clínico. Métodos: se realizó un estudio descriptivo de diseño documental. La muestra estuvo constituida por un total de 1465 resultados de cultivos positivos para Escherichia coli o Klebsiella spp. en el periodo 2022. Para la recolección de la información, se tuvo acceso a la base de datos anonimizada del laboratorio en una hoja de Excel para su posterior análisis. Los datos fueron tabulados en SPSS versión 25. Resultados: el análisis de bacterias productoras de BLEE mostró una positividad del 22,3% en E. coli y 46,1% en Klebsiella spp. E. coli presentó mayor frecuencia de negativos (77,7%) en comparación con Klebsiella spp. La presencia de E. coli fue más común en muestras de orina (90,6%) y en otras muestras como esputo y heridas cutáneas (21,3%). Se evaluaron 8 antibióticos, y se destacó la alta sensibilidad para amikacina (AK) (99,6% y 98,0%) y elevada resistencia ampicilina (AM) (91,5% y 100%) en ambas especies. Ciprofloxacino (CIP) y Trimetropin/Sulfametoxazol (STX) mostraron relativa frecuencia mayor de resistencia. Conclusión: los resultados muestran una alta frecuencia de bacterias productoras de BLEE en E. coli y Klebsiella spp., con una mayor prevalencia en Klebsiella spp. Además, la resistencia a AM, CIP y STX destaca la importancia de una gestión adecuada de la resistencia antimicrobiana.

Introduction: antibiotic resistance in pathogenic bacteria such as Escherichia coli and Klebsiella spp. producing beta-lactamases has emerged as a global public health problem. Their presence has been associated with both hospital-acquired and community-acquired infections, leading to increased morbidity and mortality in patients. Objective: to determine the frequency of betalactamase-producing E. coli and Klebsiella spp. in cultures processed in a clinical laboratory. Methods: a descriptive documentary design study was conducted. The sample consisted of a total of 1465 positive culture results for Escherichia coli or Klebsiella spp. in the year 2022. Data collection involved accessing the laboratory's anonymized database in an Excel sheet for subsequent analysis. The data were tabulated in SPSS version 25. Results: the analysis of ESBL-producing bacteria showed a positivity of 22.3% in E. coli and 46.1% in Klebsiella spp. E. coli showed a higher frequency of negatives (77.7%) compared to Klebsiella spp. The presence of E. coli was more common in urine samples (90.6%) and in other samples such as sputum and skin wounds (21.3%). Eight antibiotics were evaluated, with high sensitivity noted for amikacin (AK) (99.6% and 98.0%) and high resistance for ampicillin (AM) (91.5% and 100%) in both species. Ciprofloxacin (CIP) and Trimethoprim/Sulfamethoxazole (STX) showed a relatively higher frequency of resistance. Conclusion: the results show a high frequency of ESBL-producing bacteria in E. coli and Klebsiella spp., with a higher prevalence in Klebsiella spp. Furthermore, the resistance to AM, CIP, and STX highlights the importance of proper management of antimicrobial resistance.

Introdução: a resistência antibiótica em bactérias patogênicas como Escherichia coli e Klebsiella spp., produtoras de beta-lactamases, emergiu como um problema de saúde pública global. Sua presença tem sido associada a infecções hospitalares e comunitárias, aumentando a morbidade e a mortalidade dos pacientes. Objetivo: determinar a frequência de E. coli e Klebsiella spp. produtoras de betalactamase em culturas processadas em laboratório clínico. Métodos: foi realizado um estudo descritivo de design documental. A amostra consistiu em um total de 1465 resultados de cultura positiva para Escherichia coli ou Klebsiella spp. no ano de 2022. A coleta de dados envolveu o acesso ao banco de dados anonimizado do laboratório em uma planilha do Excel para análise subsequente. Os dados foram tabulados na versão 25 do SPSS. Resultados: a análise de bactérias produtoras de BLEE mostrou uma positividade de 22,3% em E. coli e 46,1% em Klebsiella spp. E. coli apresentou uma frequência maior de resultados negativos (77,7%) em comparação com Klebsiella spp. A presença de E. coli foi mais comum em amostras de urina (90,6%) e em outras amostras, como escarro e feridas na pele (21,3%). Foram avaliados oito antibióticos, com alta sensibilidade observada para amicacina (AK) (99,6% e 98,0%) e alta resistência para ampicilina (AM) (91,5% e 100%) em ambas as espécies. Ciprofloxacina (CIP) e Trimetoprima/Sulfametoxazol (STX) mostraram uma frequência relativamente maior de resistência. Conclusão: os resultados mostram uma alta frequência de bactérias produtoras de BLEE em E. coli e Klebsiella spp., com uma maior prevalência em Klebsiella spp. Além disso, a resistência a AM, CIP e STX destaca a importância da adequada gestão da resistência antimicrobiana.

