Abstract
Introduction: Mupirocin is used to treat patients who are nasally colonised with MRSA. Eradication rates up to 80% have been reported, but relapse at 4-weeks is more frequent with strains displaying low-level mupirocin resistance (LLR) compared to mupirocin sensitive (MupS) isolates. The aim of this study was to assess S.aureus LLR isolates for in vitro tolerance to mupirocin as a route to determining the mechanism underlying decolonisation failure.
Methods: Thirty-four clinical strains of S.aureus were evaluated for cell survival after exposure to mupirocin for 24h: 14 MupS (4 MRSA, 10 MSSA) and 20 LLR (19 MRSA, 1 MSSA). Cells were attached to mucin-coated microtitre-plate wells for 4h, planktonic cells removed and surface adherent cells challenged with 200mg/l
mupirocin for 24h. Selected strains were then observed over a time-course of 1,4,6,12 and 24h of treatment. After challenge, cell viability was determined using the metabolic-dye resazurin and the percentage decrease compared to untreated adherent cells.
Results: Following exposure to 200mg/l mupirocin (at least 6-fold above the MIC) for 24h there was no statistical difference in the proportion of MupS (mean 14%; range3-41%) and LLR (mean 16%; range 2-94%) cells that remained viable, though two LLR strains displayed tolerance (72% and 94% remained). Over a 24h imecourse all the MupS strains showed a loss in cell viability proportionate to exposure time. Nine LLR strains showed a decrease in viability comparable to the MupS isolates, whilst 6/20 showed an ability to recover before a reduction in cell viability at 24h, and 5/20 demonstrated a clear recovery at 24h. Antibiotic tolerance was genotype independent.
Discussion: Whilst MupS strains were susceptible to mupirocin, 55% (11/20) LLR strains demonstrated tolerance with two strains (10%) showing clear recovery. The tolerance exhibited by a number of LLR isolates might underlie treatment relapse observed in patients undergoing decolonisation therapy.
Methods: Thirty-four clinical strains of S.aureus were evaluated for cell survival after exposure to mupirocin for 24h: 14 MupS (4 MRSA, 10 MSSA) and 20 LLR (19 MRSA, 1 MSSA). Cells were attached to mucin-coated microtitre-plate wells for 4h, planktonic cells removed and surface adherent cells challenged with 200mg/l
mupirocin for 24h. Selected strains were then observed over a time-course of 1,4,6,12 and 24h of treatment. After challenge, cell viability was determined using the metabolic-dye resazurin and the percentage decrease compared to untreated adherent cells.
Results: Following exposure to 200mg/l mupirocin (at least 6-fold above the MIC) for 24h there was no statistical difference in the proportion of MupS (mean 14%; range3-41%) and LLR (mean 16%; range 2-94%) cells that remained viable, though two LLR strains displayed tolerance (72% and 94% remained). Over a 24h imecourse all the MupS strains showed a loss in cell viability proportionate to exposure time. Nine LLR strains showed a decrease in viability comparable to the MupS isolates, whilst 6/20 showed an ability to recover before a reduction in cell viability at 24h, and 5/20 demonstrated a clear recovery at 24h. Antibiotic tolerance was genotype independent.
Discussion: Whilst MupS strains were susceptible to mupirocin, 55% (11/20) LLR strains demonstrated tolerance with two strains (10%) showing clear recovery. The tolerance exhibited by a number of LLR isolates might underlie treatment relapse observed in patients undergoing decolonisation therapy.
| Original language | English |
|---|---|
| Pages | S39 |
| Number of pages | 1 |
| DOIs | |
| Publication status | Published - 29 Sept 2014 |
Keywords
- Mupirocin
- MRSA
- nasal decolonisation
- resistance
- LLR