The continued rise in antimicrobial resistance poses a serious threat to public health worldwide. The use of phages that can have bactericidal activity without disrupting the normal flora represents a promising alternative treatment method. This practice has been successfully applied for decades, mainly in Eastern Europe, and has recently been used as an emergency therapy for compassionate care in the United States. Here, we provide a comprehensive review of the pre-clinical and clinical applications of phage therapy concerning three major Gram-negative pathogens: Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. The advantages and the challenges of expanding the usage of phages as an alternative or adjunctive treatment for antimicrobial-resistant bacterial infections are discussed. We emphasize the virologic complexities of using the highly adaptable phage populations as molecular tools, along with antibiotic chemical compounds, to effectively combat rapidly coevolving pathogenic bacteria in the host microenvironment. Pre-clinical studies, isolated clinical reports and a few randomized clinical trials have shown that bacteriophages can be effective in treating multidrug-resistant bacterial infections. The ability of some phages to revert the resistance against antibiotics, and possibly also against the human complement and other phages, appears to be a great advantage of phage therapy despite the inevitable emergence of phage-resistant strains. Bacteriophages (or specific phage-derived products) can enhance antimicrobial efficacy by reducing bacterial virulence via the alteration of basic bacterial structures, primarily of the cellular wall and membrane. Although several issues remain open regarding their effective clinical application, it appears that phage-based therapeutics in combination with antibiotics can provide an effective solution to the spread of antimicrobial resistance.

Objectives: To evaluate the efficacy of a fixed-dose combination of berberine, white mulberry leaf extract, and chromium picolinate on body weight, body composition, and insulin sensitivity in Greek adults with obesity. Research Methodology/Design: This was a 12-week, randomized, double-blind, placebo-controlled trial. Adults with obesity and no diagnosed chronic disease were randomly assigned to receive either berberine (1000 milligrams), white mulberry leaf extract (400 milligrams standardized to 5% 1-deoxynojirimycin), and chromium picolinate (0.644 milligrams) or a matching placebo, administered in two daily doses before the main meals. Setting: The study was conducted in Greece among community-dwelling adults with obesity. Main Outcome Measures: The primary outcome was insulin sensitivity, assessed using the Matsuda Composite Insulin Sensitivity Index derived from a 75-g oral glucose tolerance test. Secondary outcomes included body mass index, total body fat mass, and visceral fat rating. Results: Ninety-three participants were randomized, with 46 assigned to the active intervention and 47 to placebo. Compared with placebo, the active intervention produced significantly greater reductions in body mass index (adjusted mean difference −1.24 kg per square meter; 95% confidence interval −2.15 to −0.33), total body fat mass (−2.35 kg; 95% confidence interval −4.12 to −0.58), and visceral fat rating (−0.92 units; 95% confidence interval −1.74 to −0.10). Insulin sensitivity improved significantly, with a 28% greater improvement in the active group than in the placebo group (adjusted geometric mean ratio 1.28; 95% confidence interval 1.14 to 1.44). Conclusions: The fixed-dose combination improved BIA-derived body-composition measures and OGTT-derived insulin sensitivity over 12 weeks compared with placebo. Because no single-agent arms were included, individual component contributions and synergy remain undetermined; confirmatory trials using direct metabolic and imaging methods are warranted.