Journal articles on the topic 'Anti-infective agents – Analysis'
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Li, Kuang-pang. "Analysis for drugs and metabolites including anti-infective agents." Microchemical Journal 43, no. 1 (February 1991): 86. http://dx.doi.org/10.1016/0026-265x(91)90043-o.
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Miller, JamesN. "Analysis for drugs and metabolites including anti-infective agents." Journal of Pharmaceutical and Biomedical Analysis 9, no. 5 (January 1991): 433. http://dx.doi.org/10.1016/0731-7085(91)80169-a.
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Atillasoy, Cem, and Panagiotis Gourlias. "1235. On the Edge of Tomorrow: Expedited Regulatory Pathways for Anti-Infective Therapies." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S637. http://dx.doi.org/10.1093/ofid/ofaa439.1420.
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Abstract Background The FDA has developed expedited review programs and pathways to increase drug development for products that have a major clinical benefit. These programs include: Fast Track, Orphan Drug Status, Accelerated Approval, Priority Review, Breakthrough Therapy (BTD) and Qualified Infectious Disease Products (QIPD). Given the heightened awareness of infectious diseases--and emerging global threats, such as resistant bacteria and Ebola—academia and industry have developed and received approval for 88 new infectious disease agents. The objective of this study was to assess the use of expedited review pathways for the 88 anti-infective agents that were approved between 2001-2020. FDA Expedited Drug Development Programs Methods We analyzed the FDA Drug Approval Database entitled, “Compilation of CDER New Molecular Entity (NME) Drug and New Biologic Approvals” for anti-infective therapies that were approved after 2000. Anti-infective therapies were defined as agents that were used to treat or prevent infectious diseases and include antibiotics, antivirals and antifungals. Our analysis focused on a comparison of the percentage of approved anti-infective agents that used each of the aforementioned designations across 2 decades (2001-2010 & 2011-2020). A drug may have one, none, or multiple of these designations. Results There were significant differences in the percentage of anti-infective agents approved with priority review, fast track and accelerated approval in 2001-2010 compared to 2011-2020 (See Results Figure 1) BTD and QIDP did not exist until 2012, thus preventing comparisons between decades. QIDP • Between 2012-2020, 16 anti-infectives have been approved with QIDP. From 2017-2020, 40% (n=10) of approved anti-infectives had QIDP. Orphan Drug Status: • Between 2017-2020, 32% of anti-infectives approved have the orphan drug designation. Comparison of FDA Expedited Drug Development Programs use between 2001-2010 and 2011-2020 Conclusion Our findings indicate Priority Review and Fast Track use has increased since 2010 among anti-infective products. Additionally, our analyses indicate that since 2017 there has been increased use of Orphan Drug Status and QIDP. However, there has been limited use of Breakthrough Therapy and Accelerated Approvals. These two pathways should be increasingly considered by academia, industry and the FDA to further expedite innovative anti-infective development. Disclosures All Authors: No reported disclosures
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Walder, Bernhard, Didier Pittet, and Martin R. Tramèr. "Prevention of Bloodstream Infections With Central Venous Catheters Treated With Anti-Infective Agents Depends on Catheter Type and Insertion Time: Evidence From a Meta-Analysis." Infection Control & Hospital Epidemiology 23, no. 12 (December 2002): 748–56. http://dx.doi.org/10.1086/502005.
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Objective:To test the evidence that the risk of infection related to central venous catheters (CVCs) is decreased by anti-infective coating or cuffing.Design:Systematic review of randomized, controlled trials comparing anti-infective with inactive (control) CVCs.Interventions:Average insertion times were taken as a measurement of the length of insertion. Dichotomous data were combined using a fixed effect model and expressed as odds ratio (OR) with 95% confidence interval (CI95).Results:Two trials on antibiotic coating (343 CVCs) had an average insertion time of 6 days; the risk of BSI decreased from 5.1% with control to 0% with anti-infective catheters. There were no trials with longer average insertion times. In three trials on silver collagen cuffs (422 CVCs), the average insertion time ranged from 5 to 8.2 days (median, 7 days); the risk of BSI was 5.6% with control and 3.2% with anti-infective catheters. In another trial on silver collagen cuffs (101 CVCs), the average insertion time was 38 days; the risk of BSI was 3.7% with control and 4.3% with anti-infective catheters. In five trials on chlorhexidine-silver sulfadiazine coating (1,269 CVCs), the average insertion time ranged from 5.2 to 7.5 days (median, 6 days); the risk of BSI decreased from 4.1% with control to 1.9% with anti-infective catheters. In five additional trials on chlorhexidine–silver sulfadiazine coating (1,544 CVCs), the average insertion time ranged from 7.8 to 20 days (median, 12 days); the risk of BSI was 4.5% with control and 4.2% with anti-infective catheters.Conclusions:Antibiotic and chlorhexidine–silver sulfadiazine coatings are anti-infective for short (approximately 1 week) insertion times. For longer insertion times, there are no data on antibiotic coating, and there is evidence of lack of effect for chlorhexidine-silver sulfadiazine coating. For silver-impregnated collagen cuffs, there is evidence of lack of effect for both short- and long-term insertion.
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Deyno, Serawit, Andrew G. Mtewa, Abiy Abebe, Ariya Hymete, Eyasu Makonnen, Joel Bazira, and Paul E. Alele. "Essential oils as topical anti-infective agents: A systematic review and meta-analysis." Complementary Therapies in Medicine 47 (December 2019): 102224. http://dx.doi.org/10.1016/j.ctim.2019.102224.
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Townshend, Alan. "Analysis for drugs and metabolites, including anti-infective agents (methodological surveys in biochemistry and analysis." Analytica Chimica Acta 254, no. 1-2 (November 1991): 253–54. http://dx.doi.org/10.1016/0003-2670(91)90039-8.
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Stojakovic, Natasa, Ranko Skrbic, Svjetlana Stoisavljevic-Satara, Dragana Babic-Djuric, Lana Nezic, and Ana Sabo. "Prescription-only drugs in Banja Luka region: Utilization analysis." Medical review 57, no. 1-2 (2004): 72–76. http://dx.doi.org/10.2298/mpns0402072s.
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Introduction Using the Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) methodology, we analyzed utilization of prescription-only drugs in Banja Luka region in 2000 - 2001. Material and methods A retrospective study on drug utilization, according to ATC classification, was conducted on the basis of data received from Central City Pharmacy Banja Luka, and results were presented in terms of DDD/1000 inhabitants/day. Results Pharmaco-epidemiological analysis showed that the list of 20 most frequently prescribed drugs in 2000 included 8 cardiovascular drugs and 6 anti-infective drugs. In 2001, 20 most frequently prescribed drugs, included 9 cardiovascular drugs, and 4 anti-infective drugs. Regarding anti-infective agents, the most frequently prescribed antibiotics were amoxicillin, doxycyline, co-trimoxazole and gentamicin. The most frequently prescribed drug in 2000 was diazepam (5,33 DDD/1000 inhabitants/day). The use of this drug significantly increased in 2001 (7,95 DDD/1000 inhabitants/day). Discussion and conclusion Based on total analysis, it can be concluded that the positive drug list, defined by the Health Insurance Fund, significantly affected the drug utilization profile, but some drugs are considered to be irrationally prescribed.
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Louis, Bruno, and Vijay K. Agrawal. "Quantitative structure-pharmacokinetic relationship (QSPkP) analysis of the volume of distribution values of anti-infective agents from j group of the ATC classification in humans." Acta Pharmaceutica 62, no. 3 (September 1, 2012): 305–23. http://dx.doi.org/10.2478/v10007-012-0024-z.
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In this study, a quantitative structure-pharmacokinetic relationship (QSPkR) model for the volume of distribution (Vd) values of 126 anti-infective drugs in humans was developed employing multiple linear regression (MLR), artificial neural network (ANN) and support vector regression (SVM) using theoretical molecular structural descriptors. A correlation-based feature selection (CFS) was employed to select the relevant descriptors for modeling. The model results show that the main factors governing Vd of anti-infective drugs are 3D molecular representations of atomic van der Waals volumes and Sanderson electronegativities, number of aliphatic and aromatic amino groups, number of beta-lactam rings and topological 2D shape of the molecule. Model predictivity was evaluated by external validation, using a variety of statistical tests and the SVM model demonstrated better performance compared to other models. The developed models can be used to predict the Vd values of anti-infective drugs.
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Gupta, Ram N. "Analysis for drugs and metabolites including anti-infective agents (Methodological Surveys in Biochemistry and Analysis, Vol. 20)." Journal of Chromatography B: Biomedical Sciences and Applications 565, no. 1-2 (April 1991): 534–35. http://dx.doi.org/10.1016/0378-4347(91)80423-a.
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Sawalha, A. F., W. M. Sweileh, S. H. Zyoud, and S. W. Jabi. "Comparative Analysis of Patient Package Inserts of Local and Imported Anti-Infective Agents in Palestine." Libyan Journal of Medicine 3, no. 4 (January 2008): 181–85. http://dx.doi.org/10.3402/ljm.v3i4.4790.
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Sawalha, AF, WM Sweileh, SH Zyoud, and SW Jabi. "Comparative Analysis of Patient Package Inserts of Local and Imported Anti-infective Agents in Palestine." Libyan Journal of Medicine 3, no. 4 (2008): 181–85. http://dx.doi.org/10.4176/080907.
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Imperatore, N., M. Foggia, A. Rispo, M. Patturelli, G. Calabrese, A. Testa, O. Nardone, et al. "P139 Prevalence of infections in patients affected by inflammatory bowel disease treated with anti-TNF-α agents: a single-centre experience." Journal of Crohn's and Colitis 14, Supplement_1 (January 2020): S206—S207. http://dx.doi.org/10.1093/ecco-jcc/jjz203.268.
