Demonstration of the Broad-Spectrum
            <i>In Vitro</i>
            Activity of Finafloxacin against Pathogens of Biodefense Interest

Barnes, Kay B.; Zumbrun, Steven D.; Halasohoris, Stephanie; Desai, Purvi D.; Miller, Loren M.; Richards, Mark I.; Russell, Paul F.; Bentley, Christine; Harding, Sarah V.

doi:10.1128/aac.01470-19

Cited by 12 publications

(16 citation statements)

References 18 publications

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“…It is possible that the environment created by the immune response fighting the infection may have resulted in an environment of lower pH that would be advantageous to finafloxacin. Finafloxacin is likely to have activity in both arenas, whereas ciprofloxacin is likely to be less effective in an intracellular, more acidic environment ( 28 , 33 ). This may account for some of the subtle differences between the efficacy of finafloxacin in the two models and may explain why 50% of the animals treated with 7 days of finafloxacin “recovered” from infection with F. tularensis when initiated late (at 72 h postchallenge).…”

Section: Discussionmentioning

confidence: 99%

“…This would be very important if either of these bacterial agents were deliberately released. As finafloxacin has also demonstrated the ability to protect mice against B. pseudomallei and has in vitro activity against larger panels of the biothreat agents, it should be considered an alternative broad-spectrum antibiotic for the treatment of all infections of this nature ( 33 , 34 ).…”

Section: Discussionmentioning

confidence: 99%

“…and orally) resulted in an improved clinical outcome over a 10-day course of ciprofloxacin in a phase 2 trial of complicated urinary tract infections (UTIs) and/or pyelonephritis, and it demonstrated the ability to treat fluoroquinolone-resistant uropathogens ( 31 , 32 ). In addition, in vitro activity has been demonstrated against all of the bacterial agents of biodefence interest, with efficacy demonstrated against inhalational infection with Burkholderia pseudomallei and intranasal infection with F. tularensis in vivo ( 33 – 35 ).…”

Section: Introductionmentioning

confidence: 99%

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Finafloxacin Is an Effective Treatment for Inhalational Tularemia and Plague in Mouse Models of Infection

Barnes

Richards

Laws

et al. 2021

Antimicrob Agents Chemother

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Infection with aerosolised Francisella tularensis or Yersinia pestis can lead to lethal disease in humans, if treatment is not initiated promptly. Finafloxacin is a novel fluoroquinolone which has demonstrated broad-spectrum activity against a range of bacterial species in vitro, in vivo and in humans, activity which is superior in acidic, infection-relevant conditions. Human equivalent doses of finafloxacin or ciprofloxacin were delivered at 24 hours (representing prophylaxis), or at 72 or 38 hours (representing treatment) post-challenge with F. tularensis or Y. pestis (respectively), in Balb/c mouse models. In addition, a short course (3 days) of therapy was compared to a longer course (7 days). Both therapies provided a high level of protection against both infections, when administered at 24 hours post-challenge, irrespective of the length of the dosing regimen, however, differences were observed when therapy was delayed. 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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Finafloxacin Is an Effective Treatment for Inhalational Tularemia and Plague in Mouse Models of Infection

Barnes

Richards

Laws

et al. 2021

Antimicrob Agents Chemother

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“…Also, a more prolonged post-antibacterial effect against multiple species was observed compared to other FQNs at acidic pH. The development of bacterial resistance to finafloxacin is less likely in acidic conditions [ 99 , 100 , 149 , 150 ].…”

Section: Compounds In Therapy Since 2000mentioning

confidence: 99%

Structural Characterization of the Millennial Antibacterial (Fluoro)Quinolones—Shaping the Fifth Generation

et al. 2021

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The evolution of the class of antibacterial quinolones includes the introduction in therapy of highly successful compounds. Although many representatives were withdrawn due to severe adverse reactions, a few representatives have proven their therapeutical value over time. The classification of antibacterial quinolones into generations is a valuable tool for physicians, pharmacists, and researchers. In addition, the transition from one generation to another has brought new representatives with improved properties. In the last two decades, several representatives of antibacterial quinolones received approval for therapy. This review sets out to chronologically outline the group of approved antibacterial quinolones since 2000. Special attention is given to eight representatives: besifloxacin, delafoxacin, finafloxacin, lascufloxacin, nadifloxacin and levonadifloxacin, nemonoxacin, and zabofloxacin. These compounds have been characterized regarding physicochemical properties, formulations, antibacterial activity spectrum and advantageous structural characteristics related to antibacterial efficiency. At present these new compounds (with the exception of nadifloxacin) are reported differently, most often in the fourth generation and less frequently in a new generation (the fifth). Although these new compounds’ mechanism does not contain essential new elements, the question of shaping a new generation (the fifth) arises, based on higher potency and broad spectrum of activity, including resistant bacterial strains. The functional groups that ensured the biological activity, good pharmacokinetic properties and a safety profile were highlighted. In addition, these new representatives have a low risk of determining bacterial resistance. Several positive aspects are added to the fourth fluoroquinolones generation, characteristics that can be the basis of the fifth generation. 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.

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“…Finafloxacin is a novel fluoroquinolone that has recently undergone Phase II clinical trials for the treatment of urinary tract infections in hospitalized patients ( Wagenlehner et al, 2018 ). It has enhanced in vitro activity in acidic conditions ( Smith et al, 1988 ; Stubbings et al, 2011 ) and is efficacious against a number of Gram negative and Gram positive organisms including Acinetobacter baumannii, Staphylococcus aureus, Burkholderia pseudomallei , and Francisella tularensis ( Higgins et al, 2010 ; Lemaire et al, 2011 ; Barnes et al, 2017 , 2019a , b ). Finafloxacin has demonstrated good cellular penetration and at acidic pH, an increased accumulation within eukaryotic cells ( Lemaire et al, 2011 ; Chalhoub et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Finafloxacin, a Novel Fluoroquinolone, Reduces the Clinical Signs of Infection and Pathology in a Mouse Model of Q Fever

et al. 2021

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Finafloxacin is a novel fluoroquinolone with optimal antibacterial activity in low pH environments, therefore offering a therapeutic advantage over some traditional antibiotics, in treating bacterial infections associated with acidic foci. Coxiella burnetii, the causative agent of Q fever, is a bacterium which resides and replicates in acidic intracellular parasitic vacuoles. 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. Finafloxacin reduced the severity of the clinical signs of infection and weight loss associated with Q fever, but did not reduce the level of bacterial colonization in tissues compared to doxycycline or ciprofloxacin. 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.

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Demonstration of the Broad-Spectrum In Vitro Activity of Finafloxacin against Pathogens of Biodefense Interest

Cited by 12 publications

References 18 publications

Finafloxacin Is an Effective Treatment for Inhalational Tularemia and Plague in Mouse Models of Infection

Finafloxacin Is an Effective Treatment for Inhalational Tularemia and Plague in Mouse Models of Infection

Structural Characterization of the Millennial Antibacterial (Fluoro)Quinolones—Shaping the Fifth Generation

Finafloxacin, a Novel Fluoroquinolone, Reduces the Clinical Signs of Infection and Pathology in a Mouse Model of Q Fever

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