Spatial and temporal analysis of MDR-TB epidemic based on SaTScan in Nanning in 2017 - 2021 / 公共卫生与预防医学

Objectives To analyze the spatial and temporal aggregation of multidrug resistant pulmonary tuberculosis (MDR-TB) incidence in Nanning at the township / street scale from 2017 to 2021, to explore the spatial and temporal characteristics of the spread of MDR-TB in Nanning, and to provide a scientific reference basis for the health administrative departments to achieve the precise implementation of MDR-TB prevention and control. Methods Based on the data of MDR-TB cases in Nanning from 2017 to 2021, the spatial-temporal scanning analysis software SaTScan v9.7 was used to retrospectively detect and analyze the areas where MDR-TB cases gathered. Results Through simple spatial scanning analysis, it was found that there were three first-class aggregation areas (the aggregation center was Fujiayuan Street, Jiangnan District, 2017, Xinyang Street, Xixiangtang District, 2019, and Zhonghe Town, Yongning District, 2020), and one second-class aggregation area (the aggregation center was Jinchai Town, Mashan County, 2020). Simple time scanning showed that the clustering occurred from May 2019 to December 2020. Temporal and spatial aggregation analysis showed that Xinyang Street in Xixiangtang District was the center of the first-class aggregation area, Zhonghe Town in Yongning District was the center of the second-class aggregation area, and Jinchai Town in Mashan County was the center of the third-class aggregation area. Conclusion The multidrug resistant pulmonary tuberculosis epidemic in Nanning is distributed in an aggregated manner, especially in Xinyang Street, Xixiangtang District, which has the highest spatial and temporal aggregation. It is necessary to focus on and take regional prevention and control measures to control the epidemic.

Role of the IL8 rs4073 polymorphism in central nervous system toxicity in patients receiving multidrug-resistant tuberculosis treatment / Papel do polimorfismo rs4073 do gene IL8 na toxicidade do sistema nervoso central em pacientes em tratamento para tuberculose multirresistente

ABSTRACT Objective: To determine the role of the IL8 rs4073 polymorphism in predicting the risk of central nervous system (CNS) toxicity in patients receiving standard pharmacological treatment for multidrug-resistant tuberculosis (MDR-TB). Methods: A cohort of 85 consenting MDR-TB patients receiving treatment with second-line antituberculosis drugs had their blood samples amplified for the IL8 (rs4073) gene and genotyped. All patients were clinically screened for evidence of treatment toxicity and categorized accordingly. Crude and adjusted associations were assessed. Results: The chief complaints fell into the following categories: CNS toxicity; gastrointestinal toxicity; skin toxicity; and eye and ear toxicities. Symptoms of gastrointestinal toxicity were reported by 59% of the patients, and symptoms of CNS toxicity were reported by 42.7%. With regard to the genotypes of IL8 (rs4073), the following were identified: AA, in 64 of the study participants; AT, in 7; and TT, in 11. A significant association was found between the dominant model of inheritance and CNS toxicity for the crude model (p = 0.024; OR = 3.57; 95% CI, 1.18-10.76) and the adjusted model (p = 0.031; OR = 3.92; 95% CI, 1.13-13.58). The AT+TT genotype of IL8 (rs4073) showed a 3.92 times increased risk of CNS toxicity when compared with the AA genotype. Conclusions: The AT+TT genotype has a tendency to be associated with an increased risk of adverse clinical features during MDR-TB treatment.

RESUMO Objetivo: Determinar o papel do polimorfismo rs4073 do gene IL8 na previsão do risco de toxicidade do sistema nervoso central (SNC) em pacientes em tratamento farmacológico padrão para tuberculose multirresistente (TBMR). Métodos: Amostras de sangue de uma coorte de 85 pacientes com TBMR que assinaram um termo de consentimento livre e esclarecido e que estavam recebendo tratamento com medicamentos antituberculosos de segunda linha foram amplificadas para o gene IL8 (rs4073) e genotipadas. Todos os pacientes foram avaliados clinicamente quanto a evidências de toxicidade do tratamento e categorizados de acordo com os achados. Foram avaliadas as associações brutas e ajustadas. Resultados: As principais queixas enquadraram-se nas seguintes categorias: toxicidade do SNC; toxicidade gastrointestinal; toxicidade cutânea; e toxicidade ocular e ototoxicidade. Sintomas de toxicidade gastrointestinal foram relatados por 59% dos pacientes, e sintomas de toxicidade do SNC foram relatados por 42,7%. Foram identificados os seguintes genótipos de IL8 (rs4073): AA, em 64 dos participantes; AT, em 7; TT, em 11. Houve associação significativa entre o modelo dominante de herança e toxicidade do SNC no modelo bruto (p = 0,024; OR = 3,57; IC95%: 1,18-10,76) e no ajustado (p = 0,031; OR = 3,92; IC95%: 1,13-13,58). O genótipo AT+TT do gene IL8 (rs4073) apresentou risco 3,92 vezes maior de toxicidade do SNC que o genótipo AA. Conclusões: O genótipo AT+TT tende a se associar a um maior risco de características clínicas adversas durante o tratamento da TBMR.

