Objective Sepsis, a life-threatening clinical syndrome, is a leading cause of mortality after experiencing multiple traumas. Once diagnosed with sepsis, patients should be given an appropriate empiric antimicrobial treatment followed by the specific antibiotic therapy based on blood culture due to its rapid progression to tissue damage and organ failure. In this study, we aimed to analyze the risk factors and outcome of sepsis in traumatic patients and to investigate the performance of metagenomic next-generation sequencing (mNGS) compared with standard microbiological diagnostics in post-traumatic sepsis. Methods The study included 528 patients with multiple traumas among which there were 142 cases with post-traumatic sepsis. Patients' demographic and clinical data were recorded. The outcome measures included mortality during the emergency intensive care unit (EICU), EICU length of stay (LOS), all-cause 28-day mortality, and total ventilator days in 28 days after admission. A total of 89 blood samples from 89 septic patients underwent standard microbiological blood cultures and 89 samples of peripheral blood (n = 21), wound secretion (n = 41), bronchoalveolar lavage fluid (BALF) (19), ascites (n = 5), and sputum (n = 3) underwent mNGS. Pathogen detection was compared between standard microbiological blood cultures and mNGS. Results The sepsis group and non-sepsis group exhibited significant differences regarding shock on admission, blood transfusion, mechanical ventilation, body temperature, heart rate, WBC count, neutrophil count, hematocrit, urea nitrogen, creatinine, CRP, D-D dimer, PCT, scores of APACHE II, sequential organ failure assessment (SOFA), and Injury Severity Score (ISS) on admission to the EICU, and Multiple Organ Dysfunction Syndromes (MODS) (P < 0.05). Multivariate logistic regression analysis showed that scores of APACHE II, SOFA, and ISS on admission, and MODS were independent risk factors for the occurrence of sepsis in patients with multiple traumas. The 28-day mortality was higher in the sepsis group than in the non-sepsis group (45.07% vs. 19.17%, P < 0.001). The mortality during the EICU was higher in the sepsis group than in the non-sepsis group (P=0.002). The LOS in the EICU in the sepsis group was increased compared with the non-sepsis group (P=0.004). The total ventilator days in 28 days after admission in the sepsis group was increased compared with the non-sepsis group (P < 0.001). Multivariate logistic regression analysis showed that septic shock, APACHE II score on admission, SOFA score, and MODS were independent risk factors of death for patients with post-traumatic sepsis. The positive detection rate of mNGS was 91.01% (81/89), which was significantly higher than that of standard microbiological blood cultures (39.33% (35/89)). Standard microbiological blood cultures and mNGS methods demonstrated double positive results in 33 (37.08%) specimens and double-negative results in 8 (8.99%) specimens, while 46 (51.69
{"title":"Risk Factors and Outcome of Sepsis in Traumatic Patients and Pathogen Detection Using Metagenomic Next-Generation Sequencing","authors":"Yiqing Tong, Jianming Zhang, Yimu Fu, Xingxing He, Qiming Feng","doi":"10.1155/2022/2549413","DOIUrl":"https://doi.org/10.1155/2022/2549413","url":null,"abstract":"Objective Sepsis, a life-threatening clinical syndrome, is a leading cause of mortality after experiencing multiple traumas. Once diagnosed with sepsis, patients should be given an appropriate empiric antimicrobial treatment followed by the specific antibiotic therapy based on blood culture due to its rapid progression to tissue damage and organ failure. In this study, we aimed to analyze the risk factors and outcome of sepsis in traumatic patients and to investigate the performance of metagenomic next-generation sequencing (mNGS) compared with standard microbiological diagnostics in post-traumatic sepsis. Methods The study included 528 patients with multiple traumas among which there were 142 cases with post-traumatic sepsis. Patients' demographic and clinical data were recorded. The outcome measures included mortality during the emergency intensive care unit (EICU), EICU length of stay (LOS), all-cause 28-day mortality, and total ventilator days in 28 days after admission. A total of 89 blood samples from 89 septic patients underwent standard microbiological blood cultures and 89 samples of peripheral blood (n = 21), wound secretion (n = 41), bronchoalveolar lavage fluid (BALF) (19), ascites (n = 5), and sputum (n = 3) underwent mNGS. Pathogen detection was compared between standard microbiological blood cultures and mNGS. Results The sepsis group and non-sepsis group exhibited significant differences regarding shock on admission, blood transfusion, mechanical ventilation, body temperature, heart rate, WBC count, neutrophil count, hematocrit, urea nitrogen, creatinine, CRP, D-D dimer, PCT, scores of APACHE II, sequential organ failure assessment (SOFA), and Injury Severity Score (ISS) on admission to the EICU, and Multiple Organ Dysfunction Syndromes (MODS) (P < 0.05). Multivariate logistic regression analysis showed that scores of APACHE II, SOFA, and ISS on admission, and MODS were independent risk factors for the occurrence of sepsis in patients with multiple traumas. The 28-day mortality was higher in the sepsis group than in the non-sepsis group (45.07% vs. 19.17%, P < 0.001). The mortality during the EICU was higher in the sepsis group than in the non-sepsis group (P=0.002). The LOS in the EICU in the sepsis group was increased compared with the non-sepsis group (P=0.004). The total ventilator days in 28 days after admission in the sepsis group was increased compared with the non-sepsis group (P < 0.001). Multivariate logistic regression analysis showed that septic shock, APACHE II score on admission, SOFA score, and MODS were independent risk factors of death for patients with post-traumatic sepsis. The positive detection rate of mNGS was 91.01% (81/89), which was significantly higher than that of standard microbiological blood cultures (39.33% (35/89)). Standard microbiological blood cultures and mNGS methods demonstrated double positive results in 33 (37.08%) specimens