Emergence of high-level mupirocin resistance in coagulase-negative staphylococci associated with increased short-term mupirocin use

Abstract

In our hospital, mupirocin has increasingly been used for peri-operative decolonization of Staphylococcus aureus. The target for mupirocin is isoleucyl tRNA synthetase (ileS). High-level resistance to mupirocin is conferred by acquisition of plasmids expressing a distinct ileS gene (ileS2). Here we evaluated the longitudinal trends in high-level mupirocin resistance in coagulase-negative staphylococci (CoNS) and linked this to the presence of ileS2 genes and mupirocin use. We assessed mupirocin resistance in CoNS bloodstream isolates from 2006 to 2011 tested by Phoenix automated testing (PAT). We evaluated the reliability of PAT results using Etest. PAT species determination was confirmed by MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) mass spectrometry. We investigated the presence of ileS2 in the first 100 consecutive CoNS bloodstream isolates of each year using RT-PCR. Mupirocin use increased from 3.6 kg/year in 2006 to 13.3 kg/year in 2010 and correlated with the increase in the percentage of CoNS isolates carrying ileS2 (8% in 2006 to 22% in 2011; Spearman's rho, 0.137; P = 0.01). The sensitivity and specificity of PAT for detecting high-level mupirocin resistance were 0.97 and 0.97, respectively. ileS2 was detected in 81 of 82 phenotypically highly mupirocin-resistant strains and associated with resistance to ciprofloxacin, erythromycin, and clindamycin. In conclusion, we found a rapid increase in high-level resistance to mupirocin and resistance to other antibiotics in CoNS associated with an increase in mupirocin use. The associated resistance to other antibiotics may result in a reduction of oral antibiotic options for prolonged treatment of prosthetic infections with CoNS.

Fig 1

Correlation between emergence of high-level mupirocin resistance and increased use of mupirocin (n = 595). Histogram bars represent the percentage of CoNS bloodstream isolates carrying the ileS2 gene and exhibiting high-level mupirocin resistance, which increased significantly from 2006 (8%) to 2011 (21%). The line shows the increase in mupirocin use from 2006 (3.6 kg) to 2010 (13.3 kg), which correlated with the increase in frequency of CoNS carrying ileS2 (Spearman's rho, 0.137; P = 0.01).