As redes vivas na produção do cuidado com o usuário na centralidade do tratamento para tuberculose multidroga resistente / Las redes vivas en la producción del cuidado con el usuario en la centralidad del tratamiento para la tuberculosis multidrogo resistente / Live networks in care production with the user at the center of the treatment for multidrugresistant tuberculosis

Vivenciamos a trajetória de uma usuária-guia no tratamento para tuberculose multidroga resistente (TB-MDR). As narrativas das redes vivas na produção de cuidado apontam para os seguintes itens: 1) cuidar no ato de viver: suplantar os estigmas e cultivar vínculos que ajudem a superar os discursos fomentados pelo medo, preconceitos, exclusão e invisibilidade dos sujeitos; 2) redes vivas de cuidado: os entremeios da norma; e 3) as interfaces de atenção usuário-trabalhador da saúde: como desmistificar o julgamento dos trabalhadores da saúde, que, subordinados a protocolos limitantes, muitas vezes estigmatizam o usuário como "abandonador de tratamento"?. A usuária-guia vislumbrou que cuidar é se desterritorializar, é colocar os desejos como potência para transformação, saindo do modus operandi rumo à criatividade, tendo o usuário no centro do processo. (AU)

Presenciamos la trayectoria de una usuaria-guía en el tratamiento para tuberculosis multidrogo resistente (TB-MDR). Las narrativas de las Redes Vivas en la producción de cuidado señalan: 1) cuidar en el acto de vivir: suplantar los estigmas y cultivar vínculos que ayuden a superar los discursos fomentados por el miedo, prejuicios, exclusión e invisibilidad de los sujetos. 2) Redes Vivas de cuidado: los entresijos de la norma y 3) las interfaces de atención usuario-trabajador de la salud: ¿cómo desmistificar el juicio de los trabajadores de la salud quienes, subordinados a protocolos limitantes, muchas veces estigmatizan al usuario como "abandonador de tratamiento"? La usuaria-guía vislumbró que cuidar es desterritorializarse, es colocar los deseos como potencia para trasformación, saliendo del modus operandi rumbo a la creatividad, colocando al usuario en el centro del proceso. (AU)

We followed the trajectory of a guiding user undergoing treatment for multidrug-resistant tuberculosis (MDR-TB). The narratives of Live Networks in care production showed: 1) Caring in the act of living: Overcoming stigmas and cultivating bonds that help overcome discourses fostered by fear, prejudice, exclusion and invisibility of subjects; 2) Live Networks of care: The in-betweens of the norm; and 3) Interfaces of user-health worker care: How can we demystify the judgment of health workers who, subordinated to limiting protocols, often stigmatize the user as someone who "abandons the treatment"? The guiding user perceived that caring means deterritorializing oneself, expressing one's desires as power for transformation, and leaving the modus operandi towards creativity, with the user at the center of the process. (AU)

Obstacles in combating multidrug resistant tuberculosis in pediatric patients: a scope review / Obstáculos no combate à tuberculose multidroga resistente em pacientes pediátricos: uma revisão de escopo

Abstract Objectives: to identify the scientific evidence on excessively resistant and multidrug resistant tuberculosis in pediatric patients. Methods: this is a scope review of the literature, with a guiding question: "What is the scientific evidence on multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis in pediatric patients?". The research used the descriptors: "extensively drug-resistant tuberculosis" OR "multidrug-resistant tuberculosis" AND "pediatrics". The research was carried out in a double-blind manner in the following databases of the Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific's Institutional Repository for Information Sharing, Embase/Elsevier and International Clinical Trials Registry Platform, with a temporal cut-off from 2011 to 2021, sending a final synthesized sample of 18 articles, which evaluated the methodological content through the level of evidence. Results: the results show the lack of research with a high level of evidence related to MDR-TB in children, the lack of adequate dosage of second-line drugs for the pediatric population and the importance of drug sensitivity testing for the cases of treatment Conclusions: it was identified that the obstacles to MDR-TB treatment were concentrated in the lack of detailed protocols, safe drug dosages with a low side effect, and mainly in the social health determinants and disease process involving MDR-TB.

Resumo Objetivos: identificar as evidências científicas sobre tuberculose excessivamente resistente e multidroga resistente em pacientes pediátricos. Métodos: trata-se de uma revisão de escopo da literatura, tendo como questão norteadora: "Quais as evidências científicas sobre tuberculose multidroga-resistente (TB-MDR) e tuberculose extensivamente resistente em pacientes pediátricos?" A pesquisa usou os descritores: "tuberculose extensivamente resistente a medicamentos" OR "tuberculose resistente a múltiplos medicamentos" AND "pediatria". A pesquisa foi realizada de modo duplo-cego nas bases de dados Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific's Institutional Repository for Information Sharing, Embase/Elsevier e International Clinical Trials Registry Platform, com um corte temporal de 2011 a 2021, sendo a amostra final sintetizada de 18 artigos, nos quais avaliou-se o conteúdo metodológico por meio do nível de evidência. Resultados: os resultados mostraram a escassez de pesquisas de alto nível de evidência relacionadas à TB-MDR em crianças, ausência de posologia adequada das drogas de segunda linha para o público pediátrico e a importância do teste de sensibilidade a drogas para o tratamento dos casos. Conclusões: identificou-se que os obstáculos do tratamento TB-MDR se concentraram na ausência de protocolos detalhados, de dosagens medicamentosas seguras e com menor efeito colateral, e, principalmente, nos determinantes sociais do processo saúde e doença que envolvem a TB-MDR.

