Empirical antibiotic regimen for ICU-treated severe CAP has long been recommended to cover the 3 most common severe CAP pathogens (S. pneumoniae, S. aureus and H.influenzae), atypical pathogens and most relevant Enterobacteriaceae species. Levofloxacin is a fluoroquinolone active against most of these pathogens, especially S. pneumoniae with or without decreased penicillin susceptibility [18, 19] . Its clinical activity in CAP has been well documented in various clinical trials in Europe and the USA [20, 21] . Some studies demonstrated the efficacy of levofloxacin used as monotherapy in severe CAP, compared to ceftriaxone plus erythromycin or cefotaxime plus ofloxacin [22, 23] . Nevertheless, experts continue to propose, for ICU-treated severe CAP, an empirical antibiotic regimen based on an anti pneumococcal β-lactam combined with either a macrolide or a fluoroquinolone. Since respiratory fluoroquinolones with enhanced activity against S. pneumoniae (levofloxacin, moxifloxacin or gemifloxacin) became available, they replaced second generation fluoroquinolones (ofloxacin or ciprofloxacin) in the guidelines [6] [7] [8] . This fluoroquinolone generation shift has never been clearly justified and, to our knowledge, no clinical study has compared these different quinolones combined with a β-lactam in severe CAP. Our results suggest that, when severe CAP causative agent is S. pneumoniae, a combination levofloxacin plus β-lactam is associated with lower mortality than a combination ofloxacin or ciprofloxacin plus β-lactam.