Altabax (retapamulin) / GSK, Almirall - LARVOL DELTA

Common Skin Conditions in Children and Adolescents: Bacterial Infections. (PubMed, FP Essent) - "Mupirocin and clindamycin are topical antibiotic options. For treatment-resistant cases, oral cephalexin or dicloxacillin is an appropriate option...In most cases, topical mupirocin or retapamulin (Altabax) is effective...Oral antibiotics are not necessary in most cases but should be prescribed for patients with severe immunocompromise or systemic signs of infection. In bacterial skin infections, methicillin-resistant S aureus coverage should be considered for patients with infections that have not improved with treatment."

Journal • Review • Dermatology • Infectious Disease • Pain

In vitro activity of ozenoxacin against Staphylococcus aureus and Streptococcus pyogenes clinical isolates recovered in a worldwide multicentre study (2020-2022). (PubMed, JAC Antimicrob Resist) - "The most active comparators against S. aureus were retapamulin (MIC90 = 0.12 mg/L), fusidic acid (MIC90 = 0.25 mg/L) and mupirocin (MIC90 = 0.5 mg/L); and against S. pyogenes were retapamulin (MIC90 = 0.03 mg/L), clindamycin (MIC90 = 0.12 mg/L) and mupirocin (MIC90 = 0.25 mg/L). On the other hand, ozenoxacin had similar activity in ciprofloxacin-susceptible and resistant S. pyogenes isolates. Ozenoxacin is a potent antimicrobial agent of topic use against Gram-positive bacteria causing SSTI, including MRSA isolates non-susceptible to ciprofloxacin."

Journal • Preclinical • Infectious Disease

Proteins à la carte: riboproteogenomic exploration of bacterial N-terminal proteoform expression. (PubMed, mBio) - "Utilizing complementary ribosome profiling strategies to map ORF boundaries, we uncovered dual-encoding ORFs generated by in-frame TIS usage in Salmonella. Besides demonstrating that alternative TIS usage may generate proteoforms with different characteristics, such as differential localization and specialized function, quantitative aspects of conditional retapamulin-assisted ribosome profiling (Ribo-RET) translation initiation maps offer unprecedented insights into the relative utilization of annotated and alternative TIS, enabling the exploration of gene regulatory mechanisms that control TIS usage and, consequently, the translation of N-terminal proteoform pairs."

Journal

Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and M enzymes of SARS-CoV-2. (PubMed, Front Cell Infect Microbiol) - "The IC for all the drugs, except ivermectin, was at the clinically achievable plasma concentration in humans, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Deciphering the molecular and cellular atlas of immune cells in septic patients with different bacterial infections. (PubMed, J Transl Med) - "Our study provides a comprehensive overview of the cellular heterogeneity and underlying mechanisms in septic patients with various bacterial infections, providing insights to inform development of stratified targeted therapies for sepsis."

Immune cell • Journal • Infectious Disease • Inflammation • Septic Shock • C1QA • CTSD • RETN

Induced fit describes ligand binding to membrane-associated cytochrome P450 3A4. (PubMed, Mol Pharmacol) - "Azamulin, retapamulin, pleuromutilin, and mibrefadil binding to CYP3A4 NDs conformed to a single-site binding model...It is unknown whether conformational heterogeneity is present before (conformational selection) or after (induced fit) ligand binding. Stopped-flow measurements of suicide inhibitors binding to nanodisc-embedded CYP3A4 combined with sophisticated numerical analyses support that induced fit describes ligand binding to this important enzyme."

Journal • CYP3A4

Efficacy of a Novel Antibacterial Agent Exeporfinium Chloride, (XF-73), Against Antibiotic-Resistant Bacteria in Mouse Superficial Skin Infection Models. (PubMed, Infect Drug Resist) - "The in vitro antibacterial activity of XF-73 and comparator antibacterial drugs, (mupirocin, fusidine, retapamulin, vancomycin, erythromycin, linezolid and daptomycin), against S. aureus (both antibiotic sensitive and resistant strains) was assessed using a broth microdilution method. SEM analysis demonstrated that this cell wall and cell membrane disruption did not lead to disintegration of the plasma membrane, and did not cause bacterial cell lysis. Therefore, XF-73 may be an effective drug alternative to combat multi-drug-resistant skin infections in the clinical setting."

