Journal articles on the topic 'Anti-fungals'
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Hata, T., Y. Furukawa, T. Konosu, and S. Oida. "Structural study of triazole anti-fungals." Acta Crystallographica Section A Foundations of Crystallography 49, s1 (August 21, 1993): c128. http://dx.doi.org/10.1107/s0108767378096324.
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Al–Harthy, Thuraya, Abdullah M. Al-Sadi, Wajdi Zoghaib, Ebrahim Moghadam, Raphael Stoll, and Raid Abdel-Jalil. "Design, Synthesis and Bioactivity of Benzimidazole–2–Carbamates as Soil–Borne Anti–Fungal Agents †,‡." Chemistry Proceedings 3, no. 1 (November 13, 2020): 64. http://dx.doi.org/10.3390/ecsoc-24-08093.
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The design and synthesis of new, safe and potent molecules to apply against soil-borne pathogens is a critical goal for organic and bio-medicinal chemists. Herein, we designed and synthesized a series of benzimidazole-based carbamate derivatives (7a–f), as soil-borne anti-fungals. The derivatives 7a–f were all synthesized in multi-step reactions with acceptable yields. The structures of 7a–f were all identified and characterized using 1H-NMR, IR, HRMS, and melting point calculations. The final compounds were tested on five soil-borne pathogens. The results of various bio-assays showed that compounds 7a-3, 7a-2, 7b-2, 7a-1 and 7b-1 significantly affected the growth of Pythium aphanidermatum, a serious pathogen affecting vegetable crops worldwide. Compounds 7a-1 and 7b-1 were the most efficacious, which resulted in a 96% growth inhibition in Pythium at 100 mg L−1. In conclusion, we reported the potent carbamate derivatives as soil-borne anti-fungals, and believe that the synthesis of more derivatives related to the current scaffold would be beneficial.
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Valladales-Restrepo, Luis Fernando, Juan Alberto Ospina-Cano, Brayan Stiven Aristizábal-Carmona, Diana Fiorella López-Caicedo, Melissa Toro-Londoño, Andrés Gaviria-Mendoza, Manuel Enrique Machado-Duque, and Jorge Enrique Machado-Alba. "Study of Prescription-Indication of Outpatient Systemic Anti-Fungals in a Colombian Population. A Cross-Sectional Study." Antibiotics 11, no. 12 (December 13, 2022): 1805. http://dx.doi.org/10.3390/antibiotics11121805.
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The inappropriate use of antifungals is associated with greater antimicrobial resistance, costs, adverse events, and worse clinical outcomes. The aim of this study was to determine prescription patterns and approved and unapproved indications for systemic antifungals in a group of patients in Colombia. This was a cross-sectional study on indications for the use of systemic antifungals in outpatients from a drug dispensing database of approximately 9.2 million people affiliated with the Colombian Health System. Sociodemographic, pharmacological, and clinical variables were considered. Descriptive, bivariate, and multivariate analyses were performed. A total of 74,603 patients with antifungal prescriptions were identified; they had a median age of 36.0 years (interquartile range: 22.0–53.0 years), and 67.3% of patients were women. Fluconazole (66.5%) was the most prescribed antifungal for indications such as vaginitis, vulvitis, and vulvovaginitis (35.0%). A total of 29.3% of the prescriptions were used in unapproved indications. A total of 96.3% of ketoconazole users used the medication in unapproved indications. Men (OR: 1.91; CI95%: 1.79–2.04), <18 years of age (OR: 1.20; CI95%: 1.11–1.31), from the Caribbean region (OR: 1.26; CI95%: 1.18–1.34), with chronic obstructive pulmonary disease (OR: 1.80; CI95%: 1.27–2.54), prescriptions made by a general practitioner (OR: 1.17; CI95%: 1.04–1.31), receiving comedications (OR: 1.58; CI95%: 1.48–1.69), and the concomitant use of other antimicrobials (OR: 1.77; CI95%: 1.66–1.88) were associated with a higher probability that the antifungal was used for unapproved indications; deep mycosis (OR: 0.49; CI95%: 0.41–0.58), prescribing fluconazole (OR: 0.06; CI95%: 0.06–0.06), and having diabetes mellitus (OR: 0.33; CI95%: 0.29–0.37), cancer (OR: 0.13; CI95%: 0.11–0.16), or HIV (OR: 0.07; CI95%: 0.04–0.09) reduced this risk. Systemic antifungals were mostly used for the management of superficial mycoses, especially at the gynecological level. In addition, more than a quarter of patients received these medications in unapproved indications, and there was broad inappropriate use of ketoconazole.
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Papachristou, Savvas, Elias Iosifidis, and Emmanuel Roilides. "Invasive Aspergillosis in Pediatric Leukemia Patients: Prevention and Treatment." Journal of Fungi 5, no. 1 (February 11, 2019): 14. http://dx.doi.org/10.3390/jof5010014.
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The purpose of this article is to review and update the strategies for prevention and treatment of invasive aspergillosis (IA) in pediatric patients with leukemia and in patients with hematopoietic stem cell transplantation. The major risk factors associated with IA will be described since their recognition constitutes the first step of prevention. The latter is further analyzed into chemoprophylaxis and non-pharmacologic approaches. Triazoles are the mainstay of anti-fungal prophylaxis while the other measures revolve around reducing exposure to mold spores. Three levels of treatment have been identified: (a) empiric, (b) pre-emptive, and (c) targeted treatment. Empiric is initiated in febrile neutropenic patients and uses mainly caspofungin and liposomal amphotericin B (LAMB). Pre-emptive is a diagnostic driven approach attempting to reduce unnecessary use of anti-fungals. Treatment targeted at proven or probable IA is age-dependent, with voriconazole and LAMB being the cornerstones in >2yrs and <2yrs age groups, respectively.
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Mandal, Narayan Chandra. "Antifungal Agents for Treatment of Mycoses." NBU Journal of Plant Sciences 9, no. 1 (2015): 14–17. http://dx.doi.org/10.55734/nbujps.2015.v09i01.002.
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Being eukaryotes the similarity of fungi with animals in great extent, it is very difficult to develop suitable antifungal compounds which target only to the fungi and spare the host compare to anti-bacterials. Concerted systematic programmes to discover and develop new antibiotics and anti-fungals have been driven to a considerable extent by the development of resistance by these organisms to the drugs commonly used against them as well as the side effects they exerted on host body. Fungal diseases are usually divided into five groups according to the level of infected tissue and mode of entry into the host which are: superficial, cutaneous, subcutaneous, systemic, and opportunistic infections. The most common types of mycoses which are responsible for humans fungal diseases are- Tinea capitis; disease of Scalp (Trichophyton spp. and Microsporum spp.), Tinea corporis: Due to social exchanges and contacts (Trichophyton spp.), Tinea cruris: Disease of itching (Epidermophyton sp.), Tinea pedis: Athletes foot, in bengali 'haza' (T. rubrum), Tinea manuum: similar disease on hands (T. rubrum), and Tinea unguium: Attacking nails (T. rubrum).
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Zafar, Humaira. "Multiplex PCR via Microarray a Surrogate for Rapid Molecular Detection of Mycobacterial and Fungal Species Along with Anti-Microbial Resistant Genes, Directly from Clinical Specimens’." Journal of Clinical Case Reports and Studies 3, no. 5 (June 18, 2022): 01–02. http://dx.doi.org/10.31579/2690-8808/115.
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Multi drug resistant Mycobacterial and invasive fungal infections imposes immense Global health burden resulting in high morbidity and mortality rates. The biggest delima is the time consuming culture and sensitivity diagnostics i.e 04 to 06 weeks for Mycobacterial and 02 to 04 weeks for fungal infections. The delay in result provision adds up to patient’s miseries especially for resistant cases. Therefore the aim of writing this short commentary was to introduce multiplex PCR via microarray bead hybridization assay. A thorough literature review was found extremely deficient. However, a limited published data concluded this technique as a surrogate for rapid molecular and resistant gene depiction for mycobacterial and fungal species directly from clinical specimens. Another biggest advantage was simultaneous genomics and resistant genes identification for Mycobacterial and Fungal isolates. The resistant genes for 1st line anti tuberculous therapy (ATT), 2nd line ATT and commonly used anti fungals can be detected easily. This cost effective test can be finalized in approximately less than 24 hours. Thus early and accurate management can be timely started for both said infections.
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Lapthorn, A. R., M. M. Ilg, J. Sullivan, P. Dziewulski, and S. Cellek. "616 Investigating if hydroxypyridone anti-fungals can target already established myofibroblasts in an in vitro model of hypertrophic scarring." Journal of Investigative Dermatology 142, no. 12 (December 2022): S287. http://dx.doi.org/10.1016/j.jid.2022.09.633.