Tuberculosis farmacorresistente y diabetes: estudio de casos y controles en un hospital peruano

Introducción: la tuberculosis farmacorresistente sigue siendo endémica y un importante problema de salud pública a nivel mundial, lo que resulta en una alta morbilidad. Las personas con diabetes son más susceptibles a las infecciones debido a la inmunosupresión, por lo que es importante reconocer los factores que predisponen a la tuberculosis farmacorresistente. Objetivo: identificar a la diabetes como factor asociado a la tuberculosis farmacorresistente en pacientes del Programa de prevención y control de la tuberculosis de un hospital peruano nivel II-2 del 2015 al 2021. Metodología: se realizó un estudio analítico de casos y controles, pareados por edad y sexo, se incluyó 66 pacientes con tuberculosis farmacorresistente (casos) y 198 pacientes con tuberculosis sensible (controles). Se utilizó la prueba de chi-cuadrado para el análisis bivariado y el cálculo del Odds Ratio. Se utilizó la regresión logística múltiple para el análisis multivariado. Resultados: el 9,1% de los casos y el 4% de los controles tenían diabetes, con OR 2,48 (IC 95% 0,68 - 8,47) y sin diferencias significativas. En el análisis multivariado, la diabetes fue estadísticamente significativa, aumentando el OR a 3,40 (IC 95% 1,01 - 11,49; p= 0,01). Conclusión: la diabetes se asoció con un mayor riesgo de tuberculosis farmacorresistente en pacientes del Programa de prevención y control de la tuberculosis en un hospital peruano nivel II-2.

Introduction: Drug-resistant tuberculosis continues to be endemic and a major public health problem worldwide, resulting in high morbidity. People with diabetes are more susceptible to infections due to immunosuppression, threfpre it is important to recognize the factors that predispose to drug-resistant tuberculosis. Objective: To identify diabetes as a factor associated with drug-resistant tuberculosis in patients of the Tuberculosis Prevention and Control Program of a level II-2 Peruvian hospital from 2015 to 2021. Methodology: An analytical case-control study was carried out, matched by age and sex, including 66 patients with drug-resistant tuberculosis (cases) and 198 patients with sensitive tuberculosis (controls). The chi-square test was used for the bivariate analysis and Odds Ratio calculation was also made. Multiple logistic regression was used for multivariate analysis. Results: 9.1% of the cases and 4% of the controls had diabetes, with OR 2.48 (95% CI 0.68 - 8.47) and without significant differences. In the multivariate analysis, diabetes was statistically significant, increasing the OR to 3.40 (95% CI 1.01 - 11.49; p= 0.01). Conclusion: Diabetes was associated with an increased risk of drug-resistant tuberculosis in patients of the Tuberculosis Prevention and Control Program at a level II-2 Peruvian hospital.

Bacteriophages as therapeutic & disinfectant agents to tackle multidrug-resistant Acinetobacter baumannii

Background & objectives: Multidrug-resistant (MDR) Acinetobacter baumannii is a serious threat for human health worldwide. The studies on agents targeting A. baumannii are imperative due to identified A. baumannii co-infections in COVID-19. Bacteriophages are promising antibacterial agents against drug-resistant bacteria. This study intended to isolate bacteriophages against MDR A. baumannii from the water of river Ganga, to be used potentially as therapeutic and disinfectant particles. Methods: Acinetobacter phages were isolated from the Ganga water collected from Kanpur and further tested on 50 MDR A. baumannii isolates to determine host range. The phages were morphologically characterized by transmission electron microscopy. The disinfectant property of the isolated phages was tested by spraying of bacteriophage cocktail on MDR A. baumannii contaminated plastic surface, analyzed by colony-forming unit (CFU) and bioluminescence assay (adenosine triphosphate monitoring). Results: A total of seven bacteriophages were isolated against MDR A. baumannii. The bacteriophages lysed three MDR A. baumannii isolates out of 50 tested, showing narrow host range. Electron microscopy revealed hexagonal heads and long tails of bacteriophages, belonging to order Caudovirales. The bacteriophage cocktail reduced the MDR A. baumannii load efficiently on plastic surface, evidenced by reduction in CFUs and bioluminescence. Interpretation & conclusions: The findings of this study suggest that the isolated bacteriophages are potential lytic agents for MDR A. baumannii clinical isolates, and may be used as potential therapeutic agents as well as disinfectant to combat MDR A. baumannii with due consideration to phage host specificity, with further characterization.n

Identification of Bacterial Isolates and Their Antimicrobial Susceptibility Pattern from Wound/Pus Sample in a Tertiary Care Hospital, Gwalior, India

Objective: The goal of this investigation was to look at the frequency and dispersal of bacteria isolated from pus/wound, as well as their susceptibility patterns. Materials and Methods?A study was conducted on 175 patients who provided pus and/or wound discharge samples in different wards (outpatient department or inpatient department). MacConkey agar and blood agar plates were immediately inoculated with samples and incubated at 37°C for 24?hours. The Gram stain and biochemical tests were used to identify all isolates after incubation. Kirby–Bauer's disc diffusion method was used to perform sensitivity tests on Mueller–Hinton agar plates. Results?This study covered 175 patients, with a bacterial isolation rate of 102 (58.28%). Males outnumbered females in the samples (M:F?=?1.8:1), with a median age of 45 years as majority were in the age group of 40 to 60 years which was 41 (40.20%). Total 90.1% samples showed monomicrobial infection, whereas 9.8% showed polymicrobial infection, and total 112 bacterial strains were isolated. Conclusion?Escherichia coli was the most prevalent isolate in present investigation, followed by Pseudomonas aeruginosa. Chloramphenicol is the only antibiotic which is effective for both gram-negative bacilli and gram-positive cocci. This report's susceptibility statistic may be worth considering for developing empiric treatment regimens for pyogenic infections.

