Correlation between Reduced Susceptibility to Vancomycin and Clinical Outcome in MRSA Blood Stream Infections

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Slide 1 :

Correlation between Reduced Susceptibility to Vancomycin and Clinical Outcome in MRSA Blood Stream Infections HM Neoh, S Hori, M Komatsu, T Oguri, F Takeuchi, L Cui, K Hiramatsu Dept. of Microbiology, Dept. of Infection Control Science Juntendo University, Tokyo

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Introduction Vancomycin has been the choice of drug for MRSA infection. Vancomycin Intermediate Staphylococcus aureus (VISA) has emerged all over the world after the first report at Juntendo University Hospital. (Hiramatsu et al, JAC, 1997) Dissemination of hetero-VISA has also been reported. (Hiramatsu et al, Lancet, 1997) Clinical impact of hetero-VISA has not been established.

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Objective To investigate the correlation between reduced vancomycin susceptibility and clinical outcome in MRSA bloodstream infections

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Materials & Methods 1) Setting Retrospective study 209 cases of MRSA blood stream infections in Juntendo University Hospital from January 1998 to October 2005. Inclusion-exclusion criteria MRSA +ve blood culture Fever > 38oC ? 5 days vancomycin treatment excluded if catheter-related infection or treated with antibiotics other than vancomycin, or insufficient trough level of vancomycin. 20 cases were eligible

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2) Medical record review The following information were retrieved from medical records of eligible patients : Age, gender, underlying conditions Initial therapeutic response parameters: Days till afebrile Days till CRP value ? 30% of maximum Vancomycin treatment response: Good / Poor Clinical outcome (Howden et al, CID, 2004): Cured / Better / Fair / Worse / Dead

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3) Laboratory investigations MRSA strains eligible for this study were subjected to vancomycin susceptibility tests: Minimum inhibitory concentration (MIC) determination with CLSI agar dilution method Analysis for vancomycin resistant subpopulations (population analysis)

Slide 7 :

Population Analysis To determine bacterial subpopulations with reduced susceptibility to vancomycin 107 cells of each tested strain were plated onto BHI agar plates containing various concentrations of vancomycin Plates were incubated at 37oC for 48 hours Number of colonies that grew for each vancomycin concentration was counted and plotted on a semi logarithmic graph to give the population analysis profile of each strain

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Results a Vancomycin, b Area Under Curve, c Days Till Afebrile, d Days Till CRP < 30% of maximum e Vancomycin Treatment Response MRSA Vancomycin Susceptibility and Patient Clinical Course

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Statistical analysis

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A case of MRSA bacteraemia which failed to be cured with vancomycin 3 MRSA serial isolates were ‘isogenic’. Vanc MIC increased: 1 ? 4 mg/L AUC increased: 11.92? 25.2 Vancomycin susceptibility reduced Clinical course was prolonged: days till afebrile ~ 25 days till CRP ? 30% ~ 36 initial strain second strain third strain

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Discussion Significant correlation between vancomycin susceptibility and patient clinical outcome in MRSA bloodstream infections Slow initial therapeutic response could be a predictor of possible involvement of vancomycin less susceptible strains. in vivo development of strains with reduced susceptibility towards vancomycin could occur during treatment.

Slide 13 :

Further investigation Prospective study More cases of MRSA bacteraemia Prevalence of clinical strains which are less susceptible to vancomycin Genetic analysis is required to understand the basis of vancomycin resistance in these clinical MRSA strains

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	hui-min@med.juntendo.ac.jp 5 Years ago.



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