Role of folate antagonists in the treatment of methicillin-resistant Staphylococcus aureus infection

Clin Infect Dis. 2008 Feb 15;46(4):584-93. doi: 10.1086/525536.


Methicillin-resistant Staphylococcus aureus (MRSA) infection has reached epidemic proportions, and therapeutic options are limited because these strains are often multidrug resistant. However, the new strains of community-acquired MRSA show decreased resistance to trimethoprim-sulfamethoxazole. Clinical and experimental reports show a mixture of successes and failures with trimethoprim-sulfamethoxazole treatment. A reason for failure might be the amount of thymidine released from damaged host tissues and bacteria, a concept strengthened by the fact that S. aureus thermonuclease releases thymidine from DNA. Thus, success or failure with trimethoprim-sulfamethoxazole may well depend on the amount of tissue damage and organism burden, rather than acquisition of a resistance gene. Clinical trials and experimental animal studies show high failure rates, perhaps because of released thymidine. The use of trimethoprim-sulfamethoxazole for community-acquired MRSA infection should not be endorsed without further research.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology
  • Anti-Infective Agents / therapeutic use*
  • Community-Acquired Infections / drug therapy
  • Community-Acquired Infections / microbiology
  • Humans
  • Methicillin Resistance*
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / drug effects*
  • Trimethoprim, Sulfamethoxazole Drug Combination / pharmacology
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*


  • Anti-Infective Agents
  • Trimethoprim, Sulfamethoxazole Drug Combination