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Background: The global increase in type 2 DM is recognized re-emerging risk and challenge to TB control in India. TB-T2D association is again at the frontline of risk factors for TB, with an estimated worldwide population attributable fraction of 34.5%. T2D not only increases TB risk 3-fold, but also TB treatment failure including death. And prognosis of diabetic tuberculosis patients as compared to non diabetic ones is poorer. Methods: An comparative analytical study was done in microbiologically confirmed 50 diabetic and 50 non diabetic TB patients registered in RNTCP OPD of tertiary healthcare hospital who were followed up for 3 months. Results: In our study we found that elderly (above 65 age group) male diabetic patients were affected more with tuberculosis as compared to young patients and data was statistically significant. Extrapulmonary involvement was seen more in diabetic patients as compared to non diabetic patients. Radiologically diabetic tuberculosis patient showed predominantly lower lobe of lung involvement as oppose to non diabetic tuberculosis patients who showed upper lobe of lung involvement and data was statistically significant. Outcomes like Multidrug Resistance and prolonged sputum positivity after intensive phase treatment was seen more with diabetic tuberculosis patients but this was not statistically significant. Conclusions: Early screening of TB patients for DM and vice versa and early initiation of treatment will prevent unfavourable outcomes of these patients.
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Background: Pseudomonas aeruginosa is one of the most frequent opportunistic microorganisms causing infections in cancer patients. The aim of the study was to determine the antibiotic susceptibility of Pseudomonas aeruginosa and multidrug-resistant (MDR) isolates in cancer patients. Methods: A retrospective study was conducted from January 2022 to December 2022 at Government Cancer Hospital, Aurangabad. A total of 143 pus samples were collected from both IPD and OPD patients. Pus samples were collected as per standard procedure and were inoculated on blood and MacConkey agar. The isolates were identified by standard protocols using biochemical tests. The antibiotic susceptibility pattern of each isolate was checked as per Clinical and Laboratory Standards Institute (CLSI) guidelines 2022 using Kirby-Bauer's disc diffusion method and VITEK 2 Automation. Data analysis was done by statical method with statistical software SPSS version 22. Results: Out of 143 clinical samples 33 samples (23%) were positive for Pseudomonas aeruginosa growth. mean age of patients was 50 years old out of 33 isolates 12 (36%) isolates were multidrug-resistant, 11 (33%) isolates were extensively drug-resistant and 1 (3%) were pan-drug-resistant. The majority of isolates were responsive to polymyxin B 32 (96%) and colistin 32 (96%); However, the resistance to gentamycin, ceftazidime, and amikacin was higher, at 66%, 60%, and 57%, respectively. Conclusions: This hospital-based retrospective study will help to implement better infection control strategies and improve the knowledge of antibiotic resistance patterns among clinicians. Thus, there is a need for an antibiotic stewardship program to monitor the resistant pattern in a tertiary care cancer hospital.
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Background: Staphylococcus aureus infections are one of the most common and serious hospital-acquired infections seen in developing countries. Methicillin resistant Staphylococcus aureus (MRSA) is an important human pathogen and normally colonized in body parts including skin, nose, perineum and throat. MRSA is resistant not only to all ?-lactam groups but also other antibiotics including aminoglycosides, tetracycline and macrolides. In the present study the efficacy of agents used in the management of MRSA infections was determined by antibiotic gradient testing. Methods: A total of 60 clinical isolates of MRSA strains were collected from various diagnostic labs in central Kerala. Clinical isolates were reconfirmed as MRSA by gram staining, yellow-coloured colonies on mannitol salt Agar (MSA). Antibiotic susceptibility testing was done by disc diffusion method as recommended by CLSI guidelines. S. aureus isolates resistant to cefoxitin (30 µg) was identified as MRSA. Antibiotic gradient testing was performed to determine the MIC of vancomycin, tigecycline, linezolid, daptomycin, ceftaroline and mupirocin against MRSA isolates. Results: All the 60 MRSA isolates tested were sensitive to vancomycin, tigecycline, linezolid, daptomycin, ceftaroline and mupirocin (100%) and none of the MRSA isolates show resistance. Conclusions: Results of present study indicates that these agents may be used alongside vancomycin in management of infection caused by MRSA.
