Xtoro (finafloxacin) / Amgen - LARVOL DELTA

Evaluation of pH-dependent effect on finafloxacin activity against Pseudomonas aeruginosa isolates (ECCMID 2024) - No abstract available

Layering vaccination with antibiotic therapy results in protection and clearance of Burkholderia pseudomallei in Balb/c mice. (PubMed, Infect Immun) - "Vaccination was also shown to improve the outcome, in a composite measure of survival and clearance. In summary, layering a subunit vaccine with the antibiotic finafloxacin is a promising therapeutic alternative for use in the treatment of B. pseudomallei infections."

Journal • Preclinical • Infectious Disease

Comparison of the in vitro antibacterial activity of ofloxacin, levofloxacin, moxifloxacin, sitafloxacin, finafloxacin, and delafloxacin against Mycobacterium tuberculosis strains isolated in China. (PubMed, Heliyon) - "SFX exhibits the highest inhibitory activity against Mtb in vitro and THP-1 cell lines, which exhibits partial-cross resistance with MFX. There might be correlation between FQs resistance and mutations in gyrB G520T and G520A.Our findings provide crucial insights into the potential clinical application of SFX and DFX in the treatment of Mtb infections."

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

In Vitro Activity of Finafloxacin against Panels of Respiratory Pathogens. (PubMed, Antibiotics (Basel)) - "Broth microdilution assays were performed at neutral and acidic pH, to determine antimicrobial activity. Finafloxacin demonstrated superior activity at reduced pH for all of the bacterial species investigated, highlighting the requirement to determine the activity of antimicrobials in host-relevant conditions."

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

Antibiotic discovery against Piscirickettsia salmonis using a combined in silico and in vitro approach. (PubMed, Microb Pathog) - "The in silico results of this work showed that flumequine (-6.6 kcal/mol), finafloxacin (-7.2 kcal/mol), rosoxacin (-6.6 kcal/mol), elvitegravir (-6.4 kcal/mol), sarafloxacin (-8.3 kcal/mol), orbifloxacin (-7.9 kcal/mol), and sparfloxacin (-7.2 kcal/mol) are docked with good affinities in the DNA binding domain of the Piscirickettsia salmonis GyrA subunit. In the in vitro inhibition assay, it was observed that most of these molecules inhibit the growth of Piscirickettsia salmonis, except for elvitegravir. We believe that this methodology could help to significantly reduce the time and cost of antibiotic discovery trials to combat Piscirickettsia salmonis within the salmonid farming industry."

Journal • Preclinical

Clinical efficacy and safety of novel antibiotics for complicated urinary tract infection: A systematic review and meta-analysis of randomized controlled trials. (PubMed, Int J Antimicrob Agents) - "While showing similar safety, the investigated novel antibiotics may be more effective than the conventional ones for patients with cUTIs. However, as the pooled evidence relating to CCR remained inconclusive, further studies are required to address this issue."

Journal • Retrospective data • Review • Infectious Disease • Nephrology

Efficacy of finafloxacin in a murine model of inhalational glanders. (PubMed, Front Microbiol) - "It is therefore recommended that cases are treated with the same therapies as used for melioidosis, which for prophylaxis, is co-trimoxazole (trimethoprim/sulfamethoxazole) or co-amoxiclav (amoxicillin/clavulanic acid). However, finafloxacin was more effective than co-trimoxazole in controlling bacterial load within tissues and demonstrating clearance in the liver, lung and spleen following 14 days of therapy. In summary, finafloxacin should be considered as a promising alternative treatment following exposure to B. mallei."

Journal • Preclinical

An Investigation into the Re-Emergence of Disease Following Cessation of Antibiotic Treatment in Balb/c Mice Infected with Inhalational Burkholderia pseudomallei. (PubMed, Antibiotics (Basel)) - "Following cessation of treatment, the infection re-established in some animals. Finafloxacin prevented the re-establishment of the infection for longer than co-trimoxazole, and it is apparent based on the protection offered, the development of clinical signs of disease, bodyweight loss and bacterial load, that finafloxacin was more effective at controlling infection when compared to co-trimoxazole."

Journal • Preclinical • Immunology • Infectious Disease

Potential new fluoroquinolone treatments for suspected bacterial keratitis. (PubMed, BMJ Open Ophthalmol) - "For example, the new generation FQs, avarofloxacin, delafloxacin, finafloxacin, lascufloxacin, nadifloxacin, levonadifloxacin, nemonoxacin and zabofloxacin have good activity against the common ophthalmic pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae and several of the Enterobacteriaceae However, because there are no published ophthalmic break-point concentrations, the susceptibility of an isolated micro-organism to a topical FQ is extrapolated from systemic break-point data and wild type susceptibility. Notably, we found significant variation in the reported corneal and aqueous FQ concentrations so that reliance on the reported mean concentration may not be appropriate, and the first quartile concentration may be more clinically relevant. The provision of the MIC for the microorganism together with the achieved lower (first) quartile concentration of a FQ in the cornea could inform management decisions such as whether to..."