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Abstract Background Although the efficacy of anti-TNF α agents has dramatically changed the current management of inflammatory bowel disease (IBD), their safety represents an important issue in prescribing anti-TNF. In particular, anti-TNF α treatment has been associated with higher risk of developing infective disease, such as tuberculosis (TBC) and cytomegalovirus (CMV) reactivation and other viral/bacterial diseases. The aim of the present study was to evaluate the incidence and prevalence of CMV, TBC, hepatitis B (HBV) and C (HCV) infection/reactivation and other infections in IBD subjects treated with anti-TNF α. Methods retrospective analysis of prospective maintained database including all IBD subjects treated with anti-TNF α (infliximab, adalimumab and golimumab) for at least 1 year in the period 2013–2018, whose infective serological status (Quantiferon TB test, Mantoux, CMV IgM/IgG, HBsAg, HBsAb, HBcAb, HBeAg, HBeAb, anti-HCV, anti-HIV, HSV IgM/IgG, VZV IgM/IgG, EBV IgM/IgG) was known before starting the treatment and during the follow-up. Incidence (number of infections per 100 patient-years) and prevalence of each infection was reported. Results Among 689 who started an anti-TNF α agent, 288 subjects (males 52.8%, mean age 28.5 + 12.2 years, Crohn’s disease 82.3%), met inclusion criteria and were enrolled. Total years/patient were 378.08 for infliximab, 627.58 for adalimumab and 8.25 for golimumab. Before starting treatment, CMV IgG antibodies were detectable in the majority (78.8%) of patients, but no case of IgM or CMV-DNA positivity was recorded; three subjects (1%) had latent TBC infection (LTBI) and were treated with isoniazide before starting anti-TNF; one case of HBV and one case of HCV infection were registered. During the anti-TNF α treatment, a total of 58 infective events (20.1%) were recorded: 63.8% during adalimumab and 36.2% during infliximab treatment. The most common infections were: urinary (34.5%), cutaneous (13.8%), HSV (13.8%), HPV (8.6%), upper respiratory infections (8.6%), gastroenteritis (6.9%), pneumonia (5.2%), bacteraemia (3.4%), VZV (3.4%) and de novo CMV (1.7%). Among them, 13 (22.4%) were considered severe, 11 (19%) needed hospitalisation and 9 (15.5%) led to anti-TNF withdrawal. No case of CMV or TBC reactivation was registered during the follow-up. The infection incidence rate was therefore 6.05/100 patient-years for adalimumab and 5.55/100 patient-years for infliximab (p = NS) (Table 1). Conclusion IBD patients are at high risk of developing infective disease during anti-TNF α therapy. The recognition of pre-exposure serological status, as well patients’ strict monitoring during maintenance treatment, dramatically reduces the risk of severe reactivation (in particular TBC and CMV reactivation).
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Fox, Neal, Lauren Haines, Rachel Bull, Zachary Jenkins, John Ballentine, Steven Burdette, and Craig Pleiman. "Potentially Inappropriate Durations of Anti-Infective Therapy at Hospital Discharge Despite Inpatient Antimicrobial Stewardship." Open Forum Infectious Diseases 4, suppl_1 (2017): S330. http://dx.doi.org/10.1093/ofid/ofx163.782.
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Abstract Background Excess durations of anti-infective therapy are a common problem that may lead to unintended consequences. Antimicrobial stewardship (AMS) is a growing field that largely focuses on inpatient anti-infective use. For this study, one site was an academic medical center whose AMS uses prospective auditing; the other was a community hospital with pharmacy-driven AMS. Little research has examined durations of anti-infective therapy at hospital discharge. Methods Patient charts were reviewed and 284 were included in the final analysis. Patients were excluded if discharged on non-oral anti-infectives or only agents for a non-study indication. Patients were included if they were discharged on oral anti-infective therapy for CAP, healthcare-associated pneumonia (HCAP), UTI, cellulitis, and superficial abscess. Evidence-based durations of therapy were utilized to determine the potential inappropriateness of anti-infective therapy. Guidelines from the study period were used. Total duration of therapy was derived from the combination of outpatient therapy plus inpatient therapy beginning with the first day of relevant coverage for the given indication. Descriptive statistics were utilized to compare durations of therapy. Chi-squared tests were utilized to examine differences in expected frequencies. All statistics were performed in SPSS v. 24. Results The average combined duration of therapy was 11.3 days. 190 patients (66.9%) were found to have a potentially inappropriate duration of oral anti-infective therapy at hospital discharge. Only 2 durations were too short. Figure 1 displays the distribution of excess days of therapy. Figure 2 shows the breakdown of potential inappropriateness of duration by diagnosis. Figure 3 displays the percentage of potentially inappropriate cases by site. There were no significant differences in the primary outcome between the sites. Conclusion CAP and cellulitis appear to be areas that are often overtreated. Discharge durations of therapy should be a focus of AMS teams. Many patients receive potentially inappropriate durations of therapy at discharge without any discernible benefit. Further research is needed in this area. Disclosures All authors: No reported disclosures.
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CHAMBERLAIN, JOSEPH. "Analysis for Drugs and Metabolites, Including Anti-infective Agents. Edited by E. Reid and I. D. Wilson." Journal of Pharmacy and Pharmacology 43, no. 2 (February 1991): 144. http://dx.doi.org/10.1111/j.2042-7158.1991.tb06654.x.
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Easton, Donna M., Shuhua Ma, Neeloffer Mookherjee, Pamela Hamill, David Lynn, Jennifer Gardy, Sarah Mullaly, et al. "Immunomodulatory activity of synthetic innate defence regulators (IDRs) (134.45)." Journal of Immunology 182, no. 1_Supplement (April 1, 2009): 134.45. http://dx.doi.org/10.4049/jimmunol.182.supp.134.45.
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Abstract Cationic host defence (antimicrobial) peptides, e.g. cathelicidin LL-37, have a variety of immunomodulatory activities that favour the safe resolution of infections. We have studied novel synthetic cationic innate defence regulator peptides that are not directly antimicrobial but are anti-infective in vivo, due to modulation of innate immunity. A range of peptides derived from the small bovine peptide bactenecin were screened for immunomodulatory activities in vitro; e.g. promotion of chemokine production and suppression of pro-inflammatory cytokines. Since innate immunity is complex, involving >1,500 gene products, a systems biology approach was utilized to characterize peptide modulation of innate immunity, including analysis of receptors, signalling pathways, transcription factors and downstream genes. To permit visualization and bioinformatic analysis of complex events, an innate immunity database (www.innatedb.ca), a network visualization tool (Cerebral) and downstream analysis tools (e.g. pathway overrepresentation analysis) were developed and provided insight into how this selective modulation occurs. In vivo data indicate that these activities provide protection in animal model infections of Gram positive and Gram negative bacterial infections as well as severe malaria. Thus IDRs have great potential for use as novel anti-infective agents. Supported by Genome BC, FNIH and CIHR.
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Aboagye, Samuel Yaw, Vincent Amarh, Paul A. Lartey, and Patrick Kobina Arthur. "Wood-decaying fungi found in Ghana: A rich source of new anti-infective compounds." AAS Open Research 2 (June 7, 2019): 20. http://dx.doi.org/10.12688/aasopenres.12957.1.
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Background: Discovery of bioactive natural products are instrumental for development of novel antibiotics. The discovery and development of natural products such as penicillin represented a major milestone in the treatment of bacterial infections. Currently, many antibiotics have lost their relevance in clinics due to the emergence of drug-resistant microbial pathogens. Hence, there is the need for continuous search of new compounds endowed with potent antimicrobial activity. Methods: In this study, wood-decaying fungi (WDF) from Ghana were explored for their potential as sources of novel antimicrobial compounds with intent of expanding the effort into a drug discovery programme in the near future. Extracts from cultures of 54 morphologically distinct WDF isolates were analyzed for the presence of antimicrobial agents. Results: The extracts from 40 out of the 54 WDF isolates exhibited significant antimicrobial activity against either Staphylococcus aureus, Escherichia coli or Candida albicans. Fractionation of these bioactive extracts, followed by bioassay of the organic fractions obtained, indicate that extracts exhibiting antimicrobial activity against more than one of the three test organisms could be attributed to the presence of different bioactive compounds. Analysis of the composition of the extracts revealed that terpenes were predominant. Conclusions: This study suggests that a significant proportion of WDF in Ghana produce antimicrobial compounds which could be potential sources of novel anti-infective agents and support the plans of developing a drug discovery programme in Ghana based on the fermentation of WDF.
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Aboagye, Samuel Yaw, Vincent Amarh, Paul A. Lartey, and Patrick Kobina Arthur. "Wood-decaying fungi found in Southern Ghana: A potential source of new anti-infective compounds." AAS Open Research 2 (August 27, 2019): 20. http://dx.doi.org/10.12688/aasopenres.12957.2.
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Background: Discovery of bioactive natural products are instrumental for development of novel antibiotics. The discovery and development of natural products such as penicillin represented a major milestone in the treatment of bacterial infections. Currently, many antibiotics have lost their relevance in clinics due to the emergence of drug-resistant microbial pathogens. Hence, there is the need for continuous search of new compounds endowed with potent antimicrobial activity. In this study, wood-decaying fungi (WDF) from Southern Ghana were explored for their potential as sources of novel antimicrobial compounds with intent of expanding the effort into a drug discovery programme in the near future. Methods: A total of 54 WDF isolates were fermented in potato dextrose broth and the secondary metabolites obtained were analyzed for the presence of antimicrobial agents using the disc diffusion assay. Chromatography techniques were used for preliminary analysis of the chemical composition of the extracts and for fractionation of the extracts that showed antimicrobial activity. Results: The extracts from 40 out of the 54 WDF isolates exhibited significant antimicrobial activity against either Staphylococcus aureus, Escherichia coli or Candida albicans. Fractionation of these bioactive extracts, followed by bioassay of the organic fractions obtained, indicate that extracts exhibiting antimicrobial activity against more than one of the three test organisms could be attributed to the presence of different bioactive compounds. Analysis of the composition of the extracts revealed that terpenes were predominant. Conclusions: This study suggests that a significant proportion of WDF in Southern Ghana produce antimicrobial compounds which could be potential sources of novel anti-infective agents and support the plans of developing a drug discovery programme in Ghana based on the fermentation of WDF.
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Madera, Laurence, Anastasia Nijnik, Matt Waldbrook, Neeloffer Mookherjee, Jennifer Gardy, Reza Falsafi, Melissa Elliott, and Robert EW Hancock. "The role of PI3-Kinase signalling in immunomodulation by a protective innate defence regulator peptide (135.6)." Journal of Immunology 182, no. 1_Supplement (April 1, 2009): 135.6. http://dx.doi.org/10.4049/jimmunol.182.supp.135.6.
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Abstract The rise of antibiotic resistance has lead to the search for new therapeutics against bacterial infections. Innate defence regulators (IDRs), synthetic versions of natural host defence peptides, are being developed as anti-infective agents due to their immunomodulatory properties. HDPs have been shown to suppress infections by boosting leukocyte recruitment, while limiting harmful inflammation. To optimize the IDR regulatory function, we developed peptide 1002, a bactenecin derivative, by screening a peptide library for enhanced leukocyte chemoattractants induction in human blood mononuclear cells (hBMC). 1002 enhanced protection in a Staphylococcus aureus murine infection model, correlating with increased chemokine production and leukocyte recruitment. 1002 also suppressed inflammatory cytokine production by lipopolysaccharide-stimulated hBMC. IDRs are being deciphered to assist in their development as therapeutics. We found that 1002 regulation is dependent on the PI3-Kinase pathway, a signal cascade that regulates immune and inflammatory responses. PI3-K inhibition abrogated 1002-mediated chemokine induction and reduced its anti-inflammatory properties. 1002 influence on PI3-K signalling was confirmed by examining responses of pathway elements and by systems biology microarray analysis of the immune network by InnateDB. Understanding the mechanisms of IDR immune regulation via PI3-K modulation will aid in their development as novel anti-infective agents. This work was supported by Genome BC and Genome Prairie for the Pathogenomics of Innate Immunity Research Program, and by FNIH and CIHR through the Grand Challenges in Global Health Initiative.
