Optimization of antimicrobial therapy for Gram-positive bacterial infections in children using a translational pharmacological approach


Ramos Martín, V (2017) Optimization of antimicrobial therapy for Gram-positive bacterial infections in children using a translational pharmacological approach. PhD thesis, University of Liverpool.

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Abstract

Nosocomial bloodstream infection (BSI) is the most common type of hospital-acquired infection in paediatric patients and a major cause of morbidity and mortality worldwide. Methicillin-resistant staphylococci (CoNS and MRSA) are a leading cause of hospital-acquired neonatal sepsis and BSI. Glycopeptides (vancomycin and teicoplanin) constitute the current mainstay of therapy. There is limited antimicrobial PK-PD data available for neonates and children and optimal drug exposures resulting in maximal efficacy and suppression of resistance are not known. A translational pharmacological approach can be used to build the evidence required to optimize the current use of antimicrobial therapy in children. Pre-clinical experimental (in vitro and in vivo) and clinical PK-PD work was conducted throughout this thesis to improve our understanding of the PK-PD relationships of vancomycin and teicoplanin against CoNS and MRSA. The in vitro HFIM defined the relevant PD indexes and free drug exposures associated with maximal bacterial killing and suppression of resistance. The in vivo models (a rabbit central-line associated BSI and a mouse neutropenic thigh infection model) validated the in vitro findings. CRP concentrations ... (continues)

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences > Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 14 Dec 2017 10:05
Last Modified: 08 Feb 2025 01:28
DOI: 10.17638/03008292
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3008292
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