and double-negative results in 8 (8.99%) specimens, while 46 (51.69","PeriodicalId":22481,"journal":{"name":"The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien des Maladies Infectieuses et de la Microbiologie Médicale","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83692136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background There have been thousands of clinical trials for COVID-19 to target effective treatments. However, quite a few of them are traditional randomized controlled trials with low efficiency. Considering the three particularities of pandemic disease: timeliness, repurposing, and case spike, new trial designs need to be developed to accelerate drug discovery. Methods We propose an adaptive information borrowing platform design that can sequentially test drug candidates under a unified framework with early efficacy/futility stopping. Power prior is used to borrow information from previous stages and the time trend calibration method deals with the baseline effectiveness drift. Two drug development strategies are applied: the comprehensive screening strategy and the optimal screening strategy. At the same time, we adopt adaptive randomization to set a higher allocation ratio to the experimental arms for ethical considerations, which can help more patients to receive the latest treatments and shorten the trial duration. Results Simulation shows that in general, our method has great operating characteristics with type I error controlled and power increased, which can select effective/optimal drugs with a high probability. The early stopping rules can be successfully triggered to stop the trial when drugs are either truly effective or not optimal, and the time trend calibration performs consistently well with regard to different baseline drifts. Compared with the nonborrowing method, borrowing information in the design substantially improves the probability of screening promising drugs and saves the sample size. Sensitivity analysis shows that our design is robust to different design parameters. Conclusions Our proposed design achieves the goal of gaining efficiency, saving sample size, meeting ethical requirements, and speeding up the trial process and is suitable and well performed for COVID-19 clinical trials to screen promising treatments or target optimal therapies.
{"title":"An Adaptive Information Borrowing Platform Design for Testing Drug Candidates of COVID-19","authors":"Liwen Su, Jingyi Zhang, Fangrong Yan","doi":"10.1155/2022/9293681","DOIUrl":"https://doi.org/10.1155/2022/9293681","url":null,"abstract":"Background There have been thousands of clinical trials for COVID-19 to target effective treatments. However, quite a few of them are traditional randomized controlled trials with low efficiency. Considering the three particularities of pandemic disease: timeliness, repurposing, and case spike, new trial designs need to be developed to accelerate drug discovery. Methods We propose an adaptive information borrowing platform design that can sequentially test drug candidates under a unified framework with early efficacy/futility stopping. Power prior is used to borrow information from previous stages and the time trend calibration method deals with the baseline effectiveness drift. Two drug development strategies are applied: the comprehensive screening strategy and the optimal screening strategy. At the same time, we adopt adaptive randomization to set a higher allocation ratio to the experimental arms for ethical considerations, which can help more patients to receive the latest treatments and shorten the trial duration. Results Simulation shows that in general, our method has great operating characteristics with type I error controlled and power increased, which can select effective/optimal drugs with a high probability. The early stopping rules can be successfully triggered to stop the trial when drugs are either truly effective or not optimal, and the time trend calibration performs consistently well with regard to different baseline drifts. Compared with the nonborrowing method, borrowing information in the design substantially improves the probability of screening promising drugs and saves the sample size. Sensitivity analysis shows that our design is robust to different design parameters. Conclusions Our proposed design achieves the goal of gaining efficiency, saving sample size, meeting ethical requirements, and speeding up the trial process and is suitable and well performed for COVID-19 clinical trials to screen promising treatments or target optimal therapies.","PeriodicalId":22481,"journal":{"name":"The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien des Maladies Infectieuses et de la Microbiologie Médicale","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77669816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Goel, Chippu Shakir, A. Tesfaye, Kuzhunellil Raghavanpillai Sabu, A. Idhayadhulla, A. Manilal, Melat Woldemariam, Nayana Vijayan, Shabna Shah
Bacterial biofilms are a big menace to industries and the environment and also in the health sector, accumulation of which is a major challenge. Despite intensive efforts to curb this issue, a definitive solution is yet to be achieved. Enzyme-templated disruption of the extracellular matrix of biofilm and its control and elimination are emerging as an efficient and greener strategy. The study describes the antibiofilm potential of alpha-amylase from the marine microorganism Pantoea agglomerans PCI05, against food-borne pathogens. Amylase exhibited stability in a wide pH range and retained 50% of its activity at temperatures as high as 100°C. Thermal analysis of the enzyme produced showed thermal stability, up to 130°C. From these findings, it can be envisaged that the alpha-amylase produced from P. agglomerans can be used for starch liquefaction; it was also evaluated for antibiofilm activity. Amylase from this marine bacterium was found to efficiently disrupt the preformed biofilms of food-borne pathogens such as Bacillus cereus, Serratia marcescens, Vibrio parahaemolyticus, Listeria monocytogenes, and Salmonella enterica enterica serotype Typhi based on the value of biofilm inhibitory concentrations.
