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

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

Antimicrobial resistance among imipenem-non-susceptible Escherichia coli and Klebsiella pneumoniae isolates, with an emphasis on novel β-lactam/β-lactamase inhibitor combinations and tetracycline derivatives: The Taiwan surveillance of antimicrobial resistance program, 2020-2022. (PubMed, J Microbiol Immunol Infect) - "This study highlights significant resistance patterns of INS-EC and INS-KP isolates in Taiwan. The declining susceptibility rates and the rising prevalence of genetic resistance determinants highlight the importance of ongoing surveillance and antimicrobial stewardship."

Journal • Infectious Disease • Pneumonia

Detection of Delafloxacin Resistance Mechanisms in Multidrug-Resistant Klebsiella pneumoniae. (PubMed, Antibiotics (Basel)) - " In our study, 43 K. pneumoniae strains were assessed, antimicrobial susceptibility testing was performed via the broth microdilution method, and the minimum inhibitory concentration (MIC) values for ciprofloxacin, delafloxacin, levofloxacin, moxifloxacin, ceftazidime, cefotaxime, and imipenem were determined. We conclude that multiple mutations in QRDRs, in combination with OqxAB and AcrAB efflux pumps, achieved delafloxacin resistance in K. pneumoniae. In our study, we report on NDM-1-producing K. pneumoniae ST147 in Hungary."

Journal • Infectious Disease • Pneumonia

The future approach for the management of acute bacterial skin and skin structure infections. (PubMed, Curr Opin Infect Dis) - "Early discharge from the hospital should be considered in patients with ABSSSI at a high risk of methicillin-resistant Staphylococcus aureus and in vulnerable patients for which hospitalization may have detrimental consequences. In elderly individuals, patients with diabetes mellitus, oncological people who need for continuing their healthcare pathway, this approach may reduce complications and costs related to hospitalization."

Journal • Diabetes • Infectious Disease • Metabolic Disorders

Assessment of in vitro interactions between delafloxacin and other antimicrobials against multi-drug resistant Pseudomonas aeruginosa strains. (PubMed, J Chemother) - "Our studies showed delafloxacin exhibited four times greater in-vitro activity against MDR-PA strains than levofloxacin compared with both MIC50 and MIC90 results. Delafloxacin + tobramycin and delafloxacin + ceftazidime/avibactam showed synergy in two out of five strains tested at concentrations equal to the MIC. The outcomes of this research also suggest that these combinations may replace therapy for MDR-PA strains."

Journal • Preclinical • Infectious Disease

Ciprofloxacin-susceptible but levofloxacin-resistant Pseudomonas aeruginosa clinical strains with Vitek®2: which mechanism involved and consequences in case of fluoroquinolone treatment? (PubMed, Eur J Clin Microbiol Infect Dis) - "The phenotype detected by the automate Vitek2® is linked to a likely efflux-pump overexpression mechanism and not fluoroquinolone-target mutation. Regarding this discordant phenotype, an alert should be provided to clinicians concerning the high risk of selecting a fluoroquinolone-resistant mutant."

Journal