Antimicrobial use in long-term care facilities: the participation of nurses / Indicação de antimicrobianos em instituições de longa permanência: participação do enfermeiro

Objective: To identify how antimicrobials are prescribed in long-term care facilities from the perspective of nurses. Methods: This descriptive study was conducted using an online survey. Participants were selected through conventional sampling methods and online recruitment. Data were collected through a 2-section self-administered questionnaire: the first section characterized the respondent and the institution, while the second investigated the antimicrobial prescription and usage in the institution. Results: Thirty-five responses were received, representing institutions from every state in Brazil. Sixty percent of the institutions had a part-time physician. More than 90% of the respondents said they contacted a prescriber to report signs and symptoms suggestive of infection, which led to subsequent antimicrobial use. Conclusions: The opinion of nurses has a significant impact on the prescriber's decision to begin antibiotic therapy in long-term care facilities, which indicates that nurses need training about the rational use of antimicrobials. (AU)

Objetivo: Identificar como ocorre a indicação de antimicrobianos nas instituições de longa permanência na perspectiva do profissional enfermeiro. Metodologia: Foi realizado um estudo descritivo por meio de um Survey online. Os participantes foram selecionados por meio de amostra convencional e o recrutamento foi realizado por meio de convite online. A coleta de dados foi feita a partir de um questionário autoaplicável constituído de dois blocos: o primeiro contemplando itens para a caracterização do respondente e da instituição; e o segundo, questões relacionadas ao uso e à indicação de antimicrobianos na instituição. Resultados: Foram recebidas 35 respostas, representando instituições de todos os estados brasileiros. A presença de médico em tempo parcial foi apontada em 60% das instituições. Mais de 90% dos participantes apontaram que acontecia o contato com prescritor para o relato de sinais e sintomas sugestivos de infecção apresentados pelo residente, implicando em uso subsequente de antimicrobianos. Conclusões: A opinião do profissional da Enfermagem tem grande impacto na decisão do prescritor em iniciar a antibioticoterapia nas instituições de longa permanência, demonstrando a necessidade de qualificação desse profissional direcionada ao uso racional de antimicrobianos. (AU)

El enfoque Una Salud y la resistencia a los antimicrobianos: Implementación en el Perú / The One Health Approach and Antimicrobial Resistance: Implementation in Peru

RESUMEN La Resistencia a los Antimicrobianos (RAM) es un problema de salud pública de alcance global. De no lograrse contener su propagación, para el año 2050 se convertiría en la primera causa de muerte a nivel mundial, con un serio impacto en la economía mundial. Esta situación ha determinado la aplicación del enfoque «Una Salud¼ para su contención. Este enfoque reconoce que la salud de las personas, los animales, las plantas y el medio ambiente están estrechamente relacionados y son interdependientes. Desde el año 2015, la Organización Mundial de la Salud, en coordinación con otras organizaciones aprobaron el Plan de Acción Mundial para enfrentar la RAM, esto determinó que los estados miembros elaboraran e implementaran sus planes nacionales. El Perú inició el abordaje para la contención de la RAM aplicando el enfoque «Una Salud¼ desde el año 2017. Se registran algunos avances en la implementación de Plan nacional pero también los retos y acciones pendientes de alcanzar.

ABSTRACT Antimicrobial Resistance (AMR) is a public health problem of global scope, whose projections if its spread is not contained indicate that by the year 2050 it would become the leading cause of death worldwide with a serious impact on the world economy. This situation has determined the application of the "One Health" approach for its containment. The approach recognizes that the health of people, animals, plants and the environment are closely related and interdependent. Since 2015, the WHO, in coordination with other organizations, approved the Global Action Plan to face AMR, this determined that the Member States elaborate and implement their national plans. Peru began the approach to contain AMR applying the "One Health" approach since 2017. Some progress has been made in the implementation of the National Plan but also the challenges and actions pending to be achieved.

Prevalence of bacterial infections and antimicrobial resistance profile in hospitalized patients with COVID-19 / Prevalência de infecções bacterianas e perfil de resistência aos antimicrobianos em pacientes internados com COVID-19 / Prevalencia de infecciones bacterianas y perfil de resistencia antimicrobiana en pacientes hospitalizados con COVID-19

Background and Objectives: bacterial resistance is an important public health problem worldwide and is related to the indiscriminate use of antimicrobials, limiting the available therapeutic options. The COVID-19 pandemic aggravated this scenario, since the lack of a standardized therapy led to a considerable increase in the prescription of these drugs. Therefore, we proposed to investigate the prevalence of bacterial infections and the profile of antimicrobial resistance in patients diagnosed with COVID-19 as well as to point out possible risk factors. Methods: a retrospective study based on the analysis of medical records of patients hospitalized with COVID-19 over the age of 18. Information such as age, gender, length of stay, hospitalization unit, bacterial species and resistance profile and previous use of antimicrobials by patients diagnosed with COVID-19 were collected and analyzed using Excel® 2016. Results: of the 268 patients with COVID-19, 162 had suspected bacterial infections, and 26 patients (9.7%) were confirmed from positive cultures. Furthermore, around 80% of these patients underwent empirical treatment with antimicrobials, the majority of whom were male and admitted to the Intensive Care Unit. A total of 32 bacterial isolates were recovered, of which 59.4% were resistant to at least one class of antimicrobials, with 21.8% being multidrug resistant. Conclusion: despite the low percentage found of patients with COVID-19 who had bacterial infections and of these 21.8% were by multidrug-resistant bacteria, the reinforcement in infection prevention policies and the adequate management in the release of antimicrobials is necessary to reduce the hospital dissemination rates of such bacteria.(AU)