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Resumen Introducción: El aumento de bacterias resistentes a múltiples fármacos destaca la necesidad de mejorar las terapias antimicrobianas. Las bombas de eflujo, que reducen la concentración de antimicrobianos en las bacterias, son clave en la resistencia, mecanismos que disminuyen la concentración de antimicrobianos en las bacterias, contribuyendo a la resistencia. Objetivo: Evaluar el efecto del inhibidor de bombas de eflujo Phenylalanine-arginine β-naphthylamide sobre la resistencia bacteriana a los antibióticos ceftazidima, clortetraciclina, ciprofloxacina, ceftriaxona, ampicilina y gentamicina en bacilos gram negativos con múltiples genes de BLEE aisladas. Materiales y Métodos: Se realizó un estudio experimental con el propósito de analizar los aislamientos de bacilos gram negativos multirresistentes asociados a infecciones procedentes de una Institución prestadora de servicios de salud de Boyacá, para esto, a partir de 81 aislamientos bacterianos se detectaron genes de resistencia antibiótico en 70 cepas mediante reacción en cadena de la polimerasa convencional y secuenciación tipo Sanger. Resultados: En los 70 aislamientos analizados se evidenció la presencia de determinantes genéticos de resistencia a antibióticos betalactámicos como: bla TEM bla SHV1, bla SHV2 y bla CTM-X , con predominancia del gen bla SHV . Conclusiones: El ensayo de interacción mostró qué en cepas multirresistentes, la terapia conjunta con inhibidores de bombas de expulsión puede ser una alternativa para el tratamiento, sin embargo, debido a la gran diversidad de las bombas de eflujo, se deben evaluar otras familias de inhibidores para identificar los que sean eficientes en un mayor número de cepas.
Abstract Introduction: The rise of bacteria resistant to multiple drugs underscores the need to enhance antimicrobial therapies. Efflux pumps, which decrease the concentration of antimicrobials in bacteria, play a key role in resistance. Objective: The objective of this study is to evaluate the effect of the efflux pump inhibitor Phenylalanine-arginine ß-naphthylamide on bacterial resistance to antibiotics ceftazidime, chlortetracycline, ciprofloxacin, ceftriaxone, ampicillin, and gentamicin in gram-negative bacilli with multiple ESBL genes isolated. Materials and Methods: An experimental study was conducted to analyze multi-resistant gram-negative bacillus isolates associated with infections from a healthcare institution in Boyacá. From 81 bacterial isolates, antibiotic resistance genes were detected in 70 strains through conventional polymerase chain reaction and Sanger sequencing. Results: The analysis of 70 isolates revealed the presence of genetic determinants for beta-lactam antibiotic resistance such as bla TEM1 , bla SHV1 , bla SHV2 y bla CTM-X ,, with a predominance of the bla SHV gene. Conclusions: The interaction assay showed that in multi-resistant strains, combination therapy with efflux pump inhibitors could be an alternative for treatment. However, due to the diverse nature of efflux pumps, other families of inhibitors should be evaluated to identify those effective across a larger number of strains.
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The overexpression of P-glycoprotein (P-gp/ABCB1) is a leading cause of multidrug resistance (MDR). Hence, it is crucial to discover effective pharmaceuticals that counteract ABCB1-mediated multidrug resistance. FRAX486 is a p21-activated kinase (PAK) inhibitor. The objective of this study was to investigate whether FRAX486 can reverse ABCB1-mediated multidrug resistance, while also exploring its mechanism of action. The CCK8 assay demonstrated that FRAX486 significantly reversed ABCB1-mediated multidrug resistance. Furthermore, western blotting and immunofluorescence experiments revealed that FRAX486 had no impact on expression level and intracellular localization of ABCB1. Notably, FRAX486 was found to enhance intracellular drug accumulation and reduce efflux, resulting in the reversal of multidrug resistance. Docking analysis also indicated a strong affinity between FRAX486 and ABCB1. This study highlights the ability of FRAX486 to reverse ABCB1-mediated multidrug resistance and provides valuable insights for its clinical application.
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Objective@#To investigate the resistance to rifampicin and isoniazid and the changing trends among patients with pulmonary tuberculosis in Luohu District, Shenzhen City, Guangdong Province from 2012 to 2022, so as to provide insights into improving drug-resistant pulmonary tuberculosis control and prevention strategies.@*Methods@#Basic information, treatment classification and drug resistance data of patients with pulmonary tuberculosis and positive pathogenic detection in Luohu District from 2012 to 2022 were collected through the Tuberculosis Surveillance System of Chinese Disease Prevention and Control Information System, and resistance rates of rifampicin and isoniazid and the changing trends were analyzed.@*Results@#A total of 2 126 patients with pulmonary tuberculosis were collected and had a median age of 34 (interquartile range, 25) years, including 1 334 males (62.75%) and 792 females (37.25%). There were 302 patients with drug-resistance in Luohu District from 2012 to 2022, with a resistance rate of 14.21%. Among them, 60 patients were monoresistant to rifampicin (2.82%), 113 patients were monoresistant to isoniazid (5.32%), and 129 patients were multidrug resistant (6.07%). The rate of rifampicin monoresistance showed a downward trend from 2012 to 2022, while the rate of multidrug resistance showed an upward trend (both P<0.05). There was no significant tendency in the rate of isoniazid monoresistance (P>0.05). The rate of multidrug resistance among patients without Shenzhen residence was higher than that among patients with Shenzhen residence; the rates of rifampicin resistance and multidrug resistance among retreated patients were higher than those among treatment-naïve patients (all P<0.05).@*Conclusions@#The rate of rifampicin monoresistance appeared a downward trend and the rate of multidrug resistance appeared an upward trend among patients with pulmonary tuberculosis in Luohu District from 2012 to 2022. Attention should be given to non-Shenzhen residence and retreated patients.