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Palermo, Amelia, Beatrice Alessi, Francesco Botrè, Xavier de la Torre, Ilaria Fiacco, and Monica Mazzarino. "In vitroevaluation of the effects of anti-fungals, benzodiazepines and non-steroidal anti-inflammatory drugs on the glucuronidation of 19-norandrosterone: implications on doping control analysis." Drug Testing and Analysis 8, no. 9 (October 20, 2015): 930–39. http://dx.doi.org/10.1002/dta.1897.
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Tsai, H., and L. A. Bobek. "Human Salivary Histatins: Promising Anti-Fungal Therapeutic Agents." Critical Reviews in Oral Biology & Medicine 9, no. 4 (October 1998): 480–97. http://dx.doi.org/10.1177/10454411980090040601.
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Histatins constitute a group of small, cationic multifunctional proteins present in the saliva of human and some nonhuman primates. The most significant function of histatins may be their anti-fungal activity against Candida albicans and Cryptococcus neoformans. Histatins have been extensively studied at both the protein and gene levels. The structure-function relationship of histatins with respect to their candidacidal activity has also been studied by means of recombinant histatin variants, as well as by chemically synthesized histatin fragments. The mechanism of histatins' action on Candida albicans is not clear, but it appears to be different from that of azole-based anti-fungal drugs which interrupt ergosterol synthesis. During the past 20 years, fungal infections have become more prevalent as a result of the emergence of AIDS, as well as, paradoxically, modern medical advances. The toxicity of current anti-fungal medicine, the emergence of drug-resistant strains, and the availability of only a few types of anti-fungal agents are the major disadvantages of current anti-fungal therapy. Therefore, the importance of the search for new, broad-spectrum anti-fungals with little or no toxicity cannot be overemphasized. The following properties make histatins promising anti-fungal therapeutic agents: (1) They have little or no toxicity; (2) they possess high cidal activities against azole-resistant fungal species and most of the fungal species tested; and (3) their candidacidal activity is similar to that of azole-based antifungals. Current research efforts focus on the development of improved histatins with enhanced cidal activity and stability, and of suitable and effective histatin delivery systems. These and other approaches may help to outpace the growing list of drug-resistant and opportunistic fungi causing life-threatening, disseminating diseases. The histatins with improved protective properties may also be used as components of artificial saliva for patients with salivary dysfunction.
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Chu, Ha Thi, Doanh Huu Le, Thieu Van Le, Binh Bui Nguyen, Janice Schwartz, and Quang Van Vu. "Pachyonychia Congenita Type PC-K6a: The first report in the Vietnamese population." Biomedical Research and Therapy 8, no. 6 (June 30, 2021): 4434–38. http://dx.doi.org/10.15419/bmrat.v8i6.681.
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Background: Pachyonychia congenita (PC) comprises a group of rare autosomal dominant genetic disorders. It is characterized by hypertrophic nail dystrophy, focal palmoplantar keratoderma, follicular keratosis, and oral leukokeratosis. It is associated with mutations in five differentiationspecific keratin genes: KRT6A, KRT6B, KRT6C, KRT16, or KRT17. The case is being reported for its rarity. To the best of our knowledge, this is the first report of PC, from Vietnam, confirmed by genetic analysis.
Case presentation: A four-year-old Vietnamese girl presented with a thickened nail and oral leukokeratosis soon after birth. She was diagnosed with onychomycosis and chronic oral candidiasis and was treated with systemic anti-fungals in children's hospitals and dermatology departments multiple times; however, no treatments were effective. In collaboration with the International Pachyonychia Congenita Research Registry (IPCRR), the clinical features were consistent with a diagnosis of PC type PC-K6a. The genetic testing, performed through the IPCRR, shows a K6a N171K mutation.
Conclusions: The IPCRR helps screen PC's clinical features and confirm a diagnosis at the molecular level, which is beneficial and crucial for validating the condition's clinical impression.
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Zafar, Humaira, Irfan Ali Mirza, Wajid Hussain, and Muhammad Fayyaz. "Black Fungus an Escalating Threat for Covid-19 Patients Calling Out Captivation." Clinical Research and Clinical Trials 4, no. 2 (August 24, 2021): 01–05. http://dx.doi.org/10.31579/2693-4779/053.
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Background Current year 2021, brought a hope for the world due to availability of various vaccines to prevent COVID 19. Researchers around the Globe, kept working around the clock to dig up various correlations of this infection. So, that morbidity and mortality rates can be reduced. In all this sprint, cases of black fungus came into light in India. The Indian researchers identified strong association of black fungus co infection in COVID patients resulting in high mortality rates. Objectives Therefore, this current systematic review was planned to identify the predisposing factors, clinical presentations and management options for black fungus in COVID 19 patients. Methodology: This ‘systematic review’ was carried out following preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines & various search engines. Total 20(N) articles were selected and included for study. After following PRISMA guidelines and based upon inclusion and exclusion criteria of study, total 05 (N) manuscripts, were included. Results Out of 05(N) selected articles, 80 %( 04) strongly supported strong association of black fungus with COVID 19 patients. The highlighted predisposing factors includes, immunosuppression, anti virals, prolong hospital stay, use of tocilizumab and steroids as management of COVID patients. Timely diagnosis and provision of anti-fungal can be helpful to reduce mortality form this co infection. Conclusion It is concluded that immunosuppression, anti virals, prolong hospital stay, use of tocilizumab and steroids as management of COVID predisposes to black fungus. Timely diagnosis and use of systematic anti fungals can reduce mortality rate form this co infection.
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Voak, Andrew A., Andy Harris, Jose Miguel Coteron-Lopez, Iñigo Angulo-Barturen, Santiago Ferrer-Bazaga, Simon L. Croft, and Karin Seifert. "Pharmacokinetic / pharmacodynamic relationships of liposomal amphotericin B and miltefosine in experimental visceral leishmaniasis." PLOS Neglected Tropical Diseases 15, no. 3 (March 2, 2021): e0009013. http://dx.doi.org/10.1371/journal.pntd.0009013.
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Background There is a continued need to develop effective and safe treatments for visceral leishmaniasis (VL). Preclinical studies on pharmacokinetics and pharmacodynamics of anti-infective agents, such as anti-bacterials and anti-fungals, have provided valuable information in the development and dosing of these agents. The aim of this study was to characterise the pharmacokinetic and pharmacodynamic properties of the anti-leishmanial drugs AmBisome and miltefosine in a preclinical disease model of VL. Methodology / Principal findings BALB/c mice were infected with L. donovani (MHOM/ET/67/HU3) amastigotes. Groups of mice were treated with miltefosine (orally, multi-dose regimen) or AmBisome (intravenously, single dose regimen) or left untreated as control groups. At set time points groups of mice were killed and plasma, livers and spleens harvested. For pharmacodynamics the hepatic parasite burden was determined microscopically from tissue impression smears. For pharmacokinetics drug concentrations were measured in plasma and whole tissue homogenates by LC-MS. Unbound drug concentrations were determined by rapid equilibrium dialysis. Doses exerting maximum anti-leishmanial effects were 40 mg/kg for AmBisome and 150 mg/kg (cumulatively) for miltefosine. AmBisome displayed a wider therapeutic range than miltefosine. Dose fractionation at a total dose of 2.5 mg/kg pointed towards concentration-dependent anti-leishmanial activity of AmBisome, favouring the administration of large doses infrequently. Protein binding was >99% for miltefosine and amphotericin B in plasma and tissue homogenates. Conclusion / Significance Using a PK/PD approach we propose optimal dosing strategies for AmBisome. Additionally, we describe pharmacokinetic and pharmacodynamic properties of miltefosine and compare our findings in a preclinical disease model to available knowledge from studies in humans. This approach also presents a strategy for improved use of animal models in the drug development process for VL.
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Yuan, Yin, and Ashleigh P. Scott. "Real-World Efficacy of Anti-Fungal Prophylaxis in Patients Treated for Acute Gastrointestinal Graft-Versus-host Disease (GI-GVHD)." Blood 132, Supplement 1 (November 29, 2018): 5697. http://dx.doi.org/10.1182/blood-2018-99-112332.
