Reversion From Methicillin Susceptibility to Methicillin Resistance in Staphylococcus aureus During Treatment of Bacteremia

J Infect Dis. 2016 Mar 15;213(6):1041-8. doi: 10.1093/infdis/jiv512. Epub 2015 Oct 26.

Abstract

Approximately 3% of Staphylococcus aureus strains that, according to results of conventional phenotypic methods, are highly susceptible to methicillin-like antibiotics also have polymerase chain reaction (PCR) results positive for mecA. The genetic nature of these mecA-positive methicillin-susceptible S. aureus (MSSA) strains has not been investigated. We report the first clearly defined case of reversion from methicillin susceptibility to methicillin resistance among mecA-positive MSSA within a patient during antibiotic therapy. We describe the mechanism of reversion for this strain and for a second clinical isolate that reverts at a similar frequency. The rates of reversion are of the same order of magnitude as spontaneous resistance to drugs like rifampicin. When mecA is detected by PCR in the clinical laboratory, current guidelines recommend that these strains be reported as resistant. Because combination therapy using both a β-lactam and a second antibiotic suppressing the small revertant population may be superior to alternatives such as vancomycin, the benefits of distinguishing between mecA-positive MSSA and MRSA in clinical reports should be evaluated.

Keywords: S. aureus bacteremia; fluctuation analysis; mecA PCR; oxacillin; oxacillin-susceptible mecA-positive S. aureus; β-lactam.

Publication types

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

MeSH terms

  • Aged
  • Amino Acid Sequence
  • Anti-Bacterial Agents / therapeutic use
  • Bacteremia / microbiology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Base Sequence
  • DNA, Bacterial / genetics
  • Frameshift Mutation
  • Gene Expression Regulation, Bacterial
  • Humans
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / genetics
  • Methicillin-Resistant Staphylococcus aureus / physiology
  • Nafcillin / administration & dosage
  • Nafcillin / therapeutic use
  • Penicillin-Binding Proteins / genetics
  • Penicillin-Binding Proteins / metabolism
  • Prosthesis-Related Infections
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology*
  • Vancomycin / administration & dosage
  • Vancomycin / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • DNA, Bacterial
  • Penicillin-Binding Proteins
  • mecA protein, Staphylococcus aureus
  • Nafcillin
  • Vancomycin