Drug Target InsightsPub Date : 2022-11-30eCollection Date: 2022-01-01DOI: 10.33393/dti.2022.2482
Ramendra Pati Pandey, Riya Mukherjee, Chung-Ming Chang
{"title":"Antimicrobial resistance surveillance system mapping in different countries.","authors":"Ramendra Pati Pandey, Riya Mukherjee, Chung-Ming Chang","doi":"10.33393/dti.2022.2482","DOIUrl":"10.33393/dti.2022.2482","url":null,"abstract":"","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"16 ","pages":"36-48"},"PeriodicalIF":2.0,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/82/dti-16-36.PMC9714473.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10433276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug Target InsightsPub Date : 2022-11-22eCollection Date: 2022-01-01DOI: 10.33393/dti.2022.2476
Pooja Sen, Mukund Vijay, Shweta Singh, Saif Hameed, Pooja Vijayaraghavan
{"title":"Understanding the environmental drivers of clinical azole resistance in <i>Aspergillus</i> species.","authors":"Pooja Sen, Mukund Vijay, Shweta Singh, Saif Hameed, Pooja Vijayaraghavan","doi":"10.33393/dti.2022.2476","DOIUrl":"https://doi.org/10.33393/dti.2022.2476","url":null,"abstract":"ABSTRACT Aspergilli are ubiquitous fungal pathogens associated with severe life-threatening infections, especially in immunocompromised patients. Azoles are the first line of defence in the fight against most Aspergillus-related infections. However, resistance to these therapeutic compounds has developed, which is mainly due to the existence of mutations in lanosterol 14 alpha-demethylase (Cyp51A), a crucial enzyme in the pathway that produces ergosterol and is the target of azole antifungals. Azole-based antifungal medications are ineffective because of infections brought on by azole-resistant Aspergillus species, leading to a high fatality rate. However, resistant Aspergillus isolates have also been isolated from azole-naïve patients. Global agricultural practices promote the use of azole fungicides to protect crops from phytopathogens. Usage of azole fungicides on a large scale has been linked to the development of resistance among Aspergillus species prevalent in the environment. The infections caused by these azole-resistant Aspergillus species cannot be treated by the available azole drugs, in turn leading to high morbidity and mortality rates. Thus, knowledge of the environmental drivers and comprehending the genetic basis of fungal drug resistance evolution is pertinent, considering increasing numbers of patients with COVID-19 infections who are sensitive to opportunistic fungal infections. This article emphasises the prevalence and underlying mechanisms of azole resistance in Aspergillus species, with a focus on environmental triggers and resistance development. It also highlights the need for regular surveillance of pesticide use in agriculture, detection of triazole-resistant Aspergillus species in environmental and clinical settings and development of new antifungal drugs.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":" ","pages":"25-35"},"PeriodicalIF":2.7,"publicationDate":"2022-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c1/e3/dti-16-25.PMC9685629.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40570481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Redefining genomic view of <i>Clostridioides difficile</i> through pangenome analysis and identification of drug targets from its core genome.","authors":"Nikita Chordia Golchha, Anand Nighojkar, Sadhana Nighojkar","doi":"10.33393/dti.2022.2469","DOIUrl":"https://doi.org/10.33393/dti.2022.2469","url":null,"abstract":"ABSTRACT Introduction: Clostridioides difficile infection (CDI) is a leading cause of gastrointestinal infections and in the present day is a major concern for global health care system. The unavailability of specific antibiotics for CDI treatment and its emerging cases worldwide further broaden the challenge to control CDI. Methods: The availability of a large number of genome sequences for C. difficile and many bioinformatics tools for genome analysis provides the opportunity for in silico pangenomic analysis. In the present study, 97 strains of C. difficile were used for pangenomic studies and characterized for their phylogenomic and functional analysis. Results: Pangenome analysis reveals open pangenome of C. difficile and high genetic diversity. Sequence and interactome analysis of 1,481 core genes was