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The disease spectrum of ABCB4 gene mutation involves various diseases such as progressive familial intrahepatic cholestasis type 3 （PFIC3）， gallstone disease， intrahepatic cholestasis of pregnancy， portal hypertension， liver cirrhosis， and even primary hepatic and biliary malignancies. A young male patient was admitted to Department of Hepatobiliary Medicine， Eastern Hepatobiliary Surgery Hospital， and was initially diagnosed with liver cirrhosis and gallstones， and he was planned to receive laparoscopic cholecystectomy. Preoperative examination showed abnormal liver function， liver cirrhosis， splenomegaly， and mild esophageal varices， and next-generation sequencing was performed to make a confirmed diagnosis of ABCB4 gene mutation-associated liver cirrhosis with gallstones. The liver function of the patient gradually returned to normal after cholagogic treatment with ursodeoxycholic acid capsules.
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Aim To establish NCI-H446/EP for small cell lung cancer resistant cells resistant to cisplatin and etoposide, and to evaluate their biological characteristics and multidrug resistance. Methods Nude mice were subcutaneously inoculated with NCI-H446 cells of SCLC to construct an in vivo model of xenograft tumor, and were given first-line EP regimen treatment for SCLC, inducing drug resistance in vivo, and stripping tumor tissue in vitro culture to obtain drug-resistant cells. The resistance coefficient, cell doubling time, cell cycle distribution, expression of multidrug resistance gene (MDR1), and drug resistance-related protein were detected in vitro, and the drug resistance to cisplatin and etoposide in vivo were verified. Results Mice with NCI-H446 tumors acquired resistance after eight weeks' EP regimen treatment, and the drug-resistant cell line NCI-H446/EP was obtained by isolation and culture in vitro. The resistance factors of this cell line to cisplatin, etoposide, SN38 and doxorubicin were 12.01, 18.36, 65.4 and 10.12, respectively. Compared with parental cells, the proportion of NCIH446/EP cells in Q
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Background: Bacteriophages offer one of the most promising solutions to the challenges of antimicrobial resistance in bacteria. The aim of this study is to investigate bacteriophages as a source of new antimicrobial therapy. Methodology: Waste water samples were randomly collected from 8 different locations in the city of Lomé for bacteriophage isolation. The phages were isolated using multi-resistant clinical isolates (Escherichia coli 1642 and Staphylococcus aureus 0868) as hosts by means of a spot test. The host range of the phages was determined also by a spot test using 8 other clinical bacterial isolates including two reference strains (E. coli ATCC 25922 and S. aureus ATCC 29213). The virulence of the phages and their effects on bacterial growth were assessed by in vitro experiments using E. coli 1642 BBec phage suspension. Results: Isolation of phages by the spot test was positive only with the host E. coli 1642. A reduced host range was observed with the other bacteria. The BBec phage suspension showed a titer of 1.6 x 107 PFU/ml. Virulence studies revealed a latency time of less than 10 minutes, a degree of absorption of 87% and a burst size of 63 PFU/cell. The effect of BBec phage suspension on E. coli 1642 showed an almost total reduction in the population of E. coli 1642 after 4 hours. Conclusion: This study provided scientific data showing the antibacterial effect of a phage suspension (BBec) on a multi-resistant clinical isolate of E. coli 1642. This phage could therefore be explored as a candidate for the development of new antibacterial therapies.