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Vedika Dadlani, Pushpendra Tripathi, and Rakesh Somani. "Design, Molecular Docking and In-Silico Analysis of Novel thiadiazole-azetidinone hybrids as Potential Antitubercular Agents." International Journal of Research in Pharmaceutical Sciences 10, no. 4 (November 29, 2019): 3694–703. http://dx.doi.org/10.26452/ijrps.v10i4.1756.
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The recent emergence of extensively drug-resistant tuberculosis has become a cause of concern for the management of tuberculosis globally. Shikimic acid pathway seems to be a potential and favorable target for the drug design of new anti-infective agents. This work aims to change the focus from traditional cell approaches to the target-based design of novel thiadiazolyl-azetidinone derivatives with Shikimate kinase as the drug target for anti-tubercular activity. Thiadiazole and azetidinone derivatives were methodically reprised to design a series of 3-chloro-4-(aryl)-1-(5-sulfanyl-1,3,4-thiadiazol-2-yl)azetidin-2-one derivatives (AZ1-AZ12). Molecular docking studies were performed on a crystal model of Mycobacterium tuberculosis Shikimate kinase (MtSK) using Vlife MDS 4.4 suite to evaluate their anti-tubercular potential. Further, drug-likeness properties and ADMET prediction were performed by molinspiration and admetSAR software to better describe the designed molecules as prospective candidates. 3-chloro-4-(4-nitrophenyl)-1-(5-sulfanyl-1,3,4-thiadiazol-2-yl)azetidin-2-one (AZ3), was found to be have better dock score when compared with the natural substrate, Shikimate. Docking studies confirmed that the molecules showed significant binding in the active site region of Shikimate kinase. Strong hydrogen bonding and hydrophobic interactions with amino acid residues and other parameters further explicate their effectiveness for inhibition of MtSK. Also, the physicochemical properties and drug scores for the designed compounds obtained by in silico studies were found to be satisfactory, signifying the overall potential of the designed molecules to be drug candidates. Thus these molecules could be explored as a lead for further anti-tubercular studies with Mycobacterium tuberculosis Shikimate kinase as the drug target.
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Karas, John A., Labell J. M. Wong, Olivia K. A. Paulin, Amna C. Mazeh, Maytham H. Hussein, Jian Li, and Tony Velkov. "The Antimicrobial Activity of Cannabinoids." Antibiotics 9, no. 7 (July 13, 2020): 406. http://dx.doi.org/10.3390/antibiotics9070406.
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A post-antibiotic world is fast becoming a reality, given the rapid emergence of pathogens that are resistant to current drugs. Therefore, there is an urgent need to discover new classes of potent antimicrobial agents with novel modes of action. Cannabis sativa is an herbaceous plant that has been used for millennia for medicinal and recreational purposes. Its bioactivity is largely due to a class of compounds known as cannabinoids. Recently, these natural products and their analogs have been screened for their antimicrobial properties, in the quest to discover new anti-infective agents. This paper seeks to review the research to date on cannabinoids in this context, including an analysis of structure–activity relationships. It is hoped that it will stimulate further interest in this important issue.
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Natarajan, D., R. Srinivasan, and M. S. Shivakumar. "Phyllanthus wightianusMüll. Arg.: A Potential Source for Natural Antimicrobial Agents." BioMed Research International 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/135082.
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Phyllanthus wightianusbelongs to Euphorbiaceae family having ethnobotanical importance. The present study deals with validating the antimicrobial potential of solvent leaf extracts ofP. wightianus. 11 human bacterial pathogens (Bacillus subtilis,Streptococcus pneumoniae,Staphylococcus epidermidis,Proteus vulgaris,Pseudomonas aeruginosa,Klebsiella pneumoniae,Salmonella typhimurium, Escherichia coli, Shigella flexneri, Proteus vulgaris, andSerratia marcescens) and 4 fungal pathogens (Candida albicans, Cryptococcus neoformans, Mucor racemosus, andAspergillus niger) were also challenged with solvent leaf extracts usingagar well and disc diffusion methods. Further, identification of the active component present in the bioactive extract was done using GC-MS analysis. Results show that all extracts exhibited broad spectrum (6–29 mm) of antibacterial activity on most of the tested organisms. The results highlight the fact that the well in agar method was more effective than disc diffusion method. Significant antimicrobial activity was detected in methanol extract againstS. pneumoniae(29 mm) with MIC and MBC values of 15.62 μg/mL. GC-MS analysis revealed that 29 bioactive constituents were present in methanolic extract ofP. wightianus,of which 9,12-octadecaenioic acid (peak area 22.82%; RT-23.97) and N-hexadecanoic acid (peak area 21.55% RT-21.796) are the major compounds. The findings of this study show thatP. wightianusextracts may be used as an anti-infective agent in folklore medicine.
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Gitawati, Retno. "Pattern of Household Drug Storage." Kesmas: National Public Health Journal 9, no. 1 (August 1, 2014): 27. http://dx.doi.org/10.21109/kesmas.v9i1.452.
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Household storage of pharmaceutical is world-widely practice, including in Indonesia. The purpose of this study was to obtain the pattern of medicine storage, the sources and reasons of medicine kept in households. Acrosssectional survey was conducted on October 2011, involving 250 adult household respondents, randomly selected from three subdistricts in North Jakarta, and have approved the written consents, and interviewed with structured questionnaire. Data were performed in univariate and bivariate analysis with chi square test. The majority of household (82%) stored drugs at home; analgesic-antipyretic nonsteroidal anti-inflammatory was the type of drugs kept by mostly (76.1%) of household. Out of 1001 stored drugs formulation encountered, about 31% were ethical drugs, mostly (64.8%) obtained from authorized pharmacies, purchased without prescription (71.9%), kept for future use (37.6%), and were leftover medicines (31.6%). Among the leftovers, 39.2% were ethical drugs including anti infective agents (31.5%). The leftover ethical medicines and anti infective agents could be indicated as inappropriate storage of pharmaceuticals and may lead to drug related problems.Penyimpanan obat di rumah tangga banyak dilakukan oleh masyarakat, namun tidak banyak informasi bagaimana obat disimpan dan digunakan oleh rumah tangga di Indonesia. Penelitian ini bertujuan memperoleh data pola obat di rumah tangga, sumber mendapatkannya, dan alasan obat disimpan. Survei potong-lintang dilakukan pada Oktober 2011, melibatkan secara acak 250 responden rumah tangga dewasa dari tiga kecamatan di Jakarta Utara yang dipilih purposif dan bersedia diwawancarai dengan menandatangani informed consent. Kuesioner terstruktur digunakan untuk memperoleh data obat. Dilakukan analisis data univariat dan bivariat dengan uji kai kuadrat. Mayoritas responden (82%) menyimpan obat, dengan jenis obat terbanyak analgesik-antipiretik dan anti-inflamasi nonsteroid (76,1%). Dari 1001 produk obat yang disimpan, 31% adalah obat etikal. Sebagian besar obat tersebut (64,8%) diperoleh dari apotek, dibeli tanpa resep dokter (71,9%), dan sengaja disimpan untuk persediaan jika sakit (37,6%) serta merupakan obat sisa resep (31,6%). Diantara obat sisa resep, sejumlah 39,2% adalah obat etikal, diantaranya termasuk anti-infeksi (31,5%). Adanya penyimpanan obat sisa resep berupa obat etikal dan anti-infeksi menggambarkan penyimpanan obat yang irasional dan dapat memicu masalah terkait obat termasuk risiko terjadinya medication error.
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Yu, Moxi, Yachen Hou, Meiling Cheng, Yongshen Liu, Caise Ling, Dongshen Zhai, Hui Zhao, et al. "Antibacterial Activity of Squaric Amide Derivative SA2 against Methicillin-Resistant Staphylococcus aureus." Antibiotics 11, no. 11 (October 28, 2022): 1497. http://dx.doi.org/10.3390/antibiotics11111497.
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Methicillin-resistant Staphylococcus aureus (MRSA)-caused infection is difficult to treat because of its resistance to commonly used antibiotic, and poses a significant threat to public health. To develop new anti-bacterial agents to combat MRSA-induced infections, we synthesized novel squaric amide derivatives and evaluated their anti-bacterial activity by determining the minimum inhibitory concentration (MIC). Additionally, inhibitory activity of squaric amide 2 (SA2) was measured using the growth curve assay, time-kill assay, and an MRSA-induced skin infection animal model. A scanning electron microscope and transmission electron microscope were utilized to observe the effect of SA2 on the morphologies of MRSA. Transcriptome analysis and real-time PCR were used to test the possible anti-bacterial mechanism of SA2. The results showed that SA2 exerted bactericidal activity against a number of MRSA strains with an MIC at 4–8 µg/mL. It also inhibited the bacterial growth curve of MRSA strains in a dose-dependent manner, and reduced the colony formation unit in 4× MIC within 4–8 h. The infective lesion size and the bacterial number in the MRSA-induced infection tissue of mice were reduced significantly within 7 days after SA2 treatment. Moreover, SA2 disrupted the bacterial membrane and alanine dehydrogenase-dependent NAD+/NADH homeostasis. Our data indicates that SA2 is a possible lead compound for the development of new anti-bacterial agents against MRSA infection.
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Sun, Peter, Zhimei Liu, Michael Kohrman, and John Bissler. "Real-world treatment profile for patients with tuberous sclerosis complex related angiomyolipoma: A U.S. Healthcare Claims Database study." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e15096-e15096. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e15096.
