Baxdela (delafloxacin) / Menarini, Melinta Therap, Ligand - LARVOL DELTA

SUSCEPTIBILITY OF MULTI-DRUG RESISTANT ESCHERICHIA COLI AND KLEBSIELLA PNEUMONIAE TO ORAL ANTIBIOTICS IN AUSTRALIA. (PubMed, J Glob Antimicrob Resist) - "The favourable results support the use of mecillinam, tebipenem, sulopenem, faropenem, fosfomycin and omadacycline against multi-drug resistant E. coli. Mecillinam, sulopenem and fosfomycin may be useful for multi-drug resistant K. pneumoniae in Australia."

Journal • Infectious Disease • Nephrology • Pneumonia

Using delafloxacin, a 4th generation fluoroquinolone, in combination with nebulised tobramycin to eradicate Pseudomonas aeruginosa in cystic fibrosis. (PubMed, Respir Med Case Rep) - "Delafloxacin, a fourth-generation fluoroquinolone, has been shown to have superior activity against Pseudomonas aeruginosa compared to ciprofloxacin in-vitro. We show herein, what we believe is the first documented successful eradication of Pseudomonas aeruginosa in a person with CF following a new isolation of the pathogen using oral delafloxacin in combination with nebulised tobramycin, instead of ciprofloxacin after the failure of first line treatment and the emergence of ciprofloxacin-resistance on antimicrobial sensitivity testing."

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

Delafloxacin and levofloxacin activities on Helicobacter pylori in Bulgaria over four years. (PubMed, Diagn Microbiol Infect Dis) - "Given that fluoroquinolone-based eradication regimens can be used as a second- or third-line therapy for H. pylori, testing the susceptibility of levofloxacin-resistant strains to delafloxacin could provide a useful option for eradication of the frequent and potentially carcinogenic bacteria. New regimens, such as the combination of vonoprazan with delafloxacin and another antibiotic deserve investigation."

Journal • Infectious Disease

Genetic Mechanisms of Antimicrobial Non-Susceptibility to Novel Fluoroquinolone Delafloxacin Among Bulgarian Clinical Isolates of Streptococcus agalactiae. (PubMed, Curr Issues Mol Biol) - "A statistical significance in the distribution of serotypes between delafloxacin-resistant and delafloxacin-susceptible strains was found. These findings highlight a concerning pattern of drug resistance developing prior to the introduction of a new medication, attributed to the extensive use of current antibiotics."

Journal

Structural basis of topoisomerase targeting by delafloxacin. (PubMed, Nat Commun) - "The unprecedented resolution allows comprehensive imaging of water-metal ion links integrating enzyme and DNA through drug-bound and active-site Mg2+ ions plus the discovery of enzyme-bound K+ ions. Our studies on delafloxacin action suggest that intrinsic target affinity contributes to its activity against quinolone-resistant bacteria."

Journal • Infectious Disease • Pneumococcal Infections • Pneumonia • Respiratory Diseases

Fluoroquinolones for Dermatologists: A Practical Guide to Clinical Use and Risk Management. (PubMed, Pharmaceuticals (Basel)) - "Delafloxacin demonstrated over 90% cure rates in trials for complicated skin infections...Resistance to ciprofloxacin exceeds 20 percent in Escherichia coli and P. aeruginosa in some populations... Fluoroquinolones remain clinically useful in dermatology when prescribed selectively. Their appropriate use requires careful attention to patient risk factors along with their evolving resistance patterns and ongoing stewardship efforts."

Journal • Review • Dermatology • Infectious Disease

Genetic determinants of gene amplifications alter frequency and evolutionary trajectory of antibiotic resistance in Staphylococcus aureus. (PubMed, bioRxiv) - "We previously showed that the opportunistic pathogen Staphylococcus aureus evolves resistance to the dual-targeting fluoroquinolone delafloxacin (DLX) that inhibits both the DNA gyrase and DNA topoisomerase IV via gene amplifications of an efflux pump encoding gene sdrM...Finally, mutants in the tyrosine recombinase XerC that is involved in chromosomal separation were deficient for sdrM amplifications, indicating that XerC is a novel modulator of amplification formation, maintenance, or selection. Thus, our work sheds light on genetic factors that alter gene amplification-mediated evolutionary trajectories to antibiotic resistance in S. aureus and can potentially unlock mechanisms by which such evolution of resistance can be inhibited."

