Detection of Heteroresistant Vancomycin-Intermediate Staphylococcus haemolyticus Among Blood Isolates

Area of Science:

• Medical Microbiology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Staphylococcus haemolyticus is a significant cause of hospital-acquired infections.
• The emergence of vancomycin heteroresistance in S. haemolyticus poses a therapeutic challenge due to vancomycin's critical role in treating severe infections.
• Understanding the prevalence and mechanisms of vancomycin heteroresistance is crucial for effective patient management.

Purpose of the Study:

• To determine the prevalence of heteroresistant vancomycin-intermediate Staphylococcus haemolyticus (hVISH) in clinical blood isolates.
• To evaluate the efficacy of brain heart infusion agar with 4 µg/mL vancomycin (BHIV4) for heteroresistance screening.
• To investigate the molecular mechanisms underlying vancomycin heteroresistance in S. haemolyticus.

Main Methods:

• Collected 166 S. haemolyticus blood isolates from hospitalized patients.
• Determined vancomycin minimum inhibitory concentration (MIC) using E-test.
• Screened for heteroresistance using BHIV4 agar and confirmed with population analysis-profile area under curve (PAP-AUC).
• Performed whole-genome sequencing on eight selected isolates.

Main Results:

• All isolates were susceptible to vancomycin by E-test, but 18.7% showed heteroresistance via PAP-AUC.
• BHIV4 demonstrated moderate sensitivity (64.5%) and high specificity (97.8%) for detecting heteroresistance.
• Whole-genome sequencing revealed mutations in various operons, including those involved in cell wall synthesis and glycopeptide resistance.

Conclusions:

• A significant proportion of S. haemolyticus blood isolates exhibit vancomycin heteroresistance, often undetected by standard susceptibility testing.
• The BHIV4 screening method has limitations in sensitivity, necessitating consideration of alternative antibiotics when vancomycin MICs approach clinical breakpoints.
• Identification of novel mutations provides insights into the genetic basis of heteroresistance, aiding in the development of improved diagnostic and therapeutic strategies.