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e15096 Background: Angiomyolipoma (AML) is a common benign neoplasm associated with tuberous sclerosis complex (TSC). The objective of this study is to examine the treatment profile for patients with TSC related AML in a real world setting. Methods: A retrospective cohort study was performed using a large US commercial healthcare claims database. Patients with a TSC claim (ICD-9CM: 759.5X) and an AML claim (ICD-9CM: 223.0X) between 2000 and 2009 and with continuous 12-month health plan enrollment after their first AML claim were included into the study. The utilization rates of thirty two medication groups, eight procedure categories, five service places and fifteen provider types were assessed and ranked respectively for the year before first AML claim and the year after the first AML claim. Repeated measures analysis was used to compare these utilization rates between the last pre-AML year and the first post-AML year. Results: The study included 180 patients with a mean age of 28.2 years on their first AML claims, and 67.8% were females. During the first post-AML year, the top five medication groups were central nervous system medications (59.4%), anti-infective agents (50.6%), hormones & synthetic substance (22.8%), cardiovascular agents (18.9%), and autonomic drugs (17.8%); the most commonly used outpatient procedures were evaluation & management procedures (99.4%), anesthesia procedures (99.4%), surgical procedures (72.8%), radiology procedures (96.1%), and medicine procedures (100.0%). More patients consume the following care in the first post-AML year than in the last pre-AML year: anti-infective agents (50.6% vs. 35.0%, p<0.05), surgical procedures (72.8% vs. 60.6%, p<0.05), emergency rooms care (31.1% vs. 18.3%, p<0.05), urologists’ care (38.9% vs. 16.1%, p<0.05), nephrologists’ care (22.3% vs. 11.7%, p<0.05). Conclusions: In a real world setting and among TSC patients with AML, treatment profile changed after the first observed AML diagnosis. Further research is needed to examine the impact of these changes on economic and clinical outcomes of healthcare for patients with TSC related AML.
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Khamitov, R. F., A. A. Malova, and I. V. Grigorieva. "Community-acquired pneumonia treatment: predictors of fatal outcomes." Kazan medical journal 95, no. 3 (June 15, 2014): 356–61. http://dx.doi.org/10.17816/kmj1513.
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Aim. To analyze the quality of the medical aid in cases of community-acquired pneumonia with fatal outcomes and further development of recommendations for optimizing treatment strategy and tactics. Methods. Retrospective analysis of 62 medical charts of in-patients who passed away from community-acquired pneumonia during the calendar year. Results. The major part of all fatal outcomes of community-acquired pneumonia were seen at the intensive care units, to which the majority of such patients (41 cases, 66.1%) were admitted right from the admission ward. Differences of treatment tactics in patients with community-acquired pneumonia were revealed depending on the department type (internal diseases, intensive care unit, pulmonology) where the patients were admitted. The treatment manipulations structure and common mistakes made in administrating antibacterial and non-anti-infective drugs in cases of community-acquired pneumonia with fatal outcomes were analyzed. Anti-microbial treatment was assessed as completely adequate only in 18% of cases. In cases of severe community-acquired pneumonia with fatal outcomes the most commonly administered antibacterial drug was ceftriaxone (41 cases, 66.1%). At the same time, the potential of semisynthetic aminopenicillins was not unlocked (only 9 cases, 14.5%). The most common contraventions of rational anti-microbial treatment principles were irrational combinations, inadequate daily dosage and antimicrobial treatment change sequence. A trend for inappropriate administration of corticosteroids in patients with severe and extremely severe community-acquired pneumonia in the intensive care units was observed. The use of other non-anti-infective drugs (anticoagulants, diuretics, mucolytic agents and bronchodilators) as components of complex treatment in patinets with life-threatening community-acquired pneumonia should be strictly limited by their indications for use. Conclusion. Rational anti-bacterial treatment performed in compliance with national recommendations (2010) is the cornerstone of treating community-acquired pneumonia.
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Htoo, Htut Htut, Nhung Ngo Thi Tuyet, Kittiporn Nakprasit, Chanat Aonbangkhen, Vorrapon Chaikeeratisak, Warinthorn Chavasiri, and Poochit Nonejuie. "Mansonone G and its derivatives exhibit membrane permeabilizing activities against bacteria." PLOS ONE 17, no. 9 (September 1, 2022): e0273614. http://dx.doi.org/10.1371/journal.pone.0273614.
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In an era where the rate of bacteria evolving to be resistant to clinically-used antibiotics far exceeds that of antibiotic discovery, the search for new sources of antibacterial agents has expanded tremendously. In recent years, interest in plant-based natural products as promising sources of antibacterial agents has taken an upward trend. Mansonones, botanically-derived naphthoqionones, having many uses in Asian traditional medicine–including anti-infective roles–have sparked interest as a possible source of antibacterial agents. Here, we show that mansonone G, extracted from Mansonia gagei Drumm. heartwoods, possessed antibacterial activities towards Bacillus subtilis, Staphylococcus aureus and Escherichia coli lptD4213, inhibiting the growth of the bacteria at 15.6 μM, 62.5 μM and 125 μM, respectively. Fourteen derivatives of mansonone G were synthesized successfully and were found to have a similar antibacterial spectrum to that of the parent compound, with some derivatives possessing improved antibacterial activities. Bacterial cytological profiling analysis showed that mansonone G harbors membrane permeabilizing activities against B. subtilis and E. coli lptD4213. Temporal analysis of SYTOX Green staining among individual cells showed that mansonone G rapidly permeabilized bacterial membrane within 10 min, with SYTOX Green intensity reaching 13-fold above that of the control. Collectively, these findings highlight the importance of mansonone G and its derivatives as potential antibacterial agents, paving the way for further modifications in order to improve their antibacterial spectrum.
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Edmiston, Charles E., Candace J. Krepel, David Leaper, Nathan A. Ledeboer, Tami-Lea Mackey, Mary Beth Graham, Cheong Lee, et al. "Antimicrobial Activity of Ceftaroline and Other Anti-Infective Agents against Microbial Pathogens Recovered from the Surgical Intensive Care Patient Population: A Prevalence Analysis." Surgical Infections 15, no. 6 (December 2014): 745–51. http://dx.doi.org/10.1089/sur.2013.172.
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Dembitsky, Valery M. "Hydrobiological Aspects of Fatty Acids: Unique, Rare, and Unusual Fatty Acids Incorporated into Linear and Cyclic Lipopeptides and Their Biological Activity." Hydrobiology 1, no. 3 (September 14, 2022): 331–432. http://dx.doi.org/10.3390/hydrobiology1030024.
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The study of lipopeptides and their related compounds produced by various living organisms from bacteria to marine invertebrates is of fundamental interest for medicinal chemistry, pharmacology, and practical clinical medicine. Using the principles of retrosynthetic analysis of linear and cyclic peptides, the pharmacological activity of unique, unusual, and rare fatty acids (FA) that are part of natural lipopeptides was investigated. To search for new biologically active natural metabolites from natural sources, more than 350 FA incorporated into linear and cyclic peptides isolated from bacteria, cyanobacteria, microalgae, marine invertebrates, fungal endophytes, and microorganisms isolated from sediments are presented. Biological activities have been studied experimentally in various laboratories, as well as data obtained using QSAR (Quantitative Structure-Activity Relationships) algorithms. According to the data obtained, several FA were identified that demonstrated strong antibacterial, antimicrobial, antifungal, or antitumor activity. Along with this, FA have been found that have shown rare properties such as antiviral, antidiabetic, anti-helmintic, anti-inflammatory, anti-psoriatic, anti-ischemic, and anti-infective activities. In addition, FA have been found as potential regulators of lipid metabolism, as well as agents for the treatment of acute neurological disorders, as well as in the treatment of atherosclerosis and multiple sclerosis. For 36 FA, 3D graphs are presented, which demonstrate their predicted and calculated activities.
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Nuță, Diana Camelia, Carmen Limban, Cornel Chiriță, Mariana Carmen Chifiriuc, Teodora Costea, Petre Ioniță, Ioana Nicolau, and Irina Zarafu. "Contribution of Essential Oils to the Fight against Microbial Biofilms—A Review." Processes 9, no. 3 (March 18, 2021): 537. http://dx.doi.org/10.3390/pr9030537.
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The increasing clinical use of artificial medical devices raises the issue of microbial contamination, which is a risk factor for the occurrence of biofilm-associated infections. A huge amount of scientific data highlights the promising potential of essential oils (EOs) to be used for the development of novel antibiofilm strategies. We aimed to review the relevant literature indexed in PubMed and Embase and to identify the recent directions in the field of EOs, as a new modality to eradicate microbial biofilms. We paid special attention to studies that explain the mechanisms of the microbicidal and antibiofilm activity of EOs, as well as their synergism with other antimicrobials. The EOs are difficult to test for their antimicrobial activity due to lipophilicity and volatility, so we have presented recent methods that facilitate these tests. There are presented the applications of EOs in chronic wounds and biofilm-mediated infection treatment, in the food industry and as air disinfectants. This analysis concludes that EOs are a source of antimicrobial agents that should not be neglected and that will probably provide new anti-infective therapeutic agents.
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Ooi, Poh Ling, Hadzliana Zainal, Qi Ying Lean, Long Chiau Ming, and Baharudin Ibrahim. "Pharmacists’ Interventions on Electronic Prescriptions from Various Specialty Wards in a Malaysian Public Hospital: A Cross-Sectional Study." Pharmacy 9, no. 4 (October 1, 2021): 161. http://dx.doi.org/10.3390/pharmacy9040161.
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Background: The emergence of new technologies in the area of health information and communication helps pharmacists to check the safety of medications used via electronic prescribing. Objectives: The study aimed to identify the rate and types of problems with electronic prescriptions (e-prescriptions) that required pharmacist intervention at an inpatient pharmacy, and to evaluate prescribers’ acceptance of these interventions. Methods: A retrospective cross-sectional study on the interventions of e-prescriptions documented by pharmacists was conducted in a public hospital inpatient pharmacy. Data were collected for descriptive analysis using a collection form, including the e-prescription interventions, types of wards, drugs involved, and acceptance of intervention by prescribers. A chi-square test was used to evaluate the association between ward pharmacist availability and the rate of interventions. Results: A total number of 11,922 (3.3%) pharmacist interventions were proposed for 357,760 e-prescriptions ordered in the 12 month study period. Of the total number of proposed interventions, 11,381 (95.5%) were accepted by prescribers. The interventions on e-prescriptions were from surgical wards (11.7%) followed by intensive care (5.6%), paediatric (3.5%) and medical specialty wards (2.9%). Anti-infective agents (33.8%) and cardiovascular medicines (27.0%) were among the drugs with the highest rate of interventions. The most common type of intervention was revising the drug regimen (58.4%), especially with anti-infective agents (33.8%). Prescribers in surgical wards showed the highest level of acceptance of pharmacist interventions, which was 97.37%. The presence of ward pharmacists showed a higher number of interventions (6.2 vs. 1.0%, p < 0.001) than wards without pharmacists, as well as a higher percentage of acceptance (96.4 vs. 91.1%, p < 0.001) towards e-prescription intervention. Conclusion: In e-prescribing, errors can be prevented by pharmacists’ interventions on e-prescriptions. This helps to prevent medication errors and thus optimise rational pharmacotherapy in patients. The role of ward pharmacists in pharmaceutical care is highly accepted by prescribers.
