Imperial College London
Alternate

ProfessorKathMaitland

Faculty of Medicine, Department of Surgery & Cancer

Professor of Tropical Paediatric Infectious Disease
 
 
 
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Contact

 

k.maitland CV

 
 
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Location

 

Based full-time at KEMRI/Wellcome Programme, KenyaQueen Elizabeth and Queen Mary HospitalSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Olupot-Olupot:2021:10.12688/wellcomeopenres.16968.1,
author = {Olupot-Olupot, P and Okiror, W and Mnjalla, H and Muhindo, R and Uyoga, S and Mpoya, A and Williams, T and terHeine, R and Burger, D and Urban, B and Connon, R and George, E and Gibb, D and Walker, S and Maitland, K},
doi = {10.12688/wellcomeopenres.16968.1},
journal = {Wellcome Open Research},
pages = {1--21},
title = {Pharmacokinetics and pharmacodynamics of azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a protocol for a Phase II randomised controlled trial [version 1; peer review: 1 approved with reservations]},
url = {http://dx.doi.org/10.12688/wellcomeopenres.16968.1},
volume = {6},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosage or length of treatment required. We therefore aimed to establish the appropriate dose of oral dispersible azithromycin as an antimicrobial treatment for children with severe malaria and to investigate whether antibiotics can be targeted to those at greatest risk of bacterial co-infection using clinical criteria alone or in combination with rapid diagnostic biomarker tests. Methods: A Phase I/II open-label trial comparing three doses of azithromycin: 10, 15 and 20 mg/kg spanning the lowest to highest mg/kg doses previously demonstrated to be equally effective as parenteral treatment for other salmonellae infection. Children with the highest risk of bacterial infection will receive five days of azithromycin and followed for 90 days. We will generate relevant pharmacokinetic data by sparse sampling during dosing intervals. We will use population pharmacokinetic modelling to determine the optimal azithromycin dose in severe malaria and investigate azithromycin exposure to change in C-reactive protein, a putative marker of sepsis at 72 hours, and microbiological cure (seven-day), alone and as a composite with seven-day survival. We will also evaluate whether a combination of clinical, point-of-care diagnostic tests, and/or biomarkers can accurately identify the sub-group of severe malaria with culture-proven bacteraemia by comparison with a control cohort of children hospitalized with severe malaria at low risk of bacterial co-infection. Discussion : We plan to study azithromycin because of its favourable microbiological spectrum, its inherent antimalarial and immunomodulatory properties and dosing and safety profile. This st
AU  - Olupot-Olupot,P
AU  - Okiror,W
AU  - Mnjalla,H
AU  - Muhindo,R
AU  - Uyoga,S
AU  - Mpoya,A
AU  - Williams,T
AU  - terHeine,R
AU  - Burger,D
AU  - Urban,B
AU  - Connon,R
AU  - George,E
AU  - Gibb,D
AU  - Walker,S
AU  - Maitland,K
DO  - 10.12688/wellcomeopenres.16968.1
EP  - 21
PY  - 2021///
SN  - 2398-502X
SP  - 1
TI  - Pharmacokinetics and pharmacodynamics of azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a protocol for a Phase II randomised controlled trial [version 1; peer review: 1 approved with reservations]
T2  - Wellcome Open Research
UR  - http://dx.doi.org/10.12688/wellcomeopenres.16968.1
UR  - https://wellcomeopenresearch.org/articles/6-161/v1
UR  - http://hdl.handle.net/10044/1/90761
VL  - 6
ER  -
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