In vivo monitoring of therapeutic efficacy and virulence profile by bioluminescent Klebsiella pneumoniae.

Fodah, Ramy Ameen

doi:10.18297/etd/2542

Cited by 2 publications

(3 citation statements)

References 169 publications

(228 reference statements)

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“…For most animal studies with bacterial infections, antibiotic treatment was usually initiated either immediately or within a few hours after infection, probably due to the rapid infection progression in mice [14]. However, patients do not get antibiotic treatment until clear infection symptoms are diagnosed.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the published data by our collaborators, NTUH-K2044 was reported to be a highly virulent strain of K. pneumoniae with a LD 50 of 23.3 but was very drug sensitive to meropenem. Full protection from respiratory disease was achieved with the 400 mg/kg/day treatment, and meropenem ED50 was estimated to be 221 mg/kg/day [14]. We then decided to use NTUH-K2044 for this study.…”

Section: Discussionmentioning

confidence: 99%

“…Our imaging data demonstrated 18 F-FDS to be a promising PET tracer to monitor disease progression [5]. Even with such a low inoculum (25 CFU/mouse), 50% death rate was seen for mice at 3 days p.i., indicating the high virulence of this strain [2,14]. For the following treatment studies, at rst we used this same infection model and started the treatment at 24 h p.i.. All mice kept active and healthy for the next 3 days with only 2 to 3 doses of meropenem treatments.…”

Section: Discussionmentioning

confidence: 99%

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Differentiation between responders and non-responders to antibiotic treatment in mice using 18F-Fluorodeoxysorbitol/PET

Li,

Zheng,

Olson

et al. 2024

Preprint

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Purpose Bacterial infection causes significant mortality and morbidity worldwide despite the availability of antibiotics. Differentiation between responders and non-responders early on during antibiotic treatment will be informative to patients and healthcare providers. Our objective was to investigate whether PET imaging with 18F-Fluorodeoxysorbitol (18F-FDS) or 18F-FDG can be used to differentiate responders from non-responders to antibiotic treatment. Procedures NTUH-K2044 was used for infection in Albino C57 female mice. Each mouse was inoculated intratrachealy with NTUH-K2044 to induce lung infection (n=8). For treatment studies, two bacterial doses for animal inoculation and two treatment starting times were compared to optimize treatment profiles. 18F-FDS or 8F-FDG /PET imaging was performed to monitor treatment progression. Results Our results demonstrated that the treatment profiles for using mice infected with 25 CFU hvKp and antibiotic treatment starting at 24 p.i. were not ideal due to no evidence of lung infection and lack of treatment efficacy. The optimal scheme is to use 250 CUF for infection and start antibiotic treatment at 24 h p.i. to monitor antimicrobial efficacy. 75% of the mice were classified as responders to antibiotic treatment. 25% of the mice were classified as non-responders. 18F-FDG was used to compare with 18F-FDS, but all mice showed increased lung uptake of 18F-FDG during 3-day treatments. Conclusions 18F-FDS is a promising PET tracer to image bacterial infection. It can be used to monitor response to treatment, and differentiate responders from non-responders to antibiotic treatment, but 18F-FDG cannot, probably due to the presence of high degree of inflammation before and after treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%