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Daptomycin-resistant Staphylococcus capitis: Mechanisms, molecular epidemiology, and clinical aspects

Junxiong Zhang1, Zhengan Wang2, Chao Gu3

  • 1Department of Microbiology Laboratory, Xihu District Center for Disease Control and Prevention (Health Supervision Institute), Hangzhou, Zhejiang, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China; Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Abstract

Insights

Methicillin-resistant Staphylococcus capitis (MRSC) shows high susceptibility to daptomycin (DAP), with one resistant strain identified. Novel mutations in mprF confer DAP resistance and increase susceptibility to beta-lactams, offering treatment insights.

Area of Science:

  • Clinical Microbiology
  • Infectious Diseases
  • Antimicrobial Resistance

Background:

  • Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, are significant nosocomial pathogens.
  • Staphylococcus capitis is an emerging pathogen with increasing clinical and epidemiological relevance.
  • Limited data exists on daptomycin (DAP) resistance in methicillin-resistant S. capitis (MRSC).

Purpose of the Study:

  • To investigate DAP susceptibility among clinical MRSC isolates.
  • To identify molecular mechanisms underlying DAP resistance in MRSC.
  • To explore potential cross-resistance patterns with other antibiotics.

Main Methods:

  • Analysis of 101 clinical MRSC strains collected between 2018-2020.
  • Determination of minimum inhibitory concentrations (MICs) using agar dilution and broth microdilution.
  • Multilocus sequence typing (MLST) for molecular characterization.
  • Whole-genome sequencing to identify resistance-associated mutations.

Main Results:

  • 99.01% of MRSC strains were DAP-susceptible; 0.99% (1/101) were resistant (MIC=4 µg/mL).
  • Reduced susceptibility (MIC > 0.5 µg/mL) was observed in 48.51% of strains.
  • Dominant sequence types (STs) were ST1, ST6, and ST3; ST6 strains showed higher DAP susceptibility than ST1.
  • No cross-resistance between DAP and vancomycin or teicoplanin was found.
  • The DAP-resistant strain harbored novel mutations: mprF-A784L and yycF-H120P.
  • Complementation of mprF restored DAP resistance and increased beta-lactam susceptibility (seesaw effect).

Conclusions:

  • This study provides crucial in vitro DAP activity data for S. capitis.
  • Novel mprF mutations are identified as key determinants of DAP resistance in MRSC.
  • The observed 'seesaw effect' on beta-lactam susceptibility offers valuable insights for MRSC infection treatment strategies.

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