Evaluation of Bacteriophage-Antibiotic Combination Therapy for Biofilm-Embedded MDR Enterococcus faecium

Area of Science:

• Microbiology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Multidrug-resistant (MDR) Enterococcus faecium poses a significant threat, causing challenging biofilm-mediated infections.
• Limited therapeutic options exist for MDR Enterococcus faecium infections.
• Lytic bacteriophages offer a potential treatment strategy due to their specific targeting and anti-biofilm activity.

Purpose of the Study:

• To investigate the synergistic efficacy of lytic bacteriophages in combination with antibiotics against clinical strains of Enterococcus faecium.
• To evaluate the ability of phage-antibiotic combinations to prevent the emergence of resistance.
• To assess the bactericidal and synergistic effects of specific phage-antibiotic combinations.

Main Methods:

• Utilized modified checkerboard MIC assays for synergy screening of antibiotics and bacteriophages, including at low multiplicity of infection (MOI).
• Conducted 24-hour time-kill analyses (TKA) to evaluate bactericidal activity.
• Employed one-way ANOVA and Tukey (HSD) tests for statistical comparison of data.

Main Results:

• Combinations of phage with daptomycin (DAP)-ampicillin (AMP), phage-DAP-ceftaroline (CPT), and phage-DAP-ertapenem (ERT) demonstrated synergistic and bactericidal effects against E. faecium.
• Phage-DAP-AMP and phage-DAP-CPT combinations successfully prevented the emergence of resistance to DAP and phages.
• For the DAP-susceptible HOU503 strain, phage-DAP-AMP exhibited the strongest killing effect, followed closely by phage-DAP-CPT, both showing significant synergy and bactericidal activity.

Conclusions:

• Lytic bacteriophages, when combined with specific antibiotics like ampicillin, ceftaroline, or ertapenem, exhibit significant synergistic and bactericidal activity against biofilm-producing Enterococcus faecium.
• These phage-antibiotic combinations are effective in preventing the development of resistance to both antibiotics and bacteriophages.
• The findings support the potential of bacteriophage-antibiotic therapy as a promising strategy to combat challenging MDR Enterococcus faecium infections.