Community-acquired pneumonia (CAP) affects approximately 4 million patients in the United States each year. Around 20% of these patients are admitted to hospitals for treatment. In patients requiring inpatient treatment, overall mortality is approximately 12%. However, it can be much higher in CAP patients requiring admission to the ICU.
When parenteral antimicrobials are required for the treatment of hospitalized patients, the mainstay of therapy for many years has included either a combination of a β-lactam antibiotic with a macrolide antibiotic, or the use of a respiratory fluoroquinolone alone. β-lactam antibiotics do not have antibacterial activity against the so-called “atypical bacteria,” including species of Mycoplasma, Chlamydia, andLegionella, which are important pathogens in CAP. Classes of antibiotics active against these atypical pathogens include macrolides, fluoroquinolones, and tetracyclines.
Urgent Need of New Antimicrobial Agents
Two important realities are beginning to impact the traditional recommendations for antimicrobial therapy in CAP. First, there is an urgent need for the development of new antimicrobial agents that are more active against resistant bacterial pathogens. Second, the rapid development of antimicrobial-resistant bacterial pathogens has compromised many of our existing antimicrobials.
“Antimicrobial resistance continues to increase
in a dramatic fashion.”
While there are many reasons for the slowing of new antimicrobial discoveries and the rapid development of antimicrobial resistance, the major factors appear to be overuse and misuse of antibiotics in both man and animals and the inability of the pharmaceutical industry to realize significant financial return on investment from new antimicrobial development. This lack of new agents has been called one of the three greatest threats to human health by the Infectious Diseases Society of America (IDSA). Yet, antimicrobial resistance continues to increase in a dramatic fashion.
Preventing Future Antimicrobial Resistance
In 2007, the IDSA and the Society for Healthcare Epidemiology of America (SHEA) published the first practice guidelines for antimicrobial stewardship in hospitals as a response to resistance concerns. IDSA and SHEA emphasize the importance of adherence to infection control techniques (eg, compliance with hand hygiene and other contact precautions) to reduce the incidence and spread of antimicrobial-resistant pathogens in hospitals. Researchers also recommend increasing the use of antibiotic heterogeneity when selecting empiric antimicrobial regimens to treat common infections requiring hospitalization.
Recently, CMS added tigecycline (Tygacil, Pfizer) to their recommendations for treating community-acquired bacterial pneumonia (CABP) in adults older than 65 in the non-ICU setting. The agent was also added to the revised guidelines for patients who cannot take another antibiotic regimen because of antibiotic allergies, renal failure, or drug interaction. That recommendation was made because two recent studies demonstrated Level 1 evidence for the administration of tigecycline in CABP.
A systematic review and meta-analysis of the effectiveness and safety of tigecycline found a higher numerical risk of mortality in the tigecycline group, but noted that the finding was not statistically significant. The lesson learned from the meta-analysis was that when using tigecycline as monotherapy for CABP, it’s important to carefully monitor patients for adverse effects or the emergence of resistant isolates. The hope is that greater adoption of these recommendations will further reduce the burden of pneumonia in the future.
Robert P. Rapp, PharmD, FCCP, has indicated to Physician’s Weekly that he has worked as a consultant for Pfizer and Ortho-McNeil and as a paid speaker for Pfizer, Ortho-McNeil, and U.S. Astellas.
Readings & Resources (click to view)
Falagas ME, Metaxas EL. Tigecycline for the treatment of patients with community-acquired pneumonia requiring hospitalization. Expert Rev Anti Infect Ther. 2009;7:913-923.
Bergallo C, Jasovich A, Teglia O, et al. Safety and efficacy of intravenous tigecycline in treatment of community-acquired pneumonia: results from a double-blind randomized phase 3 comparison study with levofloxacin. Diagn Microbiol Infect Dis. 2009;63:52-61.
Tanaseanu C, Bergallo C, Teglia O, et al; 308 Study Group: 313 Study Group. Integrated results of 2 phase 3 studies comparing tigecycline and levofloxacin in community-acquired pneumonia. Diagn Microbiol Infect Dis. 2008;61: 329-338.
Cai Y, Want R, Liang B, Bai N, Liu Y. Systemic review and meta-analysis of the effectiveness and safety of tigecycline for treatment of infectious diseases. Antimicrob Agents Chemother. 2011;55:1162-1172.
Tasina E, Haidich AB, Kokkali S, and Arvanitidou M. Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. Lancet Infect Dis. 2011;Jul 22 [Epub ahead of print].