done and eight potent drug targets are identified. Three drug targets, namely, aminodeoxychorismate synthase (PabB), D-alanyl-D-alanine carboxypeptidase (DD-CPase) and undecaprenyl diphospho-muramoyl pentapeptide beta-N-acetylglucosaminyl transferase (MurG transferase), have been reported as drug targets for other human pathogens, and five targets, namely, bifunctional diguanylate cyclase/phosphodiesterase (cyclic-diGMP), sporulation transcription factor (Spo0A), histidinol-phosphate transaminase (HisC), 3-deoxy-7-phosphoheptulonate synthase (DAHP synthase) and c-di-GMP phosphodiesterase (PdcA), are novel. Conclusion: The suggested potent targets could act as broad-spectrum drug targets for C. difficile. However, further validation needs to be done before using them for lead compound discovery.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":" ","pages":"17-24"},"PeriodicalIF":2.7,"publicationDate":"2022-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/74/da/dti-16-17.PMC9669665.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40720644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The association of ESBL <i>Escherichia coli</i> with mortality in patients with <i>Escherichia coli</i> bacteremia at the emergency department.","authors":"Pariwat Phungoen, Jessada Sarunyaparit, Korakot Apiratwarakul, Lumyai Wonglakorn, Atibordee Meesing, Kittisak Sawanyawisuth","doi":"10.33393/dti.2022.2422","DOIUrl":"https://doi.org/10.33393/dti.2022.2422","url":null,"abstract":"ABSTRACT Background: Escherichia coli is a common bloodstream infection pathogen in the emergency department (ED). Patients with extended-spectrum beta-lactamase (ESBL) E. coli have a higher risk of morbidity. However, there is still debate surrounding ESBL E. coli-associated mortality in community, intensive care unit, and tertiary care settings. In addition, there have been few studies regarding mortality in ESBL E. coli in ED settings, and results have been contradictory. Methods: This was a retrospective cohort study conducted at the Department of Emergency Medicine, Faculty of Medicine, Khon Kaen University in Thailand aimed at evaluating the possible association between ESBL E. coli bacteremia and mortality in the ED. The inclusion criteria were age 18 years or over, clinical presentation suspicious of infection, and positive blood culture for E. coli. Predictors for mortality were analyzed by logistic regression analysis. Results: During the study period, 273 patients presented at the ED with hemoculture positive for E. coli. Of those, 27 (9.89%) died. Five factors remained in the final model, of which plasma glucose levels, serum lactate levels, and ESBL E. coli were significantly associated with 28-day mortality in the ED with adjusted odds ratios of 0.970, 1.258, and 12.885, respectively. Plasma glucose of less than 113 mg/dL yielded a sensitivity of 80.95% and specificity of 64.29%, while serum lactate over 2.4 mmol/L had a sensitivity of 81.48% and specificity of 45.50%. Conclusion: ESBL E. coli, plasma glucose, and serum lactate levels were associated with 28-day mortality in patients with E. coli bacteremia presenting at the ED.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":" ","pages":"12-16"},"PeriodicalIF":2.7,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2b/73/dti-16-12.PMC9589459.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40652791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anatomical and functional responses to single brolucizumab injection in neovascular age-related macular degeneration patients not responding to antiangiogenics: a case series","authors":"S. Zuccarini, Fabrizio Puce, Alessandro Crisà","doi":"10.33393/dti.2022.2343","DOIUrl":"https://doi.org/10.33393/dti.2022.2343","url":null,"abstract":"ABSTRACT Introduction: Neovascular age-related macular degeneration (nAMD) is treated with antivascular endothelial growth factor (anti-VEGF) drugs. However, resistance to anti-VEGF therapy is observed in some patients. Brolucizumab is a new-generation anti-VEGF drug for the treatment of nAMD, with proven efficacy in fluid resolution and long-lasting effects. Methods: We report here a case series of nAMD patients not responding to previous anti-VEGF therapy showing anatomical and functional response to a single intravitreal injection of brolucizumab. Results: Nine patients with nAMD, undergoing treatment with