apramycin (EBL-1003) / Juvabis - LARVOL DELTA

Assessing the therapeutic potential of an apramycin-gallium combination for treating Acinetobacter baumannii lung infections (ESCMID Global 2025) - No abstract available

Infectious Disease • Respiratory Diseases

Characterization of blaNDM-5-bearing IncHI2 plasmid from Escherichia fergusonii in China. (PubMed, J Glob Antimicrob Resist) - "This is the first report on the characterization of blaNDM-5-bearing IncHI2 plasmid in E. fergusonii. Surveillance and control measures should be implemented to arrest the transmission of blaNDM-5 from food animals."

Journal • Infectious Disease

Isolation and Identification of Streptomyces sp. D-6 and Its Protective Effect on Crucian auratus. (PubMed, Microb Pathog) - "The optimal fermentation time of the strain was the 4th day, and its antibacterial active substances were stable, resistant to high temperature and ultraviolet light, and not affected by proteases.The MIC and MBC values of the fermentation broth and fermentation supernatant were 32 times diluted, and the corresponding antibiotic titers were 1189.95 μg/mL for apramycin and 818.06 μg/mL for kanamycin...After feeding, it was found that the strain effectively increase the specific growth rate of Carassius auratus, and the activities of ACP and CAT in serum were significantly enhanced. The whole genome analysis provides an effective scientific basis for the development and utilization of strain D-6 and lays a foundation for its application in aquaculture."

Journal • Infectious Disease

Pharmacodynamic assessment of apramycin against Mycobacterium abscessus in a hollow fibre infection model. (PubMed, J Antimicrob Chemother) - "Apramycin exhibited greater pharmacodynamic activity than amikacin against amikacin-susceptible M. abscessus isolates and may be a promising therapy for this pathogen. However, antibiotic combination strategies to minimize apramycin resistance from emerging may be necessary."

Journal • PK/PD data • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Distinct Patterns of Antibiotic Sensitivities in Ammonia-Oxidising Archaea. (PubMed, Environ Microbiol) - "The aim of this study was to test the effects of selected antibiotics (hygromycin B, neomycin, apramycin, puromycin, novobiocin) on pure cultures of three well studied AOA strains, 'Candidatus Nitrosocosmicus franklandianus C13', Nitrososphaera viennensis EN76 and Nitrosopumilus maritimus SCM1. viennensis EN76 was inhibited by trimethoprim, but not by chloramphenicol, and growth recovered within days in the presence of simvastatin, suggesting either degradation of, or spontaneous resistance against, this compound. This study highlights the physiological differences between different genera of AOA and has identified new candidate antibiotics for selective enrichment and the development of selectable markers for genetic systems in AOA."

Journal

Reproductive loss attributed to Lactococcus petauri infection in a black-and-white ruffed lemur. (PubMed, J Vet Diagn Invest) - "The antimicrobial susceptibility of isolates by the disk diffusion method revealed resistance to tylosin, gentamicin, apramycin, neomycin, amikacin, ampicillin, and florfenicol. We attributed the reproductive loss in this lemur to placental and fetal infection by L. petauri."

Journal • Hematological Disorders • Infectious Disease

Synthesis of Methyl Aprabiosaminide and 2-Hydroxyapramycin from Apramycin. (PubMed, Org Lett) - "We describe a protocol for the selective cleavage of the 2-deoxystreptamine ring from the structurally unusual aminoglycoside antibiotic apramycin, enabling for the first time the preparation of aprabiosamine derivatives. We further describe reglycosylation of the aprabiosamine core with a selectively protected optically pure streptamine derivative, giving, after deprotection, 2-hydroxyapramycin, the first apramycin derivative functionalized at the 2 position."

Journal

Pulmonary Delivery of Antibiotics to the Lungs: Current State and Future Prospects. (PubMed, Pharmaceutics) - "Side effects, safety concerns, and disappointing clinical trial results remain barriers to regulatory approval. In this review, we describe some possible approaches to address these issues and highlight prospects in this area."

Journal • Review • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

MarR family regulator LcbR2 activates lincomycin biosynthesis in multiple ways. (PubMed, Int J Biol Macromol) - "Moreover, the binding of LcbR2 to DNA can be attenuated by apramycin. This study thus characterized LcbR2 as a novel transcriptional regulator with a broad regulatory scope."

