Adjunctive Therapy in Community-Acquired Pneumonia

Abstract

Despite potent antibiotics, community-acquired pneumonia (CAP) remains the most common cause of death from infection and the eighth overall leading cause of death in the United States. For this reason, adjunctive therapeutic measures directed at the host response rather than the pathogen are attractive. The immunomodulatory effects of macrolide antibiotics may play a significant role in management of severe CAP. The existing literature does not demonstrate a clear benefit for corticosteroids, but larger prospective randomized trials are needed. Nonsteroidal antiinflammatory drugs may benefit oxygenation but have no documented effect on mortality. Statin use before CAP diagnosis is associated with improved outcome but requires further research to determine if initiation at the time of diagnosis will affect outcome positively. Activation of the coagulation system appears to be a major pathophysiological event in severe pneumonia, but neither drotrecogin alfa activated nor tifacogin (recombinant tissue factor pathway inhibitor) have demonstrated a survival benefit. Other therapies have theoretical benefit but are not yet in the stage of clinical trials.

Clearance of apoptotic neutrophils and resolution of inflammation

“…General immunosuppression by steroids and statins could be detrimental in the context of infection, whereas the dual bactericidal and pro‐resolving action of macrolides would be more advantageous. Likewise, data support that macrolide antibiotics are clearly beneficial in the treatment of community‐acquired pneumonia …”

Recent advances in our understanding of Streptococcus pneumoniae infection

“…Although many varied strategies have been tried, those considered to have the greatest potential are macrolide antibiotics, in particular, as well as corticosteroids and statins [5,38]. …”

Steroid-Decorated Antibiotic Microparticles for Inhaled Anti-Infective Therapy

“…The severity of CAP has been linked to the extent of inflammation in the body, as inflammation is the body's natural response to the invading infection‐causing pathogens . Despite advances in vaccination and antimicrobial therapy, CAP remains as a leading cause of human morbidity and mortality, and has afflicted the world population with a huge socio‐economic cost …”

“…For CAP patients with COPD, the downregulation of the unwanted excessive cytokine response by corticosteroids has the beneficial effect of reducing excessive pulmonary inflammation and accelerating clinical recovery. In addition, bronchospasms (wheezing), a common condition found in these patients, could also be treated with the corticosteroids …”

“…The use of corticosteroids in combination with antibiotics has been proven to be effective and safe in several randomized controlled trials in patients with bacterial and tuberculous meningitis, tuberculous pericarditis, septic arthritis, and septic shock . In CAP–COPD patients, coadministration of corticosteroids with antibiotics has been shown to be safe and efficacious, and is therefore frequently administered by the physician for treatment . On a further note, for smokers who are predisposed to COPD and bacterial infections (i.e., tobacco smoke compromise the antibacterial function of leukocytes, including neutrophils, monocytes, T cells, and B cells), treatment via the steroid–antibiotic combination will no doubt be a useful and timely therapeutic intervention as well.…”