Antibacterial Activity of Lawsonia inermis Leaf Extracts against Multidrug-resistant Pseudomonas aeruginosa from Infected Wounds

Background: Wound infection comprises numerous different organisms that have the ability to surface colonization of wounds. Multidrug-resistant Pseudomonas aeruginosa is one of the pathogenic bacteria associated with wound infections. Aim: This study isolated and identified multidrug-resistant Pseudomonas aeruginosa from infected wounds and determine the antibacterial activity of Lawsonia inermis leaf extracts against it. Design: This is a Clinical and laboratory-based study involving patients with defined cases of wound infections. Place and Duration of Study: This study was conducted in the Microbiology (Bacteriology) laboratory of Specialist Hospital, Bauchi, Nigeria, from February to November 2021. Methods: Twenty-eight (28) Pseudomonas aeruginosa isolates were recovered from 179 wound swabs using standard laboratory procedures and were screened for multidrug-resistant patterns according to the Kirby-Bauer disc diffusion method. Antibacterial efficacy of the aqueous, ethanolic, and methanolic leaf extracts of Lawsonia inermis was tested against the multidrug-resistant isolates using agar well diffusion techniques. The zone of inhibition was measured and the differences between means were statistically analyzed (p<0.05). Results: A total of twenty-eight (28) multidrug-resistant Pseudomonas aeruginosa were confirmed, showing resistance to Amoxicillin (64.3%), Ceftazidime (85.71%), and Cefotaxime (78.57%) but sensitivity to Imipenem (95.5%). The phytochemical screening revealed the presence of flavonoids, glycosides, saponins, steroids, and tannins among others. MDR P. aeruginosa was inhibited at varied concentrations of the extracts with the diameter mean zone of inhibition increasing as the concentration increased. The Methanol extracts showed the highest antibacterial activity against MDR P. aeruginosa with a mean zone of inhibition of 9.500±0.288mm at 400mg/ml. Conclusion: These results indicated that Lawsonia inermis leaf extracts possess antibacterial activities on Multidrug-resistant Pseudomonas aeruginosa which could be a good source for the production of plant-based antibacterial drugs., although somewhat less than the synthetic standard drugs (Imipenem) having a mean of 13.83±0.288mm.

Clinical characteristics and risk factors of poor prognosis in patients with infected pancreatic necrosis caused by multidrug-resistant bacteria / 中华肝胆外科杂志

Objective:To study the clinical features and risk factors of death in patients with infected pancreatic necrosis (IPN) caused by multidrug-resistant bacteria (MDRB).Methods:The clinical data of 219 IPN patients who were managed at the Department of General Surgery of Xuanwu Hospital, Capital Medical University from January 1, 2016 to December 31, 2021 were retrospectively analyzed. There were 142 males, and 77 females, with a median age [ M( Q1, Q3)] of 51(38, 62) years old. Based on the pre-sence or absence of MDRB infection, these patients were divided into the MDRB-infected group ( n=117) and the non-MDRB-infected group ( n=102). Clinical features and outcomes were compared between the two groups, and the risk factors resulting in death in patients with MDRB infection were analyzed. Logistic regression analysis was used to determine the risk factors for poor outcomes in patients with MDRB. Results:There were significant differences in etiologies, distribution characteristics of necrosis and degrees of pancreatic necrosis between the two groups (all P<0.05). When compared with the non-MDRB-infected group, the CT severity index, the levels of procalcitonin and interleukin-6 were significantly higher in the MDRB group on admission, while the hematocrit was significantly lower (all P<0.05). Furthermore, when compared with the non-MDRB infection group, patients with MDRB infection were significantly more likely to have fungal infections [37.6%(44/117) vs. 21.6%(22/102)] and extrapancial infections [75.2%(88/117) vs. 58.8%(60/102)], more patients underwent surgery [89.7%(105/117) vs. 67.6%(69/102)], and more surgical procedures were performed [3(2, 4) times vs. 2(1, 3) times], with a higher incidence of postoperative complications [36.2%(38/117) vs. 18.8%(13/102)], an increase in a new-onset organ failure after surgery [37.1%(39/117) vs. 21.7%(15/102)], a higher in-hospital mortality rate [25.6%(30/117) vs. 10.8%(11/102)], longer hospitalization [39(28, 67) d vs. 29(18, 35) d] and ICU stays [22(10, 42) d vs. 11(6, 18) d], and a longer need for parenteral nutrition [19(9, 37) d vs. 15(7, 25) d, all P<0.05]. On multivariate regression analysis, the risk factor for death in the MDRB-infected group was co-fungal infection ( OR=1.199, 95% CI: 1.025-1.402). On the other hand, receiving therapy containing tigacycline ( OR=0.831, 95% CI: 0.715-0.965) and minimally invasive surgery ( OR=0.698, 95% CI: 0.562-0.868) reduced the risk of death in the MDRB-infected group (all P<0.05). Conclusions:IPN patients with MDRB infection had higher levels of inflammation, more serious pancreatic necrosis, longer treatment time, and increased need for surgical treatment. Measures involving fungal infection control and the use of tigacyclin and minimally invasive surgery reduced the risks of death in patients with MDRB infection.

