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

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.