Justificativa e Objetivos: a resistência bacteriana é um importante problema de saúde pública mundial relacionado ao uso indiscriminado de antimicrobianos, limitando as opções terapêuticas disponíveis. A pandemia de COVID-19 agravou esse cenário, uma vez que a falta de uma terapia padronizada resultou no aumento considerável na prescrição desses fármacos. Diante disso, propôs-se investigar a prevalência de infecções bacterianas e o perfil de resistência aos antimicrobianos em pacientes diagnosticados com COVID-19, bem como apontar possíveis fatores de risco. Métodos: estudo retrospectivo baseado na análise de prontuários de pacientes internados com COVID-19 com idade superior a 18 anos. Informações como idade, gênero, tempo de internação, unidade de internação, espécie bacteriana e perfil de resistência e uso prévio de antimicrobianos pelos pacientes diagnosticados com COVID-19 foram coletadas e analisadas pelo software Excel® 2016. Resultados: dos 268 pacientes com COVID-19, 162 apresentaram suspeitas de infecções bacterianas, sendo 26 pacientes (9,7%) confirmados a partir de culturas positivas. Ainda, cerca de 80% desses pacientes realizaram tratamento empírico com antimicrobianos, sendo a maioria do sexo masculino e internados em Unidade de Terapia Intensiva. Foram recuperados um total de 32 isolados bacterianos, dos quais 59,4% apresentaram resistência a pelo menos uma classe de antimicrobianos, sendo 21,8% multidroga resistente. Conclusão: apesar do baixo percentual encontrado de pacientes com COVID-19 que apresentaram infecções bacterianas e, desses, 21,8% serem causados por bactérias multirresistentes, o reforço nas políticas de prevenção de infecções e o adequado gerenciamento na liberação de antimicrobianos se fazem necessários para a redução das taxas de disseminação hospitalar de tais bactérias.(AU)

Justificación y Objetivos: la resistencia bacteriana es un importante problema de salud pública en todo el mundo y está relacionada con el uso indiscriminado de antimicrobianos, lo que limita las opciones terapéuticas disponibles. La pandemia por COVID-19 agravó este escenario, ya que la falta de una terapia estandarizada llevó a un aumento considerable en la prescripción de estos fármacos. Por ello, nos propusimos investigar la prevalencia de infecciones bacterianas y el perfil de resistencia antimicrobiana en pacientes diagnosticados de COVID-19, así como señalar posibles factores de riesgo. Métodos: estudio retrospectivo basado en el análisis de historias clínicas de pacientes hospitalizados con COVID-19 mayores de 18 años. Información como edad, sexo, duración de la estadía, unidad de hospitalización, especies bacterianas y perfil de resistencia y uso previo de antimicrobianos por parte de pacientes diagnosticados con COVID-19 fueron recopiladas y analizadas mediante el software Excel® 2016. Resultados: de los 268 pacientes con COVID-19, 162 tenían sospecha de infección bacteriana, con 26 pacientes (9,7%) confirmada a partir de cultivos positivos. Además, alrededor del 80% de estos pacientes recibieron tratamiento empírico con antimicrobianos, la mayoría de los cuales eran hombres e ingresaron en la Unidad de Cuidados Intensivos. Se recuperaron un total de 32 aislados bacterianos, de los cuales el 59,4% eran resistentes a al menos una clase de antimicrobianos y el 21,8% eran resistentes a múltiples fármacos. Conclusión: a pesar del bajo porcentaje encontrado de pacientes con COVID-19 que presentaron infecciones bacterianas, y de éstas cerca del 21,8% fueron por bacterias multirresistentes, es necesario reforzar las políticas de prevención de infecciones y una gestión adecuada en la liberación de antimicrobianos para reducir las tasas de diseminación hospitalaria de dichas bacterias.(AU)

Antimicrobial prescription and bacterial resistance in a Brazilian Intensive Care Unit / Prescrição antimicrobiana e resistência bacteriana em uma Unidade de Terapia Intensiva Brasileira / Prescripción antimicrobiana y resistencia bacteriana en una Unidad de Cuidados Intensivos Brasileña

Background and Objectives: antimicrobial resistance is one of the main public health concerns worldwide. Intensive Care Units have a high prevalence of resistant microorganisms and infections, and the rational use of antibiotics is one of the main strategies for tackling this problem. This work aimed to describe patterns associated with antimicrobial drugs as well as the resistance profile of microorganisms. Methods: an observational study was carried out using data from patients hospitalized in the Intensive Care Unit who used antimicrobial agents. Results: respiratory and cardiological causes were the most frequent reasons for admission, with cephalosporins (29.02%), with penicillin (25.84%) and macrolides (16.10%) being the most used classes of antibiotics. The predominant microorganisms were Klebsiella pneumoniae (13.98%), Staphylococcus aureus (13.44%) and Acinetobacter baumannii (11.83%). Urine cultures and tracheal aspirate were the culture tests with the highest growth of gram-negative microorganisms. Patients with bacteria isolated in tracheal aspirate had longer hospital stays; 20 patients had positive surveillance cultures; and the mortality rate found was 55.45%. Conclusion: the study combined the institution's epidemiological profile with patient characteristics, isolated microorganisms and outcomes.(AU)

