apramycin (EBL-1003) / Juvabis - LARVOL DELTA

"One Health"-based epidemiological investigation reveals the emergence of carbapenem-resistant Morganella spp. across diverse ecological niches. (PubMed, J Glob Antimicrob Resist) - "CRM occur across multiple One Health niches. The findings highlight environmental and non-human reservoirs as potential contributors to their dissemination and identify blaPER-4 and aac(3)-IV as resistance-associated genes requiring further study."

Journal

High-throughput screening to enable structural and functional studies of AprL in apramycin biosynthesis | Poster Board #1143 (ACS-Fall 2026) - "Ongoing work aims to connect these biochemical observations with molecular features that govern AprL function within the apramycin pathway. More broadly, this approach demonstrates how high-throughput screening can streamline the characterization of biosynthetic enzymes and support mechanistic studies relevant to antibiotic development."

Comparative Analysis of Drug Resistance Differences and Molecular Transmission Characteristics Between Animal-Derived Diarrheagenic and Non-Diarrheagenic Escherichia coli in China (2011-2021). (PubMed, J Glob Antimicrob Resist) - "DEC showed a low prevalence in healthy farmed animals, with the host source having a greater impact on the transmission of antibiotic resistance than the pathogenic type itself. The present findings provide a scientific basis for the rational use of antibiotics and monitoring of antibiotic resistance risks in the Livestock Farming industry."

Journal

Molecular epidemiology and pathogenic potential of mcr-1-positive Escherichia coli isolated from healthy and diseased poultry in Jiangxi, China. (PubMed, Front Microbiol) - "All 24 isolates exhibited colistin resistance and 100% multidrug resistance. High resistance rates were observed for apramycin (100%), sulfisoxazole (100%), ampicillin (95.83%), ceftiofur (95.83%), tetracycline (95.83%), and sulfamethoxazole-trimethoprim (95.83%), whereas all isolates remained susceptible to meropenem...Intestinal E. coli from healthy poultry carried higher resistance burden and virulence potential, revealing a hidden reservoir. These findings suggest the need for expanded surveillance, prudent antimicrobial use, and functional validation to further assess the potential dual threat to animal and public health."

Journal • Infectious Disease

Purification and evaluation of anti-inflammatory and antioxidant properties of an apramycin-like compound from Microbacterium barkeri. (PubMed, Nat Prod Res) - "Thin-layer chromatography of the crude extract yielded six fractions, of which MB4 compound showed the highest antimicrobial activity. Molecular docking studies against IL-1 and IL-18 receptors revealed binding energies of -6.85 kcal/mol and -7.72 kcal/mol, respectively. These results highlight the pharmacological potential of the apramycin-like aminoglycoside compound from Microbacterium barkeri."

Journal • IL18

Apramycin resistance in bacteria isolated from animals: A systematic review and meta-analysis. (PubMed, Can Vet J) - "The low overall resistance rates, despite decades of apramycin use, are encouraging. However, the apparent increase over time for E. coli and the limited available data regarding the effect of apramycin use on apramycin resistance highlight the gaps in evidence and challenges in interpreting the role of apramycin use in apramycin resistance of human or animal pathogens."

Clinical • Journal • Retrospective data • Review

Gentamicin triggers fatty acid oxidation-dependent mitochondrial ROS, driving greater nephrotoxicity than apramycin and other aminoglycosides. (PubMed, Free Radic Biol Med) - "Furthermore, we found that only gentamicin and, to a lesser extent, arbekacin and kanamycin induced a prominent increase in the mitochondrial fatty acid oxidation (FAO)-dependent production of H2O2. Apramycin, paromomycin, neomycin, dibekacin, geneticin, amikacin, tobramycin, and plazomicin stimulated neither FAO nor H2O2 production in kidney mitochondria...Gentamicin congener C1, apramycin, and 10 other tested aminoglycosides do not stimulate mitochondrial ROS production, and the use of antioxidants to protect the kidneys against these aminoglycosides is not a reasonable strategy. Cilastatin protects against aminoglycoside-induced glomerular damage independent of the inhibition of aminoglycoside transport into kidney cells."

Journal

Phosphate-tagged substrate recognition by a PrmC-like methyltransferase in apramycin biosynthesis. (PubMed, Int J Biol Macromol) - "Structure-guided docking, molecular dynamics simulations, and mutational analysis show that the homodimer forms a composite, positively charged pocket for recognition of the O-5 phosphate tag, whereas the flexible loop positions the 7'-amino group of the pseudotrisaccharide substrate for methyl transfer. Together, these findings establish AprI as an unusual PrmC-like protein methyltransferase repurposed for tailoring phosphorylated natural products, and open opportunities to engineer biocatalysts for site-selective aminoglycoside diversification."

