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

Barnes, Kay B.; Richards, Mark I.; Laws, Thomas R.; Núñez, Alejandro; Thwaite, Joanne E.; Bentley, Christine; Harding, Sarah V.

doi:10.1128/aac.02294-20

Cited by 12 publications

(12 citation statements)

References 45 publications

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“…Previous work performed at Dstl has demonstrated broad spectrum in vitro activity of finafloxacin against Francisella tularensis, Yersinia pestis, Coxiella burnetii, Bacillus anthracis, Burkholderia pseudomallei , and Burkholderia mallei ( Barnes et al, 2019a ; Peyrusson et al, 2021 ). In vivo efficacy has also been demonstrated against F. tularensis, Y. pestis, C. burnetii , and B. pseudomallei ( Barnes et al, 2017 , 2019b , 2021 ; Hartley et al, 2021 ). It has been suggested that this is due to the rapid influx of finafloxacin into cells, the accumulation to high levels within the cell, and a slow efflux rate ( Chalhoub et al, 2019 ).…”

Section: Introductionmentioning

confidence: 98%

Investigation of a combination therapy approach for the treatment of melioidosis

et al. 2022

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The efficacy of finafloxacin as a component of a layered defense treatment regimen was determined in vitro and in vivo against an infection with Burkholderia pseudomallei. Doxycycline was down-selected from a panel of antibiotics evaluated in vitro and used in combination with finafloxacin in a Balb/c mouse model of inhalational melioidosis. When treatment was initiated at 24 h post-infection with B. pseudomallei, there were no differences in the level of protection offered by finafloxacin or doxycycline (as monotherapies) when compared to the combination therapy. There was evidence for improved bacterial control in the groups treated with finafloxacin (as monotherapies or in combination with doxycycline) when compared to mice treated with doxycycline. Survival comparisons of finafloxacin and doxycycline (as monotherapies) or in combination initiated at 36 h post-infection indicated that finafloxacin was superior to doxycycline. 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.

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Section: Introductionmentioning

confidence: 98%

Investigation of a combination therapy approach for the treatment of melioidosis

et al. 2022

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“…These forms are intended for the treatment of uncomplicated and complicated urinary tract infections, pyelonephritis and Helicobacter pylori infections [ 99 , 144 , 145 , 146 , 147 ]. Finafloxacin has demonstrated broad-spectrum activity against a range of pathogens [ 148 ]. This cyano-FQN is active both in vitro and in vivo against Pseudomonas aeruginosa and Staphylococcus aureus [ 99 ].…”

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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“…Antibiotic regimens were determined previously by matching to the pharmacokinetic (PK) parameter that correlated with efficacy in vivo and a human equivalent dose. For finafloxacin, the AUC/MIC over 24 h period in a human 10.3389/fmicb.2022.1057202 dose was determined and resulted in a dose in BALB/C mice of 37.5 mg/kg every 8 h (Barnes et al, 2021). For co-trimoxazole, the time above MIC achieved in humans was matched giving a dose of 78 mg/kg every 12 h (unpublished data).…”

Section: Antibiotic Regimensmentioning

confidence: 99%

Efficacy of finafloxacin in a murine model of inhalational glanders

Barnes

Bayliss²,

Davies³

et al. 2022

Front. Microbiol.

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Burkholderia mallei, the causative agent of glanders, is principally a disease of equines, although it can also infect humans and is categorized by the U.S. Centers for Disease Control and Prevention as a category B biological agent. Human cases of glanders are rare and thus there is limited information on treatment. 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). In this study, the fluoroquinolone finafloxacin was compared to co-trimoxazole as a post-exposure prophylactic in a murine model of inhalational glanders. BALB/c mice were exposed to an aerosol of B. mallei followed by treatment with co-trimoxazole or finafloxacin initiated at 24 h post-challenge and continued for 14 days. Survival at the end of the study was 55% or 70% for mice treated with finafloxacin or co-trimoxazole, respectively, however, this difference was not significant. 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.

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

Cited by 12 publications

References 45 publications

Investigation of a combination therapy approach for the treatment of melioidosis

Investigation of a combination therapy approach for the treatment of melioidosis

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

Efficacy of finafloxacin in a murine model of inhalational glanders

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