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Abstract Aim Allogeneic progenitor cell transplant (HPCT) recipients who develop acute gastrointestinal graft-versus-host disease (GI-GVHD) are at increased risk of developing invasive fungal infections (IFI). Randomised control trial data supports the use of mould-active fungal prophylaxis in HPCT patients with grade II-IV GVHD (Ullman et al. 2007). We aimed to assess our unit's use of anti-fungal prophylaxis and describe the incidence and species of breakthrough IFI in patients with GI-GVHD. Method We conducted a retrospective audit of patients who underwent HPCT at our institution between 2011-2016 and identified those who were treated for acute GI-GVHD using a minimum of prednisone 1mg/kg or equivalent. For those patients the following details were collected: presence of any prior IFIs, anti-fungal prophylaxis before and after initiation of steroids, and the incidence of new IFIs within 6 months of commencing steroids. Result Of the 551 HPCT performed during this period, 74 evaluable patients were treated for GI-GVHD. All patients received anti-fungal prophylaxis prior to steroid commencement (66.2% received fluconazole, 10.8% posaconazole, 20.2% voriconazole and 2.7% other). Post steroids 35.1% remained on fluconazole, 21.6% received posaconazole, 35.1% received voriconazole, and 8.1% received other anti-fungals. Of the 26 patients remaining on fluconazole, 9 were transitioned to mould-active prophylaxis at a later time. Twelve patients (16.2%) experienced a breakthrough IFI (6 definite and 6 probable). In the 42 patients receiving posaconazole or voriconazole, 7 (16.7%) experienced breakthrough IFI, compared with 3 (11.5%) in the fluconazole cohort. Two other cases occurred in patients who received caspofungin. Notably, patients receiving mould-active fungal prophylaxis developed mucormycosis, Fusarium and Scedosporium infections whereas fluconazole lead to invasive aspergillosis. Conclusion Despite anti-fungal prophylaxis, real-world GI-GVHD patients remain at particularly increased risk of developing IFI. Anti-mould prophylaxis is associated with lower incidence of invasive aspergillosis but higher incidence of non-Aspergillus mould. Further studies investigating optimal anti-mould strategies are warranted. Disclosures No relevant conflicts of interest to declare.
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Vijendran, P., R. Verma, N. Hazra, B. Vasudevan, M. Debdeep, V. Ruby, and N. Shekar. "A comparative study of the various patterns of oro-cutaneous fungi and their sensitivity to anti fungals between HIV patients and normal healthy individuals." Medical Journal Armed Forces India 75, no. 1 (January 2019): 50–57. http://dx.doi.org/10.1016/j.mjafi.2018.01.004.
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Alqarni, Mohammed H., Ahmed I. Foudah, Aftab Alam, Mohammad A. Salkini, Magdy M. Muharram, Nikolaos E. Labrou, and Piyush Kumar. "Development of Gum-Acacia-Stabilized Silver Nanoparticles Gel of Rutin against Candida albicans." Gels 8, no. 8 (July 27, 2022): 472. http://dx.doi.org/10.3390/gels8080472.
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Candida spp. is one of the most causative pathogens responsible for fungal infections. It is often a hospital-acquired form of sepsis with a very high number of deaths. Currently, the most effective anti-fungal agents are based on polyenes or echinocandins. However, long-term treatments or repeated use of these anti-fungals lead to therapy limitations. Current research is urgently needed to overcome existing challenges for antimicrobials from natural sources. This study aims to determine the anti-fungal activity of rutin, which has the advantage of increasing the therapeutic value. Because of its low solubility in water and oils, rutin is limited in use. To address these constraints, we encapsulated rutin in a nanocarrier system. Silver nanoparticles (SNPs) and gum acacia (GAs) are emerging as attractive components and are widely studied as biologically safe nanomaterials/carrier systems for various drugs. Still, they are barely investigated as nano-sized vectors for the targeted delivery of rutin. In the present work, GA stabilised SNPs of rutin were successfully formulated and evaluated. It was later incorporated into carbapol 940 gels and formed SNP gels. Rutin-SNPs were developed with a consistent size in the nano range of 59.67 ± 44.24 nm in size, 0.295 ± 0.014 polydispersity index (PDI), and −11.2 ± 6.66 mV zeta potential. The drug released was found to be 81. 26 ± 4.06% in 600 min by following zero-order kinetics. The rutin-SNP gel showed considerable activity against C. albicans skin candidiasis at MIC 1.56 g/mL. The developed formulation was biocompatible. This first-ever interdisciplinary study suggests that the rutin-SNPs gel could play a vital role in drug resistance in this fungal pathogen.
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Shifaa T. J. AL-Assaf, Maha A. Al-Rejaboo, and Ayad-C.AL-.Daody. "Assessing the impact of quercetin isolated from Ammi majus seeds upon Candida spp. isolants isolated from different sources." International Journal of Research in Pharmaceutical Sciences 11, no. 4 (September 23, 2020): 5141–49. http://dx.doi.org/10.26452/ijrps.v11i4.3118.
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Quercetin has been extracted from Ammi majus plant using ethanol via soxhlet system. Further, the substance was diagnosed by three binary and mono-layered chromatographical devices beside chronographical quantitative separation. Total of 45 patients was inflicted with mouth infections and urinary tract in both genders. The momentary vaginal infections among different ages of people settled in different regions of Nineveh district / Iraq were considered for the study. The study patients were identified using microscopic testing, selective differential medium (CHROM candida agar) and Vitek system. The isolation results inferred that the mouth infection is caused by most yeasts such as Candida parapsilosis (the most frequent),. The urinary tract infection is concerned, and most of the infections were reportedly caused by C. parapsilosis, C. tropicalis and C. albicans. with regards to the vaginal infections cases, C. albicans fungus has been the most frequent. Bio chemical tests were conducted using Vitek for the isolants studied, in which there were differences in the study results. Quercetin was extracted from Candid spp. The increase in the inhibition of quercetin is noted, whenever its concentration is increased. With regards to the anti-fungals Nystantin, for the concentration of 100IU/ml.and Clotrimazole 30mg/ml had inhibited the yeast Candid spp.
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Schlachter, Caleb R., Vincent Klapper, Taylor Radford, and Maksymilian Chruszcz. "Comparative studies of Aspergillus fumigatus 2-methylcitrate synthase and human citrate synthase." Biological Chemistry 400, no. 12 (December 18, 2019): 1567–81. http://dx.doi.org/10.1515/hsz-2019-0106.
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Abstract Aspergillus fumigatus is a ubiquitous fungus that is not only a problem in agriculture, but also in healthcare. Aspergillus fumigatus drug resistance is becoming more prominent which is mainly attributed to the widespread use of fungicides in agriculture. The fungi-specific 2-methylcitrate cycle is responsible for detoxifying propionyl-CoA, a toxic metabolite produced as the fungus breaks down proteins and amino acids. The enzyme responsible for this detoxification is 2-methylcitrate synthase (mcsA) and is a potential candidate for the design of new anti-fungals. However, mcsA is very similar in structure to human citrate synthase (hCS) and catalyzes the same reaction. Therefore, both enzymes were studied in parallel to provide foundations for design of mcsA-specific inhibitors. The first crystal structures of citrate synthase from humans and 2-methylcitrate synthase from A. fumigatus are reported. The determined structures capture various conformational states of the enzymes and several inhibitors were identified and characterized. Despite a significant homology, mcsA and hCS display pronounced differences in substrate specificity and cooperativity. Considering that the active sites of the enzymes are almost identical, the differences in reactions catalyzed by enzymes are caused by residues that are in the vicinity of the active site and influence conformational changes of the enzymes.
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Boursi, Ben, Ronac Mamtani, Kevin Haynes, and Yu-Xiao Yang. "The effect of past antibiotic exposure on diabetes risk." European Journal of Endocrinology 172, no. 6 (June 2015): 639–48. http://dx.doi.org/10.1530/eje-14-1163.
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ObjectiveGut microbiota influence metabolic pathways related to the pathogenesis of obesity, insulin-resistance and diabetes. Antibiotic therapy can alter the microbiota, and is commonly used in western countries. We sought to evaluate whether past antibiotic exposure increases diabetes risk.Research design and methodsWe conducted a nested case–control study using a large population-based database from the UK. The cases were defined as those with incident diagnosis of diabetes. For every case, four eligible controls matched on age, sex, practice-site, and duration of follow-up before index-date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy >1 year before index-date. Odds ratios (ORs) and 95% CIs were estimated using conditional logistic regression. The risk was adjusted for BMI, smoking, last glucose level, and number of infections before index-date, as well as past medical history of coronary artery disease and hyperlipidaemia.ResultsThe study included 208 002 diabetic cases and 815 576 matched controls. Exposure to a single antibiotic prescription was not associated with higher adjusted diabetes risk. Treatment with two to five antibiotic courses was associated with increase in diabetic risk for penicillin, cephalosporins, macrolides and quinolones with adjusted OR ranging from 1.08 (95% CI 1.05–1.11) for penicillin to 1.15 (95% CI 1.08–1.23) for quinolones. The risk increased with the number of antibiotic courses and reached 1.37 (95% CI 1.19–1.58) for more than 5 courses of quinolones. There was no association between exposure to anti-virals and anti-fungals and diabetes risk.ConclusionsExposure to certain antibiotic groups increases diabetes risk.
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Jasuja, Sanjiv, Gaurav Sagar, Anupam Bahl, and Shalini Verma. "COVID-19 Infection Clinical Profile, Management, Outcome, and Antibody Response in Kidney Transplant Recipients: A Single Centre Experience." International Journal of Nephrology 2021 (October 3, 2021): 1–10. http://dx.doi.org/10.1155/2021/3129411.
