In response to the global spread of antimicrobial resistance, there is an increased demand for novel and innovative antimicrobials. Bacteriophages have been known for their potential clinical utility in lysing bacteria for almost a century. Social pressures and the concomitant introduction of antibiotics in the mid-1900s hindered the widespread adoption of these naturally occurring bactericides. Recently, however, phage therapy has re-emerged as a promising strategy for combatting antimicrobial resistance. A unique mechanism of action and cost-effective production promotes phages as an ideal solution for addressing antibiotic-resistant bacterial infections, particularly in lower- and middle-income countries. As the number of phage-related research labs worldwide continues to grow, it will be increasingly important to encourage the expansion of well-developed clinical trials, the standardization of the production and storage of phage cocktails, and the advancement of international collaboration. In this review, we discuss the history, benefits, and limitations of bacteriophage research and its current role in the setting of addressing antimicrobial resistance with a specific focus on active clinical trials and case reports of phage therapy administration.

Resistance to antibiotics is approaching crisis levels for organisms such as the ESKAPEE pathogens (includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli) that often are acquired in hospitals. These organisms sometimes have acquired plasmids that confer resistance to most if not all beta-lactam antibiotics. We have been developing alternative means for dealing with antibiotic resistant microbes that cause infections in humans by developing viruses (bacteriophages) that attack and kill them. One of these pathogens, K. pneumoniae, has one of the highest propensities for antimicrobial resistance. We identified many phages that have lytic capacity against limited numbers of clinical isolates, and through experimental evolution over the course of 30 days, were able to vastly expand the host ranges of these phages to kill a broader range of clinical K. pneumoniae isolates including MDR (multi-drug resistant) and XDR (extensively-drug resistant) isolates. Most interestingly, they were capable of inhibiting growth of clinical isolates both on solid and in liquid medium over extended periods. That we were able to extend the host ranges of multiple naïve antibiotic resistant K. pneumoniae through experimental phage evolution suggests that such a technique may be applicable to other antibiotic-resistant organisms to help stem the tide of antibiotic resistance and offer further options for medical treatments.

Introduction: Gastrointestinal stromal tumors (GISTs) are commonly driven by activating mutations in KIT or PDGFRA . Although sequential tyrosine kinase inhibitors (TKIs) have improved outcomes in advanced disease, acquired resistance is common. Prospective studies of immune checkpoint blockade in GIST have shown limited activity, and immunotherapy is not a standard treatment. Case Presentation: A man diagnosed at age 57 with epithelioid small‐bowel GIST developed hepatic metastatic disease 7 years after his initial diagnosis. His tumor harbored a primary KIT exon 11 D579del mutation, a secondary KIT exon 17 D820G mutation, and CDKN2A/CDKN2B deletions; available molecular testing reported a low tumor mutational burden (1 mutation/Mb) and microsatellite‐stable disease. After progression or treatment‐limiting toxicity during six TKI regimens, pembrolizumab was initiated on October 28, 2025, when he was 76 years old, and administered intravenously every 3 weeks. The treatment has demonstrated stable disease on CT imaging; cycle 13 was then administered on July 28, 2026. No treatment delays or treatment‐related adverse events were reported through cycle 13. Conclusion: Pembrolizumab was associated with at least 9 months of disease control in TMB‐low, microsatellite‐stable metastatic GIST after six TKI regimens. Because contemporaneous immune profiling and complete historical dosing data were unavailable, this observation is hypothesis‐generating and does not establish that prior TKI exposure sensitized the tumor to PD‐1 blockade.