Clinical Analysis of Colistin Sulfate in the Treatment of Hematonosis Infected by Multidrug-Resistant Gram-Negative Bacteria / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of colistin sulfate in the treatment of hematonosis patients infected by multidrug-resistant (MDR) gram-negative bacteria (GNB), and discuss the possible factors that affect the efficacy of colistin sulfate.@*METHODS@#The clinical data of 85 hematologic patients infected with MDR GNB in the Soochow Hopes Hematonosis Hospital from April 2022 to November 2022 were collected and divided into clinically effective group with 71 cases and ineffective group with 14 cases according to the therapeutic efficacy of colistin sulfate. The age, gender, type of hematologic disease, status of hematopoietic stem cell transplantation, infection sites, type of pathogen, timing of administration, daily dose and duration of colistin sulfate, and combination with other antibacterial agents of patients in two groups were compared. Logistic regression was used to analyze on the meaningful variables to study the influencing factors of colistin sulfate. The adverse reactions of colistin sulfate were also evaluated.@*RESULTS@#There were no significant differences in age, gender, type of hematologic disease, hematopoietic stem cell transplantation status, infection sites and pathogen type between the effective group and the ineffective group (P>0.05). Compared with the medication time more than 7 days, meropenem used within 7 days in the clinical effective group, and timely replacement with colistin sulfate could obtain better efficacy, the difference was statistically significant (P=0.018). The duration of tigacycline before colistin sulfate did not affect the efficacy, and there was no significant difference in efficacy between the effective and ineffective groups. The therapeutic effect of colistin sulfate at daily dose of 500 000 U q8h was better than that of 500 000 U q12h, the difference was statistically significant (P=0.035). The time of colistin sulfate use in the clinically effective group was longer than that in the ineffective group, which had a statistical difference (P=0.003). Compared with the clinical ineffective group, the efficacy of combination regimens with colistin sulfate was better than that of colistin sulfate monotherapy, and the difference was statistically significant (P=0.013). Multivariate logistic regression analysis was performed on the indicators with statistical differences in the two groups of patients, which suggested that the use time of colistin sulfate (B: 2.358; OR: 10.573; CI: 1.567-71.361; P=0.015) and the combination of colistin sulfate (B: 1.720; OR: 5.586; CI: 1.210-25.787; P=0.028) were influential factors in the efficacy of colistin sulfate. During the treatment, the incidence of nephrotoxicity, hepatotoxicity and peripheral neurotoxicity were 5.9%, 1.2% and 1.2%, respectively.@*CONCLUSION@#The use of colistin sulfate improves the clinical efficacy of MDR GNB infections in hematological patients, and the timing of colistin sulfate administration and the combination of drugs are independent factors affecting its clinical efficacy, and the safety during treatment is high.

Relationship between plasma exosomal miR-346 and treatment outcomes in patients with multidrug resistant pulmonary tuberculosis / 中国热带医学

@#Abstract： Objective　To investigate the relationship between plasma exosomal microRNA (miRNA)-346 and treatment outcomes in patients with multidrug-resistant tuberculosis (MDR-TB), to provide more reference basis for the treatment of MDR-TB patients. Methods　A total of 406 patients with MDR-TB admitted to Tuberculosis Control and Prevention Institute of Shaanxi Provincial between January 2018 and May 2021 were selected as the study subjects. General clinical data of the patients were collected and analyzed. The expression level of plasma exosomal miR-346 was detected by real-time fluorescence quantitative polymerase chain reaction. The predictive value of plasma exosomal miR-346 for treatment outcome was analyzed using receiver operating characteristic (ROC) curve analysis. Furthermore, the relationship between the expression of plasma exosomal miR-346 and treatment outcome was analyzed using a multivariable logistic regression model. After standard treatment, patients were divided into good treatment outcome group (n=226) and poor treatment outcome group (n=180) according to the treatment outcome. Results　Typical exosomes were identified by transmission electron microscopy, particle size analysis and Western blot, that is, plasma exosomes were successfully extracted. In the poor treatment outcome group, more patients were complicated with diabetes or HIV infection, and the proportion of patients with pulmonary cavity, acid-fast bacilli smear positive rate >1+, previous treatment history and fluoroquinolone resistance was also significantly increased, and the levels of white blood cells, neutrophils, and monocytes were significantly increased, while the level of albumin was significantly decreased, with statistical significance (P>0.05). Compared with the good treatment outcome group [0.61 (0.46, 0.74)], the expression level of plasma exosomal miR-346 in the poor treatment outcome group [1.23 (0.60, 2.02)] was significantly higher (Z=-13.185, P<0.001). ROC curve analysis showed that the area under the curve of plasma exosomal miR-346 to predict adverse outcomes of MDR-TB treatment was 0.881 (95%CI: 0.846-0.915), with a sensitivity of 78.3% and specificity of 86.7%. The corresponding cut-off value was 0.81. Multivariate logistic regression analysis showed that diabetes, AIDS virus infection, pulmonary cavity, AFB smear positive degree>1+, previous treatment history, fluoroquinolones resistance and high expression of plasma exosomal miR-346 were independent influencing factors for poor treatment results of MDR-TB (P<0.05). Conclusions　High expression of plasma exosomal miR-346 is associated with the high risk of adverse outcome of MDR-TB treatment, and it is promising to be a useful marker for predicting the outcome of MDR-TB treatment.