anti-VEGF therapy (aflibercept, bevacizumab, or ranibizumab) but with either fluid persistence or frequent fluid recurrences in retinal compartments, were switched to intravitreal brolucizumab and examined 4 weeks postinjection. No signs of active disease were observed in all but one patient, with complete retinal fluid resolution in seven patients. Central macular thickness and visual acuity significantly improved, and changes were sustained for up to 12 weeks in a subset of three patients. No adverse reactions were observed. Conclusions: This new anti-VEGF drug showed great efficacy since the first week from the injection with a significative reduction of subretinal fluid and rapid improvement of visual acuity. In conclusion, brolucizumab administered intravitreally appears to be an effective treatment in nAMD patients, leading to both early anatomical and functional improvements.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"16 1","pages":"6 - 11"},"PeriodicalIF":2.7,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46116051","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}
Drug Target InsightsPub Date : 2022-03-07eCollection Date: 2022-01-01DOI: 10.33393/dti.2022.2355
Martino Carriero
{"title":"Erythrodermic psoriasis and palmoplantar hyperkeratosis successfully treated with secukinumab: a case report.","authors":"Martino Carriero","doi":"10.33393/dti.2022.2355","DOIUrl":"https://doi.org/10.33393/dti.2022.2355","url":null,"abstract":"ABSTRACT Introduction: Erythrodermic psoriasis (EP) is a rare and severe form of psoriasis that affects 1% to 2.25% of patients, increasing mortality risk. To date, very few therapies have been approved for the treatment of this condition. Recently, biological therapies that specifically target inflammatory cytokines have improved the management and treatment of EP. Secukinumab, a human monoclonal antibody that specifically targets interleukin-17A (IL-17A), has been shown to be beneficial in different psoriasis settings. Methods: We report the case of a 72-year-old man affected by persistent EP and severe palmoplantar hyperkeratosis whose condition was not resolved after two rounds of treatment with prednisone and therapy with cyclosporine. Results and conclusions: Treatment with secukinumab significantly improved the symptoms of palmoplantar hyperkeratosis as early as the first week, with a decrease of psoriasis area and severity index (PASI) score from 60 to 10, showing almost complete remission after 1 month. Consistent with the current literature, secukinumab treatment showed promising and encouraging clinical outcomes in the treatment of the patient’s EP. However, more studies are needed to clarify the IL-17-dependent mechanism in the pathophysiology of EP.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":" ","pages":"1-5"},"PeriodicalIF":2.7,"publicationDate":"2022-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/1b/dti-16-1.PMC8902433.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40306297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Syed Fahim Shah, Sohail Aziz Paracha, Waheed Ullah, Iqbal Muhammad, Somaid Iqbal, Aisha Gul, Mudassir Hussain, Hafiz Ullah, Sadir Zaman
{"title":"Success of 14-day triple and quadruple therapy for the control of <i>Helicobacter pylori</i> infections in Kohat district.","authors":"Syed Fahim Shah, Sohail Aziz Paracha, Waheed Ullah, Iqbal Muhammad, Somaid Iqbal, Aisha Gul, Mudassir Hussain, Hafiz Ullah, Sadir Zaman","doi":"10.33393/dti.2022.2481","DOIUrl":"https://doi.org/10.33393/dti.2022.2481","url":null,"abstract":"ABSTRACT Introduction: Helicobacter pylori is an important medical pathogen present in more than half of the world’s population. Various treatment regimen are in use for the eradication of H. pylori, but due to the emergence of antibiotic resistance, its management is a big issue for clinicians. Methods: In this study all suspected cases that had visited District Headquarters Hospital Kohat were considered for screening of H. pylori infections. Preliminary information about their age, gender, general health conditions, occupation, etc. was taken for consideration. After recording initial signs and symptoms, samples were considered for H. pylori detection using stool antigen test and endoscopy. Fourteen-day proton pump inhibitor base triple and quadruple therapy were administered to each patient. Results: In total (n = 178), there were high numbers of positivity in patients aged below 30 years (82; 46.06%), most of whom belonged to rural areas. Conclusion: This study concludes that there were high numbers of positive patients aged below 30 years, and according to this study MEL (Metronidazole + Esomeprazole + Levofloxacin) is the most effective treatment regimen for the eradication of H. pylori.