Darlow, CA;
Farrington, N;
Johnson, A;
McEntee, L;
Unsworth, J;
Jimenez-Valverde, A;
Kolamunnage-Dona, R;
Da Costa, RMA;
Ellis, S;
Franceschi, F;
et al.
Darlow, CA; Farrington, N; Johnson, A; McEntee, L; Unsworth, J; Jimenez-Valverde, A; Kolamunnage-Dona, R; Da Costa, RMA; Ellis, S; Franceschi, F; Sharland, M; Neely, M; Piddock, LJV; Das, S; Hope, W
(2022)
Flomoxef and fosfomycin in combination for the treatment of neonatal sepsis in the setting of highly prevalent antimicrobial resistance.
J Antimicrob Chemother, 77 (5).
pp. 1334-1343.
ISSN 1460-2091
https://doi.org/10.1093/jac/dkac038
SGUL Authors: Sharland, Michael Roy
|
PDF
Published Version
Available under License Creative Commons Attribution Non-commercial. Download (924kB) | Preview |
|
![]() |
Microsoft Word (.docx) (Supplementary data)
Published Version
Download (2MB) |
Abstract
BACKGROUND: Neonatal sepsis is a serious bacterial infection of neonates, globally killing up to 680 000 babies annually. It is frequently complicated by antimicrobial resistance, particularly in low- and middle-income country (LMIC) settings with widespread resistance to the WHO's recommended empirical regimen of ampicillin and gentamicin. OBJECTIVES: We assessed the utility of flomoxef and fosfomycin as a potential alternative empirical regimen for neonatal sepsis in these settings. METHODS: We studied the combination in a 16-arm dose-ranged hollow-fibre infection model (HFIM) experiment and chequerboard assays. We further assessed the combination using clinically relevant regimens in the HFIM with six Enterobacterales strains with a range of flomoxef/fosfomycin MICs. RESULTS: Pharmacokinetic/pharmacodynamic modelling of the HFIM experimental output, along with data from chequerboard assays, indicated synergy of this regimen in terms of bacterial killing and prevention of emergence of fosfomycin resistance. Flomoxef monotherapy was sufficient to kill 3/3 strains with flomoxef MICs ≤0.5 mg/L to sterility. Three of three strains with flomoxef MICs ≥8 mg/L were not killed by fosfomycin or flomoxef monotherapy; 2/3 of these were killed with the combination of the two agents. CONCLUSIONS: These data suggest that flomoxef/fosfomycin could be an efficacious and synergistic regimen for the empirical treatment of neonatal sepsis in LMIC settings with prevalent antimicrobial resistance. Our HFIM results warrant further assessment of the flomoxef/fosfomycin combination in clinical trials.
Item Type: | Article | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Additional Information: | © The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com | ||||||||||||||||||||||||||||||||||||
Keywords: | 1115 Pharmacology and Pharmaceutical Sciences, 0605 Microbiology, 1108 Medical Microbiology, Microbiology | ||||||||||||||||||||||||||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Infection and Immunity Research Institute (INII) | ||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | J Antimicrob Chemother | ||||||||||||||||||||||||||||||||||||
ISSN: | 1460-2091 | ||||||||||||||||||||||||||||||||||||
Language: | eng | ||||||||||||||||||||||||||||||||||||
Publisher License: | Creative Commons: Attribution-Noncommercial 4.0 | ||||||||||||||||||||||||||||||||||||
Projects: |
|
||||||||||||||||||||||||||||||||||||
PubMed ID: | 35170719 | ||||||||||||||||||||||||||||||||||||
Web of Science ID: | WOS:000755726700001 | ||||||||||||||||||||||||||||||||||||
Go to PubMed abstract | |||||||||||||||||||||||||||||||||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/114184 | ||||||||||||||||||||||||||||||||||||
Publisher's version: | https://doi.org/10.1093/jac/dkac038 |
Statistics
Actions (login required)
![]() |
Edit Item |