Journal • Infectious Disease

Variable In Vitro Efficacy of Delafloxacin on Multidrug-Resistant Pseudomonas aeruginosa and the Detection of Delafloxacin Resistance Determinants. (PubMed, Antibiotics (Basel)) - "Antimicrobial susceptibility testing was performed via broth microdilution, and the minimum inhibitory concentration (MIC) values for ciprofloxacin, levofloxacin, delafloxacin, ceftazidime and imipenem were determined. Multiple QRDR mutations combined with several efflux pumps confer delafloxacin resistance in P. aeruginosa. Among the different detected multidrug-resistant P. aeruginosa strains in this study, we also report on an NDM-1 producing P. aeruginosa ST316 in Hungary."

Journal • Preclinical

In Vitro Activity of Novel Antibiotics Against Corynebacterium spp. Clinical Isolates Responsible for Difficult-to-Treat Infections. (PubMed, Microb Drug Resist) - "The activity of ceftaroline (MIC90 >2 mg/L), ceftobiprole (MIC90 >8 mg/L), and delafloxacin (MIC90 >1 mg/L) was limited. By contrast, other molecules tested showed higher activity with low MIC90 values: linezolid (MIC90 ≤0.5 mg/L), tedizolid (MIC90 = 0.12 mg/L), dalbavancin (MIC90 = 0.12 mg/L), tigecycline (MIC90 = 0.12 mg/L), eravacycline (MIC90 = 0.06 mg/L), and omadacycline (MIC90 = 0.5 mg/L). One C. striatum strain exhibited a high level of daptomycin resistance after antibiotic exposure (MIC >16 mg/L). The in vitro activity of most of these novel antibiotics is excellent against Corynebacterium clinical isolates. They could represent a real alternative for treating DTT infections due to Corynebacterium spp."

Journal • Preclinical • Infectious Disease

Deciphering the Timing of DNA Repair to Sensitize Staphylococcus aureus to Fluoroquinolones (ASM Microbe 2025) - "A new FQ, delafloxacin (Dela), was recently approved for treating S. aureus infections...Interestingly, we also found that starvation increased the survival of mutants lacking recA, suggesting that alternative DNA repair and detoxification pathways could be important for S. aureus survival. The discovery of these pathways could lead to novel targets to increase the efficacy of FQ treatment."

Infectious Disease

Structural insight in understanding the impact of mutation at position 88 and 94 of DNA gyrase A of Mycobacterium tuberculosis in developing resistance against delafloxacin. (PubMed, J Biol Phys) - "Based on literature information on drug-resistance related study for DNA gyrase, we generated 4 different mutant models 3ILW_G88A, 3ILW_G88C, 3ILW_D94G, and 3ILW_D94H by inserting two mutations at each position 88 and 94 in DNA gyrase chain A. Antibiotics Clinafloxacin, Gatifloxacin, Moxifloxacin, Sitafloxacin, Prulifloxacin, Besifloxacin, Delafloxacin, Ozenoxacin were docked with 3ILW_wild to understand their stability, binding affinity, and interaction pattern with the wild-type DNA gyrase (3ILW_wild). It is worth noting that mutation at position 94 of DNA gyrase A has a very profound effect as it shows a positive contribution towards increased resistance due to reduced binding affinity with delafloxacin. This study explains the structural changes and mechanism behind the resistance against Delafloxacin, and may also guide the structural changes required in existing Delafloxacin or other antibiotics to develop new therapeutics to overcome the issue of resistance."

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

Molecular Dynamics-Guided Repositioning of FDA-Approved Drugs for PD-L1 Inhibition with In Vitro Anticancer Potential. (PubMed, Int J Mol Sci) - "From this screening, five promising compounds-vorapaxar, delafloxacin, tenofovir disoproxil, pivmecillinam, and fursultiamine-showed significant binding affinities to PD-L1 and demonstrated cytotoxic activity against A549 lung tumor cells. These findings suggest that pivmecillinam has promising immunomodulatory potential and could serve as a candidate for further development in cancer immunotherapy. Overall, this study underscores the value of integrating high-throughput MD and experimental approaches for drug repositioning to identify novel therapeutic agents."

FDA event • Journal • Preclinical • Lung Cancer • Oncology • Solid Tumor

An overview of potential combinations therapies with ceftriaxone as a treatment for gonorrhea. (PubMed, Expert Rev Anti Infect Ther) - "Of these 16 antimicrobials, we reject antimicrobials such as fosfomycin due to poor clinical efficacy and tigecycline due to its considerably longer half-life which would likely select for tetracycline resistance. The most promising agents for combination with ceftriaxone are zoliflodacin, delafloxacin, sitafloxacin, eravacycline and possibly gepotidacin and gentamicin. Clinical studies should be conducted to evaluate the efficacy of these combinations on the eradication of N. gonorrhoeae and their impact on AMR in N. gonorrhoeae and other bacterial species."

