New Funding Supports Inhaled Phage–Meropenem Therapy Against Achromobacter in Cystic Fibrosis
A new translational research grant is supporting the development of an inhaled combination of bacteriophages and the antibiotic meropenem against persistent Achromobacter lung infections in people with cystic fibrosis. Announced by Emily’s Entourage on September 3, 2026, the project is led by David T. Pride, Professor of Pathology and Medicine at the University of California San Diego School of Medicine, and builds on recent experimental evidence that some phages can work synergistically with meropenem even against bacteria that were initially classified as resistant to the antibiotic.
The project focuses particularly on Achromobacter xylosoxidans, a Gram-negative opportunistic pathogen that can establish chronic respiratory infection in people with cystic fibrosis and progressively accumulate antimicrobial resistance during repeated courses of antibiotic treatment. Compared with Pseudomonas aeruginosa, Achromobacter receives considerably less public attention, but its persistence in the cystic fibrosis lung can create a difficult therapeutic problem when isolates become multidrug resistant or extensively drug resistant and conventional treatment options narrow.
Emily’s Entourage describes the programme as its fourth Translational Research Grant of 2026. The organization has not publicly disclosed the value of the award, so the announcement should be interpreted as confirmation of a funded development programme rather than a funding round of a known size. Its objective is to move an experimentally promising phage–antibiotic combination toward an inhaled therapeutic approach and to determine more precisely why phages and meropenem can become more effective when used together.
The scientific foundation comes from work by Pride and colleagues reported in a 2026 Research Square preprint. The researchers assembled 56 clinical Achromobacter isolates collected through UC San Diego hospitals between 2022 and 2025. Twenty-three were classified as multidrug resistant and 33 as extensively drug resistant, with many originating from people with cystic fibrosis or other chronic conditions in whom infections had repeatedly challenged antibiotic treatment.
The team simultaneously developed a collection of 26 distinct bacteriophages targeting Achromobacter. Genomic characterization showed considerable viral diversity, with genome sizes extending from approximately 40 kilobases to more than 225 kilobases. Electron microscopy identified several morphological groups, including viruses resembling the traditional myovirus, siphovirus and podovirus morphotypes, while the largest isolate, Marine1, qualified as a jumbo phage.
Testing this collection against the clinical bacterial panel produced one of the strongest observations underlying the new grant. Every tested MDR or XDR isolate could be lysed by at least one phage, and many were susceptible to several. One phage, Barbera, showed activity against approximately 84% of the strains evaluated in the host-range experiments. The results suggested that resistance to conventional antibiotics did not automatically translate into resistance to bacteriophages because the two therapeutic approaches exploit fundamentally different bacterial vulnerabilities.
Pride's team did not intend to use this finding simply to replace antibiotics with phages. Antibiotics remain the established treatment for bacterial lung infections, and phage therapy is still experimental in most clinical settings. The researchers therefore examined whether bacteriophages could interact positively with existing antibiotics and potentially recover activity that had been lost through antimicrobial resistance.
Meropenem became a particularly important candidate because it is a broad-spectrum beta-lactam antibiotic from the carbapenem class and can be used against serious Gram-negative infections, including susceptible Achromobacter. Resistance can substantially restrict its usefulness, however, making it valuable to determine whether phage exposure alters bacterial susceptibility to the drug.
The in vitro experiments indicated that pairing an active phage with meropenem could produce effects not predicted from either intervention alone. In multiple bacterial isolates, the phage–antibiotic combination shifted meropenem minimum inhibitory concentrations toward levels classified as susceptible, including in some isolates that were resistant to meropenem before phage exposure. Importantly, the researchers found that pre-existing meropenem susceptibility was not required for synergy, provided that an active bacteriophage capable of attacking the bacterial isolate was available.