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Introduction. Experience of COVID-19 in kidney transplant recipients (KTRs) with clinical presentation, management, factors influencing mortality, and antibody response is limited. Material and Methods. A retrospective data of COVID-19 in KTRs was collected and analyzed. The mortality rate, risk factors, and antibody response were primary objectives, while the clinical presentation, laboratory indicators, and pharmacological management were secondary objectives. Results. The 67 KTRs with polymerase chain reaction (PCR) confirmed COVID-19 infection reported between 1 May 2020 and 31 December 2020; 61.2% of patients were hospitalized; and 20.9% needed ventilation. The overall mortality was 26.9%, while blood group A had 50% mortality. The treatment options and used were steroids (100%), convalescent plasma (32.8%), ivermectin (58.2%), doxycycline (55.2%), remdesivir (34.3%), tocilizumab (10.4%), antibiotics (61.2%), anti-fungals (26.9%), low molecular weight heparin (45.3%), and oral anti-coagulants (26.9%). Anti-nucleosides (mycophenolate or azathioprine) were discontinued in 76.1% and calcineurin inhibitors (CNI) in 26.9%. Significant mortality ( p < 0.001 ) was observed in patients presenting with SpO2 <94 needing ICU care, ventilation, dialysis/acute kidney injury (AKI), and empirical therapies like convalescent plasma and remdesivir. The age of survivors versus nonsurvivors was not significantly different ( p = 0.02 ). The positive blood culture, low serum albumin, high TLC, high blood urea, interleukin-6, and CT severity score ≥15 were statistically significant in nonsurvivors. Overall mortality, mortality of hospitalized patients, and mortality of ventilated patients was 27%, 44%, and 100%, respectively. The median value of SARS-CoV-2 (COVID-19) IgG antibody was 68.60 (IQR, 28.5–94.25) AU/ml in more than 90% of survivors. Conclusion. KTRs with COVID-19, needing ICU care, dialysis and ventilation support had poor outcomes. Recovered patients mounted adequate antibody response.
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Jasuja, Sanjiv, Gaurav Sagar, Anupam Bahl, and Shalini Verma. "COVID-19 Infection Clinical Profile, Management, Outcome, and Antibody Response in Kidney Transplant Recipients: A Single Centre Experience." International Journal of Nephrology 2021 (October 3, 2021): 1–10. http://dx.doi.org/10.1155/2021/3129411.
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Introduction. Experience of COVID-19 in kidney transplant recipients (KTRs) with clinical presentation, management, factors influencing mortality, and antibody response is limited. Material and Methods. A retrospective data of COVID-19 in KTRs was collected and analyzed. The mortality rate, risk factors, and antibody response were primary objectives, while the clinical presentation, laboratory indicators, and pharmacological management were secondary objectives. Results. The 67 KTRs with polymerase chain reaction (PCR) confirmed COVID-19 infection reported between 1 May 2020 and 31 December 2020; 61.2% of patients were hospitalized; and 20.9% needed ventilation. The overall mortality was 26.9%, while blood group A had 50% mortality. The treatment options and used were steroids (100%), convalescent plasma (32.8%), ivermectin (58.2%), doxycycline (55.2%), remdesivir (34.3%), tocilizumab (10.4%), antibiotics (61.2%), anti-fungals (26.9%), low molecular weight heparin (45.3%), and oral anti-coagulants (26.9%). Anti-nucleosides (mycophenolate or azathioprine) were discontinued in 76.1% and calcineurin inhibitors (CNI) in 26.9%. Significant mortality ( p < 0.001 ) was observed in patients presenting with SpO2 <94 needing ICU care, ventilation, dialysis/acute kidney injury (AKI), and empirical therapies like convalescent plasma and remdesivir. The age of survivors versus nonsurvivors was not significantly different ( p = 0.02 ). The positive blood culture, low serum albumin, high TLC, high blood urea, interleukin-6, and CT severity score ≥15 were statistically significant in nonsurvivors. Overall mortality, mortality of hospitalized patients, and mortality of ventilated patients was 27%, 44%, and 100%, respectively. The median value of SARS-CoV-2 (COVID-19) IgG antibody was 68.60 (IQR, 28.5–94.25) AU/ml in more than 90% of survivors. Conclusion. KTRs with COVID-19, needing ICU care, dialysis and ventilation support had poor outcomes. Recovered patients mounted adequate antibody response.
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Donowitz, Gerald R., Dennis G. Maki, Christopher J. Crnich, Peter G. Pappas, and Kenneth V. I. Rolston. "Infections in the Neutropenic Patient— New Views of an Old Problem." Hematology 2001, no. 1 (January 1, 2001): 113–39. http://dx.doi.org/10.1182/asheducation-2001.1.113.
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Abstract Infection in the neutropenic patient has remained a major clinical challenge for over three decades. While diagnostic and therapeutic interventions have improved greatly during this period, increases in the number of patients with neutropenia, changes in the etiologic agents involved, and growing antibiotic resistance have continued to be problematic. The evolving etiology of infections in this patient population is reviewed by Dr. Donowitz. Presently accepted antibiotic regimens and practices are discussed, along with ongoing controversies. In Section II, Drs. Maki and Crnich discuss line-related infection, which is a major infectious source in the neutropenic. Defining true line-related bloodstream infection remains a challenge despite the fact that various methods to do so exist. Means of prevention of line related infection, diagnosis, and therapy are reviewed. Fungal infection continues to perplex the infectious disease clinician and hematologist/oncologist. Diagnosis is difficult, and many fungal infections will lead to increased mortality even with rapid diagnosis and therapy. In Section III, Dr. Pappas reviews the major fungal etiologies of infection in the neutropenic patient and the new anti-fungals that are available to treat them. Finally, Dr. Rolston reviews the possibility of outpatient management of neutropenic fever. Recognizing that neutropenics represent a heterogeneous group of patients, identification of who can be treated as an outpatient and with what antibiotics are discussed.
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Khilnani, Gurudas, Ajeet Kumar Khilnani, and Rekha Thaddanee. "Understanding and analysing competency based curriculum in pharmacology for developing syllabus and teaching schedules." International Journal of Basic & Clinical Pharmacology 9, no. 6 (May 21, 2020): 995. http://dx.doi.org/10.18203/2319-2003.ijbcp20202197.
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The competency based curriculum has already been implemented in phase-I (1st professional MBBS) and medical institutes, through curriculum committees, are gearing up for designing and developing curricular contents for phase-II training beginning from October, 2020. We have analysed curricular components as given in CBME documents with respect to distribution of contents and time allotted for cognitive and skill training and assessment. The objectives of this analysis are to understand distinctive features, identify elements required for organization of teaching sessions and facilitate preparation of teaching schedules. We segregated competencies according to corresponding system and domain of learning to distribute teaching hours. It was observed that 64 competencies in cognitive domain shall be covered in 80 hours assigned for lectures. The new curriculum has given importance to clinically relevant topics such as drug regulations, pharmaco-economics, pharmacology of eye and skin disorders, vaccines, national health programs (would require integration), environmental pollutants, food adulterants, stings and bites, and pharmacological considerations in geriatric and paediatric therapy. Ironically, antimicrobial agents and anti-fungals do not appear in the document as separate competencies. The 138 non-lecture hours can be divided into small group discussions (seminars) and tutorials for 19 hours each and remaining 100 hours can be reserved for practicals (skill training). About 27% of time assigned for practical training shall be required for developing proficiency for certification in 4 competencies and 25 competencies in cognitive domain shall require integration. Finally, steps are described to construct subject specific sessions giving one example each for a non-integrated and an integrated session.
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Tarasenko, V. A., T. V. Prykhodko, О. F. Кuchmistova, A. M. Solomenniy, O. V. Pleshkova, O. V. Belozerova, and D. V. Drozdov. "PHARMACEUTICALS MARKETING RESEARCHES FOR USE IN DERMATOLOGY AND ON THE PHARMACEUTICAL MARKET OF UKRAINE IN GENERAL (MESSAGE I)." Fitoterapia 3, no. 3 (2021): 67–74. http://dx.doi.org/10.33617/2522-9680-2021-3-67.
