Infectious disease: how to manage Gram-positive and Gram-negative pathogen conundrums with dual beta-lactam therapy

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Abstract

Antimicrobial resistance is a global public health threat due to its associated increase in mortality, and the most appropriate treatment algorithms for resistant and persistent Gram-positive and Gram-negative infections have yet to be elucidated. Whilst combination therapy has been touted as a viable method to overcome prominent resistant mechanisms represented amongst these microbes, the optimal agents to utilize remains controversial. Beta-lactams have a safe profile and are bactericidal against most Gram-positive and Gram-negative microorganisms. Thus, the use of dual beta-lactam therapy to overcome multidrug-resistant pathogens is of supreme interest. This article reviews the mechanisms of beta-lactam resistance in Gram-positive and Gram-negative bacteria, discusses the rationale for dual beta-lactam use against multidrug-resistant infections (and other scenarios in which this strategy may be most utilized in clinical practice), explores the available in vitro, in vivo and clinical data, and provides considerations for the use of dual beta-lactam therapy against Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii pathogens.

Keywords: antimicrobial resistance, beta-lactam, combination therapy, double carbapenem therapy, dual therapy, Gram-negative, Gram-positive.

Citation: FakhriRavari A, Simiyu B, Morrisette T, Dayo Y, Abdul-Mutakabbir JC. Infectious disease: how to manage Gram-positive and Gram-negative pathogen conundrums with dual beta-lactam therapy. Drugs Context. 2022;11:2021-8-9. https://doi.org/10.7573/dic.2021-8-9

Contributions: All authors contributed equally to the preparation of this review. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2021/12/dic.2021-8-9-COI.pdf

Acknowledgements: None.

Funding declaration: There was no funding associated with the preparation of this article.

Copyright: Copyright © 2022 FakhriRavari A, Simiyu B, Morrisette T, Dayo Y, Abdul-Mutakabbir JC. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2022 FakhriRavari A, Simiyu B, Morrisette T, Dayo Y, Abdul-Mutakabbir JC. https://doi.org/10.7573/dic.2021-8-9. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/infectious-disease-how-to-manage-gram-positive-and-gram-negative-pathogen-conundrums-with-dual-beta-lactam-therapy

Correspondence: Jacinda C Abdul-Mutakabbir, Department of Pharmacy Practice, Loma Linda University School of Pharmacy, Department of Basic Sciences, Loma Linda University School of Medicine, Loma, Linda CA, USA. Email: jabdulmutakabbir@llu.edu

Provenance: Invited; externally peer reviewed.

Submitted: 24 August 2021; Accepted: 22 November 2021; Publication date: 20 January 2022.

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