Fucidin (fusidic acid) / LEO Pharma - LARVOL DELTA

Emergence and spread of ST5 methicillin-resistant Staphylococcus aureus with accessory gene regulator dysfunction: genomic insights and antibiotic resistance. (PubMed, Microbiol Res) - "This clone exhibits resistance to seven antimicrobial classes, including third-generation tetracyclines and fusidic acid, and shares phenotypic and genetic similarities with the vancomycin-intermediate S. aureus Mu50 strain, including reduced susceptibility to vancomycin, teicoplanin, and daptomycin. The agrA-I238K mutation attenuates hemolytic activity, increases biofilm formation, and reduces daptomycin susceptibility, suggesting a key role in the clone's success. Our results demonstrate the important role of agrA-I238K mutation in the widespread distribution of agr-dysfunctional MRSA and highlight the importance of genomic surveillance in tracking the spread of agr-dysfunctional ST5 MRSA."

Journal • Infectious Disease

Linker and Head-Group Exploration of Anti-MRSA Triaromatic Pleuromutilins. (PubMed, J Med Chem) - "Docking to the ribosome suggested a shifted engagement with C2469 for 21 over 6, resulting in greater multivalency, while 43/45 likely coordinates Mg2+. Lastly, conjugate 21 displayed efficacy equal to commercial Fucidin LEO (5) in a mouse Staphylococcus aureus skin infection model, highlighting its potential as a topical antibiotic lead."

Journal • Dermatology • Infectious Disease

Clonal dissemination of methicillin-resistant Staphylococcaceae between Algerian sheep farms. (PubMed, J Glob Antimicrob Resist) - "Specific clonal lineages of methicillin-resistant S. saprophyticus, S. haemolyticus, and M. lentus are widespread in Algerian sheep farms. Enhancing hygiene practices on farms is recommended to prevent further dissemination of these resistant strains to animals and humans."

Journal

Metabolic analysis of the Mode-of-Action (MoA) and Mode-of-Resistance (MoR) of fusidic acid against S.aureus. (PubMed, FEMS Microbiol Lett) - "These changes primarily impacted pathways involved in central carbon metabolism, nucleotide metabolism, and amino acid synthesis. This study highlights the complexity of FD resistance in S. aureus and offers insights into the metabolic pathways associated with antibiotic resistance."

Journal • Infectious Disease

Characterization of fusidic acid-resistant Staphylococcus aureus isolated from food animals during 2010-2021 in South Korea. (PubMed, Int J Food Microbiol) - "In addition, the majority of the isolates showed resistance to penicillin (86.6 %), while comparatively low resistance rates (7-13.9 %) were observed for erythromycin, gentamicin, kanamycin, and tetracycline. This is the first report of fusA and fusB carrying S. aureus and linkage fusB and blaZ genes in FRSA isolated from food animal products. Taken together, the FRSA in food animals with different resistance determinants and spa types could pose a threat to public health."

Journal

Jointly considering multi-medium and full-cycle to better reveal distribution and removal of antibiotic resistance genes in long-term constructed wetland. (PubMed, Sci Total Environ) - "The CW had removal effects on four types of ARGs (such as multidrugs), 16 types of fusidic acid, and nine types of ARGs (such as bleomycin) during the dormancy, start-up, and operation periods, respectively...The subtypes that were removed mainly included those containing tetracycline, efflux pump, and β-lactam, mcr-1, and mcr-5 (colistin ARGs). For individual parts of CWs, the removal effects on the total abundance of ARGs were as follows: forebay > surface flow wetland > subsurface flow wetland. These findings provide insights for optimizing the purification efficiency of CWs for ARGs."

Journal

Staphylococcus aureus population structure and the incidence of methicillin-resistant S. aureus (MRSA) and Panton-Valentine Leucocidin (PVL) toxin among cystic fibrosis patients in two CF centres (ECFS 2024) - "mecA- positive MRSA isolates were received from 7 (7.5%) of 93 patients; three adults and four paediatric patients. One paediatric patient harboured a CC88 PVL-positive methicillin-susceptible S. aureus . Isolates were comprised of 25 different Sequence Types (STs) from 19 CC’s."

Clinical • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pediatrics • Pulmonary Disease • Respiratory Diseases

Design, synthesis fusidic acid derivatives alleviate acute lung injury via inhibiting MAPK/NF-κB/NLRP3 pathway. (PubMed, Eur J Med Chem) - "On the other hand, we demonstrated a1 also role in anti-inflammatory by inhibits nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome and further inhibits Caspase-1 and inflammatory factor interleukin-1β (IL-1β). In conclusion, our study demonstrates that a1 has an anti-inflammatory effect and alleviates ALI by regulating inflammatory mediators and suppressing the MAPK, NF-κB and NLRP3 inflammasome signaling pathways."