Journal • Preclinical • Dermatology • Infectious Disease

Design, Synthesis, and Biological Activity of Thioguanine-Modified Pleuromutilin Derivatives. (PubMed, ACS Med Chem Lett) - "Antibiotic overuse has caused the increasingly serious problem of bacterial drug resistance, with numerous marketed antibiotics exhibiting significantly reduced activity against drug-resistant bacteria. Compound 6j was observed to have a rapid bactericidal effect, low cytotoxicity, and potent antibacterial activity. The in vitro results suggest that 6j has a significant therapeutic effect on local infections, and its activity is equal to that of retapamulin, an anti-Staphylococcus aureus pleuromutilin derivative."

Journal • Infectious Disease

Innovative, rapid, high-throughput method for drug repurposing in a pandemic-A case study of SARS-CoV-2 and COVID-19. (PubMed, Front Pharmacol) - "Erythromycin, pyridoxine, folic acid and retapamulin were found to inhibit SARS-CoV-2 induced CPE in Vero cells at concentrations that are clinically achievable. Additional studies may be required to further characterize the inhibitions of CPE and the possible mechanisms."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Discovery of Unannotated Small Open Reading Frames in Streptococcus pneumoniae D39 Involved in Quorum Sensing and Virulence Using Ribosome Profiling. (PubMed, mBio) - "IMPORTANCE This work employed pleuromutilin-assisted ribosome profiling using retapamulin (Ribo-RET) to identify genome-wide translation start sites in the human pathogen Streptococcus pneumoniae...The biological roles of four sORF examples are characterized: two control the regulation of a cell-cell communication (quorum sensing) system, one contributes to the ability of S. pneumoniae to colonize the upper respiratory tract of mice, and a fourth governs the translation of PrfB, a protein enabling ribosome release at stop codons. We propose that Ribo-RET is a valuable approach to identifying unstudied microproteins and difficult-to-find pheromone genes used by Gram-positive organisms, whose genomes are replete with pheromone receptors."

Journal • CNS Disorders • Infectious Disease • Otorhinolaryngology • Pneumococcal Infections • Pneumonia • Respiratory Diseases • ARSI

Genome Assembly and Genetic Traits of the Pleuromutilin-Producer Clitopilus passeckerianus DSM1602. (PubMed, J Fungi (Basel)) - "The gilled mushroom Clitopilus passeckerianus (Entolomataceae, Agaricales, Basidiomycota) is well known to produce the terpenoid pleuromutilin, which is the biotechnological basis for medically important antibiotics such as lefamulin and retapamulin...The pleuromutilin genes were reassembled with yeast-specific elements for heterologous expression in Saccharomyces cerevisiae. Our work lays the foundation for metabolic strain engineering towards higher yields of the valuable compound pleuromutilin."

Journal

Identification of Condition-Specific and Differentially Expressed Small Proteins in E. Coli UsIng Translation Initiation Profiling (ASM Microbe 2022) - "To answer this question, we are analyzing how stress conditions alter the expression profiles of small proteins by using an optimized high-throughput translation initiation profiling method - RETapamulin enhanced Ribo-seq (Ribo-RET)...Our current work aims at using deep learning tools to predict unannotated translation start sites of small proteins from the Ribo-RET dataset. Experiments are also on-going to characterize the top hits of both known and unannotated stress-induced small proteins from the Ribo-RET dataset through validation of their in-vivo expression, physiological effects of deletion and overexpression, cellular localization and identification of their potential binding partners."

