Management of Bacterial Infections in Children with Asthma

Matti Korppi

Disclosures

Expert Rev Anti Infect Ther. 2009;7(7):869-877. 

In This Article

Antibiotics for Children with Asthma

The indications of anti-infective treatment in children with asthma do not substantially differ from the indications in nonasthmatic children, and the indications according to causative microbes and clinical presentations are summarized in Table 2.

Antibiotics as Risk Factors for Asthma

Many retrospective surveys and some healthcare database studies have revealed that the use of antibiotics in early life is a risk factor for later asthma, as summarized in a meta-analysis by Marra et al..[76] In a nested case-control study, antibiotic exposure during the first 3 years of life was compared between 37 atopic children with wheezing and 37 nonatopic children who had never wheezed. An exposure to broad-spectrum antibiotics in early life increased both atopic sensitization and the expression of wheezing.[77] In a recent longitudinal birth cohort study using healthcare and antibiotic prescription databases, Kozyrskyj et al. confirmed, by adjusted analyses, that the use of antibiotics for respiratory infection, as well as for nonrespiratory infection during the first year of life, was an independent risk factor for asthma at 7 years of age.[78] The risk was dependent on the amount of courses and on the use of broad-spectrum antibiotics. On the other hand, Kusel et al. found no association between the use of antibiotics in early life and asthma at 5 years of age in 198 children followed-up from birth.[79]

Antibiotic Use in Children with Asthma

Antibiotics are prescribed more readily for respiratory tract infection in children with asthma than in those without asthma;[18,19] the figures were 64 and 2%, respectively, in a Canadian study.[80] Along with the generally decreased number of prescriptions, antibiotic use for wheezing children also declined in the 1990s, but the use of broad-spectrum antibiotics, such as the new macrolides, increased.[81] This change to broader-spectrum macrolides has taken place concomitantly with the evolution and spread of pneumococccal macrolide resistance.[82] A question has been raised as to whether wheezing children or children with asthma, along with children treated in daycare centers, could be the reservoir of resistant bacteria, in particular those resistant to macrolides.

Antibiotic Treatment for Exacerbations of Asthma

Bacterial infections in children with asthma, including those with an acute exacerbation, should be treated according to the general principles of antibiotic therapy.[83] Data from adults suggest that patients with an asthma exacerbation may benefit from treatment with macrolides, ketolides, tetracyclines or fluoroquinolones.[8,84,85] There are two main reasons why such an effect is not to be expected in children. First, 85% or even more of the wheezing episodes or asthma exacerbations are induced by viruses. Second, the occurrence of infections caused by atypical bacteria is age-dependent, and infections caused by C. pneumoniae, in particular those suggested to be associated with asthma, are rather rare before school age.[49] The benefits achieved by macrolides may be related, not only to their antimicrobial effect but also to their anti-inflammatory activity.[19,86] The drugs that are effective against atypical bacteria are bacteriostatic, relieving the infection and symptoms, but not eradicating the pathogens. Thus, the beneficial effects are expected to be transient and of short duration, with no long-term improvement of asthma in the future.

Strunk et al. determined the budesonide and salmeterol dose needed to control symptoms in 292 children over 6 years of age with moderate-to-severe asthma, and the titrated dose was used for 6 weeks.[87] Thereafter, either montelukast, azithromycin or placebo treatment was randomized in 55 children. The primary outcome was the time from randomization to inadequate asthma control. The median time in the azithromycin group was 8.4 weeks (95% CI: 4.3-17.3), compared with 13.9 weeks in the montelukast group and 19.1 weeks in the placebo group. The result was not statistically significant but strongly suggests that azithromycin is not a clinically effective corticosteroid-sparing alternative in children with asthma.

Antibiotic Treatment for Chronic Stable Asthma

In adults, long-term treatments with macrolides have improved asthma symptoms, but after cessation of therapy, the benefits have been lost within some weeks. Five studies (including 357 adults with asthma) were accepted in a Cochrane review,[88] and macrolides had a positive effect on symptoms and eosoniphilic markers of inflammation, but only in patients with serological evidence of Chlamydia infection.

There are only two preliminary studies in children. Esposito et al. studied 352 children aged 1-4 years with recurrent lower respiratory tract infections, including wheezing children.[89] Patients were randomized to receive either azithromycin (10 mg/kg/day for 3 days weekly for 3 weeks) and bronchodilators, or bronchodilators only. Thus, the study was not placebo-controlled or blinded. Macrolide therapy significantly decreased the symptoms, but only for the first month and only in children with serologic and/or PCR evidence of Chlamydia infection. Piacentini et al. randomized 16 children with asthma to receive either azithromycin or placebo for 8 weeks.[90] No significant changes were observed in lung function in either group, but bronchial reactivity to hypertonic saline improved and the number of neutrophils in mucus samples decreased in the azithromycin group. The measurements were performed immediately after the treatment. This study should be repeated in a larger patient group with a longer follow-up.

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