Journal • Infectious Disease

N-Acetyl cysteine exhibits antimicrobial and anti-virulence activity against Salmonella enterica. (PubMed, PLoS One) - "In this work, we found that N-acetyl cysteine (NAC) inhibits S. enterica at MIC of 3 mg ml-1 and synergistically activates the bactericidal activities of common antibiotics from three-fold for ampicillin and apramycin up to1000-fold for gentamycin. The whole-genome sequencing revealed that continuous exposure of S. enterica to NAC leads to the development of resistance; these resistant strains are attenuated for virulence. These results suggest that NAC may be a promising adjuvant to antibiotics for treating S. enterica in combination with other antibiotics."

Journal • Gastroenterology • Gastrointestinal Disorder • Infectious Disease

Pathogenicity and drug resistance characterization of Streptococcus agalactiae isolated from dairy cows. (PubMed, Pol J Vet Sci) - "The study revealed that S. agalactiae was fully susceptible to streptomycin, meropenem, ciprofloxacin, clindamycin, cefquinome, and cloxacillin in general laboratory settings and within milk samples. However, among the antibiotics tested, tetracycline exhibited the highest level of resistance, with rates reaching 70%. Penicillin showed a resistance level of 50%, followed by doxycycline at 30%. Additionally, the resistance rates for apramycin and cefoxitin were both 20%, whereas florfenicol resistance was observed at a rate of 10%...mellonella) larvae and mouse models. These findings contribute to understanding the relationship between the pathogenic properties of S. agalactiae and the virulence genes it carries."

Journal • Infectious Disease

Collateral Sensitivity to β-Lactam Antibiotics in Evolved Apramycin-Resistant MRSA. (PubMed, Int J Mol Sci) - "Collateral sensitivity to ampicillin, cephazolin, ceftriaxone, cefotaxime, cefepime and cefquinome occurred after MRSA were exposed to apramycin and induced to acquire resistance. We also found a decrease in the proton motive force and decreased efflux activity. These results provide new insights into collateral sensitivity-based strategies for the treatment of MRSA."

Journal • Infectious Disease

Model-informed drug development for antimicrobials: translational pharmacokinetic-pharmacodynamic modelling of apramycin to facilitate prediction of efficacious dose in complicated urinary tract infections. (PubMed, J Antimicrob Chemother) - "PKPD modelling with in vitro and in vivo PK and PD data enabled simultaneous evaluation of the different components that influence drug effect, an approach that had not yet been evaluated for antibiotics in the cUTI model and that has potential to enhance model-informed drug development of antibiotics."

Journal • PK/PD data • Infectious Disease • Nephrology

A Cell-Based Screening Assay for rRNA-Targeted Drug Discovery. (PubMed, ACS Infect Dis) - "Intermediate fluorescence was found with plazomicin, neamine, apramycin, ribostamicin, gentamicin, and amikacin. In contrast to planktonic cells, established biofilms yielded an average Z' factor of 0.61. The high sensitivity of this cell-based assay in a physiological context demonstrates significant potential for identifying potent new ribosomal binding antibiotics."

Journal • Infectious Disease

Construction of a genome-editing system for the thermophilic actinomycete streptomyces thermodiastaticus K5 strain. (PubMed, Biosci Biotechnol Biochem) - "It was found that pGEK5 could easily be lost from the transformed clone through cultivation on apramycin-free medium and spore formation, enabling its reuse for subsequent genome-editing cycles. With the aid of this plasmid, mutations were sequentially introduced to two uracil-DNA glycosylase genes (Udg1 and Udg2) and one β-glucosidase gene (Bgl1). Thus, the genome-editing system using pGEK5 enables us to start the functional modification of this thermophilic actinomycete, especially for improved conversion of lignocellulosic biomass."

Journal

The point mutation A1387G in the 16S rRNA gene confers aminoglycoside resistance in Campylobacter jejuni and Campylobacter coli. (PubMed, Antimicrob Agents Chemother) - "Monitoring revealed current low prevalence of gentamicin resistance in European Campylobacter spp...Antimicrobial susceptibility tests showed cross-resistance to apramycin, kanamycin, and tobramycin, with transformants exhibiting more than 4- to 8-fold increased MICs to apramycin and tobramycin and over 64-fold higher MICs to kanamycin compared to wild-type isolates...isolates. In-depth knowledge on resistance mechanisms contributes to optimal diagnosis and preventative measures."

Journal

Ribosomal protein L32 contributes to the growth, antibiotic resistance and virulence of Glaesserella parasuis. (PubMed, Front Vet Sci) - "Meanwhile, ΔL32 is significantly more susceptible to antimicrobials such as spectinomycin, apramycin, sulfafurazole, but not to other antibiotics used in this study. In the mouse challenge experiment, the mortality of mice infected with the mutant strain decreased by 40% compared to those infected with the wild-type strain, indicating that L32 is a virulence-associated factor which contributes to bacterial fitness in host environments. The above results show that L32 is important for the growth, stress resistance and virulence of G. parasuis, and this study also confirms for the first time that L32 plays an important role in antibiotic resistance against aminoglycosides and sulfonamides."

