Combination therapy with IV fosfomycin for adult patients with serious Gram-negative infections: a review of the literature.

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dc.contributor.authorButler, David A
dc.contributor.authorPatel, Nimish
dc.contributor.authorO'Donnell, J Nicholas
dc.contributor.authorLodise, Thomas P
dc.contributor.orcidhttps://orcid.org/0000-0001-5184-1385
dc.date.accessioned2024-11-14T14:34:52Z
dc.date.available2024-11-14T14:34:52Z
dc.date.issued2024-10-01
dc.descriptionClick on the resource link (may not be free).
dc.description.abstractTreatment of patients with serious infections due to resistant Gram-negative bacteria remains highly problematic and has prompted clinicians to use existing antimicrobial agents in innovative ways. One approach gaining increased therapeutic use is combination therapy with IV fosfomycin. This article reviews the preclinical pharmacokinetic/pharmacodynamic (PK/PD) infection model and clinical data surrounding the use of combination therapy with IV fosfomycin for the treatment of serious infections caused by resistant Gram-negative bacteria. Data from dynamic in vitro and animal infection model studies of highly resistant Enterobacterales and non-lactose fermenters are positive and suggest IV fosfomycin in combination with a β-lactam, polymyxin or aminoglycoside produces a synergistic effect that rivals or surpasses that of other aminoglycoside- or polymyxin-containing regimens. Clinical studies performed to date primarily have involved patients with pneumonia and/or bacteraemia due to Klebsiella pneumoniae, Pseudomonas aeruginosa or Acinetobacter baumannii. Overall, the observed success rates with fosfomycin combination regimens were consistent with those reported for other combination regimens commonly used to treat these patients. In studies in which direct treatment comparisons can be derived, the results suggest that patients who received fosfomycin combination therapy had similar or improved outcomes compared with other therapies and combinations, especially when it was used in combination with a β-lactam that (1) targets PBP-3 and (2) has exceptional stability in the presence of β-lactamases. Collectively, the data indicate that combination therapy with IV fosfomycin should be considered as a potential alternative to aminoglycoside or polymyxin combinations for patients with antibiotic-resistant Gram-negative infections when benefits outweigh risks.
dc.description.sponsorshipZavante Therapeutics, Inc., Delaware, USA
dc.description.urihttps://doi.org/10.1093/jac/dkae253
dc.identifier.doi10.1093/jac/dkae253
dc.identifier.issn1460-2091
dc.identifier.other39215642
dc.identifier.pii7746492
dc.identifier.pmid39215642
dc.identifier.urihttps://hdl.handle.net/20.500.14303/612
dc.language.isoen
dc.publisherAcademic Press
dc.relation.ispartofThe Journal of Antimicrobial Chemotherapy
dc.rights© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
dc.source.beginpage2421
dc.source.countryEngland
dc.source.endpage2459
dc.source.issue10
dc.source.journaltitleThe Journal of antimicrobial chemotherapy
dc.source.volume79
dc.titleCombination therapy with IV fosfomycin for adult patients with serious Gram-negative infections: a review of the literature.
dc.typeJournal Article
dc.typeReview
local.departmentprogramDepartment of Pharmacy Practice
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