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Updated: Feb 4, 2026
Multiplex PCR Assay for Typing of Staphylococcal Cassette Chromosome Mec Types I to V in Methicillin-resistant Staphylococcus aureus
Published on: September 5, 2013
qacA is a key factor in heteroresistance to vancomycin in sequence type 5 methicillin-resistant Staphylococcus aureus
Kaiting Zhang1, Lin Xi1, Qiyu Bian1
1Institute of Antibiotics, Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Abstract:
The presence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) among methicillin-resistant Staphylococcus aureus (MRSA) strains has been associated with vancomycin treatment failure, especially in cases of MRSA pneumonia. This study aimed to analyze the molecular characteristics and risk factors for hVISA among MRSA strains isolated from pneumonia patients and to validate the most important risk factors. All the MRSA clinical isolates were collected in a multicenter, prospective, observational clinical trial from July 2012 to June 2020. The hVISA strains were verified via a modified population analysis profile-area under the curve method, and the prevalence of hVISA in hospitalized pneumonia patients was 53.5% (61/114). Sequence type 5 (ST5)-MRSA, the dominant hVISA strain, and ST764-MRSA, the dominant vancomycin-susceptible S. aureus (VSSA) strain, exhibited comparable incidences (27.2% vs 36.8%) but with different hVISA detection rates (90.3% vs 21.4%, P < 0.001). Furthermore, the efflux pump gene qacA was identified by multivariate logistic regression analysis as an independent significant predictor of hVISA occurrence in ST5-MRSA (P < 0.001). This association was confirmed when both the recipient ST5-MRSA and ST764-MRSA strains that acquired the qacA-borne plasmid exhibited phenotypic transformation from VSSA to hVISA. This study provides evidence that the acquisition of qacA by the VSSA strain is associated with the formation of hVISA in MRSA isolates from hospitalized pneumonia patients.
Importance:
Methicillin-resistant Staphylococcus aureus (MRSA) is among the leading causes of pulmonary infections, and currently, vancomycin use remains an effective intervention. The irrational use of vancomycin has increased the prevalence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA)/vancomycin-intermediate S. aureus strains in pneumonia patients infected with MRSA, but the underlying molecular characteristics remain unknown. This study focused on the evidently high detection rates of hVISA strains from pneumonia patients from a prospective observational study in China and investigated the predictive risk factors for the dominant hVISA strain sequence type 5 (ST5)-MRSA. Multivariate logistic regression analysis of variables identified as significant for host, pathogen, and genetic characteristics revealed that qacA was a significant independent predictor of the development of hVISA in ST5-MRSA, which was confirmed by plasmid-based experiments. This study provides new insights and an improved understanding of the decreased vancomycin susceptibility of MRSA in pneumonia patients and provides evidence-based support for optimizing clinical treatment plans from an innovative perspective to maintain the efficacy of vancomycin.
Clinical Trials:
This study is registered with the China Clinical Trials Registry as ChiCTR-OPC-16007920 and ChiCTR-OPC-17012567 .
Insights
Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) is common in MRSA pneumonia. The efflux pump gene qacA acquisition by vancomycin-susceptible S. aureus (VSSA) transforms strains into hVISA, impacting vancomycin efficacy.
Area of Science:
- Medical Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) causes severe pulmonary infections, with vancomycin as a primary treatment.
- Increased vancomycin use correlates with rising prevalence of vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA) strains.
- Understanding the molecular basis of hVISA in MRSA pneumonia is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the molecular characteristics and risk factors associated with hVISA in MRSA strains from pneumonia patients.
- To identify predictors for hVISA development, particularly in the dominant Sequence Type 5 (ST5)-MRSA.
- To validate findings through experimental confirmation of genetic determinants of reduced vancomycin susceptibility.
Main Methods:
- Prospective, multicenter observational study of MRSA isolates from pneumonia patients (July 2012-June 2020).
- hVISA strains identified using a modified population analysis profile-area under the curve (PAP-AUC) method.
- Multivariate logistic regression analysis and plasmid-based experiments to identify and confirm genetic risk factors.
Main Results:
- The prevalence of hVISA among MRSA isolates from pneumonia patients was 53.5% (61/114).
- Sequence Type 5 (ST5)-MRSA was the dominant hVISA strain, while ST764-MRSA was the dominant vancomycin-susceptible S. aureus (VSSA) strain.
- The efflux pump gene qacA was identified as a significant independent predictor of hVISA in ST5-MRSA (P < 0.001), confirmed by phenotypic transformation experiments.
Conclusions:
- Acquisition of the qacA gene by VSSA strains is strongly associated with the development of hVISA in MRSA isolates from pneumonia patients.
- Findings provide insights into decreased vancomycin susceptibility in MRSA pneumonia.
- This study supports optimizing clinical treatment plans to maintain vancomycin efficacy against MRSA infections.
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