Journal

Systematic review of apramycin resistance in bacteria from humans and animals (ESCMID Global 2026) - No abstract available

Review

High pulmonary exposure and potent antibacterial activity of inhaled apramycin in experimental Acinetobacter baumannii pneumonia (ESCMID Global 2026) - No abstract available

Infectious Disease • Pneumonia

Physiologically-based pharmacokinetic modelling of apramycin to optimise dosing in healthy and renally impaired populations (ESCMID Global 2026) - No abstract available

Clinical • PK/PD data

The efficacy of apramycin use in animals: a scoping review. (PubMed, Vet J) - "The remaining inferred effects, either without a comparison group (uncontrolled studies) or without statistical analysis between groups. Data suggest that apramycin can be effective for the treatment and prevention of enteric disease in calves, piglets, poultry and rabbits, at least under certain production systems, predominantly against disease caused by E. coli, but more robust data and studies involving current production systems are needed."

Journal • Infectious Disease

Biosynthesis and biotechnological engineering of aminoglycosides: Pathways, enzymes, and industrial prospects. (PubMed, Int J Biol Macromol) - "The biosynthetic routes of key AGs such as neomycin (NEO), kanamycin (KAN), gentamicin (GEN), tobramycin (TOB), apramycin (APR), and sisomicin (SIS) have been mapped out, involving enzymatic steps like aminocyclitol core formation, glycosylation, and tailoring modifications. Due to rising concerns over bacterial resistance, nephrotoxicity, and ototoxicity, biotechnology approaches that modify enzymes or reprogram pathways provide promising strategies for developing next-generation AGs. This review summarizes current advances in AG biosynthesis, emphasizes enzyme-based methods, and outlines future directions for industrial production and the rational design of AG derivatives via biotechnology."

Journal • Review

CRISPR-Cas Based Plasmid Design for Multidrug Resistant Klebsiella Pneumoniae Isolates. (PubMed, FEMS Microbiol Lett) - "Minimum inhibitory concentrations (MICs) of imipenem, meropenem, and ertapenem were determined according to EUCAST guidelines...Apramycin (50 μg/mL) was identified as a suitable selection marker. The pSGKP-AmpR(Pro)-ApmR plasmid was successfully constructed, whereas Cas9 and APOBEC constructs could not be cloned. Overall, this study highlights technical challenges in developing CRISPR-based tools for MDR K. pneumoniae and emphasizes the need for isolate-specific plasmid design and gRNA optimization."

Journal • Infectious Disease • Pneumonia

G1405 Ribosomal Methyltransferase-Driven Antibacterial Resistance Affects the 4,5-Disubstituted-2-deoxystreptamine Class of Aminoglycoside Antibiotics. (PubMed, JACS Au) - "In contrast, AGA modifications that enhance affinity for the drug binding pocket will afford compounds that are not susceptible to G1405 RMTase activity, as is found for propylamycin and the apralogs. Future antibiotic discovery campaigns based on 4,5-AGAs and apramycin should take these findings into account."

Journal

Prevalence and genotyping of Pseudomonas aeruginosa from food and human sources. (PubMed, Sci Rep) - "The results of testing of 50 P. aeruginosa isolates against sixteen antibiotics revealed a relatively high antibiotic resistance for Amoxicillin (100%), Erythromycin (98%), Cephradine (90%), Colistin (82%), Oxytetracyclin, (79%), Chloramphenicol (70%), Doxycycline (70%), and Kanamycin (62%) and high susceptibility for Imipenem (96%), Apramycin (94%), Amikacin (90%), Norfloxacin (78%), Sulphamethoxazol (86%), Enrofloxacin (64%), and Ofloxacin (60%). The dendrogram investigation by ERIC-PCR of 10 clinical P. aeruginosa isolates revealed two main clusters and 10 different ERIC-PCR patterns. The presence of P. aeruginosa isolates in food may represent a potential public health concern, with the need for further epidemiological studies, as well as whole-genome sequencing and correlations of P. aeruginosa in water, food samples, and human infections."

Journal • Infectious Disease

First Isolation of Klebsiella pneumoniae from Septicaemic Piglets in Poland. (PubMed, Microorganisms) - "All the isolates obtained from affected lungs were susceptible to apramycin, ceftiofur, gentamycin, neomycin, and spectinomycin, presented intermediate susceptibility to florfenicol, and were resistant to other tested antibiotics. MLST analysis of the isolates demonstrated a complex metabolic profile of the bacteria with genes attributable to the hypervirulent phenotype. To the best of our knowledge, we documented the first outbreak of K. pneumoniae septicaemia in suckling piglets reared in Poland."

Journal • Infectious Disease • Pneumonia

Multicentre preclinical profiling of apramycin for the treatment of nontuberculous mycobacteria. (PubMed, EBioMedicine) - "For M. abscessus and M. chelonae, the APR MIC90 was four-to eight-fold lower than that of AMK, and demonstrated enhanced bacterial killing. Collectively, our findings suggest APR has potent activity against NTM and warrants consideration for further clinical development."

