Chronic rhinosinusitis
Chronic rhinosinusitis (CRS) is a highly prevalent inflammatory disease of the sinonasal mucosa, and a recalcitrant subset persists despite endoscopic sinus surgery, prolonged antibiotics, and topical therapy. Staphylococcus aureus is a dominant pathogen in this recalcitrant group, and its ability to form mucosal biofilms and survive intracellularly is strongly linked to treatment failure and disease severity. Biofilm-embedded S. aureus is up to ~1000-fold more tolerant to antibiotics than planktonic cells, so systemic and topical antibiotics frequently fail. Lytic bacteriophages are attractive here because they self-amplify at the infection site, actively penetrate and disperse biofilm (in part via phage-encoded depolymerases), can be delivered topically by sinus irrigation directly to the diseased mucosa, and kill multidrug-resistant and MRSA strains without disturbing the broader microbiome.
How phages act here
Mechanism
Anti-staphylococcal phages adsorb to surface receptors (e.g., wall teichoic acid) on S. aureus, inject their genome, replicate, and lyse the host, releasing progeny that propagate through the bacterial population. Against biofilm specifically, phages and their depolymerase/endolysin enzymes degrade the extracellular polymeric matrix, exposing deeper bacterial layers, which is why ex vivo CRS isolate studies show marked biofilm-mass reduction. Because individual phages are strain-specific, therapeutic products are formulated as defined cocktails (the AB-SA01 cocktail comprises three lytic Myoviridae, Sa83, Sa87 and J-Sa36) so that broad coverage of clinical S. aureus/MRSA strains is achieved and resistance is suppressed: single-phage exposure readily selects resistant mutants, whereas the multi-phage cocktail (CT-SA) was shown to completely prevent their emergence. Phage-antibiotic synergy and combination with biofilm-disrupting agents such as EDTA further enhance killing, and engineered/CRISPR-based anti-staphylococcal phages are an active research frontier for sharpening specificity and re-sensitizing strains to antibiotics, though these are preclinical for CRS.
Where it stands
Current evidence
Evidence runs from in vitro and ex vivo work through animal models to a completed first-in-human trial, making CRS one of the better-developed topical phage indications. The cocktail CT-SA lysed 94% (62/66) of clinical CRS S. aureus isolates and reduced biofilm ex vivo (Drilling 2014), and topical phage plus EDTA was safe and reduced biofilm in a sheep sinusitis model (Drilling 2014, IFAR). The pivotal evidence is a Phase 1, first-in-human, open-label multiple-ascending-dose trial of intranasal AB-SA01 (developed by AmpliPhi Biosciences, later Armata Pharmaceuticals; conducted at the Queen Elizabeth Hospital / University of Adelaide / Flinders University), published by Ooi et al. in JAMA Otolaryngology–Head & Neck Surgery in 2019: 9 patients with recalcitrant CRS received twice-daily sinus irrigations up to 3x10^9 PFU for 14 days. It met its primary safety/tolerability endpoint (no serious adverse events; only mild treatment-emergent effects), all 9 patients showed reduced S. aureus burden, 2 of 9 achieved eradication, and endoscopic Lund-Kennedy scores improved across cohorts (greatest in the high-dose 14-day arm). As of 2026 these remain early-phase findings; no large randomized controlled efficacy trial for the CRS indication has yet reported, and topical phage for CRS is still investigational.
Evidence confidence: medium
The data
Key studies & trials
- Ooi ML, Drilling AJ, Morales S, Fong S, Moraitis S, Macias-Valle L, Vreugde S, Psaltis AJ, Wormald PJ. Safety and Tolerability of Bacteriophage Therapy for Chronic Rhinosinusitis Due to Staphylococcus aureus. JAMA Otolaryngol Head Neck Surg. 2019;145(8):723-729. ↗
- Drilling A, Morales S, Jardeleza C, Vreugde S, Speck P, Wormald PJ. Bacteriophage reduces biofilm of Staphylococcus aureus ex vivo isolates from chronic rhinosinusitis patients. Am J Rhinol Allergy. 2014;28(1):3-11. ↗
- Drilling A, Morales S, Boase S, Jervis-Bardy J, James C, Jardeleza C, Tan NC, Cleland E, Speck P, Vreugde S, Wormald PJ. Safety and efficacy of topical bacteriophage and ethylenediaminetetraacetic acid treatment of Staphylococcus aureus infection in a sheep model of sinusitis. Int Forum Allergy Rhinol. 2014;4(3):176-186. ↗
- Fong SA, Drilling AJ, Ooi ML, Paramasivan S, Finnie JW, Morales S, Psaltis AJ, Vreugde S, Wormald PJ. Safety and efficacy of a bacteriophage cocktail in an in vivo model of Pseudomonas aeruginosa sinusitis (companion CRS phage model). Transl Res. 2019;206:41-56. (CRS phage delivery model context) ↗
Who is working on it
Programs & centers
The possibility
If a randomized controlled trial confirms the Phase 1 signal, recalcitrant CRS could become one of the first routine clinical uses of topical phage therapy, with patients self-administering personalized, culture-matched phage rinses at home instead of repeated antibiotic courses or revision surgery. Pairing phage cocktails with biofilm disruptors (EDTA, surfactants) and with phage-antibiotic synergy regimens could turn previously untreatable MRSA sinus biofilms into manageable infections. Looking further out, engineered and CRISPR-armed phages offer the prospect of precision rinses tuned to a patient's exact strain, potentially clearing intracellular reservoirs and breaking the relapse cycle that defines this disease.