Phage Therapy Against Antibiotic‐Resistant and Multidrug‐Resistant Infections Involving Nonhealing Wounds: A Mini‐Review Original paper

What Was Reviewed?

This mini-review titled “Phage Therapy Against Antibiotic-Resistant and Multidrug-Resistant Infections Involving Nonhealing Wounds and Prosthetic Joint Infections Associated With Biofilms” evaluates 27 studies published between 2017 and 2023 to determine the efficacy and safety of bacteriophage (phage) therapy in the treatment of chronic wounds (CWs) and prosthetic joint infections (PJIs), particularly those complicated by biofilm formation and antimicrobial resistance. The authors conducted a systematic literature search across PubMed, Web of Science, Cochrane, and ClinicalTrials.gov, yielding 3151 articles, of which 27 met the inclusion criteria, encompassing 130 patients and 152 distinct infections. The review focuses on the types of infections treated, microbial etiologies, therapeutic modalities employed, and clinical outcomes following phage therapy.

Who Was Reviewed?

The reviewed studies involved 130 patients, most of whom were treated for chronic wound infections (n=130 infections) and prosthetic joint infections (n=22 infections). The demographic diversity included cases from the USA, France, Germany, India, Georgia, Australia, Belgium, and Italy. Notably, infections were predominantly caused by Pseudomonas aeruginosa (36.2%) and Staphylococcus aureus (27.0%) in wound cases, and S. aureus (50%) in PJIs. Most of these infections were either antibiotic-resistant or multidrug-resistant (MDR), and 65% of MDR cases were treated with phage cocktails. Treatment modalities varied and included topical, intraarticular, intravenous, or combined applications.

Most Important Findings

Phage therapy achieved an overall success rate of 91%, highlighting its substantial potential in managing nonhealing wounds and PJIs associated with biofilms and antibiotic resistance. The data suggest that P. aeruginosa and S. aureus are major microbial associations (MMAs) in chronic and prosthetic wound infections, reaffirming their significance in dysbiotic microbiomes characterized by biofilm resilience and MDR phenotypes. Topical application was the most frequently employed modality (78.8%), particularly for chronic wounds. Despite differences in phage types, doses (ranging from 10⁶ to 10¹⁰ PFU/mL), and treatment duration (from 1 day to 7 weeks), the outcomes were predominantly favorable.

Importantly, the phages’ ability to disrupt biofilms via depolymerase activity and potentially enhance antibiotic susceptibility suggests a dual benefit in combination therapies. This was indirectly supported by observations that many patients received concurrent antibiotics, indicating possible phage-antibiotic synergy. Adverse effects were minimal, with only 4.6% of patients reporting complications, most commonly transient elevations in liver enzymes (ALT/AST), typically in S. aureus-associated PJIs. There were no serious complications directly attributable to phage therapy.

From a microbiome perspective, the consistent isolation of P. aeruginosa, S. aureus, S. epidermidis, and E. coli across chronic wound and prosthetic joint infections suggests a stable core dysbiosis pattern across these pathologies. These organisms are known for their biofilm-forming capacity and resistance mechanisms, reinforcing their designation as MMAs in wound microbiome dysbiosis. The successful targeting of these taxa using phage cocktails validates the role of phage therapy as a precision intervention to address microbial imbalances and resistant infections.

Greatest Implications

The review underscores phage therapy’s clinical viability as a microbiome-targeted strategy for managing MDR infections involving MMAs like P. aeruginosa and S. aureus, especially when biofilms are implicated. The ability to bypass traditional resistance mechanisms, dismantle biofilm matrices, and reduce persister cell populations positions phage therapy as a transformative adjunct or alternative to antibiotics. For microbiome-focused clinicians, these findings validate the consideration of phage therapy in cases where the pathogen composition is known and aligns with established MMAs. Moreover, the minimal adverse effects and high success rate justify expanded clinical trials and standardized dosing protocols, particularly for microbiome-restorative therapeutic frameworks.