Re-evaluation of FDA-approved antibiotics with increased diagnostic accuracy for assessment of antimicrobial resistance

Douglas M Heithoff; Lucien Barnes V; Scott P Mahan; Jeffrey C Fried; Lynn N Fitzgibbons; John K House; Michael J Mahan

doi:10.1016/j.xcrm.2023.101023

Re-evaluation of FDA-approved antibiotics with increased diagnostic accuracy for assessment of antimicrobial resistance

Cell Rep Med. 2023 May 16;4(5):101023. doi: 10.1016/j.xcrm.2023.101023. Epub 2023 Apr 27.

Authors

Douglas M Heithoff¹, Lucien Barnes V¹, Scott P Mahan², Jeffrey C Fried³, Lynn N Fitzgibbons⁴, John K House⁵, Michael J Mahan⁶

Affiliations

¹ Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
² Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA.
³ Department of Medical Education, Santa Barbara Cottage Hospital, Santa Barbara, CA 93105, USA; Department of Pulmonary and Critical Care Medicine, Santa Barbara Cottage Hospital, Santa Barbara, CA 93105, USA.
⁴ Department of Medical Education, Santa Barbara Cottage Hospital, Santa Barbara, CA 93105, USA; Division of Infectious Diseases, Santa Barbara Cottage Hospital, Santa Barbara, CA 93105, USA.
⁵ Faculty of Science, School of Veterinary Science, The University of Sydney, Camden, NSW 2570, Australia. Electronic address: john.house@sydney.edu.au.
⁶ Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Institute for Collaborative Biotechnologies, University of California, Santa Barbara, Santa Barbara, CA 93106, USA. Electronic address: mahan@ucsb.edu.

Abstract

Accurate assessment of antibiotic susceptibility is critical for treatment of antimicrobial resistant (AMR) infections. Here, we examine whether antimicrobial susceptibility testing in media more physiologically representative of in vivo conditions improves prediction of clinical outcome relative to standard bacteriologic medium. This analysis reveals that ∼15% of minimum inhibitory concentration (MIC) values obtained in physiologic media predicted a change in susceptibility that crossed a clinical breakpoint used to categorize patient isolates as susceptible or resistant. The activities of antibiotics having discrepant results in different media were evaluated in murine sepsis models. Testing in cell culture medium improves the accuracy by which MIC assays predict in vivo efficacy. This analysis identifies several antibiotics for treatment of AMR infections that standard testing failed to identify and those that are ineffective despite indicated use by standard testing. Methods with increased diagnostic accuracy mitigate the AMR crisis via utilizing existing agents and optimizing drug discovery.

Keywords: AMR; AST; MIC; antimicrobial resistance; antimicrobial susceptibility testing; minimum inhibitory concentration; multidrug-resistant pathogens.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

Animals
Anti-Bacterial Agents* / pharmacology
Anti-Bacterial Agents* / therapeutic use
Anti-Infective Agents*
Drug Resistance, Bacterial
Humans
Mice
Microbial Sensitivity Tests

Substances

Anti-Bacterial Agents
Anti-Infective Agents

Grants and funding

P01 HL131474/HL/NHLBI NIH HHS/United States