Justificativa e Objetivos: a resistência antimicrobiana é uma das principais preocupações de saúde pública em todo o mundo. As Unidades de Terapia Intensiva têm uma alta prevalência de microorganismos resistentes e infecções, e o uso racional de antibióticos é uma das principais estratégias para lidar com esse problema. Este trabalho teve como objetivo descrever padrões associados a medicamentos antimicrobianos, bem como o perfil de resistência dos microorganismos. Métodos: foi realizado um estudo observacional utilizando dados de pacientes hospitalizados na Unidade de Terapia Intensiva que utilizaram agentes antimicrobianos. Resultados: causas respiratórias e cardiológicas foram os motivos mais frequentes de admissão, com cefalosporinas (29,02%), penicilina (25,84%) e macrolídeos (16,10%) sendo as classes de antibióticos mais utilizadas. Os microorganismos predominantes foram Klebsiella pneumoniae (13,98%), Staphylococcus aureus (13,44%) e Acinetobacter baumannii (11,83%). Culturas de urina e aspirado traqueal foram os testes de cultura com maior crescimento de microorganismos gram-negativos. Pacientes com bactérias isoladas no aspirado traqueal tiveram internações mais longas; 20 pacientes tiveram culturas de vigilância positivas; e a taxa de mortalidade encontrada foi de 55,45%. Conclusão: o estudo combinou o perfil epidemiológico da instituição com características dos pacientes, microorganismos isolados e resultados.(AU)

Antecedentes y Objetivos: la resistencia antimicrobiana es una de las principales preocupaciones de salud pública en todo el mundo. Las Unidades de Cuidados Intensivos tienen una alta prevalencia de microorganismos resistentes e infecciones, y el uso racional de antibióticos es una de las principales estrategias para abordar este problema. Este trabajo tuvo como objetivo describir patrones asociados con medicamentos antimicrobianos, así como el perfil de resistencia de los microorganismos. Métodos: se llevó a cabo un estudio observacional utilizando datos de pacientes hospitalizados en la Unidad de Cuidados Intensivos que utilizaron agentes antimicrobianos. Resultados: las causas respiratorias y cardiológicas fueron las razones más frecuentes de admisión, con cefalosporinas (29,02%), penicilina (25,84%) y macrólidos (16,10%) siendo las clases de antibióticos más utilizadas. Los microorganismos predominantes fueron Klebsiella pneumoniae (13,98%), Staphylococcus aureus (13,44%) y Acinetobacter baumannii (11,83%). Los cultivos de orina y el aspirado traqueal fueron las pruebas de cultivo con mayor crecimiento de microorganismos gramnegativos. Los pacientes con bacterias aisladas en el aspirado traqueal tuvieron estancias hospitalarias más largas; 20 pacientes tuvieron cultivos de vigilancia positivos; y la tasa de mortalidad encontrada fue del 55,45%. Conclusión: el estudio combinó el perfil epidemiológico de la institución con las características de los pacientes, los microorganismos aislados y los resultados.(AU)

Resistencia a los inhibidores de la integrasa en niños con el virus de la inmunodeficiencia humana por transmisión vertical: primeros casos en Uruguay / Resistance to integrase inhibitors in children with vertically-transmitted human immunodeficiency virus: First cases in Uruguay

La resistencia a los antirretrovirales (ARV) es un problema de salud pública. Con el uso de inhibidores de la integrasa (INSTI) en pediatría, también comienzan a aparecer resistencias. El objetivo de esta comunicación es describir 3 casos con resistencia a los INSTI. Se describen 3 pacientes pediátricos con transmisión vertical del virus de la inmunodeficiencia humana (VIH). Iniciaron ARV de lactantes y preescolares, con mala adherencia al tratamiento, cursaron con diferentes planes secundarios a comorbilidades asociadas y fallas virológicas por resistencia. Los 3 casos clínicos describen la rápida aparición de resistencia frente a la falla virológica y el compromiso de los INSTI. La adherencia debe ser supervisada para detectar precozmente el aumento de la viremia. La falla virológica en un paciente tratado con raltegravir obliga a un rápido cambio de esquema ARV, ya que continuar utilizándolo podría favorecer nuevas mutaciones y resistencia a los INSTI de segunda generación.

Antiretroviral (ARV) drug resistance is a public health issue. Resistance has also been observed in the case of integrase strand transfer inhibitors (INSTIs) used in pediatrics. The objective of this article is to describe 3 cases of INSTI resistance. These are the cases of 3 children with vertically-transmitted human immunodeficiency virus (HIV). They were started on ARVs as infants and preschoolers, with poor treatment adherence, and had different management plans due to associated comorbidities and virological failure due to resistance. In the 3 cases, resistance developed rapidly as a result of virological failure and INSTI involvement. Treatment adherence should be monitored so that any increase in viremia can be detected early. Virological failure in a patient treated with raltegravir forces to a rapid change in ARV therapy because its continued use may favor new mutations and resistance to second-generation INSTIs.