{"title":"Antibiofilm Potential of Alpha-Amylase from a Marine Bacterium, Pantoea agglomerans","authors":"C. Goel, Chippu Shakir, A. Tesfaye, Kuzhunellil Raghavanpillai Sabu, A. Idhayadhulla, A. Manilal, Melat Woldemariam, Nayana Vijayan, Shabna Shah","doi":"10.1155/2022/7480382","DOIUrl":"https://doi.org/10.1155/2022/7480382","url":null,"abstract":"Bacterial biofilms are a big menace to industries and the environment and also in the health sector, accumulation of which is a major challenge. Despite intensive efforts to curb this issue, a definitive solution is yet to be achieved. Enzyme-templated disruption of the extracellular matrix of biofilm and its control and elimination are emerging as an efficient and greener strategy. The study describes the antibiofilm potential of alpha-amylase from the marine microorganism Pantoea agglomerans PCI05, against food-borne pathogens. Amylase exhibited stability in a wide pH range and retained 50% of its activity at temperatures as high as 100°C. Thermal analysis of the enzyme produced showed thermal stability, up to 130°C. From these findings, it can be envisaged that the alpha-amylase produced from P. agglomerans can be used for starch liquefaction; it was also evaluated for antibiofilm activity. Amylase from this marine bacterium was found to efficiently disrupt the preformed biofilms of food-borne pathogens such as Bacillus cereus, Serratia marcescens, Vibrio parahaemolyticus, Listeria monocytogenes, and Salmonella enterica enterica serotype Typhi based on the value of biofilm inhibitory concentrations.","PeriodicalId":22481,"journal":{"name":"The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien des Maladies Infectieuses et de la Microbiologie Médicale","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85106977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
X. Lyu, Ting-ting Lin, Jingtao Gao, H. Jia, C. Zhu, Zi-hui Li, Jing Dong, Q. Sun, W. Shu, Sai Wang, L. Pan, Hairong Huang, Zong-De Zhang, Qi Li
Background Bedaquiline (Bdq) exerts bactericidal effects against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains, including multidrug-resistant M. tuberculosis strains (MDR-MTBs). However, few reported investigations exist regarding Bdq effects on MDR-MTBs-infected macrophages activities and cytokine secretion. Here, Bdq bactericidal activities against MDR-MTBs and related cellular immune mechanisms were explored. Methods Macrophages infected with MDR-MTBs or H37Rv received Bdq treatments (4 h/8 h/24 h/48 h) at 1 × the minimum inhibitory concentration (1 × MIC), 10 × MIC and 20 × MIC. Intracellular colony-forming units (CFUs) and culture supernatant IL-12/23 p40, TNF-α, IL-6, and IL-10 were determined using the Luminex® 200TM system. Normally distributed continuous data (mean ± standard deviation) were analyzed using t-test or F-test (SPSS 25.0, P < 0.05 deemed statistically significant). Results (1) 100% of Bdq-treated macrophages (all doses applied over 4–48 h) survived with 0% inhibition of proliferation observed. (2) Intracellular CFUs of Bdq-treated MDR-MTBs-infected macrophages decreased over 4–48 h of treatment, were lower than preadministration and control CFUs, decreased with increasing Bdq dose, and resembled H37Rv-infected group CFUs (48 h). (3) For MDR-MTBs-infected macrophages (various Bdq doses), IL-12/23 p40 levels resembled preadministration group levels and exceeded controls (4 h); TNF-α levels exceeded preadministration group levels (24 h/48 h) and controls (24 h); IL-12/23 p40 and TNF-α levels resembled H37Rv-infected group levels (4 h/8 h/24 h/48 h); IL-6 levels exceeded preadministration and H37Rv-infected group levels (24 h/48 h) and controls (24 h); IL-10 levels resembled preadministration and H37Rv-infected group levels (4 h/8 h/24 h/48 h) and were lower than controls (24 h/48 h); IL-12/23 p40 and IL-10 levels remained unchanged as intracellular CFUs changed, with IL-12/23 p40 levels exceeding controls (4 h) and IL-10 levels remaining lower than controls (24 h/48 h); TNF-α and IL-6 levels increased as intracellular CFUs decreased (24 h/48 h) and exceed controls (24 h). Conclusion Bdq was strongly bactericidal against intracellular MDR-MTBs and H37Rv in a time-dependent, concentration-dependent manner. Bdq potentially exerted immunomodulatory effects by inducing high-level Th1 cytokine expression (IL-12/23 p40, TNF-α) and low-level Th2 cytokine expression (IL-10).