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Keywords: pharmaceutical, marketing research, medicinal product, marketing researches, active pharmaceutical ingredient, drug formulation, pharmaceutical market, wound process. The purpose of the study was to conduct complex marketing research of the current condition of the pharmaceutical market for use in dermatology to compose the well-balanced combination drugs (CD) for wound healing. Materials and methods: Conduct of complex marketing researches involved the use of general scientific, systematic, and survey research methods of informational search: bibliographical, document retrieval, content analysis, comparative approach, and system-oriented analysis. Results. The current condition of the domestic pharmaceuticals market was analysed and summed up for the availability of the Group D medicinal products according to Anatomical Therapeutic Chemical (АТС) classification system. Market dependency on import medicinal products was identified (import products share amounts to 57,8% of the market). The trends which reflect the innovation activity of the domestic pharmaceutical industry were presented in the findings. Prevailing (based on its specific density) medicinal products subgroups according to ATC classification «Corticosteroids for use in dermatology» (26,3%), «Anti-fungals for use in dermatology» (18,1%), «Antiseptics and Disinfectants» (14,1%), «Medicinal products for wound and ulcerous injuries healing» (12,7%), and «Antibiotics and chemotherapeutics» (11,5%). It was established that the main importers of the interested medicinal products groupare Germany (20,4%), India (16,2%), Poland (12,3%), Croatia (7,1%), Switzerland (6,3%), Belgium (5,2%), Austria (4,8%), and Hungary (4,2%). We found out that in the dermatology medicinal products segment, active pharmaceutical ingredients by their nature are mostly synthetic (88%), and by their composition, such medicinal products are mixed formulations with the subgroups market share between 58,5% – 76,3%. It was also shown that the optimal assortment range of modern combination drugs of dermatology medicinal products for 38 domestic producers is not yet reached. We paid attention to the perspective regarding the pharmaceutical development of new combination drugs for application therapy. Conclusions. The research of the effectiveness of different groups of medicinal products to wound healing on different stages, allowed us to conclude that the usage of imported combination effect medicinal products for wound healing is more cost-ineffective while the Ukrainian pharmaceutical market requires product differentiation and introduction of the new combined antimicrobial and anti- inflammatory effect medicinal products into production for wound healing and wound infection.
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Yvonne Zhou, Peijun, Tze Peng Lim, Si Lin Sarah Tang, Yixin Liew, Nathalie Grace Sy. Chua, Cheryl Lim, Winnie Lee, et al. "2107. Azole Therapeutic Drug Monitoring (TDM) in a Multiracial Cohort with Varied Pharmacogenetics." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S713. http://dx.doi.org/10.1093/ofid/ofz360.1787.
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Abstract Background Voriconazole (VOR) and posaconazole (POS) exhibit wide pharmacokinetic variability. Various factors including race and genetic polymorphisms are at play and this may affect treatment response. We aim to evaluate the utility of VOR/POS TDM among Southeast Asians that are predominantly intermediate/poor VOR metabolizers. Methods All adults with VOR/POS TDM performed at our institution from 2015 to 2018 were included. We determined proportion of patients and doses required to achieve TDM targets [(2 – 5.5 mg/L (VOR) or ≥ 0.7 and ≥ 1.0 mg/L (POS prophylaxis and treatment respectively)], and correlate levels with treatment efficacy and safety. Results VOR/POS TDM was performed mostly among patients with hematological malignancy or solid-organ transplant (146/174, 83.9%). Less than half (32/70, 45.7%) of patients on VOR achieved target—18 (25.7%) were < 2 mg/L while 20 (28.5%) had levels > 5.5 mg/L. Doses required to achieve TDM target ranged from 1.9–11.4 mg/kg/day. Drug interactions, critically ill state and change in drug formulation were major causes of intra-patient variability. One-fifth (n = 14) experienced transaminitis; corresponding VOR trough levels were 0.5–> 7.5 mg/L. Neurotoxicity was also seen in 3 (4.3%) patients—all 3 had VOR trough ≥ 6.7 mg/L and saw symptom resolution upon dose reduction. There appears to be no association between the achievement of TDM targets and response rates. Majority (81/104, 77.9%) of patients on POS achieved TDM targets. Patients prescribed POS tablet were significantly more likely to attain targets compared with suspension 600 mg/day [19/26 (73.0%) vs. 27/62 (43.5%), P < 0.05] and 800 mg/day [17/26 (65.3%) vs. 4/16 (25.0%), P < 0.05)]. Of 23 with sub-therapeutic levels, 19 (82.6%) responded to dose increase and/or change in acid-reducing agents. Breakthrough infection occurred despite troughs ≥ 0.7 mg/L [5/42 (11.9%) vs. 2/40 (5.0%) when < 0.7 mg/L (P = 0.3)]. Treatment failure was observed in 2 patients (troughs > 1.0 mg/L). Conclusion VOR/POS TDM should be implemented in Southeast Asians due to significant unpredictability in dose exposure and potential to avoid need for switch to alternative anti-fungals due to intolerability. Higher POS trough cutoff may be required for effective anti-fungal prophylaxis. Disclosures All authors: No reported disclosures.
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Tai, Ming-Hui, Eric M. Ammann, Shuchita Kaila, Christopher Pericone, Ajaybir Singh, Thomas S. Lin, and Faith E. Davies. "Use of Anti-Infective Prophylaxis in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma Patients Initiating Treatment with Daratumumab." Blood 136, Supplement 1 (November 5, 2020): 23–24. http://dx.doi.org/10.1182/blood-2020-134086.
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Introduction: Infections continue to be one of the main causes of morbidity and mortality in multiple myeloma (MM) patients. Compared to the general population, MM patients have a 7-fold increased risk of bacterial infections and 10-fold risk of viral infections. The recent National Comprehensive Cancer Network (NCCN) guideline has provided guidance for prevention of cancer-related infections; however, utilization of anti-infective prophylaxis among MM patients in real-world practice has not been fully established. Daratumumab, a human IgGκ monoclonal antibody targeting CD38, is approved as monotherapy and in combination with standard-of-care regimens for newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM). The primary objective of the study was to describe the proportion of MM patients who received anti-infective prophylaxis when initiating a daratumumab-based treatment regimen. Methods: Medical and pharmacy claims from the Optum's de-identified Clinformatics® Data Mart Database were obtained for a cohort of US patients with NDMM or RRMM who initiated treatment with daratumumab (in combination with other antimyeloma agents or monotherapy) between 1/1/2017 and 12/24/2019. The index date was defined as the first daratumumab treatment date in the study period. Two steps were applied to identify anti-infective prophylaxis. First, use of anti-infective prophylaxis was assessed during the period between the week prior to and the week after the date of daratumumab initiation, including anti-virals for preventing herpesviruses (i.e., herpes zoster, herpes simplex, and cytomegalovirus), systemic anti-bacterials, systemic anti-fungals, Pneumocystis jiroveci pneumonia (PJP) prophylaxis, and intravenous/subcutaneous immune globulin (IVIG/SCIG). Second, use of an anti-infective drug was defined as prophylactic if there was no diagnosis for an infection treated by the anti-infective drug (i.e., patients with infection events one week prior to and one day after the start of drug prescription were excluded). Receipt of vaccines for seasonal influenza (in the year prior to daratumumab initiation) and herpes zoster and pneumococcal infections (at any time prior in the patient's claims history) were also assessed. Results: 929 newly daratumumab-treated patients were eligible for study inclusion; 92 had NDMM (median age 74 years; 48.9% female) and 837 had RRMM (median age 72 years; 46.0% female). At the time of daratumumab initiation, antibacterial prophylaxis was administered to 12.0% of NDMM and 17.0% of RRMM patients; antifungal prophylaxis to 1.1% of NDMM and 1.3% of RRMM patients; and PJP prophylaxis to 4.4% of NDMM and 10.5% of RRMM patients (Table 1). IVIG/SCIG prophylaxis was given to 1.1% of NDMM patients and 2.5% of RRMM patients. Herpesvirus prophylaxis was administered to 57.6% of NDMM and 69.4% of RRMM patients, and 17.4% of NDMM and 11.5% of RRMM patients received vaccination for herpes zoster. Seasonal influenza and pneumococcal vaccinations were given to 56.5% and 47.8% of NDMM patients and 62.5% and 51.3% of RRMM patients, respectively. Conclusion: Use of herpesvirus prophylaxis was approximately 70% in RRMM and 60% in NDMM patients at time of daratumumab initiation, with limited use of herpes zoster vaccination, suggesting that a meaningful minority of patients may not be protected against herpesvirus as recommended by NCCN guidelines for patients treated for MM. While rates of influenza and pneumococcal vaccination were higher than for herpes zoster, nearly half of patients did not have evidence of vaccination for these two pathogens in their claims data. These results indicate that a significant percentage of MM patients are not receiving care to optimally prevent potential viral infections. Further studies are needed to understand the potential benefit of infectious prophylaxis in the clinical management of MM patients. Disclosures Tai: Janssen Scientific Affairs: Current Employment. Ammann:Janssen Scientific Affairs: Current Employment, Current equity holder in publicly-traded company. Kaila:Janssen Scientific Affairs: Current Employment. Pericone:Janssen Scientific Affairs: Current Employment, Current equity holder in publicly-traded company. Singh:Mu Sigma: Current Employment, Other: Mu Sigma was contracted by Janssen Scientific Affairs to conduct the analyses for the present study. Lin:Janssen Scientific Affairs: Current Employment, Current equity holder in publicly-traded company. Davies:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotech: Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene/BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Radha, Sistla, Tameem Afroz, Sudhir Prasad, Sandeep Reddy, Kalyan Bommakanti, and Vaishnavi Bommakanti. "Covid-19 associated mucormycosis." Indian Journal of Pathology and Oncology 9, no. 1 (February 15, 2022): 25–30. http://dx.doi.org/10.18231/j.ijpo.2022.006.