Research advances in monoclonal antibodies for treatment of drug resistance in inflammatory bowel disease / 中国生物制品学杂志

@#Inflammatory bowel disease(IBD)is a complex inflammatory disease mediated by immunity that is treated with the goal of maintaining disease remission and preventing recurrence. With the deep study of the molecular mechanism of the occurrence and development of IBD,many related target molecules have been found,and the monoclonal antibodies of corresponding targets have been used to treat the disease,while the drug resistance phenomenon generated during treatment has seriously affected the treatment effect. In this paper,monoclonal antibodies such as infliximab were reviewed for the treatment of IBD resistance,with a view to understanding its possible mechanisms and exploring effective treatments and preventive measures

Research advances in second-line therapies for hepatocellular carcinoma after resistance to targeted therapy combined with immunotherapy / 临床肝胆病杂志

In recent years， clinical studies on targeted therapy and immunotherapy for advanced hepatocellular carcinoma used alone or in combination have provided abundant evidence on efficacy and safety for the selection of first-line therapies. However， no consensus has been reached on the selection of second-line therapies in various clinical guidelines for hepatocellular carcinoma， which is caused by the fact that existing evidence is limited to the options after failure of sorafenib and that there is still a lack of high-level evidence for new first-line therapies such as second-line therapies after resistance to targeted therapy and immunotherapy for hepatocellular carcinoma. This article reviews the results of current clinical trials and summarizes the studies on second-line therapies for hepatocellular carcinoma after resistance to first-line targeted therapy and immunotherapy for hepatocellular carcinoma based on the different mechanisms of action of drugs， as well as the research advances in recent years. For hepatocellular carcinoma patients with resistance to first-line targeted therapy and immunotherapy， targeted combination therapy and dual-immune therapy are expected to improve treatment outcome and survival， and more prospective clinical studies are needed in the future to provide effective and safe treatment regimens for hepatocellular carcinoma patients with resistance to targeted therapy and immunotherapy.

Drug Resistance and Prognosis of 150 Cases of Peritoneal Dialysis-associated Peritonitis / 医药导报

Objective To analyze the pathogenic bacteria and drug resistance of peritoneal dialysis-associated peritonitis(PDAP),and provide a clinical reference for the rational use of antibiotics.Methods The demographic data of PDAP patients admitted to the peritoneal dialysis(PD)Center of the First Affiliated Hospital of Soochow University from July 1,2015 to December 30,2021 were collected,and the pathogens,drug resistance and prognosis were retrospectively analyzed.Results A total of 150 episodes of PDAP occurred in 92 patients.The positive rate of PD fluid culture was 61.33％,including 65 cases(70.65％)of Gram-positive(G+)bacteria,mainly Staphylococcus and Streptococcus.Gram-negative(G-)bacteria were in 16 cases(17.39％),mainly Escherichia coli and Enterobacter cloacae.There were 11 cases(11.96％)of multiple infections,including 5 cases of combined fungal infection.From 2016 to 2021,the incidence of G+bacteria-related PDAP decreased from 14 to 8 cases.G+strains were resistant to methicillin(35.00％),and were sensitive to linezolid(100.00％),teicoplanin(100.00％)and rifampicin(100.00％).The sensitivity rate to vancomycin was 98.59％.G-strains were sensitive to ceftazidime(86.36％),ceftizoxime(88.89％)and amikacin(100.00％).The MIC of vancomycin against Staphylococcus showed an upward trend in 2019-2021.The overall cure rate of PDAP was 81.33％in patients who responded to antibiotic treatment,and the cure rate of G+bacteria was higher than that of multiple infections(89.23％vs.36.36％,P＜0.01).The outcome of patients with multiple infections,especially those with concurrent fungal infection was poor.Conclusion The incidence of PDAP in the PD center has shown a decreasing trend in recent years.G+bacteria are still the main pathogenic bacteria causing PDAP,and they are highly resistant to methicillin,so vancomycin should be used as empirical therapy.For G-bacteria,cefotaxime and amikacin can be chosen as empirical therapy.There is a drift in the MIC values of vancomycin against Staphylococcus in the study period,so it is necessary to monitor the MIC of vancomycin against Staphylococcus and its changing trend.

Research Advances in Traditional Chinese Medicine and Natural Products for Cancer Treatment by Targeting Ferroptosis / 医药导报

Ferroptosis is a unique iron-dependent cell death pattern,a novel death phenotype distinct from apoptosis,va-rious forms of necrosis,and autophagy.Numerous active ingredients extracted from traditional Chinese medicine have been found to exert anti-cancer effects by inducing ferroptosis in various cancers.An increasing number of studies have found that the regulation of ferroptosis can influence the sensitivity of tumor cells to drugs and even reverse drug resistance.When combined with chemo-therapy drugs such as cisplatin,5-FU and gemcitabine,some natural products enhance cancer cells'sensitivity to chemothera-peutic drugs by inducing ferroptosis.This paper mainly summarizes traditional Chinese medicine and its natural products that can exert anti-cancer effects by inducing ferroptosis,providing new insights for cancer treatment and drug resistance reversal.Addition-ally,it contributes to exploring the potential advantages of traditional Chinese medicine,thereby expanding its scope of applica-tion.

