Imperial College London
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Professor James Seddon

Faculty of Medicine, Department of Infectious Disease

Professor of Global Child Health
 
 
 
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Contact

 

+44 (0)20 7594 3179james.seddon

 
 
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Location

 

235Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Srivastava:2020:10.1097/INF.0000000000002857,
author = {Srivastava, S and van, Zyl J and Cirrincione, K and Martin, K and Thomas, T and Deshpande, D and Alffenaar, J and Seddon, J and Gumbo, T},
doi = {10.1097/INF.0000000000002857},
journal = {The Pediatric Infectious Disease Journal},
pages = {1092--1100},
title = {Evaluation of ceftriaxone plus avibactam in an intracellular hollow fiber model of tuberculosis: implications for the treatment of disseminated and meningeal tuberculosis in children},
url = {http://dx.doi.org/10.1097/INF.0000000000002857},
volume = {39},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Ceftazidime-avibactam is an effective agent for the treatment of tuberculosis (TB) but requires frequent administration because of a short half-life. Due to a longer half-life, ceftriaxone could allow intermittent dosing.Methods: First, we identified the MIC of ceftriaxone with 15 mg/L avibactam in 30 clinical Mycobacterium tuberculosis isolates. Next, 2 ceftriaxone exposure-effect studies in the intracellular hollow fiber model of TB (HFS-TB) that mimics disseminated disease in young children, were performed. Ceftriaxone was administered once or twice daily for 28 days to explore percentage of time that the concentration persisted above MIC (%TMIC) ranging from 0 to 100%. In a third HFS-TB experiment, the “double cephalosporin” regimen of ceftazidime-ceftriaxone-avibactam was examined and analyzed using Bliss Independence.Conclusion: The MIC99 of the clinical strains was 32 mg/L, in the presence of 15 mg/L avibactam. Ceftriaxone %TMIC <42 had no microbial effect in the HFS-TB, %TMIC>54% demonstrated a 4.1 log10 colony-forming units per milliliter M. tuberculosis kill, while %TMIC mediating Emax was 68%. The “double cephalosporin” combination was highly synergistic. Monte Carlo experiments of 10,000 subjects identified the optimal ceftriaxone dose as 100 mg/kg twice a day.Conclusion: The combination of ceftriaxone-avibactam at 100 mg/kg could achieve Emax in >90% of children. The ceftriaxone potent activity M. tuberculosis could potentially shorten therapy in children with disseminated TB.
AU  - Srivastava,S
AU  - van,Zyl J
AU  - Cirrincione,K
AU  - Martin,K
AU  - Thomas,T
AU  - Deshpande,D
AU  - Alffenaar,J
AU  - Seddon,J
AU  - Gumbo,T
DO  - 10.1097/INF.0000000000002857
EP  - 1100
PY  - 2020///
SN  - 0891-3668
SP  - 1092
TI  - Evaluation of ceftriaxone plus avibactam in an intracellular hollow fiber model of tuberculosis: implications for the treatment of disseminated and meningeal tuberculosis in children
T2  - The Pediatric Infectious Disease Journal
UR  - http://dx.doi.org/10.1097/INF.0000000000002857
UR  - https://journals.lww.com/pidj/Fulltext/2020/12000/Evaluation_of_Ceftriaxone_Plus_Avibactam_in_an.14.aspx
UR  - http://hdl.handle.net/10044/1/81560
VL  - 39
ER  -
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