Phage-Antibiotic Combination: An Effective Method for Eradication ofStaphylococcus aureus

Abstract

Increasing antibiotic resistance poses a serious threat, especially in patients admitted to ICUs. The use of phages in combination with antibiotics as compassionate therapy has become a choice of treatment for pan-drug-resistant bacteria. Here, we studied the cumulative effect of phages with four antibiotics, fosfomycin, ciprofloxacin, vancomycin and oxacillin using three different treatment orders againstS. aureus. The antibiotic disc synergy method showed that the plaque size of the phage increased in the subinhibitory antibiotic zone. The sub-inhibitory antibiotic amended in the agar media showed that the plaque size increased between 0.25 μg/mL and 1 μg/mL of antibiotics. It increases from 0.5 ± 0.1 mm (phage-alone control) to 4 ± 0.2 mm, 1.6 ± 0.1 mm, and 1.6 ± 0.4 mm with fosfomycin, ciprofloxacin, and oxacillin, respectively. Checkerboard analysis showed that phages and antibiotics were synergistic with the FIC index of less than 0.5. So, phage-antibiotic combination treatment appeared to be effective. However, the highest efficiency was observed when the antibiotics were administered after phage treatment. A maximum of 39.4-, 39.4-, and 37.0-fold reduction relative to untreated bacterial culture was observed with fosfomycin, oxacillin, and ciprofloxacin. Vancomycin antibiotic had a least 14.7-fold reduction. Finally, our findings emphasize the potential benefits of phage-antibiotic combination therapy compared with phage-alone therapy to treatS. aureusinfections.