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

Design, Synthesis, and Biological Evaluation of 6″-Modified Apramycin Derivatives to Overcome Aminoglycoside Resistance. (PubMed, Pharmaceutics) - "Moreover, the new compounds exhibited the ability to circumvent aminoglycoside resistance mediated by enzymatic modification and showed reduced cytotoxicity in mammalian cell assays. The distinctive pharmacological properties of apramycin and its newly synthesized derivatives, particularly their resilience to common resistance mechanisms and low cytotoxicity, highlight apramycin as a valuable structural scaffold for the development of next-generation aminoglycoside antibiotics with improved efficacy and safety."

Journal • Infectious Disease

Enhanced activity of apramycin and apramycin-based combinations against Mycobacteroides abscessus. (PubMed, J Antimicrob Chemother) - "Apramycin exhibits more potent in vitro activity against a diverse set of M. abscessus and other rapidly growing mycobacteria than currently recommended aminoglycosides."

Journal • Infectious Disease • Nontuberculous Mycobacterial Disease • Otorhinolaryngology

The novel plasmid pCF1 can be acquired by sensitive Pseudomonas aeruginosa in the lungs of people with CF and cause extreme tobramycin resistance (NACFC 2025) - "This gene also produced resistance to kanamycin and gentamicin; but neither the aac(3)-like gene nor aph(3)-Ib gene conferred resistance to amikacin, netilmicin, apramycin, and plazomicin. The novel pCF1 plasmid encodes a novel aminoglycoside N-acetyltransferase that produces eTobR and can be transferred to sensitive Pa strains from other organisms within the lungs of PwCF. The plasmid produces minimal fitness costs to host Pa and is highly stable even in the absence of antibiotics. These characteristics make pCF1 acquisition a particular threat to the health of PwCF."

Infectious Disease

Structure-Guided Mechanistic Investigation of Stereochemical Inversion during the Octose Formation Catalyzed by an Atypical Transaldolase AprG in the Biosynthesis of Apramycin. (PubMed, ACS Catal) - "These findings enhance our mechanistic understanding of AprG and suggest strategies for engineering biocatalysts with tailored stereochemical properties. More broadly, this work provides a framework for modifying transaldolase activity, expanding its potential applications in chemoenzymatic synthesis and metabolic engineering."

Journal

Antibiotics and non-traditional antimicrobial agents for carbapenem-resistant Acinetobacter baumannii in Phase 1, 2, and 3 clinical trials. (PubMed, Expert Opin Investig Drugs) - "Specifically, 9 antibiotics are in Phase 1 (R-327, xeruborbactam/QPX-7728, upleganan/SPR-206, MRX-8, QPX-9003, zifanocycline/KBP-7072, apramycin/EBL-1003, zosurabalpin/RG-6006, and ANT-3310), two in Phase 2 (BV-100, OMN-6), and two in Phase 3 (zidebactam/WCK-5222, funobactam/XNW-4107) clinical trials...In particular, two monoclonal antibodies (TRL-1068, CMTX-101), a phage therapy (Phagebank), an immune-modulating agent (recombinant human plasma gelsolin/Rhu-pGSN), a microbiome-modulating agent (SER-155), and an engineered cationic antibiotic peptide (PLG-0206). Several agents with promising characteristics against CRAB infections are in clinical development (Phases 1, 2, and 3). The urgent need for therapeutic options against CRAB infections necessitates optimizing efforts and time for introducing successfully studied agents into clinical practice."

Journal • Review • Infectious Disease • GSN

Synergistic activity of silver nanoparticles and antibiotics: apramycin against Escherichia coli. (PubMed, Nanoscale Adv) - "Severe damage in bacteria walls, including double membrane rupture and cytoplasm leakage, was observed when the combination of apramycin and silver was used. In general, the presence of apramycin has promoted silver uptake by bacteria."

Journal

Prevalence and antimicrobial resistance of Streptococcus suis isolated from local pig breeds in Jiangxi Province, China. (PubMed, Front Vet Sci) - "Antimicrobial susceptibility testing revealed that >98% of isolates were susceptible to carbapenems (meropenem and imipenem), followed by doxycycline (71.6%), ceftiofur (65.9%), spectinomycin (64.4%), and amoxicillin (55.8%). High resistance rates were observed for tilmicosin (96.6%), sulfadiazine (92.8%), colistin (89.9%), apramycin (88.9%), chlortetracycline (87.5%), tiamulin (83.2%), and kanamycin (79.8%)...Multidrug-resistant S. suis strains have become widespread among local pig breeds. This study could provide evidence-based guidance for developing effective prevention and control strategies against S. suis infections and protecting valuable genetic resources of indigenous pig breeds."

Journal • Infectious Disease