This observation does not mean that phages universally reverse carbapenem resistance. The study was conducted in vitro, the effect varied according to the phage–bacterium combination, and the work available as of October 2026 remains a preprint that has not yet completed journal peer review. The new Emily’s Entourage project is partly intended to determine the biological mechanisms underlying the observed interaction and establish whether the phenomenon can support development of a practical pulmonary therapy.
Phage–antibiotic synergy can arise through several biological routes, although the exact mechanism in the UC San Diego system remains to be established. Selection for phage resistance can sometimes force bacteria to alter surface structures or other cellular functions in ways that create a fitness cost or increase antibiotic susceptibility. Antibiotics can also change bacterial physiology, morphology or growth conditions in ways that modify phage replication. In other systems, simultaneous pressure from a phage and an antibiotic can restrict the bacterial evolutionary routes available for resistance because adaptations that protect against one treatment can increase vulnerability to the other.
Understanding which of these mechanisms operates in Achromobacter will be important for designing a reproducible combination therapy. A synergistic result observed for one isolate cannot simply be assumed for another because bacteriophage susceptibility is highly strain dependent, antibiotic-resistance mechanisms differ between isolates, and interactions can change according to drug concentration, timing and bacterial physiology. The new project is therefore intended to move beyond demonstrating synergy and determine how it can be predicted and exploited.
The planned inhaled route is particularly relevant to cystic fibrosis because the infection is concentrated in the respiratory tract. Delivering phages locally could expose bacteria in the airways to high concentrations of active virus while reducing the dependence on systemic distribution. Aerosolized phage therapy nevertheless creates its own pharmaceutical challenges because bacteriophages must remain biologically viable during nebulization, reach appropriate regions of the lung and maintain activity within a respiratory environment characterized by thick mucus, inflammatory material, variable oxygen levels and structured bacterial communities.
Chronic cystic fibrosis infections are especially difficult because bacteria are not necessarily growing as rapidly or uniformly as they do in standard laboratory cultures. Achromobacter can persist within complex airway communities, and biofilm formation can further limit antimicrobial penetration and create bacterial subpopulations with different metabolic states. Phage infection itself depends on bacterial physiology, meaning that demonstrating strong activity in broth or on agar represents an important first step but does not guarantee equivalent behaviour in a chronically infected lung.
The project therefore combines two strategies that could complement each other in this environment. Phages offer highly specific bacterial killing that remains possible even when conventional resistance determinants are present, while meropenem applies a second antimicrobial pressure through inhibition of bacterial cell-wall synthesis. If the combination can exploit evolutionary or physiological trade-offs in Achromobacter, it could theoretically suppress bacterial populations more effectively than either agent alone.
There is already limited clinical precedent for using phages against Achromobacter pulmonary infections, although the evidence currently consists primarily of individual cases rather than controlled trials. A 2018 case report described a 17-year-old patient with cystic fibrosis and chronic multidrug-resistant A. xylosoxidans infection who received an Achromobacter-specific phage preparation by nebulization and orally alongside conventional clinical management. The authors reported improvement in respiratory symptoms and lung function, but the uncontrolled nature of a single case prevents conclusions about efficacy.
Another report described a 12-year-old lung-transplanted patient with cystic fibrosis and pandrug-resistant A. xylosoxidans. Phages were delivered through nebulization and direct pulmonary instillation. The therapy was reportedly well tolerated, respiratory status gradually improved, and Achromobacter eventually became undetectable during follow-up, although bacterial persistence for months after treatment illustrated the complexity of linking clinical outcomes to phage administration.
A separate pediatric case involved a 10-year-old patient with cystic fibrosis and a pan-drug-resistant Achromobacter infection treated with a bacteriophage together with cefiderocol and meropenem/vaborbactam. Pulmonary function improved and the organism was not recovered from sputum collected eight and sixteen weeks after treatment. That case is relevant to the present research because it demonstrates clinical use of an Achromobacter phage alongside carbapenem-containing antibiotic therapy, but the contribution of each component cannot be isolated from a multi-drug compassionate-treatment regimen.
