Macrolides and respiratory infection in critically ill patients: what is the next step?

Several observational studies as well as experimental data suggest that the use of macrolides is associated with better outcomes in patients with severe pneumonia. In severe community acquired pneumonia (SCAP), data demonstrate a benefit of combination therapy, including a beta-lactam plus a macrolide or floroquinolone, at least in the subgroup of patients with critical disease. Such combination seems to have a more significant impact in those with increased disease severity, particularly in those presenting with shock. In addition, data suggest that not all combinations are the same, and SCAP patients receiving combination therapy with macrolides have lower mortality than patients receiving combination with fluoroquinolones. Better results could be associated with a potential immunomodulatory effect of macrolides as well as inhibition to bacterial growth and virulence factors expression (e.g. Streptococcus pneumoniae pneumolysin). Additionally, recent studies try to incorporate these drugs to our therapeutic options in patients with other sepsis causes (e.g. nosocomial pneumonia) and pathogens (e.g. Pseudomonas aeruginosa). In this review, we will assess these issues, discussing the available evidence on macrolides use and highlighting potential research questions to be assessed on this field.