Potential Antibiotics for the Treatment of Neonatal Sepsis Caused by Multidrug-Resistant Bacteria

Darlow, Christopher A ORCID: 0000-0002-5400-3413, da Costa, Renata MA, Ellis, Sally, Franceschi, Francois, Sharland, Mike, Piddock, Laura, Das, Shampa ORCID: 0000-0002-2540-4816 and Hope, William ORCID: 0000-0001-6187-878X (2021) Potential Antibiotics for the Treatment of Neonatal Sepsis Caused by Multidrug-Resistant Bacteria. PEDIATRIC DRUGS, 23 (5). pp. 465-484.

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Official URL: http://dx.doi.org/10.1007/s40272-021-00465-z

Abstract

Neonatal sepsis causes up to an estimated 680,000 deaths annually worldwide, predominantly in low- and middle-income countries (LMICs). A significant and growing proportion of bacteria causing neonatal sepsis are resistant to multiple antibiotics, including the World Health Organization-recommended empiric neonatal sepsis regimen of ampicillin/gentamicin. The Global Antibiotic Research and Development Partnership is aiming to develop alternative empiric antibiotic regimens that fulfil several criteria: (1) affordable in LMIC settings; (2) activity against neonatal bacterial pathogens, including extended-spectrum β-lactamase producers, gentamicin-resistant Gram-negative bacteria, and methicillin-resistant Staphylococcus aureus (MRSA); (3) a licence for neonatal use or extensive experience of use in neonates; and (4) minimal toxicities. In this review, we identify five antibiotics that fulfil these criteria: amikacin, tobramycin, fosfomycin, flomoxef, and cefepime. We describe the available characteristics of each in terms of mechanism of action, resistance mechanisms, clinical pharmacokinetics, pharmacodynamics, and toxicity profile. We also identify some knowledge gaps: (1) the neonatal pharmacokinetics of cefepime is reliant on relatively small and limited datasets, and the pharmacokinetics of flomoxef are also reliant on data from a limited demographic range and (2) for all reviewed agents, the pharmacodynamic index and target has not been definitively established for both bactericidal effect and emergence of resistance, with many assumed to have an identical index/target to similar class molecules. These five agents have the potential to be used in novel combination empiric regimens for neonatal sepsis. However, the data gaps need addressing by pharmacokinetic trials and pharmacodynamic characterisation.

Item Type:	Article
Uncontrolled Keywords:	Humans, Bacteria, Sepsis, Anti-Bacterial Agents, Microbial Sensitivity Tests, Drug Resistance, Multiple, Bacterial, Infant, Newborn, Methicillin-Resistant Staphylococcus aureus, Neonatal Sepsis
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	08 Sep 2021 09:30
Last Modified:	18 Jan 2023 21:29
DOI:	10.1007/s40272-021-00465-z
Open Access URL:	https://link.springer.com/article/10.1007/s40272-0...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3136355