Journal • Review • Infectious Disease • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology • Pneumococcal Infections • Pneumonia

Investigation of a combination therapy approach for the treatment of melioidosis. (PubMed, Front Microbiol) - "Doxycycline was also unable to control the levels of bacteria within tissues to the extent that doxycycline and finafloxacin used in combination or finafloxacin (as a sole therapy) could. In summary, finafloxacin is a promising therapy for use in the event of exposure to B. pseudomallei."

Combination therapy • Journal • Infectious Disease

In Vitro Activity of Delafloxacin and Finafloxacin against Mycoplasma hominis and Ureaplasma Species. (PubMed, Microbiol Spectr) - "Finafloxacin displayed activity similar to moxifloxacin but superior to levofloxacin against M. hominis and Ureaplasma spp. Our findings demonstrate that delafloxacin is a promising fluoroquinolone with outstanding activity against fluoroquinolone-resistant M. hominis and Ureaplasma spp."

Journal • Preclinical • Infectious Disease

Delafloxacin, Finafloxacin, and Zabofloxacin: Novel Fluoroquinolones in the Antibiotic Pipeline. (PubMed, Antibiotics (Basel)) - "The introduction of these novel fluoroquinolones into daily practice extends the possible indications of antibiotics into different bacterial infections, and provides treatment options in difficult-to-treat infections. However, some reports of delafloxacin resistance have already appeared, thus underlining the importance of the prudent use of antibiotics."

Journal • Review • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Otorhinolaryngology • Pneumonia • Pulmonary Disease • Respiratory Diseases

Discovery and Development of Antibacterial Agents: Fortuitous and Designed. (PubMed, Mini Rev Med Chem) - "These include solithromycin, plazomicin, lefamulin, omadacycline, eravacycline, delafloxacin, zabofloxacin, finafloxacin, nemonoxacin, gepotidacin, zoliflodacin, cefiderocol, BAL30072, avycaz, zerbaxa, vabomere, relebactam, tedizolid, cadazolid, sutezolid, triclosan and afabiacin. This article aims to review the investigational and recently approved antibacterials with a focus on their structure, mechanisms of action/resistance, and spectrum of activity. Delving deep, their success or otherwise in various phases of clinical trials is also discussed while attributing the same to various causal factors."

Journal

Finafloxacin, a Novel Fluoroquinolone, Reduces the Clinical Signs of Infection and Pathology in a Mouse Model of Q Fever. (PubMed, Front Microbiol) - "The efficacy of finafloxacin was evaluated in vivo using the A/J mouse model of inhalational Q fever and was compared to doxycycline, the standard treatment for this infection and ciprofloxacin, a comparator fluoroquinolone. However, histopathological analysis suggested that treatment with finafloxacin reduced tissue damage associated with C. burnetii infection. In addition, we report for the first time, the use of viable counts on axenic media to evaluate antibiotic efficacy in vivo."

Journal • Preclinical • Infectious Disease

Uropathogenic Escherichia coli shows antibiotic tolerance and growth heterogeneity in an in-vitro model of intracellular infection. (PubMed, Antimicrob Agents Chemother) - "We tested antibiotics commonly-prescribed against urinary tract infections (gentamicin, ampicillin, nitrofurantoin, trimethoprim, sulfamethoxazole, ciprofloxacin) and the investigational fluoroquinolone finafloxacin. Intracellularly, kill curves showed biphasic kinetics for both fluoroquinolones, suggesting the presence of drug-tolerant subpopulations. Flow cytometry analysis of TIMERbac fluorescence revealed a marked heterogeneity in intracellular growth of individual bacteria, suggesting that the presence of subpopulations reaching a state of metabolic dormancy was the main reason for increased antibiotic tolerance of intracellular UPEC."

Heterogeneity • Journal • Preclinical • Infectious Disease • Nephrology

Intracellular activity of antibiotics against Coxiella burnetii in a model of activated human THP-1 cells. (PubMed, Antimicrob Agents Chemother) - "At clinically-relevant concentrations, the intracellular bacterial load was reduced 300-fold by levofloxacin and finafloxacin, 40-fold by doxycycline, 4-fold by ciprofloxacin, and was unaffected by azithromycin. Acidification of the culture media reduced antibiotic activity with the exceptions of doxycycline (no change) and finafloxacin (slight improvement). This model may be used to select antibiotics to be evaluated in-vivo."

Journal • Infectious Disease

Structural Characterization of the Millennial Antibacterial (Fluoro)Quinolones-Shaping the Fifth Generation. (PubMed, Pharmaceutics) - "Special attention is given to eight representatives: besifloxacin, delafoxacin, finafloxacin, lascufloxacin, nadifloxacin and levonadifloxacin, nemonoxacin, and zabofloxacin. Antibacterial quinolones class continues to acquire new compounds with antibacterial potential, among other effects. Numerous derivatives, hybrids or conjugates are currently in various stages of research."

