Abstract
Vancomycin, teicoplanin, and linezolid are the major treatment options for methicillin-resistant Staphylococcus aureus (MRSA). The phenomenon of progressive increase in the value of vancomycin minimum inhibitory concentration (MIC) for S. aureus (i.e., vancomycin MIC “creep”), has been reported; however, it is still a controversial concept because the results of research remain inconclusive. In this study, we conducted a retrospective epidemiologic investigation for more than 10 years to elucidate the dynamic changes of the MICs of vancomycin, teicoplanin, and linezolid in S. aureus in a central teaching hospital in Shanghai, China. A total of 2911 S. aureus isolates was recovered from 2008 to 2018, to which the MICs of three antimicrobials were tested by the E-test method and subsequently correlated with the characteristics of oxacillin susceptibility, clonotypes, and antimicrobial consumption during the study period. The proportion of MRSA dramatically decreased from 2008 to 2018 (from 84 to 49%, p < 0.001). Vancomycin MIC decline was identified both in MRSA and methicillin-sensitive S. aureus (MSSA) (both with p < 0.001), and both the dominating MRSA clone ST5 and pre-dominating MRSA clone ST239 displayed vancomycin MIC decline (p < 0.001, p = 0.040), while teicoplanin MIC decline was only identified in MRSA (p = 0.037). Linezolid MIC creep was identified in total S. aureus (p < 0.001), but linezolid in MRSA as well as teicoplanin and linezolid in MSSA displayed no statistically distinct trends of MIC creep or decline. Clinical consumption of linezolid increased significantly from 2012 to 2018 (p = 0.003), which correlated with vancomycin MIC decline in S. aureus (p = 0.005). The results of this study clearly demonstrate the dynamic changes of the MICs of these three primary antimicrobials in S. aureus, and suggest that changes in clinical antibiotic use may affect bacterial resistance.
Highlights
Staphylococcus aureus can cause invasive or complicated infections, including bacteremia, pneumonia, osteoarticular infections, endocarditis, and skin and soft tissue infections (Lowy, 1998)
In order to find out if minimum inhibitory concentration (MIC) creep taken place in S. aureus isolates in this hospital, and to figure out whether clone types or antimicrobial consumption would make a difference to dynamic changes of MICs, we investigated the dynamic changes of the MICs of three major clinical antimicrobials, vancomycin, teicoplanin, and linezolid, as well as their disparities between methicillinresistant Staphylococcus aureus (MRSA) and methicillinsensitive S. aureus (MSSA), and correlated these changes with the clone types and antimicrobial consumption during the study period
We found that the MIC range of linezolid in 2012 being 0.5–12 mg/L, with the detection of an isolate with a linezolid MIC identified as 12 mg/L, which is so-called heterogeneous linezolid resistant S. aureus in accordance with CLSI guidelines
Summary
Staphylococcus aureus can cause invasive or complicated infections, including bacteremia, pneumonia, osteoarticular infections, endocarditis, and skin and soft tissue infections (Lowy, 1998). According to the latest work by China Antimicrobial Surveillance Network (CHINET), S. aureus ranked third in prevalence among all clinically isolated species and first among Grampositive pathogens. While the prevalence of MRSA across China declined from 69% in 2008 to 35% in 2017, the isolation rate was much higher in Shanghai at about 49% in 2017 (Hu et al, 2018). Vancomycin has long been the preferred primary treatment option since it was first introduced for the treatment of MRSA infection (Rodvold and McConeghy, 2014). Vancomycin resistant S. aureus was first reported by Hiramatsu et al (1997) in Japan which stimulated the development of new antibiotics to cure MRSA infection. Teicoplanin was first introduced to the market in 1989 in Italy, while linezolid was introduced in 2000 in the United States, both of which have been strikingly therapeutic in the current clinical treatment of MRSA infection despite such finite indications (Liu et al, 2011)
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