{"title":"Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains","authors":"X. Lyu, Ting-ting Lin, Jingtao Gao, H. Jia, C. Zhu, Zi-hui Li, Jing Dong, Q. Sun, W. Shu, Sai Wang, L. Pan, Hairong Huang, Zong-De Zhang, Qi Li","doi":"10.1155/2022/2703635","DOIUrl":"https://doi.org/10.1155/2022/2703635","url":null,"abstract":"Background Bedaquiline (Bdq) exerts bactericidal effects against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains, including multidrug-resistant M. tuberculosis strains (MDR-MTBs). However, few reported investigations exist regarding Bdq effects on MDR-MTBs-infected macrophages activities and cytokine secretion. Here, Bdq bactericidal activities against MDR-MTBs and related cellular immune mechanisms were explored. Methods Macrophages infected with MDR-MTBs or H37Rv received Bdq treatments (4 h/8 h/24 h/48 h) at 1 × the minimum inhibitory concentration (1 × MIC), 10 × MIC and 20 × MIC. Intracellular colony-forming units (CFUs) and culture supernatant IL-12/23 p40, TNF-α, IL-6, and IL-10 were determined using the Luminex® 200TM system. Normally distributed continuous data (mean ± standard deviation) were analyzed using t-test or F-test (SPSS 25.0, P < 0.05 deemed statistically significant). Results (1) 100% of Bdq-treated macrophages (all doses applied over 4–48 h) survived with 0% inhibition of proliferation observed. (2) Intracellular CFUs of Bdq-treated MDR-MTBs-infected macrophages decreased over 4–48 h of treatment, were lower than preadministration and control CFUs, decreased with increasing Bdq dose, and resembled H37Rv-infected group CFUs (48 h). (3) For MDR-MTBs-infected macrophages (various Bdq doses), IL-12/23 p40 levels resembled preadministration group levels and exceeded controls (4 h); TNF-α levels exceeded preadministration group levels (24 h/48 h) and controls (24 h); IL-12/23 p40 and TNF-α levels resembled H37Rv-infected group levels (4 h/8 h/24 h/48 h); IL-6 levels exceeded preadministration and H37Rv-infected group levels (24 h/48 h) and controls (24 h); IL-10 levels resembled preadministration and H37Rv-infected group levels (4 h/8 h/24 h/48 h) and were lower than controls (24 h/48 h); IL-12/23 p40 and IL-10 levels remained unchanged as intracellular CFUs changed, with IL-12/23 p40 levels exceeding controls (4 h) and IL-10 levels remaining lower than controls (24 h/48 h); TNF-α and IL-6 levels increased as intracellular CFUs decreased (24 h/48 h) and exceed controls (24 h). Conclusion Bdq was strongly bactericidal against intracellular MDR-MTBs and H37Rv in a time-dependent, concentration-dependent manner. Bdq potentially exerted immunomodulatory effects by inducing high-level Th1 cytokine expression (IL-12/23 p40, TNF-α) and low-level Th2 cytokine expression (IL-10).","PeriodicalId":22481,"journal":{"name":"The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien des Maladies Infectieuses et de la Microbiologie Médicale","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87591191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recently, cases of rhinoorbital mucormycosis in people diagnosed with COVID-19 have been reported from India particularly. Diabetes mellitus though happens to be an independent risk factor both for severe COVID-19 and mucormycosis, administration of steroids is attributed as a precipitating factor for acquiring the comorbid condition. This opportunistic fungal infection is highly angioinvasive in nature because of which, clinical outcome of infection is invariably poor, especially with rhinocerebral or rhinoorbitocerebral variety of mucormycosis. However, effective management depends upon timely and accurate diagnosis and parenteral administration of amphotericin B. At the same time, judicious use of steroids is a key factor. In addition, glycemic control in those who are severely diabetic is strongly advocated. Exenteration of an eyeball may be indicated if cavernous sinus and intracranial spread are anticipated. Therefore, in order to facilitate faster healing and better penetration of antifungal drugs, surgical debridement of the paranasal sinus cavities and removal of dead tissue from the sinuses are recommended.