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Barton, Amanda, Deonne Dersch-Mills, Sydney Saunders, Tania Mysak, and Dalyce Zuk. "Pharmacist Prescribing in Pediatric and Neonatal Acute Care: An Observational Study." Journal of Pediatric Pharmacology and Therapeutics 25, no. 7 (September 1, 2020): 600–605. http://dx.doi.org/10.5863/1551-6776-25.7.600.
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OBJECTIVE The intent of this project was to objectively describe the frequency of pharmacist prescribing in acute care pediatrics and neonatology and to determine the medications most often prescribed by pharmacists practicing in a jurisdiction that permits pharmacists' prescribing. METHODS This was a subgroup analysis of a retrospective observational study using prescribing data from an electronic medical record system used in 5 acute care hospitals (1 pediatric, 4 primarily adult but with pediatric and neonatal units) within Calgary, Alberta, Canada. RESULTS Considering orders for pediatric or neonatal patients only, there was a mean (SD) of 126 (226) prescriptions per pharmacist per year, with a wide range (1–1101 per year). Considering only the 9 clinical pharmacist full-time equivalents (FTEs) assigned to pediatrics and/or neonatology (i.e., not including dispensary pharmacist FTE), this represents 572 prescriptions per clinical pharmacist FTE per year (726 in pediatrics and 380 in neonatology). The most common medication classes on pediatric units included anti-infective agents, central nervous system agents, and gastrointestinal agents. In NICUs, blood formation, coagulation and thrombosis agents (mainly iron), electrolytes, caloric and water balance agents (primarily sodium supplements), and vitamins were also commonly prescribed by pharmacists. CONCLUSIONS As the scope of pharmacy practice expands to include prescribing, health team leadership can use these data to support incorporation of this role into practice. Prescribing pharmacists can ensure appropriate use of many medications used in acutely ill infants and children, potentially improving efficiency and quality of care.
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Ragab, Ahmed, Sawsan A. Fouad, Yousry A. Ammar, Dina S. Aboul-Magd, and Moustafa S. Abusaif. "Antibiofilm and Anti-Quorum-Sensing Activities of Novel Pyrazole and Pyrazolo[1,5-a]pyrimidine Derivatives as Carbonic Anhydrase I and II Inhibitors: Design, Synthesis, Radiosterilization, and Molecular Docking Studies." Antibiotics 12, no. 1 (January 9, 2023): 128. http://dx.doi.org/10.3390/antibiotics12010128.
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Nowadays, searching for new anti-infective agents with diverse mechanisms of action has become necessary. In this study, 16 pyrazole and pyrazolo[1,5-a]pyrimidine derivatives were synthesized and assessed for their preliminary antibacterial and antibiofilm activities. All these derivatives were initially screened for their antibacterial activity against six clinically isolated multidrug resistance by agar well-diffusion and broth microdilution methods. The initial screening presented significant antibacterial activity with a bactericidal effect for five compounds, namely 3a, 5a, 6, 9a, and 10a, compared with Erythromycin and Amikacin. These five derivatives were further evaluated for their antibiofilm activity against both S. aureus and P. aeruginosa, which showed strong biofilm-forming activity at their MICs by >60%. The SEM analysis confirmed the biofilm disruption in the presence of these derivatives. Furthermore, anti-QS activity was observed for the five hybrids at their sub-MICs, as indicated by the visible halo zone. In addition, the presence of the most active derivatives reduces the violacein production by CV026, confirming that these compounds yielded anti-QS activity. Furthermore, these compounds showed strong inhibitory action against human carbonic anhydrase (hCA-I and hCA-II) isoforms with IC50 values ranging between 92.34 and 168.84 nM and between 73.2 and 161.22 nM, respectively. Finally, radiosterilization, ADMET, and a docking simulation were performed.
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Roa-Linares, Vicky, Yaneth Miranda-Brand, Verónica Tangarife-Castaño, Rodrigo Ochoa, Pablo García, Mª Castro, Liliana Betancur-Galvis, and Arturo San Feliciano. "Anti-Herpetic, Anti-Dengue and Antineoplastic Activities of Simple and Heterocycle-Fused Derivatives of Terpenyl-1,4-Naphthoquinone and 1,4-Anthraquinone." Molecules 24, no. 7 (April 2, 2019): 1279. http://dx.doi.org/10.3390/molecules24071279.
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Quinones are secondary metabolites of higher plants associated with many biological activities, including antiviral effects and cytotoxicity. In this study, the anti-herpetic and anti-dengue evaluation of 27 terpenyl-1,4-naphthoquinone (NQ), 1,4-anthraquinone (AQ) and heterocycle-fused quinone (HetQ) derivatives was done in vitro against Human Herpesvirus (HHV) type 1 and 2, and Dengue virus serotype 2 (DENV-2). The cytotoxicity on HeLa and Jurkat tumor cell lines was also tested. Using plaque forming unit assays, cell viability assays and molecular docking, we found that NQ 4 was the best antiviral compound, while AQ 11 was the most active and selective molecule on the tested tumor cells. NQ 4 showed a fair antiviral activity against Herpesviruses (EC50: <0.4 µg/mL, <1.28 µM) and DENV-2 (1.6 µg/mL, 5.1 µM) on pre-infective stages. Additionally, NQ 4 disrupted the viral attachment of HHV-1 to Vero cells (EC50: 0.12 µg/mL, 0.38 µM) with a very high selectivity index (SI = 1728). The in silico analysis predicted that this quinone could bind to the prefusion form of the E glycoprotein of DENV-2. These findings demonstrate that NQ 4 is a potent and highly selective antiviral compound, while suggesting its ability to prevent Herpes and Dengue infections. Additionally, AQ 11 can be considered of interest as a leader for the design of new anticancer agents.
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Li, Jiarong, Dongfeng Song, Shengnan Wang, Yadong Dai, Jiyong Zhou, and Jinyan Gu. "Antiviral Effect of Epigallocatechin Gallate via Impairing Porcine Circovirus Type 2 Attachment to Host Cell Receptor." Viruses 12, no. 2 (February 4, 2020): 176. http://dx.doi.org/10.3390/v12020176.
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The green tea catechin epigallocatechin gallate (EGCG) exhibits antiviral activity against various viruses. Whether EGCG also inhibits the infectivity of circovirus remains unclear. In this study, we demonstrated the antiviral effect of EGCG on porcine circovirus type 2 (PCV2). EGCG targets PCV2 virions directly and blocks the attachment of virions to host cells. The microscale thermophoresis assay showed EGCG could interact with PCV2 capsid protein in vitro with considerable affinity (Kd = 98.03 ± 4.76 μM), thereby interfering with the binding of the capsid to the cell surface receptor heparan sulfate. The molecular docking analysis of capsid–EGCG interaction identified the key amino acids which formed the binding pocket accommodating EGCG. Amino acids ARG51, ASP70, ARG73 and ASP78 of capsid were found to be critical for maintaining the binding, and the arginine residues were also essential for the electrostatic interaction with heparan sulfate. The rescued mutant viruses also confirm the importance of the key amino acids of the capsid to the antiviral effect of EGCG. Our findings suggest that catechins could act as anti-infective agents against circovirus invasion, as well as provide the basic information for the development and synthesis of structure-based anti-circovirus drugs.
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Pérez-González, Noelia, Nuria Bozal-de Febrer, Ana C. Calpena-Campmany, Anna Nardi-Ricart, María J. Rodríguez-Lagunas, José A. Morales-Molina, José L. Soriano-Ruiz, Francisco Fernández-Campos, and Beatriz Clares-Naveros. "New Formulations Loading Caspofungin for Topical Therapy of Vulvovaginal Candidiasis." Gels 7, no. 4 (December 12, 2021): 259. http://dx.doi.org/10.3390/gels7040259.
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Vulvovaginal candidiasis (VVC) poses a significant problem worldwide affecting women from all strata of society. It is manifested as changes in vaginal discharge, irritation, itching and stinging sensation. Although most patients respond to topical treatment, there is still a need for increase the therapeutic arsenal due to resistances to anti-infective agents. The present study was designed to develop and characterize three hydrogels of chitosan (CTS), Poloxamer 407 (P407) and a combination of both containing 2% caspofungin (CSP) for the vaginal treatment of VVC. CTS was used by its mucoadhesive properties and P407 was used to exploit potential advantages related to increasing drug concentration in order to provide a local effect. The formulations were physically, mechanically and morphologically characterized. Drug release profile and ex vivo vaginal permeation studies were performed. Antifungal efficacy against different strains of Candida spp. was also evaluated. In addition, tolerance of formulations was studied by histological analysis. Results confirmed that CSP hydrogels could be proposed as promising candidates for the treatment of VVC.
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Šolínová, Veronika, Petra Sázelová, Alice Mášová, Jiří Jiráček, and Václav Kašička. "Application of Capillary and Free-Flow Zone Electrophoresis for Analysis and Purification of Antimicrobial β-Alanyl-Tyrosine from Hemolymph of Fleshfly Neobellieria bullata." Molecules 26, no. 18 (September 16, 2021): 5636. http://dx.doi.org/10.3390/molecules26185636.
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The problem of a growing resistance of bacteria and other microorganisms to conventional antibiotics gave rise to a search for new potent antimicrobial agents. Insect antimicrobial peptides (AMPs) seem to be promising novel potential anti-infective therapeutics. The dipeptide β-alanyl-tyrosine (β-Ala-Tyr) is one of the endogenous insect toxins exhibiting antibacterial activity against both Gram-negative and Gram-positive bacteria. Prior to testing its other antimicrobial activities, it has to be prepared in a pure form. In this study, we have developed a capillary zone electrophoresis (CZE) method for analysis of β-Ala-Tyr isolated from the extract of the hemolymph of larvae of the fleshfly Neobellieria bullata by reversed-phase high-performance liquid chromatography (RP-HPLC). Based on our previously described correlation between CZE and free-flow zone electrophoresis (FFZE), analytical CZE separation of β-Ala-Tyr and its admixtures have been converted into preparative purification of β-Ala-Tyr by FFZE with preparative capacity of 45.5 mg per hour. The high purity degree of the β-Ala-Tyr obtained by FFZE fractionation was confirmed by its subsequent CZE analysis.
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Gilbert, Elise M., Nathaniel J. Rhodes, Milena M. McLaughlin, Jessica M. Cottreau, Marc H. Scheetz, Michael Postelnick, and Viktorija O. Barr. "Analysis of an Infectious Diseases Pharmacist on Call Pager Program to Inform Educational Efforts." Journal of Pharmacy Technology 33, no. 4 (May 9, 2017): 146–50. http://dx.doi.org/10.1177/8755122517708207.