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Bacteriophages , Drug Resistance, Multiple , Water Consumption (Environmental Health)ABSTRACT
Objectives: To compare the clinical, epidemiological, and laboratory profiles of bacterial infection or colonization among patients hospitalized in COVID-19 and non-COVID-19 intensive care units (ICUs) in Southeast Pará, Brazil. Methods:This was a retrospective analytical study based on the analyses of electronic medical records and microbiological reports of patients admitted to the ICU of a regional hospital located in Pará in the Brazilian Amazon due to complications associated with COVID-19 and other causes from March 2020 to December 2021. The sample consisted of data from the medical records of 343 patients collected after approval by the ethics and research committee (opinion number 5281433) was granted. The data extracted from the bacteriological and antibiogram culture reports were analyzed to characterize the clinical-epidemiological profile of the patients. The data were transferred and tabulated in Microsoft Excel 2019 to conduct a descriptive analysis, and the associated statistical analyses were performed using Stata 17.0 statistical soft-ware. Results: Of the total patients, 59.5% were hospitalized in the COVID-19 ICU and 40.5% were hospitalized in the non-COVID-19 ICU. Most individuals admitted to the COVID-19 ICU and non-COVID-19 ICU were aged between 66 and 78 years and between 54 and 66 years, respectively. The hospitalization duration in the COVID-19 ICU was fewer than 15 days, whereas that in the non-COVID-19 ICU was 15 to 30 days. Deaths were more frequent in the Covid-19 ICU compared to the non-Covid-19 ICU (64% versus 41%). In contrast, hospital discharge was more frequent in the non-Covid-19 ICU (58.3% versus 34.8%).The most prevalent comorbidity in both ICUs was circulatory system disease. Gram-negative bacteria were the most frequent etiological agent in both groups and were present in 63.1% of the cultures analyzed. Regarding the phenotypic profile of resistance, carbapenemase production was detected in 43.0% of the cultures analyzed. Multidrug resistance against antimicrobial drugs was more frequent in the non-COVID-19 ICU (55.7%). Most of the antimicrobial drug prescriptions for were empirical. Conclusions: The recurrence of secondary infections and bacterial colonization in both COVID-19 and non-COVID-19 ICU patients should not be underestimated. The clinical, microbiological, and bacterial resistance profiles elucidated in this study highlight the need to develop and implement holistic and assertive strategies to control and mitigate these problems. Which will contribute to an improved prognosis for patients and quality of life patients (AU).
Objetivos: Comparar o perfil clínico, epidemiológico e laboratorial das infecções ou colonizações bacterianas entre pacientes internados em UTI COVID-19 e não-COVID-19 no Sudeste do Pará, Brasil. Métodos: Trata-se de um estudo analítico retrospectivo baseado na análise de prontuários eletrônicos e laudos microbiológicos de pacientes internados em um hospital regional localizado no Pará, na Amazônia brasileira, devido a complicações associadas à COVID-19 e outras causas no período de março de 2020 a dezembro de 2021. A amostra foi constituída por dados dos prontuários de 343 pacientes coletados após aprovação pelo Comitê de ética em Pesquisa (parecer número 5281433). Os dados extraídos dos laudos de cultura bacteriológica e antibiograma foram analisados para caracterizar o perfil clínico-epidemiológico dos pacientes. Foram realizadas análises descritivas e inferenciais utilizando o Stata 17.0 statistical software. Resultados: Do total de pacientes, 59,5% estavam internados na UTI COVID-19 e 40,5% na UTI não-COVID-19. A maioria dos indivíduos apresentavam idades entre 54 e 78. O tempo de internação na UTI COVID-19 foi inferior a 15 dias, enquanto na UTI não-CO-VID-19 foi de 15 a 30 dias. Os óbitos foram mais frequentes na UTI Covid-19 em relação à UTI não-Covid-19 (64% versus 41%). Em contrapartida, a alta hospitalar foi mais frequente na UTI não Covid-19 (58,3% versus 34,8%). A comorbidade mais prevalente em ambas as UTIs foi a doença do aparelho circulatório. As bactérias Gram-negativas foram os agentes etiológicos mais frequentes em ambos os grupos e estiveram presentes em 63,1% das culturas analisadas. Em relação ao perfil fenotípico de resistência, a produção de carbapenemase foi detectada em 43,0% das culturas analisadas. A multirresistência aos antimicrobianos foi mais frequente na UTI não COVID-19 (55,7%). A maioria das prescrições de antimicrobianos foram empíricas. Conclusões: A recorrência de infecções secundárias e colonizações bacterianas em pacientes com COVID-19 e não COVID-19 em UTIs não devem ser subestimadas. Os perfis de resistência bacteriana elucidados neste estudo destacam a necessidade da implementação de estratégias holísticas e assertivas visando o controle e mitigação dessa problemática, o que contribuirá para a melhoria do prognóstico, bem como, a qualidade e segurança dos paciente (AU).