{"title":"COVID-19 and Mucormycosis Coinfection: How Challenging It Is","authors":"N. Nayak, E. Khan, D. Panigrahi","doi":"10.1155/2022/8617212","DOIUrl":"https://doi.org/10.1155/2022/8617212","url":null,"abstract":"Recently, cases of rhinoorbital mucormycosis in people diagnosed with COVID-19 have been reported from India particularly. Diabetes mellitus though happens to be an independent risk factor both for severe COVID-19 and mucormycosis, administration of steroids is attributed as a precipitating factor for acquiring the comorbid condition. This opportunistic fungal infection is highly angioinvasive in nature because of which, clinical outcome of infection is invariably poor, especially with rhinocerebral or rhinoorbitocerebral variety of mucormycosis. However, effective management depends upon timely and accurate diagnosis and parenteral administration of amphotericin B. At the same time, judicious use of steroids is a key factor. In addition, glycemic control in those who are severely diabetic is strongly advocated. Exenteration of an eyeball may be indicated if cavernous sinus and intracranial spread are anticipated. Therefore, in order to facilitate faster healing and better penetration of antifungal drugs, surgical debridement of the paranasal sinus cavities and removal of dead tissue from the sinuses are recommended.","PeriodicalId":22481,"journal":{"name":"The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien des Maladies Infectieuses et de la Microbiologie Médicale","volume":"86 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79848518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lijin Chen, L. Luo, Yanxin Chen, Yinzhou Wang, Jing Li, Xiaoyun Zheng, Ting Yang, Jianda Hu
Patients with hematological malignancies (HM) often develop the invasive fungal disease (IFD), causing important morbidity/mortality. While treatment guidelines are available, risk stratification models for optimizing antifungal therapy strategies are few. Clinical records from 458 HM patients with IFD were retrospectively analyzed. Following Chinese treatment guidelines, patients received empirical (n = 239) or diagnostic-driven therapy (n = 219). The effectiveness rate was 87.9% for the empirical and 81.7% for the diagnostic-driven therapy groups (P ≥ 0.05). The incidence of adverse reactions was 18.4% and 16.9%, respectively (P ≥ 0.05). All risk factors of IFD in HM patients were estimated in the univariate analyses and multivariate analyses by the chi-square test and logistic regression model. Duration ≥14 days (OR = 18.340, P=0.011), relapsed/refractory disease (OR = 11.670, P=0.005), IFD history (OR = 5.270, P=0.021), and diabetes (OR = 3.120, P=0.035) were significantly associated with IFD in the multivariate analysis. Patients with more than 3 of these factors have a significant difference in effective rates between the empirical (85.7%) and diagnostic-driven (41.6%) therapy (P=0.008). Empirical and diagnostic-driven therapy effective rates were 80.6% and 70.9% in the patients with two risk factors (P > 0.05) and 85.1% and 85.4% in the patients with one risk factor (P > 0.05). Thus, there was no significant difference in effectiveness in patients with one or two risk factors. The abovementioned risk stratification can guide clinical antifungal therapy. The patients with 3 or more risk factors benefit from empirical therapy.
{"title":"Antifungal Strategy in Patients with Invasive Fungal Disease Associated with Hematological Malignancies Based on Risk Stratification","authors":"Lijin Chen, L. Luo, Yanxin Chen, Yinzhou Wang, Jing Li, Xiaoyun Zheng, Ting Yang, Jianda Hu","doi":"10.1155/2022/1743596","DOIUrl":"https://doi.org/10.1155/2022/1743596","url":null,"abstract":"Patients with hematological malignancies (HM) often develop the invasive fungal disease (IFD), causing important morbidity/mortality. While treatment guidelines are available, risk stratification models for optimizing antifungal therapy strategies are few. Clinical records from 458 HM patients with IFD were retrospectively analyzed. Following Chinese treatment guidelines, patients received empirical (n = 239) or diagnostic-driven therapy (n = 219). The effectiveness rate was 87.9% for the empirical and 81.7% for the diagnostic-driven therapy groups (P ≥ 0.05). The incidence of adverse reactions was 18.4% and 16.9%, respectively (P ≥ 0.05). All risk factors of IFD in HM patients were estimated in the univariate analyses and multivariate analyses by the chi-square test and logistic regression model. Duration ≥14 days (OR = 18.340, P=0.011), relapsed/refractory disease (OR = 11.670, P=0.005), IFD history (OR = 5.270, P=0.021), and diabetes (OR = 3.120, P=0.035) were significantly associated with IFD in the multivariate analysis. Patients with more than 3 of these factors have a significant difference in effective rates between the empirical (85.7%) and diagnostic-driven (41.6%) therapy (P=0.008). Empirical and diagnostic-driven therapy effective rates were 80.6% and 70.9% in the patients with two risk factors (P > 0.05) and 85.1% and 85.4% in the patients with one risk factor (P > 0.05). Thus, there was no significant difference in effectiveness in patients with one or two risk factors. The abovementioned risk stratification can guide clinical antifungal therapy. The patients with 3 or more risk factors benefit from empirical therapy.","PeriodicalId":22481,"journal":{"name":"The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien des Maladies Infectieuses et de la Microbiologie Médicale","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73030377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xu-Hui Zhu, Ting Ye, Hong Zhong, Yaxuan Luo, Jian Xu, Qin Zhang, X. Luo, Qin Wang, Liyuan Zhang, Peipei Song, Jun Zhang
By studying the distribution and drug resistance of bacterial pathogens associated with lower respiratory tract infection (LRTI) in children in Chengdu and the effect of the COVID-19 on the distribution of pathogens and by analyzing the epidemic trend and drug resistance changes of the main pathogens of LRTI, this research is supposed to provide a useful basis for the prevention of LRTI in children and the rational use of drugs in clinical practice. Hospitalized children clinically diagnosed with LRTI in Chengdu Women and Children's Central Hospital from 2011 to 2020 were selected as the study subjects. The pathogens of LRTI in children and the distribution of pathogens in different ages, genders, seasons, years, and departments and before and after the pandemic situation of COVID-19 were counted. The drug resistance distribution of the top six pathogens with the highest infection rate in the past three years and the trend of drug resistance in the past decade were analyzed. A total of 26,469 pathogens were isolated. Among them, 6240 strains (23.6%) were Gram-positive bacteria, 20152 strains (76.1%) were Gram-negative bacteria, and 73 strains (0.3%) were fungi. Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, and Staphylococcus aureus were highly isolated in the group of infants aged 0-1 (P < 0.01), Moraxella catarrhalis and Streptococcus pneumoniae were highly isolated in children aged 1–6 (P < 0.01), and Haemophilus influenzae was highly isolated in children over 1 (P < 0.01). The isolation rates of Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Staphylococcus aureus, and Candida albicans in the lower respiratory tract of 0-1 year-old male infants were higher than those of female infants (p < 0.05). Haemophilus influenzae was highly isolated in spring and summer, and Moraxella catarrhalis was highly isolated in autumn and winter, while the infection of Streptococcus pneumoniae was mainly concentrated in winter. This difference was statistically significant (P < 0.01). Affected by the COVID-19 pandemic, the isolation rates of Haemophilus influenzae and Streptococcus pneumoniae were significantly lower than those before the pandemic, and the isolation rate of Moraxella catarrhalis was significantly higher. The difference was statistically significant (P < 0.01). The proportion of isolated negative bacteria in NICU and PICU was higher than that in positive bacteria, and the infection rates of Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, and Acinetobacter baumannii were higher than those in other departments. The differences were statistically significant (P < 0.01). The results of drug sensitivity test showed that the drug resistance of Haemophilus influenzae and Moraxella catarrhalis was mainly concentrated in Ampicillin, First- and Second-generation cephalosporins, and Cotrimoxazole, with stable sensitivity to Third-generation cephalosporins, while the drug resis
{"title":"Distribution and Drug Resistance of Bacterial Pathogens Associated with Lower Respiratory Tract Infection in Children and the Effect of COVID-19 on the Distribution of Pathogens","authors":"Xu-Hui Zhu, Ting Ye, Hong Zhong, Yaxuan Luo, Jian Xu, Qin Zhang, X. Luo, Qin Wang, Liyuan Zhang, Peipei Song, Jun Zhang","doi":"10.1155/2022/1181283","DOIUrl":"https://doi.org/10.1155/2022/1181283","url":null,"abstract":"By studying the distribution and drug resistance of bacterial pathogens associated with lower respiratory tract infection (LRTI) in children in Chengdu and the effect of the COVID-19 on the distribution of pathogens and by analyzing the epidemic trend and drug resistance changes of the main pathogens of LRTI, this research is supposed to provide a useful basis for the prevention of LRTI in children and the rational use of drugs in clinical practice. Hospitalized children clinically diagnosed with LRTI in Chengdu Women and Children's Central Hospital from 2011 to 2020 were selected as the study subjects. The pathogens of LRTI in children and the distribution of pathogens in different ages, genders, seasons, years, and departments and before and after the pandemic situation of COVID-19 were counted. The drug resistance distribution of the top six pathogens with the highest infection rate in the past three years and the trend of drug resistance in the past decade were analyzed. A total of 26,469 pathogens were isolated. Among them, 6240 strains (23.6%) were Gram-positive bacteria, 20152 strains (76.1%) were Gram-negative bacteria, and 73 strains (0.3%) were fungi. Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, and Staphylococcus aureus were highly isolated in the group of infants aged 0-1 (P < 0.01), Moraxella catarrhalis and Streptococcus pneumoniae were highly isolated in children aged 1–6 (P < 0.01), and Haemophilus influenzae was highly isolated in children over 1 (P < 0.01). The isolation rates of Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Staphylococcus aureus, and Candida albicans in the lower respiratory tract of 0-1 year-old male infants were higher than those of female infants (p < 0.05). Haemophilus influenzae was highly isolated in spring and summer, and Moraxella catarrhalis was highly isolated in autumn and winter, while the infection of Streptococcus pneumoniae was mainly concentrated in winter. This difference was statistically significant (P < 0.01). Affected by the COVID-19 pandemic, the isolation rates of Haemophilus influenzae and Streptococcus pneumoniae were significantly lower than those before the pandemic, and the isolation rate of Moraxella catarrhalis was significantly higher. The difference was statistically significant (P < 0.01). The proportion of isolated negative bacteria in NICU and PICU was higher than that in positive bacteria, and the infection rates of Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, and Acinetobacter baumannii were higher than those in other departments. The differences were statistically significant (P < 0.01). The results of drug sensitivity test showed that the drug resistance of Haemophilus influenzae and Moraxella catarrhalis was mainly concentrated in Ampicillin, First- and Second-generation cephalosporins, and Cotrimoxazole, with stable sensitivity to Third-generation cephalosporins, while the drug resis","PeriodicalId":22481,"journal":{"name":"The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien des Maladies Infectieuses et de la Microbiologie Médicale","volume":"163 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86454867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Robin Rauniyar, Aman Mishra, S. Kharel, Subarna Giri, R. Rauniyar, S. Yadav, Gajendra Chaudhary
Background There is limited information available regarding the management of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2. We performed a systematic review and meta-analysis to evaluate the optimal treatment using IVIG alone versus IVIG plus glucocorticoids. Methods PubMed, Google Scholar, EMBASE, and Cochrane databases were searched along with other secondary searches. Studies published within the time frame of January 2020 to August 2021 were included. We screened records, extracted data, and assessed the quality of the studies using NOS. Studies that directly compare the two treatment groups were included. Analyses were conducted using the random-effects model (DerSimonian-Laird analysis) if I2 > 50% and fixed-effects model was used if I2 < 50%. Results We included three studies in the final quantitative analysis. The initial therapy with the IVIG plus glucocorticoids group significantly lowered the risk of treatment failure (OR 0.57, 95% CI (0.42, 0.79), I2 45.36%) and the need for adjunctive immunomodulatory therapy (OR 0.27, 95% CI (0.20, 0.37), I2 0.0%). The combination therapy showed no significant reduction in occurrence of left ventricular dysfunction (OR 0.79, 95% CI (0.34, 1.87), I2 58.44%) and the need for inotropic support (OR 0.83, 95% CI (0.35, 1.99), I2 75.40%). Conclusion This study supports the use of IVIG with glucocorticoids compared to IVIG alone, as the combination therapy significantly lowered the risk of treatment failure and the need for adjunctive immunomodulatory therapy.
