Cholangitis & biliary-stent infection
Cholangitis and biliary-stent infections arise when bile stasis and indwelling plastic or metal stents let enteric bacteria colonize the biliary tree and form occluding biofilm "sludge." Sonication studies of explanted stents show the dominant colonizers are Enterococcus species (~22%) and Enterobacteriaceae such as Klebsiella and E. coli (~10% Klebsiella alone), with occlusion progressing to cholangitis or cholestasis in roughly a third of occluded stents. These organisms are increasingly multidrug-resistant (VRE, ESBL/carbapenem-resistant Klebsiella), and antibiotics penetrate biofilm and obstructed, poorly-perfused bile poorly, so infections recur until the device is exchanged. Lytic bacteriophages are well suited here because they self-amplify at the site of infection, kill antibiotic-resistant strains, degrade biofilm matrix via depolymerases, and can be delivered into the biliary tree (orally, IV, or potentially via ERCP/biliary catheter) with minimal off-target damage to the surrounding microbiota.
How phages act here
Mechanism
Phages bind strain-specific surface receptors (capsular polysaccharide, LPS, pili), so a defined cocktail is matched to the patient's Enterococcus/Enterobacteriaceae isolate and avoids collateral dysbiosis, an advantage demonstrated when an oral anti-Klebsiella cocktail lowered Kp without broad microbiome disruption. Against device biofilm, virion-associated and capsule-degrading depolymerases strip the exopolysaccharide that shields embedded cells, letting phage and antibiotic reach persister populations; phage-antibiotic synergy (PAS) has eradicated biofilm-embedded MDR Enterococcus faecium with daptomycin/ampicillin while preserving phage susceptibility. Phages also drive evolutionary trade-offs: receptor-loss escape mutants can become re-sensitized to antibiotics or lose virulence, as seen when phage pressure shifted a vancomycin-resistant E. faecium population back toward vancomycin susceptibility. Engineered and CRISPR-armed phages (sequence-specific kill of resistance/virulence genes) and purified endolysins are active research angles for Enterococcus and Klebsiella, though for biliary disease the published evidence to date is natural lytic cocktails rather than synthetic constructs.
Where it stands
Current evidence
As of 2026 the evidence for this specific indication is preclinical plus extrapolated compassionate-use case reports rather than completed biliary-specific trials. The most direct study is Ichikawa, Nakamoto and colleagues (Nature Communications, 2023, with phage company BiomX Ltd.), who isolated Klebsiella pneumoniae and Enterococcus gallinarum from primary sclerosing cholangitis patients and showed a lytic K. pneumoniae phage cocktail suppressed the pathogen and attenuated hepatobiliary inflammation in mice via both oral and IV dosing. For the Enterococcus arm, Duan et al. (Nature, 2019) and Mendes et al. (Viruses, 2022) from Bernd Schnabl's UC San Diego group built an oral cytolytic-E. faecalis phage cocktail that abolished liver injury in humanized mice and was advanced toward a clinical trial. Real-world human use closest to the biliary/abdominal setting includes Paul et al. (Viruses, 2021), an IV two-phage magistral preparation that cleared a vancomycin-resistant E. faecium intra-abdominal infection in a liver-transplanted infant. No registered phase 2/3 RCT for cholangitis or biliary-stent infection specifically had reported results by 2026; current human use proceeds via expanded-access/magistral pathways (e.g., UCSD IPATH, Belgium's Queen Astrid Military Hospital, Eliava Institute).
Evidence confidence: medium
The data
Key studies & trials
- Schneider J, Hapfelmeier A, Fremd J, et al. Biliary endoprosthesis: a prospective analysis of bacterial colonization and risk factors for sludge formation. PLoS One. 2014;9(10):e110112. (343 sonicated stents; Enterococcus spp. most prevalent at 22%, Klebsiella spp. 10%; biofilm/sludge drives stent occlusion and cholangitis.) ↗
- Ichikawa M, Nakamoto N, Kredo-Russo S, et al. Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis. Nat Commun. 2023;14(1):3261. ↗
- Duan Y, Llorente C, Lang S, et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature. 2019;575(7783):505-511. ↗
- Paul K, Merabishvili M, Hazan R, et al. Bacteriophage Rescue Therapy of a Vancomycin-Resistant Enterococcus faecium Infection in a One-Year-Old Child following a Third Liver Transplantation. Viruses. 2021;13(9):1785. ↗
Who is working on it
Programs & centers
The possibility
The natural endpoint is a phage-eluting or phage-flushed biliary stent: a depolymerase-armed Enterococcus/Klebsiella cocktail matched to the patient's isolate at ERCP, instilled directly into the biliary tree or impregnated into the device, that keeps the stent patent and breaks the cycle of repeat exchanges and recurrent cholangitis. Paired with phage-antibiotic synergy dosing, phages could re-sensitize VRE and carbapenem-resistant Klebsiella to the drugs that no longer work alone, turning a last-resort device infection into a curable one. With companies like BiomX already running biliary-relevant phage programs and magistral pathways delivering phages bedside today, a registered trial in stent-associated cholangitis is a realistic next-decade step rather than science fiction.