Prevention and Management of Community-Acquired Pneumonia in Adults

Abstract

Community-acquired pneumonia (CAP) is an important cause of morbidity and mortality worldwide. CAP is one of the major contributors of antibiotic consumption and thus contributes to development of antibiotic resistance through selective antibiotic pressure. Streptococcus pneumoniae is the most commonly identified bacterial pathogen for CAP in all age groups. In this thesis, the role of pneumococcal vaccination in the prevention of CAP in elderly and the effectiveness of different empirical antibiotic treatment strategies for adults hospitalized with CAP are discussed.

Part one describes the results of the “Community-Acquired Pneumonia immunization Trial in Adults” (CAPiTA), a double-blind randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) in the prevention of vaccine-type (VT) CAP and invasive pneumococcal disease (IPD). A total of 84,496 immunocompetent adults aged 65 years and above were randomized to receive PCV13 or placebo. After a follow-up of four years PCV13 had prevented 38% of VT-CAP and 76% of VT-IPD episodes (modified intention-to-treat analysis). Efficacy of the vaccine depended on the age of the participants at baseline and on the baseline risk to acquire a CAP episode, with the highest efficacy in participants with the lowest risk of CAP. Implementation of the vaccine not only depends on the efficacy but also on the burden of disease caused by the 13 pneumococcal serotypes contained in the vaccine. This is expected to decrease further due to herd protection from child immunization with PCV’s.

Part two describes the results of the “Community-Acquired Pneumonia - Study on the initial Treatment with Antibiotics of lower Respiratory Tract infections” (CAP-START). In this cluster-randomized cross-over trial, hospitals were randomized for different empirical treatment strategies for periods of four months: beta-lactam monotherapy, beta-lactam / macrolide combination, and fluoroquinolone monotherapy. The study shows that beta-lactam monotherapy as preferred empirical treatment is non-inferior compared to the other strategies for 90-day mortality. Also, there were no clinically relevant differences in other outcomes and there was no difference in costs. This is a relevant finding as from an ecological perspective, beta-lactam monotherapy is preferred as it causes less selection pressure for development of resistant pathogens. Therefore, beta-lactam monotherapy should be the preferred treatment for patients with CAP hospitalized to non-ICU wards. Whether treatment can be further narrowed to small-spectrum beta-lactams such as penicillin without compromising patient outcome is subject for future research.