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Background: An on call infectious diseases (ID) pharmacist may be used as a resource for physicians, pharmacists, and other health care providers to help answer questions regarding anti-infective agents. Objective: To assess type, requestor, resources dedicated, and temporal trends of questions received through an ID pharmacist on call pager program. A secondary objective was to gather insight as to how this information was utilized to inform educational initiatives. Methods: This was a retrospective study of questions received by the ID pharmacist on call via pager at a large academic medical center. Question data were documented in a central database and analyzed to assess temporal trends and question type, and qualitatively analyzed to determine areas for targeted educational efforts. Results: The ID pharmacist on call recorded 545 questions during the 1-year study period; questions were composed of various antimicrobial agent–related queries, including antibiotic spectrum and selection (n = 251, 46.1%), dosing of antimicrobials (n = 195, 35.8%), and drug monitoring (n = 26, 4.8%). Targeted educational initiatives secondary to questions received included pharmacist education regarding the use of polymyxin antibiotics and antibiotic dosing protocol updates. Conclusions: An ID pharmacist on call pager program was utilized to inquire about antibiotic spectrum and selection for the majority of questions. Records of questions received may be utilized to direct educational efforts and create or revise targeted resources for pharmacists and other clinicians.
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Picone, Mary Frances, James P. New, Matthew Hunter Johnson, Nihal Nilesh Desai, and Matthew Hebbard. "Analysis of dosing-button compliance." American Journal of Health-System Pharmacy 76, no. 21 (October 15, 2019): 1770–76. http://dx.doi.org/10.1093/ajhp/zxz192.
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Abstract Purpose A project was undertaken at an academic medical center to assess use of available dosing buttons within the computerized provider-order-entry (CPOE) system in order to identify opportunities for optimization of medication builds. Methods A retrospective observational study was conducted to identify medication records within a CPOE system meeting prespecified inclusion and exclusion criteria. A report capturing all inpatient adult medication orders associated with the identified medication records over a 6-month period was generated. The primary endpoint was percent dosing-button compliance, calculated as the number of orders with doses consistent with existing dosing-button options divided by the total number of orders during the study period. Secondary study objectives included a comparison of high- and low-performing medication record samples and identification of potential reasons for lack of dosing-button use. Results A total of 2,506 CPOE medication records associated with a total of 694,877 medication orders entered during the study period were analyzed. Median percent dosing-button compliance was 99.92% (interquartile range, 83.33–100%). High-performing records (n = 1243) were more likely to be associated with anti-infective medications (p = 0.041) and medications not on formulary at the study institution (p < 0.001). Medications in the sample of poor-performing CPOE records (n = 614) were more likely to be agents delivered via the i.v. route (p < 0.001). There were 45 records for which poor dosing-button compliance was attributed to lack of a clinically reasonable dosing option. Conclusion A high level of dosing-button compliance was demonstrated despite the lack of routine revalidation of dosing buttons after initial medication builds. Some opportunity for optimization was identified during the project, which established a quality assurance method to facilitate future auditing of medication builds.
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Jonas, Brian A., Courtney D. Dinardo, Nicola Fracchiolla, Alexander Pristupa, Kenichi Ishizawa, Jie Jin, Marina Konopleva, et al. "CYP3A inhibitors and impact of these agents on outcomes in patients with acute myeloid leukemia treated with venetoclax plus azacitidine on the VIALE-A study." Blood 136, Supplement 1 (November 5, 2020): 50–52. http://dx.doi.org/10.1182/blood-2020-134850.
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Background: In the Phase 3 randomized, placebo-controlled VIALE-A study, venetoclax (Ven) + azacitidine (Aza) improved overall survival (OS) and complete response (CR) rates vs Aza + placebo (Pbo; DiNardo et al. N Engl J Med. 2020. In Press). Neutropenia and related infections are common in acute myeloid leukemia (AML) and exacerbated by Ven combinations. Antimicrobial prophylaxis is used variably in patients (pts) with AML receiving low-intensity therapies. Ven dose modifications are required for concomitant use of commonly used antimicrobials that are strong or moderate cytochrome P450 3A inhibitors (CYP3Ai). A previous report's findings showed that Ven dose reductions with CYP3Ai do not affect Ven exposure (Wei et al. Blood. 2020;135:2137). This analysis evaluated the use of prophylactic anti-infective CYP3Ai and these agents' effects on infections and efficacy outcomes in the VIALE-A study (NCT02993523). Methods: Pts with newly diagnosed AML, aged ≥75 y or 18-75 yand ineligible for induction therapy were enrolled. Pts were randomized 2:1 to receive Ven (daily, orally) + Aza (75 mg/m2 d 1-7, subcutaneously/intravenously) or Pbo + Aza in 28-d cycles. Anti-infective prophylaxis was required for pts with absolute neutrophil count <500/µL. For concomitant use of CYP3Ai, Ven dose was reduced from the intended target dose of 400 mg to 200 mg (Cycle 1 ramp-up: d 1, 50 mg; d 2, 100 mg; d 3, 200 mg) for moderate CYP3Ai and 50 mg (Cycle 1 ramp-up: d 1, 10 mg; d 2, 20 mg; d 3, 50 mg) for strong CYP3Ai. Use of anti-infective CYP3Ai agents reported as being given for prophylaxis during Cycles 1 and 2 was assessed; there was a possibility that CYP3Ai agents were used for nonprophylactic purposes not documented as such. The effects of concomitant use of these agents with the required Ven dose reductions on infection and efficacy outcomes were evaluated. Results: In total, 286 pts were randomized to Ven + Aza and 145 to Pbo + Aza. Within the first 2 cycles of therapy, concomitant anti-infective prophylaxis agents considered moderate CYP3Ai were received by 41/286 pts (14%) in the Ven + Aza arm and 18/145 (12%) in the Pbo + Aza arm. Concomitant anti-infective prophylaxis agents considered strong CYP3Ai were received in the first 2 cycles by 22/286 pts (8%) treated with Ven + Aza and 13/145 pts (9%) treated with Pbo + Aza. The median duration of each prophylactic CYP3Ai agent use was 12.5 d (range, 1-614) in the Ven + Aza arm and 15 d (range, 1-731) in the Pbo + Aza arm. The rates of CR+CR with incomplete marrow recovery (CRi) as a best response during the study were similar with concomitant use of moderate (61%; CR, 24%; CRi, 37%) or strong (64%; CR, 27%; CRi, 36%) CYP3Ai with adjusted-dose Ven vs no use of CYP3Ai (67%; CR, 39%; CRi, 27%; Table 1). The relatively lower CR and higher CRi rates appear to be due to delay in recovery of peripheral blood counts in pts who received strong CYP3Ai during the first 2 cycles (Table 2). The median time to first CR+CRi was 1.2 mo (range, 0.6-9.9), 1.4 mo (range 1.0-5.5), and 1.4 mo (range, 0.9-5.4) in those receiving no, moderate, and strong CYP3Ai agents, respectively, in the Ven + Aza arm. Median OS was not statistically different regardless of use of moderate or strong CYP3Ai in both arms, as noted by overlapping CIs (Table 1). The 24-month estimated OS was 26.2% (95% CI, 8.1-48.9) for pts receiving strong CYP3Ai vs 37.9% (95% CI, 30.2-45.6) for those receiving no CYP3Ai. Rates of any-grade or Grade 3/4 infections within the first 2 cycles varied between those with or without use of moderate CYP3Ai reported as being given as prophylaxis in both treatment arms (Table 1). Rates of invasive fungal infections were 3%, 12%, and 9% with Ven + Aza and 0%, 0%, and 15% with Pbo + Aza in pts receiving no, moderate, and strong CYP3Ai agents, respectively. Rates of discontinuation from infections were similar in both arms regardless of CYP3Ai use. Conclusions:Antimicrobial prophylaxis with moderate or strong CYP3Ai was used in neutropenic pts in the VIALE-A study, with overall similar composite remission rates with Ven dose reductions. The use of CYP3Ai did not increase rates of discontinuation from infections. Analysis of differences in baseline characteristics, rates of infections, and efficacy outcomes for pts who began anti-infective prophylaxis at the initiation of therapy is ongoing. Disclosures Jonas: Amgen: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; GlycoMimetics: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Celgene: Consultancy, Research Funding; Jazz: Consultancy, Research Funding; Takeda: Consultancy; Tolero: Consultancy; Treadwell: Consultancy; Forty Seven: Research Funding; Accelerated Medical Diagnostics: Research Funding; AROG: Research Funding; Daiichi Sankyo: Research Funding; F. Hoffmann-La Roche: Research Funding; Forma: Research Funding; AbbVie: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Genentech/Roche: Research Funding; Sigma Tau: Research Funding; Hanmi: Research Funding; Pfizer: Research Funding; LP Therapeutics: Research Funding; Incyte: Research Funding; Pharmacyclics: Research Funding. Dinardo:Takeda: Honoraria; Notable Labs: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Daiichi Sankyo: Consultancy, Research Funding; Calithera: Research Funding; Celgene: Research Funding; Agios: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; ImmuneOnc: Honoraria. Fracchiolla:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau. Pristupa:Beigene: Honoraria, Research Funding; State Institution of Health of the Ryazan Regional Clinical Hospital: Current Employment; Pfizer: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Takeda: Honoraria, Research Funding, Speakers Bureau; Daiichi Sankyo: Honoraria, Research Funding; Paraxel: Honoraria, Research Funding; Acerta: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding; Geron: Honoraria, Research Funding. Ishizawa:Takeda: Honoraria; Ono: Honoraria; Chugai: Honoraria; Eizai: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria; SymBio: Research Funding; Bayer: Research Funding; AbbVie: Research Funding. Jin:The First Affiliated Hospital of Zhejiang University: Current Employment. Konopleva:Rafael Pharmaceutical: Research Funding; F. Hoffmann La-Roche: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Eli Lilly: Research Funding; Sanofi: Research Funding; Calithera: Research Funding; Kisoji: Consultancy; AstraZeneca: Research Funding; AbbVie: Consultancy, Research Funding; Amgen: Consultancy; Ascentage: Research Funding; Reata Pharmaceutical Inc.;: Patents & Royalties: patents and royalties with patent US 7,795,305 B2 on CDDO-compounds and combination therapies, licensed to Reata Pharmaceutical; Ablynx: Research Funding; Forty-Seven: Consultancy, Research Funding; Stemline Therapeutics: Consultancy, Research Funding; Cellectis: Research Funding; Agios: Research Funding. Ofran:AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy; Rambam Health Care: Current Employment; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy. Kovacsovics:Pfizer: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Jazz: Honoraria; Astella: Honoraria; Agios: Honoraria. Kantarjian:Daiichi-Sankyo: Honoraria, Research Funding; BMS: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oxford Biomedical: Honoraria; Janssen: Honoraria; Delta Fly: Honoraria; BioAscend: Honoraria; Jazz: Research Funding; Abbvie: Honoraria, Research Funding; Sanofi: Research Funding; Aptitute Health: Honoraria; Adaptive biotechnologies: Honoraria; Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Immunogen: Research Funding; Ascentage: Research Funding. Hong:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Duan:AbbVie: Current Employment, Other: may hold stock or options. Ainsworth:AbbVie: Current Employment, Current equity holder in publicly-traded company. Potluri:AbbVie: Current Employment, Other: may hold stock or stock options. Werner:AbbVie: Current Employment, Current equity holder in publicly-traded company. Svensson:AbbVie: Current Employment, Current equity holder in publicly-traded company. Pratz:Millennium: Research Funding; Daiichi Sankyo: Research Funding; Agios: Other: Scientific Advisory Board, Research Funding; Jazz Pharmaceutical: Consultancy; Celgene: Other: Scientific Advisory Board; Boston BioMedical: Consultancy; AbbVie: Other: Scientific Advisory Board, Research Funding; Astellas: Other: Scientific Advisory Board, Research Funding.