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Humans , Drug Resistance, Multiple , Evidence-Based Medicine , Coinfection , COVID-19 , Intensive Care UnitsABSTRACT
Background: Increasing bacterial resistance to antimicrobial agents is resulting in high morbidity and mortality. Antimicrobial stewardship (AMS) programs aim at rationale use of antimicrobial agents in clinical settings by development and implementation of antibiotic policy. As the patterns of antimicrobial resistance vary with organism and time, there is a need for periodic surveillance. Aims and Objectives: The aim of the study was to study the impact of AMS program on appropriate use of antimicrobial agents and clinical outcomes in patients with multidrug-resistant Gram-negative bacterial (MDR GNB) infections. Materials and Methods: This is a prospective observational study that included patients diagnosed with multidrug-resistance Gram-negative bacterial infections during June to July 2019. Identification of multidrug-resistant organisms was performed as per clinical and laboratory standards institute guidelines 2016. Information on the use of empirical antibiotic and other antimicrobial agents after culture and sensitivity report were collected and assessed for appropriateness. All the patients were followed up till discharge. Results: From 170 patients, there were 211 specimens sent for culture and sensitivity and 249 pathogens were isolated. The most frequent pathogen isolated was Escherichia coli (42.6%) followed by Klebsiella spp. (22.9%). Isolates were most resistant to cefazolin (86.7%) and ceftriaxone (83.9%), and most sensitive to polymyxin B (100%) and tigecycline (97.2%). All patients were administered antimicrobial agents as per antibiotic policy of the institute and 154 (90.6%) patients have recovered from illness with a mean length of hospital stay of 19.4 ± 6.6 days. Conclusion: Adherence to antimicrobial policy helps in improved outcomes in patients with MDR GNB infections. Hence, the need to implement AMS program in all hospitals.
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Resumen El abuso y mal uso de los antimicrobianos aceleró la propagación de bacterias resistentes. La asociación entre las infecciones que presentan resistencia a antimicrobianos (RAM) en humanos y el uso de antimicrobianos en la producción agropecuaria es compleja, pero está bien documentada. Proporcionamos una revisión sistemática y metaanálisis sobre la diseminación de la resistencia a antimicrobianos designados como críticamente importantes por la Organización Mundial de la Salud (OMS) en cerdos, aves y bovinos de producción intensiva y extensiva en Argentina. Se buscó información en bases de datos electrónicas (Medline-PubMed, Web of Science, SciELO, Sistema Nacional de Repositorios Digitales de Argentina) y en la literatura gris. Se incluyeron estudios epidemiológicos sobre la RAM en las principales bacterias transmitidas por los alimentos - Salmonella spp., Campylobacter spp., Escherichia coli y Enterococcus spp. - y bacterias causantes de mastitis aisladas de cerdos, pollos y bovinos. Los resultados de este estudio apoyan la hipótesis de que la RAM de las bacterias transmitidas por los alimentos alcanza niveles alarmantes. Los metaanálisis seguidos de análisis por subgrupos mostraron asociación entre la RAM y (a) el animal (p<0,01) para estreptomicina, ampicilina y tetraciclina o (b) el sistema productivo (p<0,05) para estreptomicina, cefotaxima, ampicilina, ácido nalidíxico y tetraciclina. La mayor prevalencia conjunta de multirresistencia se detectó en cerdos (0,47 [0,29; 0,66]) y producción intensiva (0,62 [0,34; 0,83]), mientras que la menor correspondió a bovinos de leche (0,056 [0,003; 0,524]) y producción extensiva (0,107 [0,043; 0,240]). Se observó un vacío de información respecto de los bovinos de feedlot. Es urgente adoptar medidas políticas para coordinar y armonizar la vigilancia de la RAM y regular el uso de antimicrobianos en animales.
Abstract Abuse and misuse of antimicrobial agents has accelerated the spread of antimicrobial-resistant bacteria. The association between antimicrobial-resistant infections in humans and antimicrobial use in agriculture is complex, but well-documented. This study provides a systematic review and meta-analysis of the dissemination of antimicrobial resistance (AMR) to antimicrobials defined as critically important by the WHO, in swine, chicken, and cattle from intensive and extensive production systems in Argentina. We conducted searches in electronic databases (MEDLINE-PubMed, Web of Science, SciELO, the National System of Digital Repositories from Argentina) as well as in the gray literature. Inclusion criteria were epidemiological studies on AMR in the main food-transmitted bacteria, Salmonella spp., Campylobacter spp., Escherichia coli and Enterococcus spp., and mastitis-causing bacteria, isolated from swine, chicken, dairy and beef cattle from Argentina. This study gives evidence for supporting the hypothesis that AMR of common food-transmitted bacteria in Argentina is reaching alarming levels. Meta-analyses followed by subgroup analyses confirmed the association between the prevalence of AMR and (a) animal species (p<0.01) for streptomycin, ampicillin and tetracycline or (b) the animal production system (p<0.05) for streptomycin, cefotaxime, nalidixic acid, ampicillin and tetracycline. Moreover, swine (0.47 [0.29; 0.66]) and intensive production (0.62 [0.34; 0.83]) showed the highest pooled prevalence of multidrug resistance while dairy (0.056 [0.003; 0.524]) and extensive production (0.107 [0.043; 0.240]) showed the lowest. A research gap regarding beef-cattle from feedlot was identified. Finally, there is an urgent need for political measures meant to coordinate and harmonize AMR surveillance and regulate antimicrobial use in animal production.