Application of metagenomic next-generation sequencing in the outbreak of healthcare-associated infection with carbapenem-resistant Acinetobacter baumannii / 中国感染控制杂志

Objective To explore the application of metagenomic next-generation sequencing(mNGS)technology in the investigation of healthcare-associated infection(HAI)outbreaks of carbapenem-resistant Acinetobacter bau-mannii(CRAB).Methods Pathogenic detection by mNGS and conventional pathogen culture were performed on 5 patients in the intensive care unit(ICU)of a hospital from June 8 to 22,2023 from whom CRAB were detected.Microbial sampling was carried out in potentially contaminated environment.Bacterial culture,identification,and antimicrobial susceptibility testing were conducted.Comprehensive control measures were taken,and the effect was evaluated.Results The time required for reporting results by mNGS was shorter than the culture time([3.92± 1.05]days vs[6.24±0.25]days,P＜0.001).CRAB was isolated from the specimens of 5 patients.mNGS de-tected OXA-23 resistance genes from all patients.After comprehensive assessment by experts,4 patients were HAI and 1 patient was due to specimen contamination.According to the definition from Guidelines for HAI outbreak control,this event was considered an outbreak of HAI.The monitoring results of environmental hygiene showed that the detection rate of CRAB in the environment during the outbreak was 51.30％(59/115),mainly from the hands of health care workers and the surface of ventilators.After implementing multidisciplinary infection control measures,clinicians'hand hygiene compliance rate and implementation rate of ventilator disinfection increased from 40.83％(49/120)and 33.33％(16/48)to 82.61％(95/115)and 83.33％(30/36),respectively.The prognosis of patients was good,and no new case emerged during subsequent monitoring.The outbreak of HAI in this hospital has been effectively controlled.Conclusion mNGS is characterized by high precision,less time consumption,and high accuracy,and can be applied to the prevention and control of HAI outbreak and the study of antimicrobial-re-sistant genomes.It is of great significance for the anti-infection treatment of patients with multidrug-resistant orga-nism infection as well as the formulation of HAI prevention and control measures.Continuous improving disinfec-tion effectiveness and hand hygiene compliance is important for preventing and controlling CRAB infection.

Research advances in epidemiology and drug resistance of Elizabethkingia / 中国感染控制杂志

In recent years,the incidence of Elizabethkingia infection has increased significantly.Elizabethkingia can cause pneumonia,meningitis,and bacteremia,etc.The high rate of drug resistance leads to prolonged hospital stay and increased mortality,posing a heavy burden to patients and society.This paper reviews the epidemiology,pathogenesis and drug resistance of Elizabethkingia,with a view to providing a reference for the clinical diagnosis,treatment,prevention and control of Elizabethkingia infection.

Advances in research on the role of biliary tract microecology in gallstone formation / 中国基层医药

Cholelithiasis, a prevalent disease of the digestive system, is characterized by its intricate and diverse mechanisms, which are influenced by a complex interplay of genetic, environmental, lifestyle, and other factors. Recently, with the widespread application of molecular biology techniques, the role of the biliary tract microecological environment in the pathogenesis of gallstones has garnered increasing attention. This review includes the most recent and pertinent literature on the association between biliary tract microecology and gallstones, summarizing the latest research advancements in this field. Furthermore, it delves into the role of the biliary tract microecology in the formation of both cholesterol and pigment gallstones.

Research progress of B7-H3 in tumor growth,drug resistance formation and immunotherapy / 中国免疫学杂志

B7-H3(also known as CD276)is a newly discovered immune costimulatory molecule and a member of the B7 family of immune costimulatory molecules.Since the receptor of B7-H3 has not been identified yet,the specific mechanism of its immune function and intracellular signal transmission has not yet been clarified.B7-H3 is highly expressed in many malignant tumors,which indicates that not only B7-H3 can be used as a tumor marker for many malignant tumors to assist clinical diagnosis,which can be used as an effective target for tumor targeted therapy.This review mainly introduces the history of the development of the costimulatory mole-cule B7-H3 and its possible role in the development of various malignant tumors and the development of anti-tumor drug resistance,as well as the current mainstream therapeutic approaches targeting B7-H3.

Virulence determinants and genetic diversity of foodborne Yersinia enterocolitica isolated from Wenzhou / 中国人兽共患病学报

The aim of this study was to investigate the virulence determinants and genetic diversity of foodborne Yersinia enterocolitica from Wenzhou.A total of 71 strains of Yersinia enterocolitica were isolated from food and foodborne diarrhea ca-ses in Wenzhou,and their biotypes,serotypes,and drug resistance were analyzed.On the basis of whole genome sequencing,we assessed virulence gene profiles,and performed multilocus sequence typing(MLST)and core gene multilocus sequence typ-ing(cgMLST).A total of 94.4％(67/71)of isolates belonged to biotype 1A,and the highest proportion had serotype lA/O∶5(29.6％,21/71).The sensitivity rates of the isolates to 14 antibiotics exceeded 95.8％.A total of 16 categories and 126 viru-lence genes were identified,with two strains carrying the pYV plasmid and chromosome-related virulence genes.ST3(31.6％,12/38)was the most widespread MLST type,and cgMLST analysis revealed no dense clusters of genotypes except for strains sharing the same ST.In conclusion,pathogenic strains were identified from foodborne Yersinia enterocolitica in Wenzhou and were found to exhibit high genetic polymorphism.Enhanced regulatory supervision is essential to prevent the outbreak of food-borne diseases caused by Yersinia enterocolitica.