Design, synthesis and biological evaluation of novel pleuromutilin derivatives possessing 4-aminothiophenol linker as promising antibacterial agents. (PubMed, Bioorg Chem) - "12 Compounds possessed superior antibacterial activity against MRSA compared with valnemulin and retapamulin (MIC = 0.0625 µg/mL)...In addition, compound 19 had barely inhibitory effect on RAW 264.7 and 16HBE cells at 8 µg/mL. In molecular docking study, upon docking into the 50S ribosomal subunit, the binding free energy (ΔG) of compound 12 and 19 was calculated to be -9.02 kcal/mol and -9.89 kcal/mol, respectively."

Journal • Infectious Disease

Design, synthesis and antibacterial activity of novel pleuromutilin derivatives with thieno[2,3-d]pyrimidine substitution. (PubMed, Eur J Med Chem) - "Compound A11 was the most active and displayed bacteriostatic activities against methicillin-resistant S. aureus, with MIC values as low as 0.00191 μg/mL, which is 162 and 32 times lower than that of the marketed antibiotics tiamulin and retapamulin, respectively. Furthermore, the mechanism of action of A11 was confirmed by molecular docking studies."

Journal

Structural characterization of the homotropic cooperative binding of azamulin to human cytochrome P450 3A5. (PubMed, J Biol Chem) - "Homotropic cooperativity was not observed for the binding of related pleuromutilin antibiotics, tiamulin, retapamulin and lefamulin to 3A5, which are larger and unlikely to bind in the distal site in a stacked orientation. Formation of the 3A5 complex with two azamulin molecules may prevent time dependent inhibition that is seen for 3A4 by restricting alternate product formation and/or access of reactive intermediates to vulnerable protein sites. These results also contribute to a better understanding of sites for cooperative binding and the differential structural plasticity of 3A5 and 3A4 that contribute to differential substrate and inhibitor binding."

Journal

Screening FDA approved drug and drug metabolite libraries against VanA-type vancomycin-resistant Enterococcus faecium in the absence and presence of vancomycin (ACS-Sp 2022) - "Four appeared to act synergistically with vancomycin, and checkerboard analysis confirmed synergy for three of these – retapamulin, rifapentine, and valnemulin. Four appeared to be antagonized by vancomycin (rifabutin, rifaximin, rifampin, and gemcitabine). Only mupirocin showed significantly improved activity after microsomal metabolism – indicative of a more active metabolite, but efforts to identify an active metabolite were so far unsuccessful...Gemcitabine showed modest activity against several VRE faecium and faecalis strains, but this activity was substantially less than its activity in MRSA. Floxuridine and 5-fluorouracil showed weak activity against only 2 of 8 VRE strains, both faecium."

FDA event • Oncology

Emerging Treatment Strategies for Impetigo in Endemic and Nonendemic Settings: A Systematic Review. (PubMed, Clin Ther) - "This review highlights the limited research into new drugs used for the treatment of impetigo in endemic and nonendemic settings. Limited recent evidence supports the use of topical ozenoxacin or retapamulin for impetigo treatment in nonendemic settings, whereas systemic antibiotics and the mass drug administration strategy have evidence for use in endemic settings. Given the troubling increase in resistance to existing treatments, there is a clear need to ensure the judicious use of antibiotics and to develop new treatments and alternative strategies; this is particularly important in endemic settings. PROSPERO identifier: CRD42020173042."

Journal • Review • Dermatology

Characterization of a vga gene variant recovered from a Staphylococcus saprophyticus causing a community-acquired urinary tract infection: report from the SENTRY Antimicrobial Surveillance Program 2017. (PubMed, Diagn Microbiol Infect Dis) - "A patient with a history of UTI acquired an isolate of Staphylococcus saprophyticus that was resistant to clindamycin, streptogramin A, pleuromutilins (LSPs), and oxacillin. A plasmid-located vga variant was identified in this pathogen, and the encoded protein showed a 39% to 67% identity to other previously characterized vga."