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: Corona virus disease-2019 (COVID-19) is associated with various opportunistic, bacterial, and fungal infections. High risk groups include people with diabetes especially diabetic ketoacidosis, solid organ transplantation, long-term systemic corticosteroid use, and iron overload. Many cases of mucormycosis were reported worldwide. Mucormycosis is an invasive fungal infection with high morbidity and mortality. Early diagnosis and treatment with appropriate anti-fungals lead to improved outcomes. The aim of this study is to establish the factors associated with mucormycosis in a COVID-19 setting, like comorbidities and treatment protocols for treatment of COVID-19. The histological patterns and tissue reactions to mucormycosis also were studied. In patients with ongoing COVID-19 infection and in a post COVID-19 scenario, we studied the biopsy findings of mucormycosis in various sites like rhino-orbital, lung, gastric and trachea. Material for this study is from a tertiary care hospital in South India. Patient age ranged from 30 years to 74 years. Mean age of the patients was 51 years. Male to female ratio was 1:1.1. Tissue from sino- nasal mucosa, peri orbital tissue, exenterated eyeball, lung tissue and tissue from rare sites like gastric and tracheal mucosal lesions were also included in this study. Tissue was fixed in 10% buffered formalin. Routine Haematoxylin and Eosin(H&E) stains were done. Gomori’s Methenamine silver (GMS) stains were done on all cases. Tissue was submitted for fungal cultures in all the cases.Total of twenty-three cases were diagnosed as mucormycosis based on the morphology and special stains in this analysis. Histology revealed areas of infarction in all cases with neutrophilic infiltration. Granulomatous reaction was seen in seven cases and melanin pigment was seen in two cases. 100% of patients were diabetics. There was neutrophilia in 100% of cases. Lymphopenia was seen in 85.7%, C-Reactive Protein (CRP) was elevated in 100% of cases.Ferritin was done in 14 patients and D-dimer was done in 17 patients and in all patients, these were elevated. All patients were treated with steroids according to the treatment protocol for COVID-19, Remdesivir was given in 72.7% of cases and second immunomodulator drugs like Tocilizumab in four cases and Baricitinib in one case.Mucormycosis is an emerging problem with COVID-19. It is important to carefully monitor blood glucose levels and take into account underlying medical conditions of patients before initiation of steroid therapy. Early recognition of symptoms and early diagnosis has a better outcome in patients with mucormycosis associated with COVID-19 infection.
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Kapoor, Ashutosh, Sheeba Shaikh, and Alexander Lewis. "LBODP072 Squamous Cell Carcinoma Or Fungal Infection? An Unusual Presentation Of Anterior Hypopituitarism." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A476. http://dx.doi.org/10.1210/jendso/bvac150.988.
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Abstract Introduction Intracranial squamous cell carcinomas are rare tumours with a poor prognosis. Lack of specific imaging characteristics mandates a high index of clinical suspicion and ultimately histopathological confirmation. Chronic invasive fungal rhinosinusitis (CIFRS) is often difficult to distinguish from Sino nasal squamous cell carcinomas (SNSCC) in clinical practice. Our case draws attention to the fact that biopsy results are necessary in discriminating between the two entities, due to the diagnostic conundrum in context of Anterior Hypopituitarism. Case detailsWe report a case of 78-year-old lady who presented with a 3-month history of increasing headache, lethargy and confusion. There was no change in urinary habit. On examination she had right sided ptosis and restricted eye movements with a reported 4-week duration. Primary care physicians referred her for ophthalmic assessment. Past medical history was significant for absent vision in the affected eye due to Ischaemic optic neuropathy since 2018. A CT Angiogram was organised which revealed a large soft tissue mass that could not be differentiated from the optic chiasma. Differentials included chondrosarcoma, chordoma, invasive pituitary macroadenoma and skull base Plasmacytoma. Subsequent MRI imaging suggested appearances could be consistent with aggressive fungal sinusitis. Endocrine investigations showed partial anterior hypopituitarism. ManagementEmpiric treatment was started with Intravenous anti-fungals and steroids, alongside appropriate pituitary hormone replacement. Her case was discussed in the Skull Base Multi-disciplinary Team (MDT) meeting. She was then transferred to the regional tertiary centre for surgical intervention, where she underwent debridement of the Ethmoid sinus, Sphenoid Sinus and Anterior base of skull for presumed chronic invasive fungal sinusitis. Post-operative imaging displayed satisfactory debulking of the central skull base tumour. Histopathology from sphenoid sinus reported invasive squamous cell carcinoma. The post-operative imaging and histopathology results were discussed in the regional MDT and considering the advanced stage a decision was made for best supportive care. Within 2 months neurological symptoms progressed and further imaging demonstrated radiological tumour progression. Discussion Sinonasal Squamous cell carcinoma (SNSCC) is a rare tumour and thus pose difficulty in detection. Presentation usually occurs at an advanced stage since initial symptoms are nonspecific and the tumour remains indolent for many months to years. There is limited evidence in relation to detection and follow up of these cases. Clinical presentation and radiological appearance can be varied. This case highlights the need for histological confirmation of the diagnosis to guide appropriate treatment pathways and ensure compassionate, appropriate care. Presentation: No date and time listed
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Bagirova, N. S., I. N. Petukhova, Z. V. Grigorievskaya, A. V. Sytov, P. V. Slukin, E. A. Goremykina, O. E. Khokhlova, N. K. Fursova, and A. E. Kazimov. "Oral microbiota in patients with oropharyngeal cancer with an emphasis on <i>Candida</i> spp." Head and Neck Tumors (HNT) 12, no. 3 (December 13, 2022): 71–85. http://dx.doi.org/10.17650/2222-1468-2022-12-3-71-85.
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Introduction. Interactions between the 2 microbiota components – bacteria and fungi – are of interest as diagnostic and prognostic markers in selection of treatment tactics for oncological patients.Aim. To study microbiota of the oral cavity in patients with primary squamous cell carcinoma of the oropharyngeal area before and after surgical intervention to find biomarkers for rational selection of antifungal drugs.Materials and methods. At the Surgical Department of Head and Neck Tumors of the N. N. Blokhin National Research Center of Oncology, three-component study was performed: investigations of spectrum of Candida spp. isolates, Candida spp. strains’ resistance to antifungals, and oral washes in primary patients before and after surgery. mALDI-Tof microflex LT (Biotyper, Bruker Daltonics, germany) was used for strain identification; Sensititre Yeast ONE, YO10 (Trek Diagnostic System, united kingdom) plates were used for determination of minimal inhibiting concentrations of anti fungals. values of minimal inhibiting concentrations were evaluated based on the European Committee on Antimicrobial Susceptibility Testing (EuCAST) criteria (version 10.0).Results. four-year observation of patients at the surgical department of head and neck tumors of the N. N. Blokhin National Research Center of Oncology showed that the most common species of Candida is C. albicans (73.5 % of cases). Candida spp. resistance to antifungals was detected only for fluconazole (9.3 % of cases) and micafungin (8.0 % of cases), mostly among C. albicans strains. In 31.8 % of primary patients, oral washes prior to surgery showed growth of Candida spp. (probably, tissue colonization). After surgical intervention, Candida spp. growth was detected in 36.4 % of cases, only 1 of which was diagnosed as invasive mycosis. In 54.5 % of cases before and in 72.7 % of cases after surgery, gram-negative rods were detected. After surgical intervention, percentage of enterobacteria and non-fermenters significantly increased: 59.1 % versus 27.3 % (p <0.05) and 63.6 % versus 27.3 % (p <0.02), respectively. prior to surgery, non-fermenting gram-negative bacteria were represented only by P. aeruginosa; after surgery, the spectrum of non-fermenting gram-negative bacteria became wider but percentage of P. aeruginosa remained high: 71.4 %. ERG11 gene was identified only in 1 strain: C. albicans. FKS1 gene also was identified only in 1 strain: C. inconspicua. virulence factor genes were detected in 57.1 % of strains.Conclusion. Surgical intervention is associated with changes in bacterial microbiota but not fugal microbiota. presence of virulence factor genes and resistance genes in Candida spp. strains should be considered a biomarker allowing to differentiate between colonization and candida infection and can be used for rational selection of antifungal drugs in prevention and treatment of invasive candidiasis, especially in the absence of criteria for interpretation of measured minimal inhibiting concentrations of antifungals.
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Madarang, Ellen, Jillian Lykon, Wenhui Li, Sunil Iyer, Michele Stanchina, Nina Nguyen, Terrence Bradley, et al. "Octogenarians with AML Can Have Durable Remissions with Venetoclax and Hypomethylating Agent Therapy Despite Significant Dose Reductions." Blood 138, Supplement 1 (November 5, 2021): 1259. http://dx.doi.org/10.1182/blood-2021-151738.
