Reduced Vancomycin Susceptibility in Staphylococcus aureus , Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

Howden, Benjamin P.; Davies, John K.; Johnson, Paul D. R.; Stinear, Timothy P.; Grayson, M. Lindsay

doi:10.1128/cmr.00042-09

Cited by 962Antimicrobial Resistance in StaphylococcusAntibiotic Resistance in BacteriaAntibiotic Use and Resistance

Reduced Vancomycin Susceptibility in Staphylococcus aureus , Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

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Howden, Benjamin P., Davies, John K., Johnson, Paul D. R., Stinear, Timothy P., Grayson, M. Lindsay·2010·Clinical Microbiology Reviews

DOI 10.1128/cmr.00042-09PMC PMC2806658

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Abstract

SUMMARY: The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) over the past decade has provided a challenge to diagnostic microbiologists to detect these strains, clinicians treating patients with infections due to these strains, and researchers attempting to understand the resistance mechanisms. Recent data show that these strains have been detected globally and in many cases are associated with glycopeptide treatment failure; however, more rigorous clinical studies are required to clearly define the contribution of hVISA to glycopeptide treatment outcomes. It is now becoming clear that sequential point mutations in key global regulatory genes contribute to the hVISA and VISA phenotypes, which are associated predominately with cell wall thickening and restricted vancomycin access to its site of activity in the division septum; however, the phenotypic features of these strains can vary because the mutations leading to resistance can vary. Interestingly, changes in the staphylococcal surface and expression of agr are likely to impact host-pathogen interactions in hVISA and VISA infections. Given the subtleties of vancomycin susceptibility testing against S. aureus , it is imperative that diagnostic laboratories use well-standardized methods and have a framework for detecting reduced vancomycin susceptibility in S. aureus .

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Due to difficulties in detecting these strains, vancomycin failures have been increasingly reported in deep-seated infections.
“Due to the difficulties on detecting these strains, vancomycin failures have been increasingly reported in deep-seated infections.”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [101]
S. aureus within the range of susceptibility, with vancomycin MICs > 1 and ≤ 2 μg/ml, have been more frequently associated with the hVISA phenotype.
“Indeed, S. aureus within the range of susceptibility, with vancomycin MICs > 1 and ≤ 2 μg/ml have been more frequently associated with the hVISA phenotype.”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [101]
These global homeostatic changes appear to lead to reduced autolytic activity with thickened cell wall and an increased amount of free D-Ala-D-Ala dipeptides with less peptidoglycan cross-linking.
“These global homeostatic changes appear to lead to a reduced autolytic activity with thickened cell wall and an increase amount of free D-Ala-D-Ala dipeptides with less peptidoglycan cross-linking (101, 104).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [101]
Phenotypically, hVISA/VISA strains exhibit distinct metabolic characteristics that may include increased fructose utilization, increased fatty acid metabolism, impaired acetate metabolism and tricarboxylic acid cycle, decreased glutamate availability, and increased expression of cell wall synthesis genes.
“Phenotypically, hVISA/VISA strains exhibit distinct metabolic characteristics that may include i) increase in fructose utilization, ii) increased fatty acid metabolism, iii) impaired acetate metabolism and tricarboxylic acid cycle, iv) decrease in glutamate availability, and iv) increase expression of cell wall synthesis genes.”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [101]
Detection of hVISA is very challenging, and some S. aureus strains reported as susceptible to vancomycin by standard susceptibility testing may still exhibit this phenotype.
“As the “resistant” subpopulation is difficult to identify, detection of hVISA becomes very challenging and some S. aureus strains reported as “susceptible” to vancomycin by standard susceptibility testing may still exhibit this phenotype (101).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [101]

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Authors: Howden, B. P., Davies, J. K., Johnson, P. D. R., Stinear, T. P., & Grayson, M. L.
Affiliations: The University of Melbourne (AU)
Monash University (AU)
ORCID: Howden, Benjamin P.
Johnson, Paul D. R.
Stinear, Timothy P.
Venue: Clinical Microbiology Reviews
Publisher: American Society for Microbiology
Published: 2010-01
Volume: 23
Issue: 1
Pages: 99-139
ISSN: 0893-8512 (ISSN-L)
1098-6618
DOI: 10.1128/cmr.00042-09
PMC: PMC2806658
OpenAlex: W2126915534
Cited by: 962
References: 406
Citations by year: 2026: 42 · 2025: 41 · 2024: 48 · 2023: 58 · 2022: 45 · 2021: 52 · 2020: 49 · 2019: 60 · 2018: 54 · 2017: 51 · 2016: 63 · 2015: 83 · 2014: 69 · 2013: 88 · 2012: 72
FWCI: 9.15
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Clinical Microbiology Reviews (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
Keywords: vancomycin-intermediate Staphylococcus aureus, heterogeneous vancomycin-intermediate Staphylococcus aureus, reduced vancomycin susceptibility, glycopeptide resistance, cell wall thickening, agr gene, vancomycin susceptibility testing, treatment failure, host-pathogen interaction
MeSH terms: Anti-Bacterial Agents, Humans, Microbial Sensitivity Tests, Staphylococcal Infections, Staphylococcus aureus, Vancomycin, Treatment Outcome, Vancomycin Resistance

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Reduced Vancomycin Susceptibility in Staphylococcus aureus , Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

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