A new mini-review published in Frontiers in Antibiotics by researchers from the U.S. Army Medical Research Institute of Infectious Diseases and the UK Defence Science and Technology Laboratory highlights recent progress in identifying antibiotic candidates with potential to counter high-priority biothreat pathogens. The study, funded in part by the Defense Threat Reduction Agency and the UK Ministry of Defence, evaluates seven antibiotics—finafloxacin, levofloxacin, delafloxacin, omadacycline, gepotidacin, tebipenem, and sulopenem—for their efficacy, spectrum of activity, and clinical readiness.
Key Biothreat Pathogens and Treatment Gaps
Bacterial agents such as Yersinia pestis (plague), Francisella tularensis (tularaemia), Burkholderia pseudomallei (melioidosis), B. mallei (glanders), Bacillus anthracis (anthrax), and Coxiella burnetii (Q fever) represent serious public health and biodefense concerns. These infections are difficult to treat due to rapid progression, severe systemic illness, and potential chronic persistence. Current options, including ciprofloxacin, doxycycline, gentamicin, and carbapenems, are effective but have limitations when resistance emerges or when late-stage disease complicates treatment.
Promising New Antibiotics
The review identifies several drugs that could broaden the biodefense antibiotic arsenal:
- Finafloxacin – Shows superior activity in acidic conditions typical of infected tissues, outperforming ciprofloxacin in certain animal models of melioidosis and tularaemia.
- Delafloxacin – Approved for pneumonia and skin infections, it demonstrated efficacy against anthrax and melioidosis in preclinical studies.
- Levofloxacin – Already FDA-approved for plague and anthrax, it remains a cornerstone with proven efficacy in primate and small animal models.
- Omadacycline – A next-generation tetracycline with strong results against plague and anthrax, including resistant strains.
- Gepotidacin – The first-in-class novel bacterial topoisomerase inhibitor, recently FDA-approved for urinary tract infections, effective in nonhuman primate models of plague and tularaemia.
- Tebipenem and Sulopenem – Orally available β-lactams, important for outpatient or mass casualty scenarios, with demonstrated protective effects against plague and anthrax.
Collectively, these agents represent both refinements of existing antibiotic classes and novel mechanisms of action that may overcome resistance.
Implications for Public Health Preparedness
For public health security, the development of versatile, orally available antibiotics is particularly important. In a bioterrorism or outbreak scenario, the ability to rapidly distribute and self-administer effective antibiotics outside of hospitals could mean the difference between containment and widespread crisis. Beyond protecting deployed military forces, these drugs bolster national resilience to deliberate or naturally emerging high-consequence infections. Ensuring stockpiles, streamlined regulatory pathways, and international coordination around such antibiotics is central to biodefense preparedness.
The Road Ahead
While encouraging, most of these antibiotics were not originally developed with biodefense in mind. Continued investment in preclinical efficacy studies, clinical data generation, and regulatory engagement will be required to ensure they can be deployed in emergencies. As the authors note, robust evaluation in animal models, where human trials are not feasible, remains a cornerstone for advancing countermeasures.
By drawing attention to these promising options, the review underscores the importance of aligning biomedical innovation with national security needs. For professionals in public health, biosecurity, and policy, these findings highlight tangible progress toward a stronger antibiotic toolbox in the face of evolving biological threats.
Meinig JM, Nelson M, Cote CK, et al. An evaluation of antibiotic options for the treatment of biothreat pathogens. Frontiers in Antibiotics, 13 August 2025.