Journal • Review • Infectious Disease

Suicidal thoughts and behaviors associated with fluoroquinolone antibiotics: a real-world pharmacovigilance analysis. (PubMed, Front Pharmacol) - "This study aimed to systematically and scientifically investigate the potential associations between the use of fluoroquinolone antibiotics (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, norfloxacin, and delafloxacin) and suicidal thoughts and behaviors using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Subgroup analysis revealed a slight increase in the RORs for suicidal thoughts and behaviors in the <18 years and the 18-24 years age group; however, no significant safety signal was detected based on the EBGM05s in these populations. Further comprehensive and prospective studies are necessary to confirm and validate these findings."

Adverse events • Journal • Real-world evidence • Psychiatry • Suicidal Ideation

The latest updates on the proper use of fluoroquinolones - Actualisation 2025 update by the SPILF and the GPIP. (PubMed, Infect Dis Now) - No abstract available

Clinical guideline • Journal

Newly developed antibiotics against multidrug-resistant and carbapenem-resistant Gram-negative bacteria: action and resistance mechanisms. (PubMed, Arch Microbiol) - "Porin modifications reduce the influx of antibiotics, whereas overexpression of efflux pumps, particularly those in the resistance-nodulation-cell division (RND) family, actively expels antibiotics from bacterial cells, significantly lowering intracellular drug concentrations and leading to treatment failure.This review examines the mechanisms of action, resistance profiles, and pharmacokinetic/pharmacodynamic characteristics of newly developed antibiotics designed to combat infections caused by MDR and carbapenem-resistant Gram-negative pathogens. The antibiotics discussed include ceftazidime-avibactam, imipenem-relebactam, ceftolozane-tazobactam, meropenem-vaborbactam, aztreonam-avibactam, delafloxacin, temocillin, plazomicin, cefiderocol, and eravacycline."

Journal • Review • Critical care • Infectious Disease

In vitro activity of delafloxacin against Escherichia coli isolates producing bacteraemia with different susceptibility profiles to ciprofloxacin and levofloxacin (ESCMID Global 2025) - No abstract available

Preclinical

Delafloxacin as the only anionic flouroquinolone with excellent activity against multi-drug resistant bacteria especially in acidic environments: an in vitro study (ESCMID Global 2025) - No abstract available

Preclinical

Assessment of the use of delafloxacin for the treatment of prosthetic joint infections caused by quinolone-resistant strains and anaerobes (ESCMID Global 2025) - No abstract available

Infectious Disease

Effect of pH on the bacteriostatic and bactericidal activities of delafloxacin against Escherichia coli isogenic strains harboring diverse chromosomal and plasmid-mediated fluoroquinolone resistance mechanisms (ESCMID Global 2025) - No abstract available

Clinical outcomes of delafloxacin in osteoarticular infections: a multicentre study in northern Spain (ESCMID Global 2025) - No abstract available

Clinical • Clinical data • Infectious Disease

A case of ulceroglandular tularemia with prolonged-relapsing course for a period of five years finally successfully treated with an oral combination therapy with delafloxacin and rifampicin for the first time (ESCMID Global 2025) - No abstract available

Clinical • Combination therapy

In vitro activity of delafloxacin against quinolone-resistant Staphylococcus aureus should always be tested (ESCMID Global 2025) - No abstract available

Preclinical

Comparative phenotypic and genotypic antimicrobial susceptibility surveillance in Achromobacter spp. through whole genome sequencing. (PubMed, Microbiol Spectr) - "Newer agents like delafloxacin, plazomicin, and omadacycline showed little or no activity, while minimum inhibitory concentrations were low for eravacycline. In general, the species other than A. xylosoxidans showed lower MIC50 and MIC90, especially to carbapenems and β-lactamase inhibitor combinations like piperacillin-tazobactam, meropenem-vaborbactam, and imipenem-relebactam...Our study provides phenotypic data regarding identification and susceptibility testing and correlates this with the genotypic characterization of 109 clinical isolates belonging to Achromobacter spp. This comprehensive study sheds light on the phenotypic and genotypic character of this bacteria, that is of increasing clinical relevance in hospital-acquired infections."

Journal • Infectious Disease

COPAT: Comparing Oral Versus Parenteral Antimicrobial Therapy (clinicaltrials.gov) - P4 | N=90 | Terminated | Sponsor: West Virginia University | N=135 ➔ 90 | Trial completion date: Aug 2024 ➔ Feb 2025 | Enrolling by invitation ➔ Terminated | Trial primary completion date: Aug 2024 ➔ Feb 2025; DSMB recommendation based on safety benefit in Experimental (oral) arm

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Respiratory Diseases • Urology