akinohanayuki ブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.







  • 1960年代、MRSAが報告されました。
  • Lancet. 1968;2(7571):741.

  • VCMが使われました。
  • 感染制御は、まだ手探りでした。

  • 1980年代、VREが報告されました。
  • N Engl J Med. 1988;319(3):157.
  • Lancet. 1988;1(8575-6):57.
  • VISAが報告されました。
  • J Antimicrob Chemother. 1997;40(1):135.

  • hVISAが報告されました。
  • Lancet. 1997;350(9092):1670.


  • 2002年にVRSAが報告されました。
  • MMWR Morb Mortal Wkly Rep. 2002;51(26):565.


  • 2008年にLZD耐性ブドウ球菌が報告されました。
  • Antimicrob Agents Chemother. 2008;52(6):2244.

UpToDate より抜粋

Infection control measures should be implemented as for MRSA

Failure of treatment for methicillin-resistant Staphylococcus aureus (MRSA) infection with vancomycin should prompt consideration of infection with vancomycin-intermediate S. aureus (VISA), vancomycin-resistant S. aureus (VRSA), or heteroresistant S. aureus strains. Evaluation and management should involve cooperation between infectious disease specialists, laboratory personnel, and epidemiologists.

●The Clinical and Laboratory Standards Institute definitions for S. aureus vancomycin minimal inhibitory concentrations are as follows 
•Vancomycin susceptible – ≤2 mcg/mL
•Vancomycin intermediate – 4 to 8 mcg/mL
•Vancomycin resistant – ≥16 mcg/mL


We suggest treatment with at least one antimicrobial agent to which the organism is susceptible (Grade 2C). 

alternative antistaphylococcal agents such as daptomycin, linezolid, telavancin, ceftaroline, minocycline, or quinupristin-dalfopristin

For patients with persistent MRSA bacteremia in the setting of vancomycin treatment failure, the optimal approach is uncertain
  • high-dose daptomycin (10 mg/kg/day) in combination with another agent (such as gentamicin 1 mg/kg intravenously [IV] every eight hours, rifampin 600 mg by mouth (PO)/IV daily or 300 to 450 mg PO/IV twice daily, linezolid 600 mg PO/IV twice daily, or trimethoprim-sulfamethoxazole 5 mg/kg IV twice daily) may be considered
  • Clin Infect Dis. 2011;52(3):e18.
combination of daptomycin with a beta-lactam has been shown to be effective in several cases of refractory S. aureus bacteremia
  • Clin Infect Dis. 2011 Jul;53(2):158-63.
Using vancomycin in combination with a second antistaphylococcal antibiotic may not improve its therapeutic efficacy
  • vancomycin and rifampin vs vancomycin 
  • randomized trial
  • 42 patients with MRSA endocarditis
  • prolongation of bacteremia (median nine versus seven days)
  • Ann Intern Med. 1991;115(9):674.

VISA and VRSA isolates have demonstrated variable susceptibility
  • chloramphenicol, rifampin, and trimethoprim-sulfamethoxazole
  • Even if reported as susceptible, quinolones should not be used for the treatment of these infections due to the risk of resistance emerging during therapy.

Duration of therapy 
  • The duration of therapy depends upon the site of infection and should parallel the duration of therapy for MRSA infections. In addition, treatment must include removal of implicated sources of infection, such as central venous catheters; depending on individual patient circumstances, surgical debridement and/or removal of prosthetic material may also be required.

VISA Mechanism

Reduced susceptibility to vancomycin in vancomycin-intermediate S. aureus (VISA) isolates is due to the synthesis of an unusually thickened cell wall containing dipeptides (D-Ala-D-Ala) capable of binding vancomycin, thereby reducing availability of the drug for intracellular target molecules.

VRSA Mechanism

The mechanism of vancomycin resistance in vancomycin-resistant S. aureus (VRSA) is plasmid-mediated transfer of the vanA gene cluster from enterococci with vancomycin resistance (via mobile genetic element Tn1546) . A number of different plasmids, including those containing both enterococcal and staphylococcal plasmid DNA, have been identified that are capable of transferring the Tn1546 transposon. Resistance in VRSA isolates is due to the synthesis of an alternative cell wall terminal peptide (D-ala-D-lac), rather than the normal terminal peptide (D-ala-D-ala). Vancomycin is unable to bind to the former peptide. Expression of the vanA genes is only initiated by exposure to vancomycin so that there is limited effect on the fitness of the isolate (in contrast with the vancomycin-intermediate S. aureus [VISA] strains).


Clin Infect Dis. 2008;46(2):193.
Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia.
  • Mortality associated with MRSA bacteremia was significantly higher when the empirical antibiotic was inappropriate and when vancomycin was empirically used for treatment of infection with strains with a high vancomycin MIC (>1 microg/mL).
Antimicrob Agents Chemother. 2008;52(9):3315.
Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin.
  • vancomycin MIC of>or=1.5 mg/liter was independently associated with failure 
  • adjusted risk ratio, 2.6; 95% confidence interval, 1.3 to 5.4; P = 0.01
Clin Infect Dis. 2012 Mar;54(6):755-71.
The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis.
  • Vancomycin MIC was significantly associated with mortality for MRSA infection irrespective of the source of infection or MIC methodology
  •  OR1.64; 95% CI 1.14-2.37; P<.01

Antimicrob Agents Chemother. 2008;52(6):2244.
First report of cfr-mediated resistance to linezolid in human staphylococcal clinical isolates recovered in the United States.
  • Linezolid resistance has dominantly been mediated by mutations in 23S rRNA or ribosomal protein L4 genes. 
JAMA. 2010;303(22):2260.
Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit.
  • 12 patients with LRSA were identified. In 6 patients, LRSA caused ventilator-associated pneumonia and in 3 patients it caused bacteremia
Clin Infect Dis. 2010;51(7):796.
Multicity outbreak of linezolid-resistant Staphylococcus epidermidis associated with clonal spread of a cfr-containing strain.
  • Thirty-nine isolates were obtained from 2 hospitals.