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Objetivo. Evaluar la asociación entre el sobrepeso/obesidad y la multidrogoresistencia en pacientes con y sin antecedentes de tratamiento para tuberculosis. Materiales y métodos. Estudio transversal realizado a través de un análisis secundario de la base de datos de una cohorte de tuberculosis, que incluyó datos de pruebas antropométricas y pruebas de sensibilidad a drogas en la visita basal de pacientes con y sin tratamiento previo para tuberculosis. Resultados. Se evaluaron 3,734 casos nuevos y 766 con antecedente de haber recibido tratamiento para tuberculosis. El sobrepeso/obesidad no se asoció a la multidrogoresistencia en pacientes con antecedente de tratamiento para tuberculosis, mostrando una razón de prevalencia de 0,97 con un intervalo de confianza al 95% de 0,68-1,38. Conclusiones. El sobrepeso/obesidad no está asociado a la multidrogoresistencia en tuberculosis; siendo el sobrepeso/obesidad un proceso dinámico que puede influir en las relaciones entre el sistema inmune y el sistema metabólico.
Objective. To evaluate the association between overweight/obesity and multidrug resistance in patients with and without a history of tuberculosis treatment. Materials and methods. Cross-sectional study of secondary data from a tuberculosis cohort, which included anthropometric and drug-sensitivity testing data at the baseline visit of patients with and without previous tuberculosis treatment. Results. We evaluated 3,734 new cases and 766 with a history of having received treatment for tuberculosis. Overweight/obesity was not associated with multidrug resistance in patients with a history of tuberculosis treatment, with a prevalence ratio of 0.97 and a 95% confidence interval of 0.68-1.38. Conclusions. Overweight/obesity is not associated with multidrug resistance in tuberculosis. Overweight/obesity is a dynamic process that may influence the relationship between the immune system and the metabolic system.
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Humans , Male , Female , Adult , Middle AgedABSTRACT
OBJECTIVE@#To explore the genotyping characteristics of human fecal Escherichia coli( E. coli) and the relationships between antibiotic resistance genes (ARGs) and multidrug resistance (MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data.@*METHODS@#Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs, multilocus sequence typing (MLST), and polymorphism trees were analyzed using whole-genome sequencing data (WGS).@*RESULTS@#This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal (49/70) and healthy groups (15/24).@*CONCLUSION@#We developed a random forest (RF) prediction model of TEM.1 + baeR + mphA + mphB + QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers.
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Humans , Escherichia coli/genetics , Escherichia coli Infections/epidemiology , Multilocus Sequence Typing , Genotype , Beijing , Drug Resistance, Multiple, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Diarrhea , Microbial Sensitivity TestsABSTRACT
Aims@# Hundreds of uropathogenic Escherichia coli (UPEC) lineages with diverse virulence-associated traits have been reported worldwide. However, the complex interactions between the bacterial traits and host factors remain largely unexplored. This study was aimed to determine the distribution of virulence-associated traits, phylogenetic background and antimicrobial resistance profiles of the UPEC isolates in relation to the host factors. @*Methodology and results@#Polymerase chain reactions (PCRs) were conducted to determine the prevalence of 32 virulence genes (VGs), eight pathogenicity island (PAI) markers and phylogroups of 105 UPEC isolates. The antimicrobial susceptibility testing was performed using the disc diffusion method. Results suggest that the virulenceassociated traits and antimicrobial resistance profiles of the UPEC strains were associated with phylogenetic background, host age and gender. Most of the virulence-associated traits tested were distributed prevalently in phylogroup B2, age group 40-59 and male gender, including papC, papG II_III, papG allele III, sfa/focDE, yfcV, hlyA, cnf1, cdtB, malX, PAI I536, PAI II536, PAI ICFT073, PAI IICFT073 and PAI IIJ96. Besides, higher rates of multidrug resistance (MDR) were significantly associated with non-phylogroup B2 (25/38; 65.8%; p<0.05) and age group 60-79 (29/42; 69.0%; p<0.05) but not with male gender (14/25; 56.0%; p=0.527). The UPEC strains collected from males and age 60-79 were significantly resistant to cefuroxime, cefotaxime and ceftazidime (all p<0.05). @*Conclusion, significance and impact of study@#Research findings elucidate the key molecular characteristics of the UPEC strains in relation to the host age and gender.
