Effects of phage endolysin SAL200 combined with antibiotics on Staphylococcus aureus infection [PublishAheadOfPrint]

Phages and its derivatives are increasingly reconsidered for the treatment of bacterial infections, due to rising antibiotic resistance. We assessed the anti-staphylococcal effect of the endolysin SAL200 in combination with standard-of-care (SOC) antibiotics. SAL200 activity combined with SOC antibiotics was assessed in vitro by checkerboard and time-kill assays, and in vivo with murine bacteremia and Galleria mellonella infection models. SAL200 reduced SOC antibiotic MICs and showed a ≥3-log₁₀CFU/mL reduction of S. aureus within 30 minutes in time-kill assays. Combinations of SAL200 and SOC antibiotics achieved a sustained decrease of >2-log₁₀CFU/mL. SAL200 significantly lowered blood bacterial density within 1 hour by > 1 log₁₀CFU/mL in bacteremic mice (P<0.05 vs untreated mice), and SAL200 and SOC antibiotic combinations achieved the lowest levels of bacteremia. Bacterial density in splenic tissue at 72 h post-infection was lowest in mice treated with SAL200 and SOC antibiotic combinations. SAL200 combined with SOC antibiotics also improved Galleria mellonella larvae survival at 96 h post-infection.

The combination of phage endolysin SAL200 with SOC anti-staphylococcal antibiotics showed synergistic effects in vitro and in vivo. The combination of SAL200 with SOC antibiotics could help in the treatment of difficult S. aureus infections.

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