Biofilm-driven chronic rhinosinusitis: review reframes recalcitrance as immune and ecological dysregulation

This is a narrative review synthesizing mechanistic and therapeutic evidence on biofilm-associated chronic rhinosinusitis (CRS). The authors frame treatment recalcitrance as a consequence of persistent microbial biofilms that function not only as physical barriers to antibiotics but as active immune modulators perpetuating mucosal dysbiosis.

Mechanistically, the review describes how biofilm-derived pathogen-associated molecular patterns (PAMPs) trigger release of epithelial alarmins — TSLP, IL-33, and IL-25 — fueling a maladaptive Type 2 inflammatory loop. The authors also examine bacterial survival strategies, including small colony variants (SCVs) and intracellular "Trojan Horse" reservoirs, which the authors state render conventional functional endoscopic sinus surgery (FESS) and antimicrobial monotherapies insufficient for complete eradication.

The review highlights a diagnostic disconnect in which standard cultures fail to detect biofilm burdens, limiting recognition of the underlying driver in routine practice. Building on this, the authors propose a therapeutic paradigm shift from a purely bactericidal approach toward ecological restoration, integrating matrix-degrading enzymes, bacteriophage cocktails, and Nasal Microbiota Transplantation (NMT) into a multi-dimensional framework aimed at restoring sinonasal homeostasis.

As a narrative synthesis, the piece does not report pooled effect estimates, comparative efficacy data, or adverse-event rates for the emerging strategies discussed, and safety and tolerability of phages, enzymatic debridement, or NMT were not quantified in the abstract. The proposed framework is conceptual rather than evidence-graded.

For clinicians managing recalcitrant CRS, the review supports considering biofilm biology and host immune response when conventional FESS and antibiotics fail, and anticipating emerging adjuncts that target matrix, microbial ecology, and Type 2 inflammation rather than bacterial killing alone.