Antimicrobial resistance among pediatric respiratory tract infections: clinical challenges

https://doi.org/10.1053/j.spid.2004.01.003Get rights and content

Abstract

Considerable development of antimicrobial resistance has occurred in the major pediatric bacterial pathogens, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. However, most of the respiratory infections that children suffer are viral and self-limiting, and only a small percentage of them will develop secondary bacterial infections with the pathogens listed. The challenge for rational antibiotic use is to determine which patients can be treated conservatively and which require antimicrobial intervention to avoid prolonged discomfort or development of permanent sequelae. The basis for rational use of antibiotic in the era of resistance in these major pathogens is to avoid overuse of antimicrobial agents, tailor treatment to identified pathogens as much as possible, and base empiric treatment on the disease being treated and the susceptibility of the probable pathogens at breakpoints based on pharmacokinetic and pharmacodynamic parameters. With appropriate dosing regimens based on these parameters and despite development of resistance, amoxicillin is still one of the most active oral agents against S. pneumoniae and non-β-lactamase producing strains of H. influenzae, whereas amoxicillin-clavulanate is active against β-lactamase-producing strains of H. influenzae and M. catarrhalis. Parenteral ceftriaxone and oral and parenteral fluoroquinolones are active against all 3 species, but fluoroquinolones should be used with utmost caution when all other options have been considered because of concerns about toxicity and development of resistance. Introduction of a 7-valent conjugate pneumococcal vaccine in the United States in 2000 reduced the prevalence of invasive pneumococcal disease in children younger than 2 years old, but, as of 2001, had not had a major impact on decreasing antimicrobial resistance.

Section snippets

Challenges in treating respiratory tract infections

To tailor chemotherapy to a known pathogen with a known drug susceptibility profile is ideal (Table 1). Unfortunately, isolating the causative agent before beginning treatment often is difficult or impractical and often impossible after any antimicrobial treatment has begun.11 In younger children especially, acquisition of appropriate respiratory specimens is challenging, rendering identifying the causative agent difficult.12 Surveillance data provide a useful basis for choosing empiric

Streptococcus pneumoniae

S. pneumoniae is a leading bacterial cause of pneumonia, meningitis, otitis media, and sinusitis. S. pneumoniae accounts for more than one-third of acute bacterial rhinosinusitis in children, more than half of community-acquired bacterial pneumonia, and nearly one-third of childhood AOM. Not only is S. pneumoniae the most common pathogen associated with AOM, it is the least likely of the three major pathogens to resolve without treatment.17, 18 The 90 immunologically distinct serotypes of S.

Viral infections

Viruses are the most common cause of respiratory infections and generally are self-limiting, but they often are precursors of bacterial respiratory infections and, therefore, will be discussed briefly. The viral cause of pediatric lower respiratory infections most frequently identified is respiratory syncytial virus (RSV). It occurs most commonly in children younger than 2 years of age and is responsible for 15 to 30 percent of pediatric community-acquired pneumonia.6, 62 In children younger

Antimicrobial agents

Because the largest number of prescriptions for antimicrobials is for respiratory infections, considerable selective pressure has been placed on the pathogens causing these diseases. This selective pressure generally occurs at the site of carriage of these bacteria such as the nasopharynx, which facilitates the spread of resistant clones.70 The most important risk factors for the carriage and spread of resistant pneumococci include recent use of antibiotics, young age (with highest carriage

Clinical disease and bacterial resistance

Bacterial resistance has a significant effect on treatment options in countries where the prevalence of resistance is high (Table 7). The implications of bacterial resistance on each disease are discussed below.

Acute otitis media

AOM is one of the most common pediatric infections, second only to the common cold in prevalence, accounting for nearly 30 million medical office visits per year in the United States. It occurs most often in children between 6 months and 3 years of age, especially in those with frequent viral upper respiratory infections. Incidence of otitis media, both acute and chronic, decreases as children get older. The inverse relationship between age and incidence of otitis media often is attributed to

Sinusitis

Most upper respiratory infections are viral, with bacterial superinfection occurring in approximately 2 percent of viral upper respiratory infections.10, 91 The pathogens associated with bacterial sinusitis in pediatric patients follow a somewhat different distribution from adult patients. As in adults, S. pneumoniae and H. influenzae predominate, but M. catarrhalis, at 21 to 18 percent (compared with 2–10% in adults), and anaerobes are more prevalent than in adult patients.10

The best method of

Community acquired pneumonia

An estimated 4 million deaths caused by acute respiratory infections occur worldwide every year in children younger than age 5 years.93 In the United States, pneumonia accounted for 507 deaths in children younger than age 15 years in 1999 (307 younger than 1 year), and another 93 (63 younger than 1 year) died from “other acute lower respiratory infections,” mostly bronchitis and bronchiolitis.94 It is a major cause of morbidity in people of all ages. The most common bacterial cause of pneumonia

Effect of vaccination

The Hib vaccine uses protein-conjugated Hib capsular polysaccharide to protect against Hib infections, but it does not provide coverage for other types of H. influenzae or for untypeable strains. The incidence of H. influenzae pneumonia has decreased since the introduction of the vaccine because type b was the H. influenzae serotype most often associated with pneumonia.6

The heptavalent pneumococcal conjugate vaccine, Prevnar (Wyeth Vaccines), is produced using the 7 most common pneumococcal

Conclusion

The basis for rational antibiotic use in the era of resistance in the major pathogens is to avoid overuse of antimicrobial agents, tailor treatment to identified pathogens as much as possible, and base empiric treatment on the disease being treated and the susceptibility of the probable pathogens at breakpoints established by PK and PD parameters.

Most of the respiratory infections that children suffer are viral and self-limiting. A small percentage of them will develop bacterial complications,

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