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"16 ","pages":"49-53"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/37/55/dti-16-49.PMC9768595.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10459522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"AMR research: a perspective from personal experience.","authors":"Vijay Kothari","doi":"10.33393/dti.2022.2545","DOIUrl":"https://doi.org/10.33393/dti.2022.2545","url":null,"abstract":"<jats:p>...</jats:p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"16 ","pages":"69-70"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c6/8e/dti-16-69.PMC9798424.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10493801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sim Yi Xing, Lee Qiao Wei, Aisha Abushelaibi, Kok Song Lai, Swee Hua Erin Lim, Sathiya Maran
{"title":"Current molecular approach for diagnosis of MRSA: a meta-narrative review.","authors":"Sim Yi Xing, Lee Qiao Wei, Aisha Abushelaibi, Kok Song Lai, Swee Hua Erin Lim, Sathiya Maran","doi":"10.33393/dti.2022.2522","DOIUrl":"https://doi.org/10.33393/dti.2022.2522","url":null,"abstract":"ABSTRACT Introduction: Detection and diagnosis of methicillin-resistant Staphylococcus aureus (MRSA) are important in ensuring a correct and effective treatment, further reducing its spread. A wide range of molecular approaches has been used for the diagnosis of antimicrobial resistance (AMR) in MRSA. This review aims to study and appraise widely used molecular diagnostic methods for detecting MRSA. Methods: This meta-narrative review was performed by searching PubMed using the following search terms: (molecular diagnosis) AND (antimicrobial resistance) AND (methicillin-resistant Staphylococcus aureus). Studies using molecular diagnostic techniques for the detection of MRSA were included, while non-English language, duplicates and non-article studies were excluded. After reviewing the libraries and a further manual search, 20 studies were included in this article. RAMESES publication standard for narrative reviews was used for this synthesis. Results: A total of 20 full papers were reviewed and appraised in this synthesis, consisting of PCR technique (n = 7), deoxyribonucleic acid (DNA) Microarray (n = 1), DNA sequencing (n = 2), Xpert MRSA/SA BC assay (n = 2), matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) (n = 2), MLST (n = 4), SCCmec typing (n = 1) and GENECUBE (n = 1). Discussion: Different diagnostic methods used to diagnose MRSA have been studied in this review. This study concludes that PCR has been extensively used due to its higher sensitivity and cost-effectiveness in the past five years","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"16 ","pages":"88-96"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/77/1b/dti-16-88.PMC9906022.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10688896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unmet needs for management of drug-resistant infections: low- and middle-income countries' viewpoint.","authors":"Monica Sharma, Kamini Walia, Nitin Bansal","doi":"10.33393/dti.2022.2532","DOIUrl":"https://doi.org/10.33393/dti.2022.2532","url":null,"abstract":"ABSTRACT Drug-resistant infections are a serious threat globally which demands cost-effective solutions to meet the unmet needs in their diagnosis and treatment. Gram-negative pathogens, drug-resistant tuberculosis, and multidrug-resistant Salmonella typhi have been reported as cause of resistant infections in developing countries. Here, we discuss the priority pathogens and conditions for which feasible solutions adaptable to low-resource settings are required to address the antimicrobial resistance in pathogens. These solutions will be helpful in containing the spread of antimicrobial resistance and better patient outcomes.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"16 ","pages":"78-80"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/76/d0/dti-16-78.PMC9823287.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}