Journal • Review

Finafloxacin is an effective treatment for inhalational tularemia and plague in mouse models of infection. (PubMed, Antimicrob Agents Chemother) - "A benefit was demonstrated with finafloxacin, when compared to ciprofloxacin in both models, when therapy was delivered later in the infection. These studies suggest that finafloxacin is an effective alternative therapeutic for the prophylaxis and treatment of inhalational infections with F. tularensis or Y. pestis."

Journal • Preclinical

Fluoroquinolones structural and medicinal developments (2013-2018): Where are we now? (PubMed, Bioorg Med Chem) - "Fluoroquinolones are considered one of the widely utilized antibiotics, specifically, with the recent development of newer generations such as moxifloxacin, delafloxacin and finafloxacin which possess a wider spectrum of activity and improved bioavailability...At present, quinolone scaffold diverse biological activities prompted the fortuitous discovery of novel antimicrobial and anticancer derivatives. Herein, the opponent arguments (2013-2015) regarding the structure activity relationships of fluoroquinolones' antibacterial, anticancer, antifungal activities are inscribed."

Journal • Review • Oncology

Activity of finafloxacin, ciprofloxacin, and imipenem against intracellular Burkholderia thailandensis, Yersinia pseudotuberculosis, and Francisella philomirargia in media at neutral or acidic pH (ECCMID 2019) - "For intracellular infection, human THP-1 monocytes were incubated with bacteria opsonized by human serum, after which non-phagocytosed bacteria were eliminated by incubation with gentamicin (10-100 X its MIC) during 1h. This work highlights the interest of fluoroquinolones for markedly reducing the intracellular reservoirs of B. thailandensis, Y. pseudotuberculosis, and F. philomirargia, with finafloxacin showing additional advantage in acidic environments that are prevalent in infected tissues."

Infectious Disease • Tuberculosis

Treatment of urinary tract infections in the era of antimicrobial resistance and new antimicrobial agents. (PubMed, Postgrad Med) - "The recommended first-line empiric antibiotic therapy for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females is a 5-day course of nitrofurantoin, a 3-g single dose of fosfomycin tromethamine, or a 5-day course of pivmecillinam. High rates of resistance for trimethoprim-sulfamethoxazole and ciprofloxacin preclude their use as empiric treatment of UTIs in several communities, particularly if patients who were recently exposed to them or in patients who are at risk of infections with extended-spectrum β-lactamases (ESBLs)-producing Enterobacteriales...Parenteral treatment options for UTIs due to ESBLs-producing Enterobacteriales include piperacillin-tazobactam (for ESBL-E coli only), carbapenems including meropenem/vaborbactam, imipenem/cilastatin-relebactam, and sulopenem, ceftazidime-avibactam, ceftolozane-tazobactam, aminoglycosides including plazomicin, cefiderocol, fosfomycin, sitafloxacin, and finafloxacin. Ceftazidime-avibactam,..."

Journal • Complement-mediated Rare Disorders • Infectious Disease • Nephrology • Pneumonia • Respiratory Diseases

Pharmacokinetics of intravenous finafloxacin in healthy volunteers. (PubMed, Antimicrob Agents Chemother) - "Individual elimination processes should be evaluated in more detail. Finafloxacin exhibited a favorable safety/tolerability profile."

Journal • Biosimilar • Renal Disease

Developments on antibiotics for multidrug resistant bacterial Gram-negative infections. (PubMed, Expert Rev Anti Infect Ther) - "Recently approved antibiotic formulations; and agents in advanced stages of development, including combinations of β-lactam/β-lactamase inhibitor, novel cephalosporins (cefiderocol), tetracyclines (eravacycline), aminoglycosides (plazomicin), quinolones (delafloxacin and finafloxacin) and pleuromutilins (lefamulin) are discussed in this review...However, most of the new compounds are based on modifications of traditional antibiotic structures challenging their longevity as therapeutic options. More investment is needed for the discovery and clinical development of truly innovative and effective antibiotics without cross resistance to currently used antibiotics."

Journal

Treatment of multidrug-resistant Gram-negative skin and soft tissue infections. (PubMed, Curr Opin Infect Dis) - "MDR-GNB play a major role in SSTIs in patients with underlying immunodeficiency, as well as burn or trauma-related injuries. With the alarming global rise in MDR-GNB resistance, antibiotic therapy for SSTIs is challenging and must be guided by in-vitro susceptibility results. Currently, data extrapolated from other indications and combination therapy can be used empirically pending microbiological data and susceptibilities. Novel antibiotics are currently under development. It is hoped that future clinical trials will be designed to address MDR-GNB SSTIs."

Journal

Demonstration of the broad spectrum in vitro activity of finafloxacin against pathogens of biodefence interest. (PubMed, Antimicrob Agents Chemother) - "In all instances, finafloxacin demonstrated superior activity at low pH. These results highlight the importance of evaluating antimicrobial efficacy in conditions relevant to those encountered in vivo."

Journal • Preclinical