"Two Is Better Than One": The Multifactorial Nature of Phage-Antibiotic Combinatorial Treatments Against ESKAPE-Induced Infections.

Phage-antibiotic synergy (PAS) has been extensively explored over the past decade, with the aim of developing more effective treatments against multidrug-resistant organisms. However, it remains unclear how to effectively combine these two approaches. To address this uncertainty, we assessed four main aspects of PAS interactions in this review, seeking to identify commonalities of combining treatments within and between bacterial species. We examined all literature on PAS efficacy toward ESKAPE pathogens and present an analysis of the data in papers focusing on: (1) order of treatment, (2) dose of both phage and antibiotics, (3) mechanism of action, and (4) viability of transfer from in vivo or animal model trials to clinical applications. Our analysis indicates that there is little consistency within phage-antibiotic therapy regimens, suggesting that highly individualized treatment regimens should be used. We propose a set of experimental studies to address these research gaps. We end our review with suggestions on how to improve studies on phage-antibiotic combination therapy to advance this field.

Evaluation of Phage Delivery Systems on Induced Motile Aeromonas Septicemia in Oreochromis niloticus.

Background: The success of phage therapy is affected by the method of treatment delivery. This study focused on comparing different phage delivery routes, specifically oral (phage-impregnated feed), intraperitoneal (IP), and bath (immersion), in treatment of induced motile Aeromonas septicemia (MAS). Materials and Methods: The efficacy of Aeromonas hydrophila phage cocktail in treating MAS-infected Oreochromis niloticus through different delivery routes was assessed by challenging the fish with 100% lethal dose of A. hydrophila and conducting a 15-day treatment regimen. Blood and kidney samples were analyzed for bacterial and phage concentrations. Results: All routes exhibited reduction of disease symptoms, significant (p < 0.05) decrease in bacterial count, and increase in phage count. Notably, IP route showed significant activity in reducing bacterial load. Conclusions: Phage therapy through IP route is the most effective yet invasive in controlling MAS infection in O. niloticus. The efficacy of oral route depends on the fish's intake of feeds, whereas the bath route was the least effective.