Overcoming bacteriophage insensitivity in Staphylococcus aureus using clindamycin and azithromycinat sub-inhibitory concentrations

Allergy. 2021 Apr 30. doi: 10.1111/all.14883. Online ahead of print.

ABSTRACT

Staphylococcus aureus is a pathogen of major concern in both acute infections as well as chronic conditions such as chronic rhinosinusitis (CRS). Bacteriophage (phage) therapy has been considered in Western countries as early as the 1920s and has recently regained interest for its potential to treat infections caused by antibiotic resistant strains including Methicillin Resistant Staphylococcus aureus (MRSA). However, bacteria can adapt and become resistant to phages. The ability to overcome phage resistance is considered critically important for phage therapy applications. Here we show that sub-inhibitory concentrations of Protein Synthesis Inhibitor (PSI) antibiotics clindamycin, erythromycin and azithromycin could sensitise phage-resistantS. aureus strains to phages in vitro and in vivo. All 3 antibiotics showed synergy when combined with multiple lytic phages against 9 S. aureus clinicalisolates in planktonic growth and 2 strains forming biofilms. The combination of clindamycin and phages was safe and could eradicate S. aureussinonasal biofilms in a murine model of sinusitis. This data supports the potential use of phage-PSI antibiotic combination therapies in particular for difficult to treat infections with phage-resistantS. aureus and MRSA strains.

PMID:33930199 | DOI:10.1111/all.14883