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Abstract Introduction Venetoclax in combination with a hypomethylating agent (VEN-HMA) has become a standard of care for older or unfit patients with newly diagnosed AML. Although primarily administered in the outpatient setting, VEN-HMA is associated with significant cytopenias and infectious complications, requiring careful monitoring and dose adjustments. Patients treated with VEN-HMA on clinical trials had a median age of ~75 years. The optimal dose and schedule, safety, and efficacy of VEN-HMA in octo- and nonagenarians is not clearly defined. Methods We performed a retrospective analysis of AML patients ≥80-years-old who received at least 1 day of VEN-HMA at our institution from 11/2018 to 7/2021. Patients with de novo or secondary AML with or without prior HMA or chemotherapy were included. Venetoclax starting dose was 200-400 mg for 14-28 days. Dose adjustments for drug interactions with azole anti-fungals were implemented. HMA was started at 50-75 mg/m2 for 5-7 days of azacitidine or 20mg/m2 for 5 days of decitabine. Dose reduction was defined as any decrease from the starting dose and schedule. Patients who did not complete cycle 1 were included in the overall survival and safety analysis but excluded from response assessment. Results Among 21 patients ≥80-years-old treated with VEN-HMA (20 newly diagnosed, 1 relapsed/refractory), median age was 82 years (range: 80-89) (Table 1), 57% had antecedent MDS, and 38% received HMAs previously. Most patients (81%) were ELN adverse risk, 38% had a complex karyotype, 24% had a TP53 mutation, and 43% had ECOG PS of 2-3. Median overall survival for all patients was 8.0 months (0.5-31.4 months). At time of analysis, 12 patients (57%) were still alive and in remission on VEN-HMA with a median follow-up of 11.5 months (range 2.3-31.4 months). Five patients (24%) died during cycle 1 from sepsis. Of these 5 patients, 4 had a TP53 mutation, 3 had prior MDS, and 3 had received prior therapy for lymphoma. In the remaining 16 patients, median overall survival was 9.9 months (2.3-31.4 months) and the CR/CRh rate was 81% (13/16 patients). Median duration of response was 8.9 months (range 1.0-30.0). Consistent with previous reports, all patients who achieved CR/CRh did so by the end of cycle 2 (median 2 cycles). Most patients also received the standard dose and schedule of VEN (75%) and HMA (57%) during the first cycle. All patients (100%) required venetoclax dose and schedule reduction, with a median final venetoclax dose of 200 mg and duration of 14 days. Average final cycle length was 35 days. Most patients (69%) also required dose reduction of HMA. Median duration of treatment was 7.5 months (range 0.5-31.4). Treatment emergent grade 3-4 anemia occurred in 67% of patients, thrombocytopenia in 81%, and neutropenia in 86%; 17 patients (81%) had treatment emergent febrile neutropenia. There were no infectious deaths in patients who survived cycle 1. The median number of neutropenic fever episodes per patient was 1 (0 to 2). The 4 deaths after cycle 1 were due to progressive disease (n=3) or relapse (n=1). Conclusion VEN-HMA can be safely and effectively given to octogenarians with careful monitoring and dose adjustments. All patients required dose reduction of venetoclax after CR/CRh was achieved, and most also required adjustment of HMA. Despite this, over half of patients achieved durable remissions. The greatest risk of infectious death was in the first cycle, in patients who were heavily pre-treated and enriched for TP53 mutations. When compared to historical controls, outcomes in octogenarians who survive the first cycle appear similar to younger age groups. This work highlights the need for a prospective multi-center effort to optimize the dose and schedule of VEN-HMA in older patient populations. Figure 1 Figure 1. Disclosures Bradley: AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sekeres: Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Watts: Rafael Pharmaceuticals: Consultancy; Genentech: Consultancy; Bristol Myers Squibb: Consultancy; Takeda: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Aptevo Therapeutices: Research Funding.
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A. M. Zaed, , M. Khlifa. "Synthesis of Anti-Fungals, from Chiral imidazolyl-imino and amino Compounds." Journal of natural sciences, life and applied sciences 1, no. 1 (March 30, 2017). http://dx.doi.org/10.26389/ajsrp.m15716.
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This work describes the synthesis of novel nonracemic derivatives of imidazole. Some oxidation reactions using Mn(II), Se(II) and nitric acid were employed for the synthesis of the starting materials, imidazolyl carboxaldehydes in straightforward steps. These key step compounds were then subjected to schiff bases and reductive amination processes for the synthesis imidazolylimio and imidazolylamino compounds using standard conditions. Attempts to purify some imidazolylamino compounds using kugelrohr distillation technique have been unsuccessful. However, recrystallization from acetonitrile allowed isolation some compounds in good yields. The new compounds that were synthesised were potential ligands for complexation of metals. Ag(I) was used to synthesis of several metal complexes. These compounds were characterised by nuclear magnetic resonance (NMR) and fourier transform infrared spectroscopy (FTIR) as well as elemental analysis method. These imidazole derivatives have been screened for activity against Candida albicans. Although the S-enantiomer of N-[(1E)-1-benzyl imidazol-2-ylmethylene]-N′-(1-phenylethyl)amine was found inactive against C. albicans, the R-enantiomer showed moderate activity. However, in two instances the activity was greater than that for ketoconazole which is a common agent to cure candida infestation.
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Lapthorn, Alice Ruth, Marcus Maximillian Ilg, Justine Victoria Sullivan, Peter Dziewulski, and Selim Cellek. "Phenotypic screening identifies hydroxypyridone anti-fungals as novel medicines for the prevention of hypertrophic scars." European Journal of Pharmacology, November 2022, 175374. http://dx.doi.org/10.1016/j.ejphar.2022.175374.
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Hamilton, David O., Tosin Lambe, Alexander Howard, Patricia Crossey, Jennifer Hughes, Rui Duarte, and Ingeborg D. Welters. "Can Beta-D-Glucan testing as part of the diagnostic pathway for Invasive Fungal Infection reduce anti-fungal treatment costs?" Medical Mycology, May 18, 2022. http://dx.doi.org/10.1093/mmy/myac034.
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Abstract We performed a cost comparison of the current diagnostic and treatment pathway for invasive fungal infection (IFI) versus a proposed pathway that incorporates Beta-D-Glucan (BDG) testing from the NHS perspective. A fungal pathogen was identified in 58/107 (54.2%) patients treated with systemic anti-fungals in the Critical Care Department. Mean therapy duration was 23 days (standard deviation [SD] = 22 days), and cost was £5590 (SD = £7410) per patient. Implementation of BDG tests in the diagnostic and treatment pathway of patients with suspected IFI could result in a mean saving of £1643 per patient should a result be returned within two days.
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Dadachova, Ekaterina, and Drauzio E. N. Rangel. "Highlights of the Latest Developments in Radiopharmaceuticals for Infection Imaging and Future Perspectives." Frontiers in Medicine 9 (February 11, 2022). http://dx.doi.org/10.3389/fmed.2022.819702.
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COVID-19 pandemic has heightened the interest toward diagnosis and treatment of infectious diseases. Nuclear medicine with its powerful scintigraphic, single photon emission computer tomography (SPECT) and positron emission tomography (PET) imaging modalities has always played an important role in diagnosis of infections and distinguishing them from the sterile inflammation. In addition to the clinically available radiopharmaceuticals there has been a decades-long effort to develop more specific imaging agents with some examples being radiolabeled antibiotics and antimicrobial peptides for bacterial imaging, radiolabeled anti-fungals for fungal infections imaging, radiolabeled pathogen-specific antibodies and molecular engineered constructs. In this opinion piece, we would like to discuss some examples of the work published in the last decade on developing nuclear imaging agents for bacterial, fungal, and viral infections in order to generate more interest among nuclear medicine community toward conducting clinical trials of these novel probes, as well as toward developing novel radiotracers for imaging infections.
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Baraka, Mohamed A., Lina Hussain AlLehaibi, Hind Nasser AlSuwaidan, Duaa Alsulaiman, Md Ashraful Islam, Badriyah Shadid Alotaibi, Amany Alboghdadly, et al. "Patterns of infections and antimicrobial drugs’ prescribing among pregnant women in Saudi Arabia: a cross sectional study." Journal of Pharmaceutical Policy and Practice 14, no. 1 (January 14, 2021). http://dx.doi.org/10.1186/s40545-020-00292-6.
