Introduction*

Abstract

Respiratory tract infections (RTIs) remain a significant cause of morbidity and mortality, despite the wide range of antimicrobial agents available. Lower RTIs – community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB) – are among the top 10 causes of death from infectious disease in the developed world and are now estimated to be responsible for over 4.3 million deaths globally per year [1]. Upper respiratory tract infections – sinusitis, tonsillitis/pharyngitis and otitis media – while not life threat-ening, are a cause of significant discomfort and absenteeism from work, and can lead to more serious complications if not managed effectively. Therefore, they too have a significant socio-economic impact. The clinical management of RTIs presents an increasing challenge to physicians. The selection of a suitable first-line treatment is complicated by both the difficulty in establishing microbial etiology and the increasing prevalence of antimicrobial resistance and cross-resistance among bacterial pathogens. Levels of resistance to β-lactams among Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, the major bacterial causes of RTIs, continue to increase on a global scale [2]. Resistance to macrolide–lincosamide–streptogramin agents has also reached alarming levels amongst Gram-positive pathogens, and has been linked to the consumption of newer macrolide antimicrobials [3]. While new ‘extended-spectrum’ fluoroquinolones have recently become available, pneumococcal resistance to these new agents is already beginning to emerge [4], and may increase if they become widely prescribed in the community. Although the problem of antimicrobial resistance amongst respiratory tract pathogens has been recognized for some time, the clinical impact is only beginning to be realized and several studies have now demonstrated a link between bacterial resistance and poor clinical outcome [5,6]. These challenges have highlighted the need to re-evaluate current management guidelines and have driven the search for novel antimicrobial agents that provide coverage against the likely causative pathogens, even those that are resistant to existing agents, and that will minimize the further development of resistance. Of the new agents that are emerging, the ketolides are particularly promising with regard to these issues. This Supplement is based on papers presented at the symposium ‘The ketolides – an innovative solution to an evolving world of respiratory pathogens’ held at the 10th European Congress on Clinical Microbiology and Infectious Diseases in Stockholm, Sweden (30 May 2000), which focused on the development of telithromycin, the first ketolide antimicrobial to undergo clinical development. The first three papers, by David Felmingham, Stephen Douthwaite and Roland Leclercq, provide a comprehensive overview of the drug’s microbiological profile and structure–activity relationship. At the time of writing, telithromycin is under evaluation in Europe and the USA for approval as a once-daily, short-course treatment for CAP, AECB, sinusitis and tonsillitis/pharyngitis. The pharmacokinetic and pharmacodynamic considerations that support this dosage regimen are reviewed by George Drusano. In the last paper, Roger Finch discusses the current management guidelines for CAP and presents the clinical experience with telithromycin in this indication.