More recent work has continued to explore inhaled Achromobacter phages. A report published in the Yale Journal of Biology and Medicine described nebulized administration of two lytic phages against chronic multidrug-resistant Achromobacter, with stabilization of respiratory status and particular attention to evolutionary trade-offs that might make phage-resistant bacteria less pathogenic or more susceptible to antibiotics. Together, these cases provide evidence that pulmonary delivery of Achromobacter-targeting phages is technically possible, but they do not substitute for prospective controlled development.
The newly funded UC San Diego programme is therefore distinct from compassionate phage therapy. Rather than identifying an individualized phage after conventional options have failed and administering it to a single patient, the objective is to understand a reproducible phage–meropenem interaction and develop it toward an inhaled therapeutic strategy that could eventually be tested systematically.
The size and diversity of the UC San Diego phage collection could help that transition. A bank of 26 characterized phages provides multiple candidates for targeting genetically different Achromobacter isolates and potentially allows researchers to select combinations that maximize bacterial coverage while preserving favourable interactions with antibiotics. The finding that the clinical isolates tested remained susceptible to phages despite MDR or XDR antibiotic profiles further supports the idea that phage banks can provide therapeutic options against organisms whose conventional antimicrobial susceptibility has progressively narrowed.
There are nevertheless several steps between these experiments and a clinical product. Candidate phages would need to undergo genomic and biological safety characterization, production and purification would have to satisfy pharmaceutical requirements, and an inhaled formulation would need to preserve phage infectivity during storage and aerosolization. Researchers would also need to establish dosing, stability, distribution in the respiratory tract and interactions with simultaneously administered antibiotics.
The possibility of resistance remains important even when phages initially display broad activity. Achromobacter can evolve resistance to individual phages through changes in receptors, surface structures or intracellular defence mechanisms. A key advantage of studying phage–antibiotic combinations is that those adaptations may sometimes carry exploitable costs, but whether this occurs consistently enough to provide therapeutic benefit must be demonstrated rather than assumed.
The April 2026 preprint itself is also an important limitation when evaluating the strength of the evidence. The reported 26-phage collection, broad activity against MDR and XDR isolates and meropenem interactions provide a strong experimental rationale for further investigation, but the findings have not yet undergone peer review in a scientific journal. The Emily’s Entourage award effectively supports the next stage of that investigation rather than confirming the effectiveness of an established treatment.
The project has a broader relevance for phage therapy because many development programmes are increasingly examining phages in combination with antibiotics rather than presenting the two approaches as competitors. Phages and antibiotics attack bacteria through fundamentally different mechanisms, creating opportunities for complementary activity and evolutionary interactions that may be especially valuable against resistant pathogens.
For cystic fibrosis, this approach is particularly attractive because patients with chronic pulmonary infections frequently receive repeated antibiotic courses over long periods, progressively selecting bacterial populations adapted to antimicrobial exposure. An intervention that could preserve or recover the usefulness of an existing antibiotic would offer a different therapeutic objective from simply adding another antimicrobial agent.
The focus on Achromobacter also expands phage development beyond the pathogens that dominate most clinical programmes. Pseudomonas aeruginosa has received substantial attention because of its prevalence in chronic respiratory disease, but people with cystic fibrosis can develop persistent infections involving several less common Gram-negative organisms for which therapeutic options are limited and commercial antibiotic development is comparatively sparse.
Emily’s Entourage has previously supported related work in this area. Its 2024 grants included research led by David Pride, Douglas Conrad and Daria Van Tyne aimed at expanding phage collections and evaluating phage–antibiotic combinations against antibiotic-resistant pathogens in cystic fibrosis. In 2025, the organization funded Anca Segall at San Diego State University to optimize phage cocktails targeting multidrug-resistant Achromobacter and investigate resistance evolution and antibiotic re-sensitization. The new Pride grant therefore continues a broader programme of investment in phage-based approaches for hard-to-treat CF infections.
