Optimal pharmacological therapy for community-acquired pneumonia: the role of dual antibacterial therapy

Abstract

The optimal pharmacological therapy of community-acquired pneumonia (CAP) is one of the most ardently debated issues in medicine. Presently, most guidelines recommend either a fluoroquinolone alone or dual therapy with a third-generation cephalosporin plus a macrolide in patients hospitalised with CAP, but few provide clinicians with specific considerations for selecting from these agents. Despite a similar spectrum of activity and favourable resistance patterns (for fluoroquinolones and third-generation cephalosporins) against CAP pathogens, there is emerging evidence that dual therapy may be superior to monotherapy in certain populations.In patients with non-severe CAP, the evidence supports the use of either monotherapy or dual therapy in most patients; however, patients with severe CAP or bacteraemic pneumococcal CAP experience improved survival when treated with dual therapy. It is unclear from this evidence if any specific combination of agents is the most effective, but the combination of a third-generation cephalosporin plus a macrolide is the most extensively studied. Dual therapy was superior to monotherapy irrespective of the susceptibility of the aetiological pathogen, thus insufficient antimicrobial spectrum does not explain the disparity. The most likely explanation for improved outcomes with dual therapy is the combined effect of optimised antimicrobial spectrum (including atypicals), decreased impact of resistance to a single agent and the immunomodulatory effects of macrolides. Increasing resistance in patients with non-severe CAP warrants the consideration of dual therapy and perhaps a reappraisal of agents usually reserved for second-line therapy, including doxycycline, in these populations as well. In light of the available evidence, dual therapy should be strongly considered in all patients with severe CAP, especially when complicated by pneumococcal bacteraemia.