Comment on: linezolid use in sepsis due to methicillin-susceptible Staphylococcus aureus.

De Gascun and colleagues report on a case of methicillinsusceptible Staphylococcus aureus (MSSA) sepsis treated successfully with linezolid after initial failure of a triple regimen of apparently appropriate antibiotics. They ascribe the observed efficacy of linezolid to an anti-toxin effect of the antibiotic. Linezolid acts by inhibiting bacterial protein synthesis, and it, therefore, blocks the production of bacterial toxins and other virulence factors. The suggested anti-toxin effect is attractive to explain the observed efficacy of linezolid. Yet, linezolid was initiated at a time when all cultures were negative, whereas toxin production requires a bacterial source to be present. De Gascun and colleagues looked for such a source but were unable to find one. Yet, presence of a source with access difficulties for the initial triple antibiotic regimen but not for linezolid seems possible. Such a source might explain the negative blood cultures (elimination of bacteria leaking from the source into the bloodstream) as well as the worsening symptoms of sepsis (continued toxin release into the bloodstream from bacteria surviving in the source) observed during treatment with the initial triple antibiotic regimen. Superior penetration of linezolid into the source on the other hand, in combination with an anti-toxin effect, might then have prevented further toxin release into the bloodstream, with regressing sepsis symptoms and eventual recovery as a result. Even if it seems possible to link the patient’s recovery to linezolid, multiple factors can interfere with this evolution. Aggressive initial treatment with drugs such as drotrecogin alpha (activated) or substitutive doses of corticosteroids could, by themselves, have improved the patient’s condition. A randomized trial of conservative therapy versus linezolid would be of the highest interest to confirm its use in this setting. Widespread use could induce S. aureus resistance.