关于与SARS-CoV-2相关的儿童多系统炎症综合征(MIS-C)的管理信息有限。我们进行了系统回顾和荟萃分析，以评估单独使用IVIG与IVIG加糖皮质激素的最佳治疗。方法检索PubMed、Google Scholar、EMBASE、Cochrane等数据库，并进行二次检索。纳入了在2020年1月至2021年8月期间发表的研究。我们筛选记录，提取数据，并使用NOS评估研究的质量。直接比较两个治疗组的研究被纳入。I2 > 50%采用随机效应模型(DerSimonian-Laird分析)，I2 < 50%采用固定效应模型。结果我们在最后的定量分析中纳入了3项研究。IVIG +糖皮质激素组的初始治疗显著降低了治疗失败的风险(OR 0.57, 95% CI (0.42, 0.79)， I2 45.36%)和辅助免疫调节治疗的需求(OR 0.27, 95% CI (0.20, 0.37)， I2 0.0%)。联合治疗显示左心室功能障碍发生率(OR 0.79, 95% CI (0.34, 1.87)， I2 58.44%)和肌力支持需求(OR 0.83, 95% CI (0.35, 1.99)， I2 75.40%)无显著降低。结论与单独使用IVIG相比，本研究支持IVIG与糖皮质激素的联合使用，因为联合治疗显著降低了治疗失败的风险和辅助免疫调节治疗的需要。
{"title":"IVIG plus Glucocorticoids versus IVIG Alone in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: A Systematic Review and Meta-Analysis","authors":"Robin Rauniyar, Aman Mishra, S. Kharel, Subarna Giri, R. Rauniyar, S. Yadav, Gajendra Chaudhary","doi":"10.1155/2022/9458653","DOIUrl":"https://doi.org/10.1155/2022/9458653","url":null,"abstract":"Background There is limited information available regarding the management of multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2. We performed a systematic review and meta-analysis to evaluate the optimal treatment using IVIG alone versus IVIG plus glucocorticoids. Methods PubMed, Google Scholar, EMBASE, and Cochrane databases were searched along with other secondary searches. Studies published within the time frame of January 2020 to August 2021 were included. We screened records, extracted data, and assessed the quality of the studies using NOS. Studies that directly compare the two treatment groups were included. Analyses were conducted using the random-effects model (DerSimonian-Laird analysis) if I2 > 50% and fixed-effects model was used if I2 < 50%. Results We included three studies in the final quantitative analysis. The initial therapy with the IVIG plus glucocorticoids group significantly lowered the risk of treatment failure (OR 0.57, 95% CI (0.42, 0.79), I2 45.36%) and the need for adjunctive immunomodulatory therapy (OR 0.27, 95% CI (0.20, 0.37), I2 0.0%). The combination therapy showed no significant reduction in occurrence of left ventricular dysfunction (OR 0.79, 95% CI (0.34, 1.87), I2 58.44%) and the need for inotropic support (OR 0.83, 95% CI (0.35, 1.99), I2 75.40%). Conclusion This study supports the use of IVIG with glucocorticoids compared to IVIG alone, as the combination therapy significantly lowered the risk of treatment failure and the need for adjunctive immunomodulatory therapy.","PeriodicalId":22481,"journal":{"name":"The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien des Maladies Infectieuses et de la Microbiologie Médicale","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86227268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaishun Zhao, C. Tu, Wei Chen, Haiying Liang, Wenjing Zhang, Yilei Wang, Ye Jin, Jianrong Hu, Ya-meng Sun, Jun Xu, Yanfang Yu
Mycobacterium tuberculosis antimicrobial resistance has been continually reported and is a major public health issue worldwide. Rapid prediction of drug resistance is important for selecting appropriate antibiotic treatments, which significantly increases cure rates. Gene sequencing technology has proven to be a powerful strategy for identifying relevant drug resistance information. This study established a sequencing method and bioinformatics pipeline for resistance gene analysis using an Oxford Nanopore Technologies sequencer. The pipeline was validated by Sanger sequencing and exhibited 100% concordance with the identified variants. Turnaround time for the nanopore sequencing workflow was approximately 12 h, facilitating drug resistance prediction several weeks earlier than that of traditional phenotype drug susceptibility testing. This study produced a customized gene panel assay for rapid bacterial identification via nanopore sequencing, which improves the timeliness of tuberculosis diagnoses and provides a reliable method that may have clinical application.