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Subasinghage, Anusha P., J. Michael Conlon, and Chandralal M. Hewage. "Development of potent anti-infective agents from Silurana tropicalis: Conformational analysis of the amphipathic, alpha-helical antimicrobial peptide XT-7 and its non-haemolytic analogue [G4K]XT-7." Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 1804, no. 4 (April 2010): 1020–28. http://dx.doi.org/10.1016/j.bbapap.2010.01.015.
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Li, Franco K. K., Federico I. Rosell, Robert T. Gale, Jean-Pierre Simorre, Eric D. Brown, and Natalie C. J. Strynadka. "Crystallographic analysis of Staphylococcus aureus LcpA, the primary wall teichoic acid ligase." Journal of Biological Chemistry 295, no. 9 (January 22, 2020): 2629–39. http://dx.doi.org/10.1074/jbc.ra119.011469.
Full textAbstract:
Gram-positive bacteria, including major clinical pathogens such as Staphylococcus aureus, are becoming increasingly drug-resistant. Their cell walls are composed of a thick layer of peptidoglycan (PG) modified by the attachment of wall teichoic acid (WTA), an anionic glycopolymer that is linked to pathogenicity and regulation of cell division and PG synthesis. The transfer of WTA from lipid carriers to PG, catalyzed by the LytR–CpsA–Psr (LCP) enzyme family, offers a unique extracellular target for the development of new anti-infective agents. Inhibitors of LCP enzymes have the potential to manage a wide range of bacterial infections because the target enzymes are implicated in the assembly of many other bacterial cell wall polymers, including capsular polysaccharide of streptococcal species and arabinogalactan of mycobacterial species. In this study, we present the first crystal structure of S. aureus LcpA with bound substrate at 1.9 Å resolution and those of Bacillus subtilis LCP enzymes, TagT, TagU, and TagV, in the apo form at 1.6–2.8 Å resolution. The structures of these WTA transferases provide new insight into the binding of lipid-linked WTA and enable assignment of the catalytic roles of conserved active-site residues. Furthermore, we identified potential subsites for binding the saccharide core of PG using computational docking experiments, and multiangle light-scattering experiments disclosed novel oligomeric states of the LCP enzymes. The crystal structures and modeled substrate-bound complexes of the LCP enzymes reported here provide insights into key features linked to substrate binding and catalysis and may aid the structure-guided design of specific LCP inhibitors.
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Ballo, Olivier, Eva-Maria Kreisel, Fagr Eladly, Uta Brunnberg, Jan Stratmann, Peter Hunyady, Michael Hogardt, et al. "Use of carbapenems and glycopeptides increases risk for Clostridioides difficile infections in acute myeloid leukemia patients undergoing intensive induction chemotherapy." Annals of Hematology 99, no. 11 (September 24, 2020): 2547–53. http://dx.doi.org/10.1007/s00277-020-04274-1.
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Abstract Patients with acute myeloid leukemia (AML) are often exposed to broad-spectrum antibiotics and thus at high risk of Clostridioides difficile infections (CDI). As bacterial infections are a common cause for treatment-related mortality in these patients, we conducted a retrospective study to analyze the incidence of CDI and to evaluate risk factors for CDI in a large uniformly treated AML cohort. A total of 415 AML patients undergoing intensive induction chemotherapy between 2007 and 2019 were included in this retrospective analysis. Patients presenting with diarrhea and positive stool testing for toxin-producing Clostridioides difficile were defined to have CDI. CDI was diagnosed in 37 (8.9%) of 415 AML patients with decreasing CDI rates between 2013 and 2019 versus 2007 to 2012. Days with fever, exposition to carbapenems, and glycopeptides were significantly associated with CDI in AML patients. Clinical endpoints such as length of hospital stay, admission to ICU, response rates, and survival were not adversely affected. We identified febrile episodes and exposition to carbapenems and glycopeptides as risk factors for CDI in AML patients undergoing induction chemotherapy, thereby highlighting the importance of interdisciplinary antibiotic stewardship programs guiding treatment strategies in AML patients with infectious complications to carefully balance risks and benefits of anti-infective agents.
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Zavriev, S., and A. Kolesnikov. "Risks and Threats in Biosecurity Area: Problem Analysis and Search for Optimal Solutions in Contemporary Conditions." World Economy and International Relations, no. 9 (2015): 57–68. http://dx.doi.org/10.20542/0131-2227-2015-9-57-68.
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Current political climate is unfavorable for setting up broad international programs aimed at risk assessment and threat control in the field of biosecurity. At the same time, spread of emerging and re-emerging diseases, development of sophisticated antibiotic resistance mechanisms, grown threat of bioterrorism, and loss of disease control due to ecological damage and globalization dictate the urgent development of a national biosecurity program capable to address these risks and threats. Although Russian Federation is technologically and methodologically adept in the field of epidemiological and medical control of biological select agents, the expertise in latest technologies of treatment, prevention, and detection of potential biohazards is lagging. There is an urgent need for updating of state biosecurity programs, especially in the field of new vaccines and biologicals development for control and prevention of hazardous infections. Key elements of these programs include: well-justified list of priority targets and technologies; list of highest risk infectious agents to be addressed in development of countermeasures; identification of most efficient countermeasures for each agent of concern; selection of the most appropriate partnership model for scientific collaboration and formation of multidisciplinary teams, as well as for cooperation between science and biotech industry. The latter is particularly important for prompt conversion of scientific findings into solid technologies and prospective drug and vaccine candidates. By combining state funding and infrastructure with growing competence of Russian biotech and pharma industry, the likelihood of successful implementation of biosecurity programs will increase significantly. Strong aspects of Russian microbiological programs, such as development of anti-infective vaccines and bacteriophages, should be exploited in full. Despite current political turbulence, it is necessary to note that combined effort of various countries is required to protect the world population from risks of the globalization-fueled infectious diseases and bioterrorism threats emergence. Pathogens neglect borders and political issues, whereas poor coordination and collaboration at the international level can result in significant social and economic losses globally. Success in development and implementation of national biosecurity program in Russia based on the state-of-the-art scientific and technical achievements will help initiate a true international cooperation in biosafety/biosecurity area.
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Muslim, Zamharira. "ANTIBIOTIC PRESCRIPTION TO PEDIATRIC IN HOSPITAL BENGKULU, INDONESIA: ATC/DDD INDEX." International Journal of Pharmacy and Pharmaceutical Sciences 10, no. 5 (May 1, 2018): 31. http://dx.doi.org/10.22159/ijpps.2018v10i5.25291.
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Objective: The aim of this study was to evaluate the utilization of antibiotics for children in the General Hospital of Dr. M. Yunus Bengkulu, Indonesia by using the ATC/DDD index, which is accepted as a standard method.Methods: This study was descriptive analytic research with qualitative methods. Observations conducted over six months collecting retrospective prescribing data antibiotics in children admitted in January to June 2014. Data obtained assessed antibiotics prescribed in a quantity which is calculated using ATC/DDD index. In this study, DDDs of anti-infective agents are listed for systemic use, according to ATC/DDD 2016 Index. Data pediatric patients hospitalized amounted to 447 patients while fulfilling the inclusion criteria amounted to 103 medical records and the use of antibiotics which recorded 175 prescriptions.Results: The kind of antibiotics that are widely used are gentamicin (34.9%) and ampicillin (34.3%). The highest ACI based group is penicillin group antibiotics (ampicillin) is 26 DDD/100 bed-days. Highest DDDs in this study is ampicillin (101.7). Utilization of antibiotics in hospitals in Bengkulu, Indonesia to pediatric patient higher than suggested by the WHO is based on a quantitative analysis using the ACT/DDD index.Conclusion: Analysis of antibiotic use in children is not rationally quantitatively seen from the total value of ACI in one of the government hospital is very high compared to WHO standard and based on the most antibiotic type was ampicillin followed by gentamicin.
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Jackson Seukep, Armel, Yong-Li Zhang, Yong-Bing Xu, and Ming-Quan Guo. "In Vitro Antibacterial and Antiproliferative Potential of Echinops lanceolatus Mattf. (Asteraceae) and Identification of Potential Bioactive Compounds." Pharmaceuticals 13, no. 4 (March 30, 2020): 59. http://dx.doi.org/10.3390/ph13040059.
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Many species belonging to the genus Echinops are widely used in traditional medicine to treat infectious diseases and cancers. The present study aimed to evaluate the antibacterial and antiproliferative properties of Echinops lanceolatus Mattf. (Asteraceae). The activity of the methanolic extract and subsequent partition fractions was investigated against drug-resistant bacteria (Gram-negative and Gram-positive) and human tumor cell lines using broth microdilution and sulforhodamine B (SRB) assay, respectively. Our findings revealed weak to moderate antibacterial activities of tested extracts, with the recorded minimal inhibitory concentrations ranging from 256 to 1024 µg/mL. The ethyl acetate fraction (EL-EA) was found to be the most effective. Likewise, that fraction displayed strong antiproliferative potential with recorded IC50 of 8.27 µg/mL and 28.27 µg/mL on A549 and HeLa cells, respectively. An analysis based on the ultra-performance liquid chromatography–electrospray ionization tandem mass spectrometry (UPLC–ESI–MS/MS) of the EL-EA fraction allowed the identification of 32 compounds, of which quinic acid and derivatives, cinnamic acid derivatives, dihydrokaempferol, naringenin-7-O-glucoside, apigenin-7-O-d-glucoside, naringin, apigenin, rhoifolin, coniferyl aldehyde, and secoisolariciresinol are well-known compounds of biological importance. This study is first to report on the biological activity and phytochemical profile of E. lanceolatus. We provide a baseline to consider E. lanceolatus as a valuable source of anti-infective and antiproliferative agents.
