An in vitro investigation of meticillin resistant Staphylococcus aureus (MRSA) decolonisation treatment failure

Mupirocin is used to treat patients who are nasally colonised with MRSA. Despite following the recommended guidelines, failure of nasal decolonisation therapy and relapses occur with reports of only 32% of treated individuals remaining MRSA free one-year later. The aim of this study was to assess the in vitro ability of surface-attached MRSA to tolerate repeated exposure to mupirocin mimicking therapy. Three clinical MRSA isolates were evaluated for cell survival after repeated exposure to mupirocin twice a day for five days. Cells of a mupirocin-sensitive MRSA (MS) and two mupirocin low-level resistant MRSA (LLR) were attached to mucin-coated microtitre-plate wells for 4h, planktonic cells removed and surface-adherent cells challenged with 200mg/l mupirocin (at least 6-fold above the MIC) for 1h. Adherent cells were then allowed to recover in antibiotic-free broth for 11h prior to the next antibiotic exposure. After each antibiotic treatment, cell viability was determined. A comparison of cell death and the extent of recovery was then determined between treatments, relative to untreated controls. The first three doses of mupirocin inhibited replication of the surface-adherent cells of all strains, though as the cell number increased in a maturing biofilm the impact of treatments was reduced. Five days of treatment reduced the MS viable cell number to 15% of the control, whereas for the two LLR strains 39% and 43% of cells remained compared to untreated biofilms. In summary, the tolerance exhibited by LLR strains to repeated mupirocin exposure mimicking treatment might underlie the higher rate of relapse following decolonisation treatment with LLR strains.