Journal • Infectious Disease • Nephrology

Identification of Translation Start Sites in Bacterial Genomes. (PubMed, Methods Mol Biol) - "We recently found that the pleuromutilin antibiotic retapamulin (RET) is a specific inhibitor of translation initiation that traps ribosomes specifically at start codons, and we used it in combination with ribosome profiling to map start codons in the Escherichia coli genome...Here, we provide a detailed Ribo-RET protocol for E. coli. Ribo-RET can be adapted for mapping the start codons of the protein-coding sequences in a variety of bacterial species."

Journal

A comparative review of current topical antibiotics for impetigo. (PubMed, Expert Opin Drug Saf) - "Cost or insurance coverage may be a limiting factor in choosing the best therapeutic agent, with mupirocin ointment having the lowest cost...Ozenoxacin and retapmulin are effective alternatives but may entail higher cost. Retapamulin is indicated for lesions of impetigo that are colonized by MSSA and streptococcus S. pyogenes but not MRSA based on clinical efficacy of phase III trials. Fusidic acid, available in other countries is a non-FDA approved medication although rising resistance rates represent a growing concern."

Clinical • Journal • Review • Dermatology • Pediatrics • Pruritus

Attenuator LRR - a regulatory tool for modulating gene expression in Gram-positive bacteria. (PubMed, Microb Biotechnol) - "Due to the limited performance and context-dependence of riboswitches, only a few of them (such as theophylline, tetracycline and ciprofloxacin riboswitches) have been utilized as regulatory tools in biotechnology...Specifically, it offers a 60-fold change in expression in the presence of retapamulin and a low level of leaky expression of about 1-2% without antibiotics...Furthermore, we demonstrate its ability to control melanin metabolism in B. thuringiensis BMB171. Our results show that LRR can be applied to regulate gene expression, construct genetic circuits and tune metabolic pathways, and has great potential for many applications in synthetic biology."

Journal

Retapamulin Activity Against Pediatric Strains of Mupirocin-resistant Methicillin-resistant Staphylococcus aureus. (PubMed, Pediatr Infect Dis J) - "DNA sequence analysis of rplC and cfr identified one rplC strain variant that did not demonstrate reduced phenotypic susceptibility to retapamulin. These results demonstrate that retapamulin may be a useful alternative therapy for mupirocin-resistant community-acquired methicillin-resistant S. aureus, especially in disease clusters."

Clinical • Journal • Pediatrics

Do Antimicrobial Resistance Patterns Matter? An Algorithm for the Treatment of Patients With Impetigo. (PubMed, J Drugs Dermatol) - "When prescribing antibiotics, it is essential to know the local trends in antibiotic resistance. Ozenoxacin cream 1% is highly effective against S. pyogenes and S. aureus, including methycyllin-susceptible and resistant strains (MRSA), and may be a suitable option for localized impetigo.J Drugs Dermatol. 2021;20(2):134-142. doi:10.36849/JDD.2021.5475 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS."

Clinical • Journal • Complement-mediated Rare Disorders • Dermatology • Dermatopathology • Infectious Disease • Pediatrics

In vitro and in vivo antibacterial properties of peptide AMC-109 impregnated wound dressings and gels. (PubMed, J Antibiot (Tokyo)) - "The present work demonstrates that AMC-109 displays a significantly higher antibacterial activity with up to a seven-log reduction in bacterial loads compared to current clinical standard therapy; Altargo cream (1% retapamulin) and Fucidin cream (2% fusidic acid) in the in vivo wound models. It is thus concluded that AMC-109 represents a promising entry in the development of new and effective remedies for various skin infections."

Journal • Preclinical • Dermatology • Infectious Disease

Identification of a novel tedizolid resistance mutation in rpoB of MRSA after in vitro serial passage. (PubMed, J Antimicrob Chemother) - "To the best of our knowledge, this is the first time that an rpoB mutation has been implicated in resistance to PhLOPSa antimicrobials. The mechanism of resistance remains unclear, but is likely indirect, involving σ-factor binding or other alterations in transcriptional regulation."

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