Journal • CNS Disorders • Immunology • Infectious Disease • Rheumatology

Resistance against aminoglycoside antibiotics via drug or target modification enables community-wide antiphage defense. (PubMed, Microlife) - "Furthermore, we confirmed the antiphage impact of aminoglycosides in a community context by coculturing phage-susceptible, apramycin-resistant Streptomyces venezuelae with the apramycin-producing strain Streptoalloteichus tenebrarius. Given the prevalence of aminoglycoside resistance among natural bacterial isolates, this study highlights the ecological relevance of chemical defense via aminoglycosides at the community level."

Journal • Infectious Disease

A series of vectors for inducible gene expression in multidrug-resistant Acinetobacter baumannii. (PubMed, Appl Environ Microbiol) - "Here, we present a series of freely replicating and Tn7-insertion vectors that rely on selectable markers to less frequently encountered antibiotics, apramycin, and hygromycin. Strain AB5075 is an established model strain for present-day A. baumannii, due in part to its genetic tractability and because it is a representative isolate of the globally disseminated multidrug-resistant clade of A. baumannii, global clone 1. In addition to the drug-selection markers facilitating use in strains resistant to more commonly used antibiotics, the vectors allow for controllable expression driven by several regulatory systems, including isopropyl β-D-1-thiogalactopyranoside (IPTG), arabinose, anhydrotetracycline, and toluic acid."

Journal

Optimizing aminoglycoside: Ribosome interactions for the development of next generation aminoglycoside antibiotics (ACS-Fall 2024) - "This lecture will focus on work in the author's laboratories on the design and development of next generation aminoglycoside antibiotics for the treatment of multidrug resistant bacterial infections with the emphasis on apramycin and its analogs and the nature of their interactions with the decoding A site of the bacterial ribosome."

Infectious Disease

Apramycin has high in vitro activity against Mycobacterium tuberculosis. (PubMed, J Med Microbiol) - "Aminoglycoside antibiotics such as amikacin and kanamycin are important components in the treatment of Mycobacterium tuberculosis (Mtb) infection. Apramycin shows high in vitro activity against the Mtb clinical isolates, especially the MDR-TB clinical isolates. This encouraging discovery calls for more research on the functions of apramycin in vivo and as a possible antibiotic for the treatment of drug-resistant TB."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Safety of Intravenous Apramycin in Adults (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Completed | Trial completion date: May 2024 ➔ Oct 2023 | Trial primary completion date: May 2024 ➔ Oct 2023

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease

Neonatal sepsis due to NDM-1 and VIM-2 co-producing Pseudomonas aeruginosa in Morocco. (PubMed, J Antimicrob Chemother) - "The isolation of XDR P. aeruginosa isolates expressing several carbapenemases in a neonatal intensive care unit is of great concern due to the reduced treatment options, relying only on colistin, but not recommended in neonates, and apramycin, not yet approved for human therapy. Concerns were further elevated due to the resistance to cefiderocol and ATM/AVI, two novel and last-resort antibiotics recommended to treat infections caused by Gram-negative bacteria, particularly XDR P. aeruginosa in adults."

Journal • Critical care • Infectious Disease • Septic Shock

Pharmacodynamic Assessment of Apramycin against Mycobacterium abscessus in a Hollow Fiber Infection Model (ASM Microbe 2024) - "Amikacin (AMI) is often used as part of an antibiotic combination in both the initial and the continuation treatment phases for M. abscessus infections. Apramycin exhibited promising pharmacodynamic activity against M. abscessus and may be a useful aminoglycoside for treating pulmonary infections caused by this pathogen. However, none of the doses were capable of entirely preventing regrowth, suggesting that apramycin should be used as part of a combination."

PK/PD data • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Quantifying the Contribution of Resistance Genes to Apramycin MICs in Carbapenem-Resistant Klebsiella Pneumoniae (ASM Microbe 2024) - "The apramycin susceptibility breakpoint of ≤4 mg/L was extrapolated from the CLSI amikacin breakpoints. Overall, CR-Kp isolates were highly susceptible to apramycin, suggesting that it may be a promising aminoglycoside to combat infections caused by this pathogen. Resistance to apramycin in CR-Kp was associated with the presence of aac(3)-IV and an aac(3)-II allele. Molecular diagnostic tests that predict phenotypic resistance based on genotype could help with antibiotic selection."

Infectious Disease • Pneumonia