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Chemotherapy is one of the important methods to treat cancer, and the emergence of multidrug resistance (MDR) is one major cause for the failure of cancer chemotherapy. Almost all anti-tumor drugs develop drug resistance over a period of time of application in cancer patients, reducing their effects on killing cancer cells. Chemoresistance can lead to a rapid recurrence of cancers and ultimately patient death. MDR may be induced by multiple mechanisms, which are associated with a complex process of multiple genes, factors, pathways, and multiple steps, and today the MDR-associated mechanisms are largely unknown. In this paper, from the aspects of protein-protein interactions, alternative splicing (AS) in pre-mRNA, non-coding RNA (ncRNA) mediation, genome mutations, variance in cell functions, and influence from the tumor microenvironment, we summarize the molecular mechanisms associated with MDR in cancers. In the end, prospects for the exploration of antitumor drugs that can reverse MDR are briefly discussed from the angle of drug systems with improved targeting properties, biocompatibility, availability, and other advantages.
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@#Abstract: Objective To investigate the efficacy of capreomycin adjuvant therapy for multidrug-resistant pulmonary tuberculosis (MDR-TB) and its effect on quality of life and immune function. Methods Eighty-eight elderly pulmonary tuberculosis patients admitted to Affiliated Hospital of Hebei University from October 2019 to October 2020 were selected and divided into two groups according to the random number table method. The control group (n=44) used 4-6Am-Mfx（Lfx）-Pto-Cfz-Z-Hhigh-dose-E/5 Mfx（Lfx）-Cfz-Z-E, the research group (n=44) used capreomycin on the basis of the control group. The 6-Minute Walk Test (6MWT) measured value/predicted value and quality of life [36-Item Short Form Health Survey Questionnaire (SF-36)] scores, safety evaluation results, chest CT cavity and lesion absorption rate and sputum culture turned negative were compared between the two groups, and the serum procalcitonin (PCT) expression levels and immune function were detected before and after treatment. Results The 6MWT measured value/predicted value of the research group and control group before the treatment were (0.48±0.11) and (0.64±0.13), which were significantly higher than corresponding (0.51±0.12) and (0.58±0.14) after treatment (t=6.23, 2.520, P<0.05), the measured/expected value of 6MWT increased in both groups after treatment. Compared with the same group before treatment, the SF-36 scores for each dimension increased in both groups after treatment (P<0.01). The expression levels of serum PCT in the research group and control group before the treatment were (0.37±0.09) ng/mL and (0.12±0.03) ng/mL versus (0.36±0.11) ng/mL and (0.21±0.06) ng/mL after treatment (t=17.480, 7.940, P<0.01). Compared with the same group before treatment, serum PCT expression levels decreased in both groups after treatment. Compared with the same group before treatment, CD3+, CD4+ and CD4+/CD8+ were elevated in both groups after treatment (P<0.05 or P<0.01); after treatment, CD3+, CD4+, and CD4+/CD8+ were significantly higher in research group compared to the control group (t=4.21, 8.02, 2.04, P<0.05). The absorption rate of chest CT cavity and lesions and negative rate of sputum culture in the research group were 88.64% (39/44) and 81.82% (36/44), which were significantly higher than corresponding 63.64% (28/44) and 61.36% (27/44) in the control group (P<0.05). Conclusions Capreomycin can improve the quality of life of MDR-TB patients, extend the 6-minute walking distance, and regulate serum PCT expression levels and immune function, to promote the absorption of chest CT cavity and lesions, and sputum culture to turn negative, and the security is acceptable.
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Objective:To analyze the antimicrobial resistance and genomic characteristics of Salmonella enterica serovar Derby strains isolated from human and food sources in Hangzhou. Methods:A total of 60 Salmonella enterica serovar Derby strains isolated in Hangzhou during the period from 2015 to 2020 were subjected to antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE) typing and whole-genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and the identification of antimicrobial resistance genes were performed using the sequencing data. Phylogenetic tree based on the single nucleotide polymorphism (SNP) sites in the 60 genomes from Hangzhou and 379 genomes from public databases was constructed. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Hangzhou. The multidrug resistance (MDR) rate was 76.7% (46/60). All of the 60 Salmonella Derby strains were positive for the antimicrobial resistance genes aac(6′)- Iaa and fosA7. The 60 strains were subtyped into 46 molecular types by PFGE and 53 molecular types by cgMLST(HC2). Except for one strain belonging to ST3220, the other Salmonella Derby strains were ST40. The phylogenetic analysis showed that some strains isolated in Hangzhou were close to the strains in Southeast Asia, suggesting the possibility of cross-border transmission of ST40 strains, with the main food sources being pork and fish; other strains were close to those circulating in Beijing, Guangzhou, Hubei, Chongqing and other provinces, suggesting the possibility of cross-province transmission of the strains, with the main food sources being pork, beef and chicken. Conclusions:The epidemic of Salmonella Derby in Hangzhou was mainly caused by the spread of ST40 strains and MDR was common. Clinical infections might be closely related to the consumption of pork, beef, chicken and fish. There was the possibility of cross-border transmission of Salmonella Derby between Hangzhou and Southeast Asia and cross-province transmission in China.
