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Oral amoxicillin and amoxicillin–clavulanic acid: properties, indications and usage

Huttner, A; Bielicki, J; Clements, MN; Frimodt-Møller, N; Muller, AE; Paccaud, J-P; Mouton, JW; (2020) Oral amoxicillin and amoxicillin–clavulanic acid: properties, indications and usage. Clinical Microbiology and Infection , 26 (7) pp. 871-879. 10.1016/j.cmi.2019.11.028. Green open access

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Abstract

BACKGROUND: Amoxicillin has been in use since the 1970s; it is the most widely used penicillin both alone and in combination with the beta-lactamase clavulanic acid. OBJECTIVES: In this narrative review, we re-examine the properties of oral amoxicillin and clavulanic acid and provide guidance on their use, with emphasis on the preferred use of amoxicillin alone. SOURCES: Published medical literature (MEDLINE database via Pubmed) CONTENT: While amoxicillin and clavulanic acid have similar half-lives, clavulanic acid is more protein-bound and even less heat-stable than amoxicillin, with primarily hepatic metabolism. It is also more strongly associated with gastrointestinal side effects, including Clostridium difficile infection, and thus, in oral combination formulations, limits the maximum daily dose of amoxicillin that can be given. The first ratio for an amoxicillin-clavulanic acid combination was set at 4:1 due to clavulanic acid's high affinity for beta-lactamases; ratios of 2:1, 7:1, 14:1 and 16:1 are currently available in various regions. Comparative effectiveness data for the different ratios are scarce. Amoxicillin-clavulanic acid is often used as empiric therapy for many of the World Health Organisation's Priority Infectious Syndromes in adults and children, leading to extensive consumption, when some of these syndromes could be handled with a delayed-antibiotic-prescription approach or amoxicillin alone. IMPLICATIONS: Using available epidemiologic and pharmacokinetic data, we provide guidance on indications for amoxicillin versus amoxicillin-clavulanic acid and on optimal oral administration, including choice of combination ratio. More data are needed, particularly on heat stability, pharmacodynamic effects and emergence of resistance in "real-world" clinical settings.

Type: Article
Title: Oral amoxicillin and amoxicillin–clavulanic acid: properties, indications and usage
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cmi.2019.11.028
Publisher version: https://doi.org/10.1016/j.cmi.2019.11.028
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: appropriate therapy, clavulanic acid, indications, oral amoxicillin, pharmacokinetics, stewardship
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10089375
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