High vancomycin minimum inhibitory concentration is a predictor of mortality in meticillin-resistant Staphylococcus aureus bacteraemia

Wi, Yu Mi; Kim, June Myung; Joo, Eun-Jeong; Ha, Young Eun; Kang, Cheol-In; Ko, Kwan Soo; Chung, Doo Ryeon; Song, Jae-Hoon; Peck, Kyong Ran

doi:10.1016/j.ijantimicag.2012.04.003

Cited by 29 publications

(22 citation statements)

References 30 publications

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“…Tan et al (Tan, Ng, Tan and Huang, 2007) (Wi et al, 2012). For this reasons, MICs values offer more information than results of susceptibility obtained by disc diffusion.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

A meta-analysis of in vitro antibiotic synergy against Acinetobacter baumannii

March

Bratos

2015

Journal of Microbiological Methods

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“…Tan et al (Tan, Ng, Tan and Huang, 2007) (Wi et al, 2012). For this reasons, MICs values offer more information than results of susceptibility obtained by disc diffusion.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

A meta-analysis of in vitro antibiotic synergy against Acinetobacter baumannii

March

Bratos

2015

Journal of Microbiological Methods

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“…Vancomycin remains the mainstay of therapy for MRSA BSIs and is currently recommended in the MRSA treatment guidelines from the Infectious Diseases Society of America (IDSA) (4). Numerous reports have associated vancomycin treatment failure with elevated MICs still within the susceptible range, in particular, with a vancomycin MIC of Ͼ1 mg/liter; however, this remains an area of clinical debate (5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Daptomycin Improves Outcomes Regardless of Vancomycin MIC in a Propensity-Matched Analysis of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

Claeys

Zasowski

Casapao

et al. 2016

Antimicrob Agents Chemother

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“…The second resistance phenotype comprises both vancomycinintermediate (VISA) and -heteroresistant (hVISA) S. aureus strains. MRSA isolates in the VISA/hVISA category have lower MICs (2 to 8 g/ml) but remain clinically relevant and are linked to a higher incidence of persistent bloodstream infection and treatment failure (5)(6)(7)(8).…”

mentioning

confidence: 99%

Decreased Vancomycin Susceptibility in Staphylococcus aureus Caused by IS 256 Tempering of WalKR Expression

McEvoy

Tsuji

Gao

et al. 2013

Antimicrob Agents Chemother

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f Vancomycin-intermediate Staphylococcus aureus (VISA) strains often arise by mutations in the essential two-component regulator walKR; however their impact on walKR function has not been definitively established. Here, we investigated 10 MRSA strains recovered serially after exposure of vancomycin-susceptible S. aureus (VSSA) JKD6009 to simulated human vancomycin dosing regimens (500 mg to 4,000 mg every 12 h) using a 10-day hollow fiber infection model. After continued exposure to the vancomycin regimens, two isolates displayed reduced susceptibility to both vancomycin and daptomycin, developing independent IS256 insertions in the walKR 5= untranslated region (5= UTR). Quantitative reverse transcription-PCR (RT-PCR) revealed a 50% reduction in walKR gene expression in the IS256 mutants compared to the VSSA parent. Green fluorescent protein (GFP) reporter analysis, promoter mapping, and site-directed mutagenesis confirmed these findings and showed that the IS256 insertions had replaced two SigA-like walKR promoters with weaker, hybrid promoters. Removal of IS256 reverted the phenotype to VSSA, showing that reduced expression of WalKR did induce the VISA phenotype. Analysis of selected WalKR-regulated autolysins revealed upregulation of ssaA but no change in expression of sak and sceD in both IS256 mutants. Whole-genome sequencing of the two mutants revealed an additional IS256 insertion within agrC for one mutant, and we confirmed that this mutation abolished agr function. These data provide the first substantial analysis of walKR promoter function and show that prolonged vancomycin exposure can result in VISA through an IS256-mediated reduction in walKR expression; however, the mechanisms by which this occurs remain to be determined.

show abstract

High vancomycin minimum inhibitory concentration is a predictor of mortality in meticillin-resistant Staphylococcus aureus bacteraemia

Cited by 29 publications

References 30 publications

A meta-analysis of in vitro antibiotic synergy against Acinetobacter baumannii

A meta-analysis of in vitro antibiotic synergy against Acinetobacter baumannii

Daptomycin Improves Outcomes Regardless of Vancomycin MIC in a Propensity-Matched Analysis of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

Decreased Vancomycin Susceptibility in Staphylococcus aureus Caused by IS 256 Tempering of WalKR Expression

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