The organization focuses particularly on the approximately 10% of people with cystic fibrosis who do not benefit from currently available mutation-targeted CFTR modulators. For these patients, therapies addressing infection and inflammation can provide an important way of preserving health while genetic or molecular treatments for the underlying disease continue to be developed.
The September 2026 award does not announce a human clinical trial, and no evidence has yet been presented that the proposed inhaled phage–meropenem combination safely restores antibiotic susceptibility in patients. The immediate objective is translational: define the synergy observed in laboratory isolates, understand its mechanism and develop a pulmonary treatment strategy capable of eventually advancing toward clinical testing.
If that programme succeeds, its importance could extend beyond Achromobacter. A reproducible framework for identifying phage–antibiotic pairs that convert difficult-to-treat bacteria into therapeutically vulnerable populations could influence how phages are incorporated into antimicrobial development more broadly. Instead of viewing a phage solely as an alternative drug used when antibiotics fail, the virus could become a tool for altering bacterial physiology and restoring the usefulness of antibiotics that resistance had previously compromised.
For now, the UC San Diego project provides a particularly focused test of that idea. Twenty-six phages, a collection of highly resistant clinical Achromobacter isolates and a preliminary signal of synergy with meropenem have created the experimental foundation. The new funding will determine whether that interaction can be understood well enough to support an inhaled therapy for one of the less visible but particularly difficult chronic infections affecting people with cystic fibrosis.
Sources :
Emily’s Entourage — “New Emily’s Entourage Grant to Fund Novel Phage-Based Therapy for Drug-Resistant Infections in Cystic Fibrosis,” September 3, 2026. The announcement confirms the David T. Pride grant, the inhaled phage–meropenem strategy, focus on Achromobacter xylosoxidans and planned investigation of phage–antibiotic synergy.
https://www.emilysentourage.org/new-emilys-entourage-grant-to-fund-novel-phage-based-therapy-for-drug-resistant-infections-in-cystic-fibrosis/
Pride D., Orlatti M., Turki N. et al. — “Antibiotic resistant Achromobacter xylosoxidans are highly susceptible to bacteriophages and often are killed synergistically by phage/antibiotic combinations.” Research Square preprint, April 30, 2026. The study reports 26 phages, 56 MDR/XDR clinical isolates and in vitro restoration of meropenem susceptibility in multiple phage-susceptible isolates. The manuscript is explicitly identified as a preprint and has not yet undergone journal peer review.
https://doi.org/10.21203/rs.3.rs-9371970/v1
Emily’s Entourage — Awarded Grants. The organization documents earlier phage-development programmes involving David Pride, Douglas Conrad, Daria Van Tyne and Anca Segall targeting antibiotic-resistant CF pathogens and Achromobacter.
https://www.emilysentourage.org/awarded-grants/
Hoyle N., Zhvaniya P., Balarjishvili N. et al. — “Phage therapy against Achromobacter xylosoxidans lung infection in a patient with cystic fibrosis: a case report.” Research in Microbiology 169 (2018).
https://doi.org/10.1016/j.resmic.2018.05.001
Gainey A.B., Burch A.K., Brownstein M.J. et al. — “Combining bacteriophages with cefiderocol and meropenem/vaborbactam to treat a pan-drug resistant Achromobacter species infection in a pediatric cystic fibrosis patient.” Pediatric Infectious Disease Journal (2020).
https://pubmed.ncbi.nlm.nih.gov/32662948/
“A Case of Phage Therapy against Pandrug-Resistant Achromobacter xylosoxidans in a 12-Year-Old Lung-Transplanted Cystic Fibrosis Patient.” Viruses 13, 60 (2021).
https://doi.org/10.3390/v13010060
“Inhaled Bacteriophage Therapy for Multi-Drug Resistant Achromobacter.” Yale Journal of Biology and Medicine (2022).
https://pubmed.ncbi.nlm.nih.gov/36568830/
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