Introduction: childhood respiratory diseases: management in an era of antibiotic resistance.

Bacterial respiratory diseases remain a major health problem in children worldwide and are the main reason for medical visits. However, the true incidence, disease burden, and health-care economic impact are not well quantified in most countries. In resource-poor countries, each year millions of children die of pneumonia and the burden of disease is considerable. In wealthy countries mortality has dramatically decreased, but a high morbidity is still present. North American and European pediatric hospitals are routinely faced with complicated pneumonia, especially with empyema. Bacterial respiratory diseases are also the main reason for the prescription of antibiotics in children 3 years, leading to antibiotic resistance, which is a worldwide concern and priority of the World Health Organization. In the last decade, vaccines for the prevention of bacterial respiratory diseases in young children (Haemophilus influenzae type b and Streptococcus pneumoniae) have been licensed on one hand, and, on the other hand, many countries and scientific societies have issued guidelines on the diagnosis and management of common bacterial respiratory infections. The profusion of guidelines illustrates the need for rationalizing both diagnosis and the use of antibiotics. Only a few studies have actually evaluated the impact of the guidelines, although some data are available from the United States and the Netherlands. The findings in these studies suggest that the guidelines are theoretically accepted, but not necessarily implemented in daily clinical practice. The concept of watchful waiting for acute otitis media (OM) introduced by most guidelines is often difficult to implement. Some of the reasons are: (1) the definition and diagnosis of childhood bacterial diseases is often only possible or probable; (2) physicians fear individual complications (the risk of severe complications of acute OM is difficult to assess, even in Western countries), and (3) resistance to behavior modification is very difficult to overcome and most guidelines are very recent. The current supplement reports on the considerations made on childhood bacterial diseases that were discussed during a Global Master Class that took place in Brussels in March 2008; this was supported by an unrestricted educational grant from GlaxoSmithKline Biologicals. The objectives of this Master Class were to review the epidemiology and pathogenesis, prevention and management of selected childhood bacterial respiratory diseases, review the experience gained in the first decade of pneumococcal conjugate vaccines (PCVs), and find a rationale for future vaccine development and use. The Master Class participants were international experts from different countries with an experience in management of respiratory bacterial disease and expertise of pediatrics, pediatric infectious diseases, otorhinolaryngology, public health, epidemiology, and medical microbiology. The 4 main respiratory bacteria that have a major impact on diseases worldwide are Neisseria meningitidis, Hib, S. pneumoniae, and nontypeable H. influenzae (NTHi). Altogether, these account for about 75% of the serious bacterial respiratory infections worldwide or respiratory-originated infections and a high proportion of systemic infections in pediatric patients. The Master Class concentrated on S. pneumoniae and NTHi, but one cannot talk about epidemiology, pathogenesis, prevention, or management of these without referring to the experience gained in various aspects of N. meningitidis and H. influenzae b infections in infants and children. Heptavalent PCV-7 started to be administered to children almost 10 years ago. In this relatively short period considerable experience was gained, some of which provides answers, more of which raises questions. It is for this reason that the Master Class covered the issue of protective correlates associated with PCV-7, as it relates to invasive pneumococcal disease, pneumonia and otitis media. In “Microbial Interactions in the Respiratory Tract” Murphy et al explain how upper respiratory tract infections are caused by the synergistic and antagonistic interactions of upper respiratory tract viruses and bacterial pathogens and review the interactions between these microorganisms in the pathogenesis of upper respiratory tract infections. In “Childhood Bacterial Respiratory Diseases: Past, Present, and Future” Nohynek et al examine the causes of global childhood mortality, the distribution of childhood pneumonia mortality and morbidity, the risk factors that affect pneumonia incidence, and the potential effectiveness of available vaccines to reduce the burden of childhood bacterial respiratory diseases. They show that the risk of children aged between 0 and 4 years developing pneumonia is 0.03 episodes per child year in wealthy countries and 0.29 episodes per child year in resource-poor countries. Consequences of childhood pneumonia and its significant morbidity and mortality are preventable by the optimized use of vaccines against measles and pertussis, and expanding the use of Hib and PCVs. The implementation of proven cost-effective interventions that can save millions of lives appears both feasible and of utmost importance and vaccines play a critical role in this regard. Finally, Pelton and Leibovitz, in “Recent advances in Otitis Media,” examine the epidemiology and pathogenesis of OM, treatAccepted for publication July 10, 2009. From the *Pediatric Infectious Diseases Unit, Soroka University Medical Center, Beer Sheva, Israel; and †Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium. Disclosure: Dr. Dagan has received grant/research support from Berna/Crucell, Wyeth and MSD. He has been a scientific consultant for Berna/Crucell, GlaxoSmithKline, Novartis, Wyeth, Protea and MSD. He has received speaker honoraria from Berna/Crucell, GlaxoSmithKline and Wyeth, and has shares with Protea. Dr. Lepage has received consulting honorarium from GlaxoSmithKline and has received travel grants from Wyeth and Aventis Pasteur. Address for correspondence: Ron Dagan, MD, Director, Pediatric Infectious Disease Unit Soroka University Medical Center POB, 151 Beer-Sheva 84101 Israel, E-mail: rdagan@bgu.ac. il and Philippe Lepage, MD, PhD, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, 15, av JJ Crocq, 1020 Brussels, Belgium. E-mail: Philippe.LEPAGE@huderf.be. Copyright © 2009 by Lippincott Williams & Wilkins ISSN: 0891-3668/09/2810-0119 DOI: 10.1097/INF.0b013e3181b6d7d5