Journal • Acute Lung Injury • Inflammation • Pneumonia • Respiratory Diseases • IL1B • IL6 • MAPK8 • NFKBIA • NLRP3 • TNFA

Effects of thiram exposure on liver metabolism of chickens. (PubMed, Front Vet Sci) - "Metabolomics analysis shows that 62 metabolites were down-regulated (ginsenoside F5, arbekacin, coproporphyrinogen III, 3-keto Fusidic acid, marmesin, isofumonisin B1, 3-Hydroxyquinine, melleolide B, naphazoline, marmesin, dibenzyl ether, etc.) and 35 metabolites were up-regulated (tetrabromodiphenyl ethers, deoxycholic acid glycine conjugate, L-Palmitoylcarnitine, austalide K, hericene B, pentadecanoylcarnitine, glyceryl palmitostearate, quinestrol, 7-Ketocholesterol, tetrabromodiphenyl ethers, etc.) in thiram-induced chickens, mainly involved in the metabolic pathways including glycosylphosphatidylinositol (GPI)-anchor biosynthesis, porphyrin and chlorophyll metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis and steroid hormone biosynthesis. Taken together, this research showed that thiram exposure significantly altered hepatic metabolism in chickens. Moreover, this study also provided a basis for regulating the use and disposal of thiram to..."

Journal • Metabolic Disorders

Decreased efficacy of antimicrobial agents in a polymicrobial environment. (PubMed, ISME J) - "In this work, we investigate how polymicrobial cultures comprised of key CF-associated pathogens respond to challenge with species-specific antimicrobial agents; colistin (targets Pseudomonas aeruginosa), fusidic acid (targets Staphylococcus aureus), and fluconazole (targets Candida albicans). This was subsequently confirmed through further genetic analyses. Our findings indicate that the polymicrobial nature of the CF airways is likely to have a significant impact on the clinical response to antimicrobial therapy."

Journal • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Comparative genome analysis of multidrug-resistant and susceptible Glaesserella parasuis strains isolated from diseased pigs in China. (PubMed, Vet Microbiol) - "We also detected 30,599 single nucleotide polymorphisms (SNPs), including nonsynonymous SNPs in the aminoglycoside resistance gene aph(3'')-Ib, the fusidic acid resistance gene fusA, and the two rifampicin resistance genes rpoC and rpoB in HPS-1. These findings improve our understanding of the differences between MDR and susceptible isolates and will aid the development of treatment strategies to decrease the prevalence and disease burden caused by G. parasuis."

Journal • Complement-mediated Rare Disorders

High-Resolution DNA Dual-rulers Reveal a New Intermediate State in Ribosomal Frameshifting. (PubMed, Chembiochem) - "This indicates a ribosome conformation that is different from the conventional model of three reading frames. Our work reveals uniquely precise mRNA motions and subtle conformational changes that will complement structural and fluorescence studies."

Journal

The Diverse Search for Synthetic, Semisynthetic and Natural Product Antibiotics From the 1940s and Up to 1960 Exemplified by a Small Pharmaceutical Player. (PubMed, Front Microbiol) - "The discovery process included contemporary approaches such as open innovation; targeting specific pathogens and/or specific organs in the patient; examining the effects of antimicrobial compounds on bacterial virulence as well as on antibiotic-resistant variants, and searching for antibiotic producers among microorganisms not previously well explored. These activities were promoted by the collaboration with a renowned Danish clinical microbiologist, K. A. Jensen, as well as company expertise in fermentation technologies, chemical synthesis and purification of bioactive compounds from organic materials."

Journal • Review • Infectious Disease • Tuberculosis

Identification and characterization of virulent Aeromonas hydrophila Ah17 from infected Channa striata in river Cauvery and in vitro evaluation of shrimp chitosan. (PubMed, Food Sci Nutr) - "indicus). Thus, the present study isolated virulent A. hydrophila Ah17 from the environmental source and characterized in vitro with shrimp chitosan."

Journal • Preclinical • ELANE

Emergence of Methicillin-Resistant Staphylococcus aureus Belonging to Clonal Complex 15 (CC15-MRSA) in Kuwait Hospitals. (PubMed, Infect Drug Resist) - "The 42 isolates belonged to sequence type ST1535-harbored SCCmec type V and spa types t084 (36 isolates), t346 (3 isolates) and one of t114, t228 and t7583. All 42 isolates were resistant to gentamicin, kanamycin, fusidic acid and cadmium acetate; 38 isolates were resistant to tetracycline...The isolates belonged to accessory gene regulator type II and capsular polysaccharide group 8 but lacked genes for Staphylococcus enterotoxins, toxic shock syndrome toxin, collagen-binding adhesins and Panton-Valentine leukocidin. This study revealed the emergence and transmission of a previously rare MRSA clone among human patients in Kuwait hospitals and highlights the increasing infiltration of rare MRSA into the human population."

Clinical • Journal

Efficacy and Safety of Fucicort® Lipid Cream Compared to Combination Treatment With Fucidin® Cream Followed by Betamethasone (Lianbang Beisong®) Cream and Fucicort® Lipid Cream Vehicle in Clinically Infected Atopic Dermatitis/Eczema (clinicaltrials.gov) - P3; N=68; Terminated; Sponsor: LEO Pharma; N=550 ➔ 68; Trial completion date: Jan 2020 ➔ May 2019; Recruiting ➔ Terminated; Trial primary completion date: Jan 2020 ➔ May 2019; Due to business strategic reasons, LEO Pharma has decided to close down the FCF-38 trial.

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination