Investigation of a combination therapy approach for the treatment of melioidosis

Barnes, Kay B.; Richards, Mark I.; Burgess, Gary; Armstrong, Stuart J.; Bentley, Christine; Maishman, Thomas C.; Laws, Thomas R.; Nelson, Michelle; Harding, Sarah V.

doi:10.3389/fmicb.2022.934312

Cited by 7 publications

(10 citation statements)

References 48 publications

(53 reference statements)

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“…This could be an important factor with clinical relevance and suggests that further studies are needed. These could include the investigation of the effect of both of these parameters when the window of opportunity is extended for finafloxacin used as a monotherapy 10.3389/fmicb.2022.1057202 and also as a combination therapy, demonstrated to be a successful approach with B. pseudomallei (Barnes et al, 2022).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Efficacy of finafloxacin in a murine model of inhalational glanders

Barnes

Bayliss²,

Davies³

et al. 2022

Front. Microbiol.

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“…Following an aerosol exposure with 20 LD 50 equivalents of strain K96243, Dstl observes high levels of bacteria in the lungs, liver and spleen and some kidney, brain and blood samples at 24 h post-challenge. By 36 h post-challenge, all organs are colonized, with untreated animals succumbing to infection by day 3–4 post-challenge [ 32 , 39 , 43 ].…”

Section: Preparation and Aerosolization Of B Pseudomallei ...mentioning

confidence: 99%

The BALB/c Mouse Model for the Evaluation of Therapies to Treat Infections with Aerosolized Burkholderia pseudomallei

et al. 2023

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Burkholderia pseudomallei, the causative agent of the disease melioidosis, has been isolated from the environment in 45 countries. The treatment of melioidosis is complex, requiring lengthy antibiotic regimens, which can result in the relapse of the disease following treatment cessation. It is important that novel therapies to treat infections with B. pseudomallei be assessed in appropriate animal models, and discussions regarding the different protocols used between laboratories are critical. A ‘deep dive’ was held in October 2020 focusing on the use of the BALB/c mouse model and the inhalational route of infection to evaluate new antibiotic therapies.

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“…injections of either research-grade CD200-Fc, haCD200-Fc (1.25 mg/kg to 3 mg/kg) or relevant IgG1 control. For the first 7 days post-infection, all groups were orally administered daily with doxycycline monohydrate (Vibramycin; Pfizer) (100 mg/kg); the dose chosen is known to be a suboptimal therapeutic dose ( 18 ). A final group of mice received phosphate-buffered saline (PBS) via the oral and i.p.…”

Section: Observationmentioning

confidence: 99%