Dear Editor,
We read with great interest the article by Spellberg et al,1 which advocated for sustainable solutions for antimicrobial resistance. We commend the authors for highlighting key strategies, including incentivizing antimicrobial stewardship, funding programs that decrease reliance on antibiotics, and a partnership between nonprofit and for-profit drug-development organizations. Those directions make sense; however, the authors neglected an essential strategy for mitigating the continued rise of antimicrobial-resistant infections: treatment diversification.
Antibiotic selection prior to susceptibility testing often results in empiric one-size-fits-all treatment for a given pathogen. Neisseria gonorrhoeae, 1 of the top 5 urgent antimicrobial-resistant threats to public health,2 is nearly exclusively treated with ceftriaxone. It is not surprising, therefore, that strains of N gonorrhoeae harboring high-level ceftriaxone resistance have now achieved sustained international transmission. Diversifying therapy at the point-of-care requires the availability of 1 of 2 options: effective alternative agents or rapid resistance tests.
For N gonorrhoeae, 2 new antimicrobials are in late-stage development and are expected to soon enter the market. Modeling work supports the need to implement the novel regimens rapidly and simultaneously to prolong the duration of effectiveness before resistance develops, rather than in sequence.3 A similar approach can be applied to numerous other infections with available alternative therapies; provider- and institution-level treatment practices per pathogen must attempt to use a variety of effective options. Antimicrobial stewardship has traditionally focused on minimizing the use of unnecessary antibiotics and of agents with unnecessarily broad coverage; however, diversifying the selection of empiric regimens will further reduce selective pressure towards resistance.
Rapid molecular assays that are commercially available predict resistance for a range of drug–pathogen combinations, including ciprofloxacin resistance in N gonorrhoeae, macrolide resistance in Mycoplasma genitalium, methicillin resistance in Staphylococcus aureus, and clarithromycin and levofloxacin resistance in Helicobacter pylori. The use of such assays has been incorporated into treatment guidelines, is increasingly common, and has been shown in prospective studies to be effective.4 Further, modeling work in N gonorrhoeae demonstrated that resistance-guided therapy can extend the usefulness of ceftriaxone by several years.5
Treatment diversification can and should be incentivized through the same mechanisms outlined by Spellberg et al. Increasing the variety of effective empiric regimens should be a topic within antimicrobial stewardship programs, while novel compound development will benefit from prioritizing the parallel development of resistance assays to facilitate appropriate usage. Treatment diversification must be an essential component of sustainable solutions for mitigating the continued emergence of antimicrobial resistance.
Supplementary Material
Contributor Information
Lao-Tzu Allan-Blitz, Division of Global Health Equity: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States.
Jeffrey D Klausner, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States.
Supplementary material
Supplementary material is available at Health Affairs Scholar online.
Funding
J.D.K. is funded, in part, by the Antibacterial Resistance Leadership Group and the National Institute of Allergy and Infectious Diseases (K23AI182453 to L.-T.A.-B. and UM1AI104681 to J.D.K.).
Notes
- 1. Spellberg B, Gilbert DN, Baym M, et al. Sustainable solutions to the continuous threat of antimicrobial resistance. Health Aff Sch. 2025;3(2):qxaf012. 10.1093/haschl/qxaf012 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Centers for Disease Control and Prevention . 2019. Accessed February 5, 2025. 10.15620/cdc:82532 [DOI]
- 3. Reichert E, Yaesoubi R, Ronn MM, Gift TL, Salomon JA, Grad YH. Resistance-minimising strategies for introducing a novel antibiotic for gonorrhoea treatment: a mathematical modelling study. Lancet Microbe. 2023;4(10):e781–e789. 10.1016/S2666-5247(23)00145-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Klausner JD, Bristow CC, Soge OO, et al. Resistance-guided treatment of gonorrhea: a prospective clinical study. Clin Infect Dis. 2021;73(2):298–303. 10.1093/cid/ciaa596 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Tuite AR, Gift TL, Chesson HW, Hsu K, Salomon JA, Grad YH. Impact of rapid susceptibility testing and antibiotic selection strategy on the emergence and spread of antibiotic resistance in gonorrhea. J Infect Dis. 2017;216(9):1141–1149. 10.1093/infdis/jix450 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.