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Abstract Background Antimicrobial agents are among the most commonly prescribed drugs in pregnancy due to the increased susceptibility to infections during pregnancy. Antimicrobials can contribute to different maternal complications. Therefore, it is important to study their patterns in prescription and utilization. The data regarding this issue is scarce in Saudi Arabia. Therefore, the aim of this study is to generate data on the antimicrobial agents that are most commonly prescribed during pregnancy as well as their indications and safety. Methods This is a retrospective study focusing on pregnant women with a known antimicrobial use at Johns Hopkins Aramco Healthcare (JHAH). The sample included 344 pregnant women with a total of 688 antimicrobial agents prescribed. Data was collected on the proportion of pregnant women who received antimicrobial agents and on the drug safety during pregnancy using the risk categorization system of the U.S. Food and Drug Administration (FDA). Results The results showed that urinary tract infections (UTIs) were the most reported (59%) infectious diseases. Around 48% of pregnant women received antimicrobial medications at some point during pregnancy. The top two antimicrobial agents based on prescription frequency were B-lactams (44.6%) and azole anti-fungals (30%). The prescribed drugs in the study were found to be from classes B, C and D under the FDA risk classification system. Conclusion The study revealed a high proportion of antimicrobials prescribed during pregnancy that might pose risks to mothers and their fetuses. Future multicenter studies are warranted to evaluate the rational prescription of antimicrobial medications during pregnancy.
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Rupali, Priscilla, Jisha Sara John, Amita Jacob, Rajiv Karthik, Hanna Alexander, Sushil Selvarajan, and Biju George. "1763. A study on the effectiveness of a pharmacist led Antifungal stewardship program, in immunocompromised patients of a tertiary care teaching hospital in South-India." Open Forum Infectious Diseases 9, Supplement_2 (December 1, 2022). http://dx.doi.org/10.1093/ofid/ofac492.1393.
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Abstract Background Anti-fungal stewardship (AFS) is a less explored area of an anti-microbial stewardship (AMS) program as the patients prone to fungal infections are mostly immunocompromised, post-chemotherapy or post-transplant. In a Low-and- Middle income country (LMIC) like India, there is a dearth of Infectious Disease (ID) trained physicians and pharmacists. We aimed to study the effectiveness of a pharmacist led AFS program to ensure rational prescribing of antifungals via a post-prescription review and feedback method. Methods In this prospective interrupted time series analysis from June 2021 to November 2021, AFS was done on adult in-patients in the department of Hematology in a tertiary care teaching hospital in South India. The study had a pre-intervention phase and intervention phase of 3 months each. In the pre-intervention phase, patients on anti-fungal therapy > 48 hours were identified and base line data were collected and no recommendations were given. In the intervention phase, in those on antifungals >48 hours, appropriate recommendations were made with regard to modification and discontinuation of the anti-fungals based on patients’ clinical condition under the supervision of an ID physician. Acceptance and impact of the intervention were monitored and recorded. METHOD OF THE STUDY The study was a prospective study with 2 phases : pre-intervention and intervention. In the intervention phase, the appropriateness of the Anti-fungal therapy was analyzed and recommendations were given. Results A total of 193 patients were analyzed over 6 months, of which 107 patients with a mean age of 42.1 ± 14.2 belonged to the pre-intervention phase and 86 patients aged 40.2 ±12.6 years were in the intervention phase. There was no statistically significant difference in the in-hospital mortality [26.16% vs 23. 25% (p = 0.64)] between the two groups. In the intervention phase, 15 (17.44%) prescriptions were found to be inappropriate. Among these 66% of the recommendations were accepted by the treating physician. The days of therapy per 100 patient days were calculated for each individual anti-fungal drug and there was a significant reduction in consumption of Anidulafungin [29.648 Vs 14.28 (p < 0.0007)], Amphotericin B [42.05 Vs 22.18 (p< 0.0001)] and Voriconazole [56.41 Vs 35.77 (p< 0.00001)] in the intervention phase. Outcome measurements Conclusion A pharmacist led AFS program resulted in statistically significant reduction in the consumption of antifungals, without a significant difference in the in-hospital mortality. Disclosures Priscilla Rupali, MD, DTM&H, PFIZER: Grant/Research Support|PFIZER: Grant/Research Support.
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Nmom, F. W., R. R. Nrior, and F. S. Jumbo. "In vitro and In vivo Control of Fungal Cobweb Disease of Pleurotus ostreatus (Jacq), Using Organic Materials." Journal of Advances in Biology & Biotechnology, September 23, 2022, 1–10. http://dx.doi.org/10.9734/jabb/2022/v25i730290.
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Aim: Assessment of In vitro and In vivo Control of Fungal Cobweb Disease of Pleurotus ostreatus (Jacq), using organic materials.
Study Design: This study was designed to control the disease by using plant materials as organic control agent; both In vitro and in vivo.
Methodology: In Pleurotus ostreatus. In the In vitro test; food poison method was used while the in vivo test was undertaken by inoculation of fully colonized substrate bags of Pleurotus ostreatus infected with cobweb disease with crude extracts of Piper guineense and lime juice as treatment stock.
Results: The results indicated P. guineense inhibition of the growth of the pathogen at 22mm while lime juice did not show any impact on the growth of the pathogen. Additionally, P. guineense inhibited the growth of the pathogen in fully colonized but infected substrates bags of P. ostreatus invivo; such that the treated samples grew and developed the fruiting bodies of the mushroom, 3 days after treatment; whereas the one treated with lime juice developed the cobweb disease.
Conclusion: The study showed that effectiveness of P. guineense extract on the pathogen was possibly due to the bioactive chemicals such as phenols, tannins, flavonoid etc which concentration in the plant material occurred in surplus. These may have interfered with the molecular targets of the pathogen and caused it to loose cellular integrity and leakage of cell content. Alternatively, the study revealed that lime juice was ineffective; possibly because of the solvent used for it's preparation which could not enhance the release of the essential bioactive chemicals in lime juice for anti fungals. Consequently, this study recommends the use of P. guineense to mushroom farmers against fungal cobweb disease of oyster mushrooms.
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Kartika, Riskah. "UJI DAYA HAMBAT JAMUR ENDOFIT AKAR BAKAU Rhizophora apiculata TERHADAP BAKTERI Staphylococcus aureus dan Escherichiae coli." Jurnal e-Biomedik 2, no. 1 (February 13, 2014). http://dx.doi.org/10.35790/ebm.2.1.2014.3648.
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Abstract: Endophytic Fungus is a microbial resources whichexist in the plant tissues and produce bioactive compounds which potentially could be developed into raw materials for drugs/medicine, such as anticancer and antibiotics. Endophytic Fungi could be found on many plants, such as Rhizophora apiculata, one of the mangroves found in Indonesia. This research aims to procure the endophytic fungal isolates from the mangrove roots Rhizophora apiculataand to test the activity of anti-bacterial of endophytic fungi on bacterium Staphylococcus aureus andEscherichiae coli. This research was done in Pharmacology Laboratory Faculty of Medicine on Sam Ratulangi University, Manado from November 2013 to January 2014. This research was an experimental research in the laboratory using the Control Trial Design. The endophytic fungi was cultured on carbohydrate-rich media, and then the bioactivity on the experimental bacterium was tested. The result of the research showed that there were two endophytic fungals isolates procured, which were black fungi and white fungi. As antibacterial activity, both of the endophytic fungi showed that there was an inhibition at the two experimental fungis. The antibacterial’s activity testing of mangrove roots Rhizophora apiculataon the growth of bacterial Staphylococcus aureusandEscherichiae coliwas showing an inhibitory effect to both of the fungi. Advance study are needed. Keyword: Antibacterial, endophytic fungi, endophytic microbes, Rhizophora apiculata Abstrak: Jamur endofit merupakan suatu sumber daya mikroba yang terdapat dalam jaringan tumbuhan dan memproduksi senyawa-senyawa bioaktif yang potensial untuk dikembangkan menjadi bahan baku obat, seperti antikanker dan antibiotik. Jamur endofit dapat ditemukan pada berbagai jenis tumbuhan, seperti misalnya Rhizophora apiculata, salah satu tumbuhan bakau yang banyak dijumpai di Indonesia. Penelitian ini bertujuan untuk memperoleh isolat jamur endofit dari akar bakau Rhizophora apiculata, dan menguji aktivitas antibakteri jamur endofit tersebut terhadap bakteri Staphylococcus aureus dan Escherichiae coli. Penelitian ini dilakukan di Laboratorium Farmakologi Fakultas Kedokteran Universitas Sam Ratulangi Manado Sejak bulan November 2013 hingga Januari 2014. Penelitian ini merupakan penelitian eksperimental laboratorium dengan menggunakan rancangan control trial. Secara umum, jamur endofit dikultur dalam media kaya karbohidrat, kemudian diuji bioaktivitasnya terhadap bakteri uji. Hasil penelitian menunjukkan bahwa terdapat dua isolat jamur endofit yang dihasilkan, yaitu jamur hitam dan jamur putih. Pada pengujian antibakteri, kedua jamur endofit tersebut menunjukkan adanya daya hambat pertumbuhan kedua bakteri uji. Uji aktivitas antibakteri akar bakau Rhizophora apiculata terhadap pertumbuhan bakteri Staphylococcus aureus dan Escherichiae coli memberikan efek penghambatan terhadap kedua bakteri tersebut. Perlu diadakan penelitian lebih lanjut. Kata kunci: Antibakteri, Jamur endofit, Mikroba endofit, Rhizophora apiculata