Analysis of drug resistance and its influencing factors in different infection sites of patients / 中国热带医学

@#Abstract： Objective　To analyze the characteristics and corresponding drug resistance of pathogenic bacterial spectrum in eight major infection sites of hospitalized patients, and to provide epidemiological data for the rational selection of antibiotics in clinical practice. Methods　A total of 396 bacterial strains isolated from clinical specimens of hospitalized patients in member institutions of the Hainan Provincial Bacterial Resistance Monitoring Network from September 1, 2020, to September 30, 2022, were included in this study. Data were screened and filtered from the database of MH120 Microbial Identification and Drug Sensitivity Analysis System based on the technical scheme of the National Bacterial Drug Resistance Surveillance Network and Science and Technology Basic Resources Investigation Project research plan in 2020. The testing data were integrated, summarized, and analyzed using EXCEL and WHONET 5.6 software, and statistical analysis was conducted using SPSS 26.0 software. Results　Among of 396 strains of bacteria, 78 (19.7%) were isolated from respiratory tract specimens, 74 (18.7%) from urinary tract specimens, 72 (18.2%) from blood specimens, 54 (13.6%) from abdominal cavity specimens, 48 (12.1%) from skin and soft tissue specimens 48 strains (12.1%), 30 (7.6%) from reproductive tract specimens, 22 (5.6%) from central nervous system specimens, 18 (4.5%) from digestive tract specimens. Gram-negative bacteria accounted for 69.4% of the isolates, while gram-positive bacteria accounted for 30.6%. The top five gram-negative bacteria isolated were Klebsiella pneumoniae (14.9%), Escherichia coli (14.4%), Pseudomonas aeruginosa (10.4%), Acinetobacter baumannii (5.3%), and Salmonella species (4.5%). The top five gram-positive bacteria were Staphylococcus aureus (11.1%), Streptococcus agalactis (7.8%), Enterococcus faecalis (3.0%), Enterococcus faecium (2.8%), and Streptococcus suis (1.8%). Respiratory failure and bloodstream infection were independent influencing factors of treatment response (P<0.01). The resistance rate of Escherichia coli to ampicillin was 81.4%, and the resistance rate of Staphylococcus aureus to gentamicin and levofloxacin were both below 7%. Conclusions　The pathogen spectra vary with different infection sites of patients, and rational selection of antibiotics based on drug susceptibility testing is crucial to shorten the treatment time of patients and avoid the unnecessary emergence of drug-resistant strains caused by drug abuse.

Real-world study of ceftazidime-avibactam in the treatment of multidrug-resistant gram-negative bacterial infections / 中国临床药理学与治疗学

AIM: To describe and evaluate the clinical characteristics, treatment management and clinical outcomes of ceftazidime-avibactam (CZA) in the treatment of patients with multidrug-resistant gram-negative bacterial (MDR-GNB) infections. METHODS: A retrospective cohort study was performed on patients hospitalized in the Affiliated Hospital of Xuzhou Medical University from September 2019 to December 2021. Adult patients who received CZA for ≥ 72 hours consecutively were eligible for inclusion. The primary outcome was clinical failure, defined as a composite of 30-day all-cause mortality, microbiological failure and / or failure to resolve or improve signs and symptoms of infection during treatment with CZA. RESULTS: A total of 198 patients with MDR-GNB infections were described and evaluated, including 132 in the carbapenem-resistant Enterobatceriaceae (CRE) cohort and 66 in the Pseudomonas spp. cohort. The main infection sites were lung infection (92.42%), abdominal infection (10.61%), and intracranial infection (10.61%), among which 63 patients (31.82%) were positive for blood culture. Clinical failure, 30-day all-cause mortality and microbiological failure occurred in 61 (30.81%), 33(16.67%) and 11(5.56%) patients, respectively. Body mass index (BMI), acute physiology and chronic health evaluation scoring system (APACHE Ⅱ) and polymicrobial infections were positively associated with clinical outcome failureadjusted OR 1.109, 95%CI 1.017, 1.209; adjusted OR 1.071, 95%CI 1.015, 1.129; adjusted OR 2.844, 95%CI 1.391, 5.814, however, initiation of CZA within 48 hours of admission was protective (adjusted OR 0.424, 95%CI 0.205, 0.879). A total of 15 patients had adverse reactions possibly related to CZA, including 2 cases of rash, 6 cases of nausea and vomiting, and 7 cases of antibiotic-related diarrhea. CONCLUSION: CZA can be used to treat infections caused by a range of MDR-GNB, including Pseudomonas spp. and CRE.

Diagnosis and Treatment Outcomes and Influencing Factors of Multidrug-Resistant Tuberculosis Based on Patient Pathway / 中国医学科学院学报

Multidrug-resistant tuberculosis (MDR-TB) has become one of the major challenges in the global tuberculosis (TB) control.Despite years of efforts on MDR-TB control,the treatment success rates in China have increased slowly,which indicates possible deficiencies in the management of prevention and control work.Therefore,it is necessary to analyze the current status of MDR-TB prevention and treatment based on the patient pathway.This review summarizes the current drop-out situation of MDR-TB patients in the diagnosis and treatment pathway and the factors affecting patients' outcomes in the whole pathway,so as to provide a scientific reference for the prevention and control of MDR-TB.