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ALVES, C. M. O. S., D. A. O. SILVA, A. E. C. S. AZZOLINI, C. M. MARZOCCHI-MACHADO, Y. M. LUCISANO-VALIM, M. C. ROQUE-BARREIRA, and J. R. MINEO. "Galectin-3 is essential for reactive oxygen species production by peritoneal neutrophils from mice infected with a virulent strain ofToxoplasma gondii." Parasitology 140, no. 2 (September 14, 2012): 210–19. http://dx.doi.org/10.1017/s0031182012001473.
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SUMMARYToxoplasma gondiistimulates a potent pro-inflammatory response and neutrophils are involved in early infection. Galectin-3 (Gal-3) is an endogenous modulator of inflammatory processes and anti-infective agents, but its interaction with neutrophils inT. gondiiinfection is still unclear. Here, we evaluated the role of Gal-3 in peritoneal inflammation, reactive oxygen species (ROS) production by neutrophils and survival, afterin vivo T. gondiiinfection with virulent RH strain, using Gal-3 deficient and wild type mice. Animals were inoculated with thioglycollate or tachyzoites, and peritoneal cells were harvested for analysis of the influx of leukocytes. Neutrophils were isolated from peritoneal exudates from infected mice and stimulated with phorbol myristate acetate (PMA) to evaluate ROS production by luminol-dependent chemiluminescence assay. Our results showed that: (1) Gal-3 upregulates peritoneal inflammation, with enhanced recruitment of neutrophils and lymphocytes after thioglycollate stimulation, but does not influence the enhanced neutrophil influx after earlyT. gondiiinfection; (2) Gal-3 upregulates ROS generation by inflammatory peritoneal neutrophils from infected mice, but downregulates its production in non-infected mice and (3) Gal-3 does not influence the survival of mice after infection with the virulentT. gondiistrain. In conclusion, Gal-3 is essential for ROS generation by neutrophils in the initial acute phase ofT. gondiiinfection and this phenomenon may constitute an attempt to control parasite growth duringin vivoinfection with theT. gondiivirulent strain.
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Kieser, Ryan Blair, Jiaqiong Xu, Ethan Burns, Ibrahim Muhsen, Shivan M. Shah, Godsfavour Umoru, Charisma Mylavarapu, et al. "Outcomes of patients with advanced urothelial cancer who develop infection while on treatment with pembrolizumab." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): 4573. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.4573.
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4573 Background: Over the past decade, studies have shown the benefit of immune checkpoint inhibitors (IO) in patients with advanced urothelial cancer. These agents work by reconditioning the adaptive anti-cancer immune response within the tumor microenvironment. Immune-related adverse events have been well documented, but there is limited data evaluating infections in patients treated with IO. We performed a retrospective analysis to assess the incidence of infection and its effect on morbidity and mortality in patients treated with pembrolizumab for advanced urothelial cancer. Methods: Data was collected from a network of 7 hospitals for patients who received pembrolizumab for advanced urothelial cancer from 1/1/2017-8/1/2021. Date of last follow up was 12/1/2021. Covariates compared among infected and non-infected cohorts included age, gender, race, comorbidities, ECOG, anti-infective therapy at IO initiation, and line of therapy (1L, 2L, > 2L). Univariable analysis with reported odds ratio (OR) and 95% confidence interval (CI) was used to assess risk factors for infection. Outcome measures included all-cause emergency department (ED) visits, inpatient and intensive care unit (ICU) admissions, median number of IO cycles, and overall survival (OS). OS was evaluated using the Kaplan-Meier model. All analyses were deemed statistically significant if the p-value was < 0.05. Results: A total of 51 patients were identified. Of these, 34 (66.7%) had at least one documented infection and 17 (33.3%) had no reported infections. Baseline characteristics were similar across cohorts. Compared to non-infected patients, infected patients received fewer cycles of IO (median 4 vs 8, p = 0.016). At last follow-up, 20 (58.8%) patients in the infected cohort and 4 (23.5%) in the non-infected cohort died (p = 0.017). Median OS was 7.4 months (95% CI: 3.4-24.9) among patients with infection while not reached in those without infection (p = 0.014). ED visits (p = 1.00), inpatient admissions (p = 0.21), and ICU admissions (p = 0.17) did not significantly differ between cohorts. Univariable analysis did not identify significant risks among covariates. Conclusions: The incidence of infection in patients treated with pembrolizumab for advanced urothelial cancer is high and associated with fewer cycles of IO therapy and shorter OS. Further study of infectious process prevention is of value to maximize immunotherapy benefit.
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Kamel, Ahmed S., Ahmed F. Mohamed, Mostafa A. Rabie, Marwa E. Elsherbiny, Kawkab A. Ahmed, Mahmoud M. Khattab, and Noha F. Abdelkader. "Experimental Evidence for Diiodohydroxyquinoline-Induced Neurotoxicity: Characterization of Age and Gender as Predisposing Factors." Pharmaceuticals 15, no. 2 (February 19, 2022): 251. http://dx.doi.org/10.3390/ph15020251.
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Though quinoline anti-infective agents-associated neurotoxicity has been reported in the early 1970s, it only recently received regulatory recognition. In 2019, the European Medicines Agency enforced strict use for quinoline antibiotics. Thus, the current study evaluates the relation between subacute exposure to diiodohydroxyquinoline (DHQ), a commonly misused amebicide, with the development of motor and sensory abnormalities, highlighting age and gender as possible predisposing factors. Eighty rats were randomly assigned to eight groups according to their gender, age, and drug exposure; namely, four control groups received saline (adult male, adult female, young male, and young female), and the other four groups received DHQ. Young and adult rats received DHQ in doses of 176.7 and 247.4 mg/kg/day, respectively. After 4 weeks, rats were tested for sensory abnormality using analgesiometer, hot plate, and hind paw cold allodynia tests, and for motor function using open field and rotarod tests. Herein, the complex behavioral data were analyzed by principal component analysis to reduce the high number of variables to a lower number of representative factors that extracted components related to sensory, motor, and anxiety-like behavior. Behavioral outcomes were reflected in a histopathological examination of the cerebral cortex, striatum, spinal cord, and sciatic nerve, which revealed degenerative changes as well demyelination. Noteworthy, young female rats were more susceptible to DHQ’s toxicity than their counterparts. Taken together, these findings confirm previous safety concerns regarding quinoline-associated neurotoxicity and provide an impetus to review risk/benefit balance for their use.
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Li, Guoli, Xinyang Li, Yuye Wu, Juan Xu, and Fang He. "Genomic Insights into the Colistin Resistant mcr-Carrying Escherichia coli Strains in a Tertiary Hospital in China." Antibiotics 11, no. 11 (November 1, 2022): 1522. http://dx.doi.org/10.3390/antibiotics11111522.
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Colistin is an important antimicrobial agent in the treatment of infections caused by multidrug resistant (MDR) Gram-negative bacteria. The horizontal transfer of mobile colistin resistance gene (mcr) poses a major threat to the public health worldwide. In this study, a total of thirteen mcr-carrying Escherichia coli (MCREC) strains were recovered from a tertiary hospital in Zhejiang, China, between 2016 and 2019. The minimum inhibitory concentration (MIC) of antimicrobial agents, epidemiological characteristics, and transmission dynamics of mcr-carrying isolates were analyzed using antimicrobial susceptibility testing, whole-genome sequencing, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and southern blotting analysis. All strains were discovered to be resistant to colistin, and the majority displayed MDR phenotype. However, none of the 13 MCREC strains were resistant to carbapenems. The 13 MCREC isolates were divided into 10 different STs, including ST744, ST156, ST453, ST410, ST57, ST131, ST7034, ST2599, ST457, and ST13239, in which ST13239 was discovered for the first time. Based on core genome single nucleotide polymorphism (cgSNP) analysis, no clear epidemiological link was discovered in these strains with the exception of EC2118 and EC3807, which differ by just one SNP. A total of 35 antimicrobial resistance genes which can be divided into 14 classes were identified from the 13 MCREC isolates. According to S1-PFGE and southern blotting analyses, all 13 MCREC strains had plasmid-mediated mcr-1, and nine of them carried conjugative plasmids. In conclusion, our study revealed the emergence and dissemination of colistin-resistant E. coli isolates carrying mcr-1 in a Chinese hospital, which poses a potential risk to anti-infective therapy. More efforts should be taken to monitor the prevalence of mcr-1-carrying bacteria in China.
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Zhang, Huili, Kairui Zhou, Xinglong He, and Xin Yuan. "Comparative study on the changes of bacterial species and severity of antimicrobial resistance during 13 years." PLOS ONE 16, no. 8 (August 25, 2021): e0256375. http://dx.doi.org/10.1371/journal.pone.0256375.
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Background With the widespread use of broad-spectrum antibiotics, the problem of bacterial resistance has become a global crisis. To monitor bacterial resistance in our hospital, the distribution of specimens, the detection of pathogens and their drug resistance from July 2005 to June 2007 (13 years ago) and July 2018 to June 2020 were compared and analyzed. Methods Ordinary specimens (such as sputum, urine, feces, and secretion) were inoculated in blood AGAR media, MacConkey medium, chocolate medium, double SS medium and selective culture medium. Blood, cerebrospinal fluid, pleural effusion, joint cavity effusion and other sterile body fluid samples were inoculated in aerobic and anaerobic blood culture flasks. Automatic microbial identification, drug sensitivity analysis and mass spectrometry analysis were used to determine their drug sensitivity. Results Compared with the results obtained 13 years ago, the number of specimens submitted for inspection in the past two years has increased significantly, exhibiting a growth rate of 283%. The changes in the pathogen species were obvious. Gram-positive cocci were the dominant bacteria 13 years ago, and Gram-negative bacilli were the dominant bacteria in the past two years. In addition, the resistance of several major Gram-negative bacilli to piperacillin/tazobactam, cefoperazone/sulbactam, meropenem and imipenem all showed an increasing trend. Conclusion The variety of pathogenic bacteria in our hospital has changed significantly in the past two years compared with that 13 years ago, and the clinical isolates of Gram-negative bacilli have increased significantly compared with Gram-positive cocci. In the clinical treatment of anti-infective diseases, antimicrobial agents should be selected according to the bacterial distribution characteristics and drug resistance in each hospital.