Investigation,traceability analysis,and discussion of food poisoning caused by Salmonella typhimurium ST19 / 中国人兽共患病学报

To perform a comprehensive analysis of the pathogenic causes of a food poisoning case in a district of Wuhan Cit-y,we investigated the molecular epidemiological relationships among pathogenic bacteria,to aid in traceability analysis of food-borne disease outbreaks,as well as clinical diagnosis and treatment.The pathogenic bacteria in this food poisoning case were i-solated and identified according to GB789.4-2016.The isolated strains were subjected to genotyping with pulsed field gel elec-trophoresis(PFGE).Drug resistance gene analysis,multi-locus sequence typing(MLST),and genome-wide single-nucleotide polymorphism analysis(wgSNP)were conducted via whole genome sequencing(WGS).The evolutionary tree for cluster analy-sis was constructed in fasttree software.Drug susceptibility testing was conducted with the broth microdilution method.A total of 12 strains of Salmonella were detected in seven anal swab samples and two fecal samples from the case,as well as three anal swab samples from unaffected individuals.The serotype of the strains was Salmonella typhimurium.The strain exhibited severe multiple drug resistance,including resistance to amikacin,ampi-cillin,cefazolin,gentamicin,piperacillin,and tetracycline,but susceptibility to other antibiotics.The coincidence rate between drug resistance genes and drug resistance phenotypes was high.PFGE revealed that nine strains from this food poisoning case were highly homologous.WGS revealed that the MLST type was ST19,and varying numbers of SNPs(1-6)were present a-mong strains.The phylogenetic tree revealed nine isolated strains forming a distinct cluster,differing from other Salmonella strains in the database and belonging to a novel clonal branch.The single nucleotide site in the strains was highly homologous to that of GCF in Jiangxi_020221795.1.The food poisoning case was caused by Salmonella typhimurium ST19,and all nine iso-lated strains originated from the same source.The chef is closely connected to this food poisoning case.This strain of Salmo-nella typhimurium belongs to a new clonal branch and exhibits multiple drug resistance.

Relationship between GLI1 expression and tumor immune infiltration and clinical prognosis of gastric cancer / 中国现代普通外科进展

Objective:To investigate the correlation between the expression of GLI1 and im-mune invasion and clinical prognosis in gastric cancer.To study the effect of GLI1 expression on drug resistance in gastric cancer.Methods:The expression difference of GLI1 in gastric cancer and normal tissues was analyzed by using TCGA database,and the effect of clinical features and GLI1 gene ex-pression level on prognosis of patients with gastric cancer was analyzed.The correlation between GLI1 gene expression and tumor immune cell infiltration in gastric cancer tissues was analyzed to explore its influence on drug resistance of chemotherapy drugs and targeted drugs.Clinical samples were collect-ed to analyze the difference of GLI1 expression in gastric cancer and paracancer tissues.Results:The expression of GLI1 in gastric cancer tissues was 1.7 times that in normal tissues,and the overall sur-vival and disease-free survival of patients with high expression are shorter than those with low ex-pression(P＜0.05).The interstitial score,immune score and abundance of immunoinfiltrating cells were higher in the high expression of GLI1 in gastric cancer tissues.High expression of GLI1 reduces drug sensitivity and is positively correlated with the expression of immune checkpoint markers PDCD1(P＜0.05).GLI1 expression was significantly increased in patients with subdifferentiated gastric cancer.Conclusions:GLI1 expression is associated with the prognosis and immune infiltration of patients with gastric cancer,and it may lead to poor prognosis of patients by regulating chemotherapy resis-tance,which may be a potential therapeutic target and molecular marker for gastric cancer.

Predictive value of serum glycoprotein non-metastatic melanoma protein B in patients with non-small cell lung cancer accompanied by epidermal growth factor receptor amplification with mutation / 中国医科大学学报

Objective To evaluate the clinical value of free glycoprotein non-metastatic melanoma protein B(GPNMB)as a drug resis-tance and prognostic marker for non-small cell lung cancer(NSCLC)patients with epidermal growth factor receptor(EGFR)amplifica-tion accompanied by mutations.Methods Fifty-five cases of NSCLC patients with EGFR amplification associated with mutations who received treatment from March 2018 to September 2019 were included as the observation group.All patients received an EGFR-tyrosine kinase inhibitor(EGFR-TKI)as the first-line treatment;67 blood samples from the physical examination center during the same period were randomly included as healthy control.We compared the expression levels of free GPNMB between the two groups,explored the correlation between GPNMB expression and the clinicopathological information in the observation group;and combined the clinical efficacy to evaluate its value as a drug resistance marker.Through follow-up,the progress free survival(PFS)of patients was statistically analyzed,and through multivariate Cox regression analysis,independent risk factors affecting the survival in the observation group were explored.Results Compared with that in the control group,the expression level of free GPNMB in the observation group was signi-ficantly up-regulated.The expression level of free GPNMB in the observation group is significantly related to the clinical efficacy of EGFR-TKI(P = 0.016).Patients with high GPNMB expression have significantly stronger drug resistance,and patients with high GPNMB expression have significantly shorter PFS duration(P = 0.032).A high free GPNMB expression(HR = 4.029,95%CI:1.942-8.358,P＜0.001)is also an independent risk factor affecting patient survival.Conclusion The expression level of free GPNMB in patients with EGFR amplification accompanied by mutant NSCLC is significantly up-regulated,and its high expression is significantly related to the enhancement of the patient's drug resistance.High GPNMB expression is significantly related to the poor prognosis of patients and is an independent risk factor affecting patient survival.