Cost-Effectiveness Analysis of Combined Chemotherapy Regimen Containing Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis in China / 生物医学与环境科学（英文）

OBJECTIVE@#This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline (BR) and the conventional treatment regimen (CR, not containing Bedaquiline) for the treatment of adults with multidrug-resistant tuberculosis (MDR-TB) in China.@*METHODS@#A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years. The model parameter data were synthesized from the literature, the national TB surveillance information system, and consultation with experts. The incremental cost-effectiveness ratio (ICER) of BR vs. CR was determined.@*RESULTS@#BR ( vs. CR) had a higher sputum culture conversion rate and cure rate and prevented many premature deaths (decreased by 12.8%), thereby obtaining more quality-adjusted life years (QALYs) (increased by 2.31 years). The per capita cost in BR was as high as 138,000 yuan, roughly double that of CR. The ICER for BR was 33,700 yuan/QALY, which was lower than China's 1× per capita Gross Domestic Product (GDP) in 2020 (72,400 yuan).@*CONCLUSION@#BR is shown to be cost effective. When the unit price of Bedaquiline reaches or falls below 57.21 yuan per unit, BR is expected to be the dominant strategy in China over CR.

Analysis of drug resistance and risk factors of multi drug resistant bacteria in bloodstream infection / 中国热带医学

@#Abstract: Objective To analyze the antimicrobial resistance rate and risk factors of multi drug resistant organisms (MDRO) in bloodstream infection for rational treatment. Methods　A total of 696 cases of bloodstream infections of Staphylococcus aureus, Enterococcus, Enterobacteriaceae (excluding Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter in our hospital from 2017 to 2021 were selected, and 711 pathogenic strains were isolated from their whole blood samples. The antimicrobial resistance rates of various multi drug resistant strains were analyzed and the risk factors of MDRO infection were analyzed. Results　696 non repeated cases were screened out from 13 187 whole blood culture specimens, with a positive rate of 5.3%, and a total of 711 blood influenza pathogens were detected, among them, 350 strains of MDRO were detected with a detection rate of 49.23% (350/711). Among the pathogenic bacteria of bloodstream infection, Escherichia coli was the most, with 277 strains accounting for 38.96% (277/711), of which 201 strains were MDRO, accounting for 57.43% (201/350); followed by Klebsiella pneumoniae and Staphylococcus aureus, with 155 strains accounting for 21.80% (155/711) and 89 strains accounting for 12.52% (89/711), among which 43 strains of Klebsiella pneumoniae MDRO accounted for 12.29% (43/350) and 38 strains of Staphylococcus aureus MDRO accounted for 10.86% (38/350). The change trend of the three pathogens during 2017-2021 was not obvious. The drug sensitivity test showed that Escherichia coli and Klebsiella pneumoniae were highly resistant to cephalosporins and fluoroquinolones, and the drug resistance rate of aminoglycosides was relatively low. They had almost no resistance to cephalosporins and carbapenems. Staphylococcus aureus has a high resistance rate to lincomycin and macrolides, but no resistance to oxazolidinone, glycopeptides and glycylcyclins. There were 350 cases of MDRO infection and 361 cases of non MDRO infection. Univariate analysis showed that the age, sex, cardiovascular and cerebrovascular history, renal insufficiency, lung disease, hypoalbuminemia, hepatobiliary disease, electrolyte disorder and anemia of the patients had no statistical significance in MDRO infection (P>0.05); diabetes, urinary tract infection, surgical operation and burn were the influencing factors of MDRO (P<0.05). According to logistic analysis, diabetes, urinary tract infection, surgical operation and burn were the risk factors of MDRO infection (P<0.05). Conclusion　The infection of MDRO in patients with bloodstream infection is serious, and early prevention and control should be paid attention to, and the principle of graded use of antibiotics should be strictly observed, and the rational application should be carried out to actively and effectively control the production of MDRO.

Analysis of Nosocomial Infection in a Cancer Hospital from 2019 to 2021 / 中山大学学报(医学科学版)

ObjectiveTo understand the situation of nosocomial infection in cancer hospitals and its changing trend， so as to provide a basis for adjusting the focus of nosocomial infection prevention and control in cancer hospitals. MethodsData of nosocomial infection quality control indices of Sun Yat-sen University Cancer Center from 2019 to 2021 were obtained through the nosocomial infection monitoring system， and the changes of these indices across the three years were analyzed by Chi-square test and Cochran-Armitage trend test. ResultsFrom 2019 to 2021， the incidence rates of nosocomial infection in this hospital were 0.80%， 0.78% and 0.57%， which decreased significantly year by year （P<0.001）. Among them， surgical site and respiratory system infection were more common， accounting for 35.75% and 31.08%， respectively. Gram-negative bacteria and fungi were the main pathogens. The incidence rate of multidrug-resistant bacteria in hospital increased year by year， from 0.08‰ to 0.14‰ （P<0.001）， among which methicillin-resistant staphylococcus aureus， carbapenem-resistant Enterobacter and bacteria producing ultra-broad spectrum β-lactamase （ESBLs） bacteria increased significantly. The incidence rates of three-tube associated infections were no different across 3 years （P>0.05）， which were still at high levels. ConclusionFrom 2019 to 2021， the prevention and control of nonsocomial infection in the cancer hospital has been improved overall. Meanwhile， the infections of respiratory system and surgical sites， ESBLs related multidrug-resistant bacteria and three-tube are weak links in cancer specialized hospitals， which need to be emphasized and improved.