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@#Abstract: Objective To investigate the occurrence of multidrug-resistance among tuberculosis patients in Hainan Province from 2014 to 2020 and to analyze the influencing factors, aiming to provide reference for formulating drug-resistant tuberculosis control strategies in this region. Methods This study collected sputum samples from the patients with pulmonary tuberculosis admitted to the Second Affiliated Hospital of Hainan Medical University from 2014 to 2020, and performed isolation and identification of Mycobacterium tuberculosis and drug susceptibility testing. After the strains were identified as positive, drug sensitivity tests were conducted, and multi-drug resistant patients were found. Clinical data was retrospectively collected, and chi-square test and unconditioned logistic regression were used to analyze the influencing factors of multidrug resistance. Results A total of 2 672 patients underwent sputum culture, strain identification, and drug susceptibility testing in TB designated hospitals in Hainan Province from January 1, 2014 to December 31, 2020. Among them, 1 942 patients with available drug susceptibility test results and complete clinical data were enrolled, among which 398 cases with drug-resistant TB were included in the case group, and 1 544 cases without drug resistance were included in the control group. Multivariate logistic regression analysis showed that farmers, rural residence, treatment history of retreatment, irregular medication history, number of pulmonary cavities ≥3, and BMI<18.5 were independent risk factors for MDR-TB. The risk of MDR-TB in farmers was higher than that in non-farmers (OR=1.542, 95%CI: 1.150-2.020); patients living in rural areas had a higher risk of multidrug resistance than those living in urban areas (OR=1.445, 95%CI: 1.095-1.907); the risk of MDR in the retreatment patients was higher than that in the initial treatment patients (OR=5.616, 95%CI: 4.250-7.421); the risk of multi-drug resistance in patients with irregular medication was higher than that in patients with regular medication (OR=2.665, 95%CI: 2.012-3.531); the risk of multidrug resistance in patients with pulmonary cavity number ≥3 was higher than that in patients with pulmonary cavity number <3 (OR=5.040, 95%CI: 3.768-6.740); compared with patients with BMI<18.5, patients with BMI=18.5-24.0 and BMI≥24.0 had a lower risk of multidrug resistance (OR=0.735, 95%CI: 0.555-0.975 and OR=0.447，95%CI:0.225-0.888, respectively). Conclusions Retreatment, farmer occupation, rural residence, irregular medication and low BMI may be the risk factors for multidrug resistance in Hainan Province.
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This study explored the effect and underlying mechanism of Stellera chamaejasme extract(SCE) on multidrug resistance of breast cancer. The chemotherapy-sensitive breast cancer cell line MCF-7 and adriamycin(ADR)-resistant cell line MCF-7/ADR were used as experimental subjects. MTT assay was used to detect cell proliferation activity. Pi staining was used to detect the cell cycle. 4',6-Diamidino-2-phenylindole, dihydrochloride(DAPI) staining and flow cytometry were used to detect apoptosis. Dansylcadaverine(MDC) staining and GFP-LC3B-Mcherry adenovirus transfection were used to detect autophagy. The protein expression of Bcl-2, Bax, caspase-9, caspase-3, LC3B, p62, and Beclin-1 was detected by Western blot. The results showed that SCE could significantly inhibit the proliferation of both sensitive and resistant breast cancer cell lines. The drug resistance factor was 0.53, which was significantly lower than 59 of ADR. Meanwhile, the proportion of sensitive/resistant cells in the G_0/G_1 phase increased significantly after SCE treatment. In addition, DAPI staining showed that a series of apoptosis phenomena such as nuclear pyknosis, staining deepening, and nuclear fragmentation appeared in sensitive/resistant cell lines after SCE administration. Moreover, the results of flow cytometry double staining showed that the proportion of apoptotic cells in sensitive/resistant cell lines increased significantly after SCE administration. Besides, Western blot showed that the protein expression levels of caspase-3, caspase-9, and Bcl-2 significantly decreased and the expression level of Bax protein significantly increased in both breast cancer cell lines after SCE administration. Furthermore, SCE could also increase the positive fluorescent spots after MDC staining and yellow fluorescent spots after GFP-LC3B-mcherry transfection, and up-regulate the expression levels of autophagy-related proteins LC3B-Ⅱ, p62, and Beclin-1 in breast cancer cells. In summary, SCE may play the role of anti-multidrug resistance by blocking the cell cycle of breast cancer multidrug-resistant cells, blocking autophagy flow, and ultimately interfering with the apoptosis resistance of drug-resistant cells.