{"title":"Rapid Identification of Drug-Resistant Tuberculosis Genes Using Direct PCR Amplification and Oxford Nanopore Technology Sequencing","authors":"Kaishun Zhao, C. Tu, Wei Chen, Haiying Liang, Wenjing Zhang, Yilei Wang, Ye Jin, Jianrong Hu, Ya-meng Sun, Jun Xu, Yanfang Yu","doi":"10.1155/2022/7588033","DOIUrl":"https://doi.org/10.1155/2022/7588033","url":null,"abstract":"Mycobacterium tuberculosis antimicrobial resistance has been continually reported and is a major public health issue worldwide. Rapid prediction of drug resistance is important for selecting appropriate antibiotic treatments, which significantly increases cure rates. Gene sequencing technology has proven to be a powerful strategy for identifying relevant drug resistance information. This study established a sequencing method and bioinformatics pipeline for resistance gene analysis using an Oxford Nanopore Technologies sequencer. The pipeline was validated by Sanger sequencing and exhibited 100% concordance with the identified variants. Turnaround time for the nanopore sequencing workflow was approximately 12 h, facilitating drug resistance prediction several weeks earlier than that of traditional phenotype drug susceptibility testing. This study produced a customized gene panel assay for rapid bacterial identification via nanopore sequencing, which improves the timeliness of tuberculosis diagnoses and provides a reliable method that may have clinical application.","PeriodicalId":22481,"journal":{"name":"The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien des Maladies Infectieuses et de la Microbiologie Médicale","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76187967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parisa Behruznia, M. Sadredinamin, A. Hashemi, Bahareh Hajikhani, Neda Yousefi Nojookambari, Mahboobeh Behruznia, Z. Ghalavand
Azithromycin (AZT) has widely been used for the treatment of shigellosis in children. Recent studies showed a high rate of decreased susceptibility to azithromycin due to different mechanisms of resistance in Shigella isolates. Accordingly, the purpose of this study was to investigate the role of azithromycin resistance mechanisms of Shigella isolates in Iran during a two-year period. In this study, we investigated the mechanisms of resistance among Shigella spp. that were isolated from children with shigellosis. The minimum inhibitory concentration (MIC) of Shigella isolates to azithromycin was determined by the agar dilution method in the presence and absence of Phe-Arg-β-naphthylamide inhibitor. The presence of 12 macrolide resistance genes was investigated for all isolates by PCR for the first time in Tehran province in Iran. Among the 120 Shigella spp., only the mph(A) gene (49.2%) was detected and other macrolide resistance genes were absent. The phenotypic activity of efflux pump was observed in 1.9% of isolates which were associated with over expression of both omp(A) and omp(W) genes. The high prevalence of the mph(A) gene among DSA isolates may indicate that azithromycin resistance has evolved as a result of antimicrobial selection pressures and inappropriate use of azithromycin.
{"title":"Decreased Susceptibility of Shigella Isolates to Azithromycin in Children in Tehran, Iran","authors":"Parisa Behruznia, M. Sadredinamin, A. Hashemi, Bahareh Hajikhani, Neda Yousefi Nojookambari, Mahboobeh Behruznia, Z. Ghalavand","doi":"10.1155/2022/4503964","DOIUrl":"https://doi.org/10.1155/2022/4503964","url":null,"abstract":"Azithromycin (AZT) has widely been used for the treatment of shigellosis in children. Recent studies showed a high rate of decreased susceptibility to azithromycin due to different mechanisms of resistance in Shigella isolates. Accordingly, the purpose of this study was to investigate the role of azithromycin resistance mechanisms of Shigella isolates in Iran during a two-year period. In this study, we investigated the mechanisms of resistance among Shigella spp. that were isolated from children with shigellosis. The minimum inhibitory concentration (MIC) of Shigella isolates to azithromycin was determined by the agar dilution method in the presence and absence of Phe-Arg-β-naphthylamide inhibitor. The presence of 12 macrolide resistance genes was investigated for all isolates by PCR for the first time in Tehran province in Iran. Among the 120 Shigella spp., only the mph(A) gene (49.2%) was detected and other macrolide resistance genes were absent. The phenotypic activity of efflux pump was observed in 1.9% of isolates which were associated with over expression of both omp(A) and omp(W) genes. The high prevalence of the mph(A) gene among DSA isolates may indicate that azithromycin resistance has evolved as a result of antimicrobial selection pressures and inappropriate use of azithromycin.","PeriodicalId":22481,"journal":{"name":"The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien des Maladies Infectieuses et de la Microbiologie Médicale","volume":"88 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84137954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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