Analysis of risk factors of multidrug-resistant organism infection in lung transplant recipients based on restricted cubic spline model / 器官移植

Objective To summarize current status of multidrug-resistant organism (MDRO) infection in lung transplant recipients and analyze the risk factors of MDRO infection. Methods Clinical data of 321 lung transplant recipients were retrospectively analyzed. According to the incidence of postoperative MDRO infection, they were divided into the MDRO group (n=122) and non-MDRO infection group (n=199). The incidence of MDRO infection in lung transplant recipients was summarized. The risk factors of MDRO infection in lung transplant recipients were analyzed by logistic regression model. The dose-response relationship between MDRO infection and time of ventilator use was determined by restricted cubic spline model. Results Among 321 lung transplant recipients, 122 cases developed MDRO infection, with an infection rate of 38.0%. Two hundred and twenty-nine strains of pathogenic bacteria were detected in the MDRO infection group, mainly Gram-negative bacteria (92.6%), and the top three strains were carbapenem-resistant acinetobacter baumannii (46.3%), carbapenem-resistant pseudomonas aeruginosa (22.3%) and carbapenem-resistant klebsiella pneumoniae (14.8%), respectively. MDRO infection mainly consisted of lower respiratory tract infection (61.5%), followed by ventilator-associated pneumonia (26.2%). Univariate analysis showed that the risk factors of MDRO infection in lung transplant recipients were single-lung transplantation, long-time postoperative use of extracorporeal membrane oxygenation (ECMO), long operation time, long-time urinary catheterization, long-time central venous catheterization and long-time ventilator use (all P < 0.05). Multivariate logistic regression analysis indicated that single-lung transplantation and long-time ventilator use were the independent risk factors for MDRO infection in lung transplant recipients (both P < 0.05). Results of restricted cubic spline model analysis showed that the risk of infection continued to increase with the prolongation of ventilator use time within 20 d. After 20 d, prolonging the time of ventilator use failed to increase the risk of infection, showing a plateau effect. Conclusions The MDRO infection rate tends to decline in lung transplant recipients year by year. Single-lung transplantation and long-time ventilator use are the independent risk factors for MDRO infection in lung transplant recipients.

Study on treatment outcome and risk factors of multidrug-resistant pulmonary tuberculosis patients in Shanghai / 上海预防医学

ObjectiveTo describe the characteristics of treatment outcomes of multidrug-resistant tuberculosis （MDR-TB） patients enrolled in second-line treatment in Shanghai from 2017 to 2018， and to analyze the influencing factors of treatment outcomes. MethodsTotally 182 MDR-TB patients were analyzed by using data collected from the China tuberculosis management information system， the hospital's electronic medical record information system， whole genome sequencing results and a questionnaire survey， and logistic regression analysis was used to analyze the factors affecting the success of treatment. ResultsIn 182 MDR-TB patients， the success rate of treatment was 65.4%， the loss to follow-up rate was 8.2%， the mortality rate was 4.9%， the unassessable rate was 13.7%， and the drug withdrawal rate was 7.7%. The factors affecting the success of treatment in MDR-TB patients included age （35‒ years old， OR=5.28， 95%CI： 1.58‒17.59， P=0.007； 55‒ years old， OR=16.30， 95%CI： 4.36‒60.92， P<0.001） and compliance to medication （OR=0.55， 95%CI： 0.42‒0.72， P<0.001）. ConclusionThe treatment success rate of MDR-TB patients in Shanghai from 2017 to 2018 is significantly higher than the average level in China. Older patients and patients with less compliant are at higher risk of adverse treatment outcomes.

The pharmaceutical care of a multidrug-resistant bacterial infection patient with tigecycline-induced hypofibri-nogenemia / 中国药房

OBJECTIVE To provide reference for pharmaceutical care of multidrug-resistant bacterial infection patients with tigecycline-induced hypofibrinogenemia and the safe use of tigecycline. METHODS Clinical pharmacists participated in a case of hypofibrinogenemia caused by tigecycline with multidrug-resistant bacterial infection， to determine the correlation of hypofibrinogenemia and tigecycline， and to analyze the risk factors and possible mechanisms of the occurrence of hypofibrinogenemia caused by tigecycline in combination with relevant literature. Clinical pharmacists recommended that physicians discontinued tigecycline and provided human fibrinogen and plasma for correction. RESULTS & CONCLUSIONS Tigecycline was associated with hypofibrinogenemia of the patient. The physician followed the advice of clinical pharmacists and the patient’s fibrinogen level returned to normal. The risk factors of hypofibrinogenemia induced by tigecycline included high dose， long course of treatment， and complication with renal dysfunction. Clinical pharmacists should timely advise physicians to stop taking the drug， and give human fibrinogen and blood product infusion for correction when necessary， so as to avoid the occurrence of serious life- threatening coagulation disorders and ensure the safety of tigecycline use.