Changes in the isolation and drug resistance rate of Escherichia coli in a hospital over the past 10 years / 中国医科大学学报

Objective To summarize the isolation and drug resistance rate of Escherichia coliin The First Hospital of China Medical University over the past 10 years,in order to provide evidence for the efficacies of clinical anti-infection treatments.Methods The data was collected from Escherichia coli isolated from patients treated at The First Hospital of China Medical University between 2013 and 2022.VITEK 2 and VITEK MS were used for bacterial identification,VITEK2 and KB method were used for drug sensi-tivity testing,and WHONET 5.6 software was used for analysis.Results From 2013 to 2022,6 845 strains were isolated,including 80.5%from inpatients and 19.5%from emergency and outpatients.The specimens were most commonly found in the urine(57.8%),blood(15.0%),secretions(9.2%),and drainage fluid(8.1%).The isolation rate of extended-spectrumβ-lactamase(ESBL)producing Escherichia coli was 57.2%(54.3%to 61.5%).The drug resistance rate of Escherichia coli to carbapenems was low,at only 1.2%(0.2%to 2.6%).Conclusion Escherichia coli remains an important pathogen in clinical infections,with varying degrees of resist-ance to multiple antibiotics,and the resistance rate is increasing.Clinical physicians should pay sufficient attention to this issue.

Down-regulation of miR-152-3p expression reduces resistance to paclitaxel of paclitaxel-resistant ovarian cancer cells A2780T / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect and mechanism of miR-152-3p on the resistance to paclitaxel(PTX)of PTX-resistant ovarian cancer cells(A2780T cells).METHODS ① Ovarian cancer parent cells(A2780 cells)and A2780T cells were treated with PTX(1.875,3.75,7.5,17 and 23 μmol·L-1)for 48 h.Cell viability was evaluated by MTT assay,and the 50%inhibitory concentration(IC50)and drug resistance index of A2780T cells were calculated.Western blotting was used to detect the expres-sions of resistance protein P-glycoprotein(P-gp),multidrug resistance related protein 1(MRP1)and adenosine triphosphate binding transporter G superfamily member 2(ABCG2).② Real-time fluorescent quantita-tive PCR(RT-qPCR)was used to detect the expressions of miR-152-3p in A2780 and A2780T cells.The lipid-mediated transient transfection technique was employed to transfect the miR-152-3p inhibitor to reduce miR-152-3p expression in A2780T cells(miR-152-3p inhibitor group),while the negative control(miR-152-3p NC)group was established.RT-qPCR was used to detect transfection efficiency,and the MTT method,scratch experiment,and flow cytometry were used to investigate the effects of the trans-fecting miR-152-3p inhibitor on survival,migration and apoptosis of A2780T cells.Western blotting was used to detect the protein expressions of Bax and Bcl-2 in A2780T cells.③ Bioinformatics analysis of databases including miRDB,Targetscan,miRWalk,and Starbase predicted the target genes of miR-152-3p that were verified by Western blotting to detect the protein expression of PTEN in A2780T cells of the miR-152-3p inhibitor and miR-152-3p NC groups,and RT-qPCR to detect the PTEN mRNA expression in A2780 and A2780T cells.Then,the lipid-mediated transient transfection technique was used to transfect PTEN siRNA to silence PTEN expression in A2780T cells(PTEN siRNA group).The siRNA negative control(siRNA NC)group was established.RT-qPCR was used to detect transfection efficiency,the MTT method was employed to measure the survival rate and IC50 value,and Western blotting was used to assess the protein expressions of P-gp,MRP1,and ABCG2 in A2780T cells after silencing PTEN expression.RESULTS ①After treatment with PTX,the cell survival rates were decreased in A2780 and A2780T cells(P<0.05),and the resistance index of A2780T cells was 2.8.Compared with A2780 cells,the protein expressions of P-gp and MRP1 and ABCG2 were highly expressed in A2780T cells(P<0.05,P<0.01).② RT-qPCR showed that the expression of miR-152-3p in A2780T cells was higher than that of A2780 cells(P<0.01).Compared with the miR-152-3p NC group,A2780T cell viability(P<0.05,P<0.01)and cell migration capability(P<0.05)were significantly inhibited,while the apoptosis rate increased(P<0.01)in miR-152-3p inhibitor group.Moreover,the protein expression of Bax was increased(P<0.01),but Bcl-2 decreased(P<0.05).③ Bioinformatics analysis suggested that PTEN was a target gene of the miR-152-3p,and the verified results showed that the PTEN protein expression in A2780T cells of the miR-152-3p inhibitor group was lower than that of the miR-152-3p NC group(P<0.05),and PTEN mRNA expression in A2780T cells was higher than that in A2780 cells(P<0.01).After silencing the expression of PTEN in A2780T cells,the cell viability was significantly reduced(P<0.05,P<0.01),while the IC50 value was reduced(P<0.01)compared with the siRNA NC group.In addition,the protein expressions of P-gp,MRP1 and ABCG2 were decreased(P<0.05,P<0.01).CONCLUSION miR-152-3p is highly expressed in A2780T cells,and down-regulation of its expression may inhibit proliferation and migration,prompt apoptosis and reduce the resistance to PTX of A2780T cells,which is made possible by inhibiting expression of its target gene PTEN.