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Macrolides and bronchiolitis in infants

Dept of Paediatrics, Tampere University and University Hospital, Tampere University, Tampere, Finland.

To the Editors:

In a recent issue of the European Respiratory Journal, Tahan et al. 1 presented their results on clarithromycin therapy in respiratory syncytial virus (RSV) bronchiolitis in 12 infants aged 7 months, compared with nine controls. They concluded that clarithromycin had a beneficial effect assessed by: the length of hospital stay; the need for oxygen therapy; the need for ß₂-agonist treatment; and the rate of readmission to hospital within the subsequent 6 months 1. The authors explained their findings in terms of suppression of airway hyperresponsiveness, since there are experimental in vitro data indicating that macrolides may inhibit cholinergic stimulation of airway smooth muscle 2. In addition, macrolides are known to have various anti-inflammatory effects 3. Supporting the effects on airway inflammation and responsiveness, the 3-week clarithromycin treatment was associated with decreases in plasma interleukin (IL)-4, IL-8 and eotaxin concentrations 1.

Three questions are raised when reading the study by Tahan et al. 1. First, only one out of 12 children in the clarithromycin group, compared with four out of nine in the placebo group, was readmitted. However, this difference is not, at least when calculated with my computer, statistically significant. In addition, statistical calculations may not be justified when the numbers of cases are so small. Secondly, the need for ß₂-agonists may not be a useful outcome measure, since these drugs are rarely effective in infantile bronchiolitis 4. Thirdly, RSV antigen detection was the only microbiological method available. Normal white blood cell counts and C-reactive protein concentrations do not rule out infections caused by atypical intracellular bacteria, such as Bordetella pertussis, Chlamydia trachomatis and Simkania negevensis. There are two recent studies reporting that mixed RSV and B. pertussis infections are common in nonvaccinated infants 5, 6. In some populations, S. negevensis involvement seems to be common in RSV bronchiolitis 7, 8.

Thus, the beneficial effects of clarithromycin in the acute phase of respiratory syncytial virus bronchiolitis may have been based on the coexistence of atypical bacteria. Clinically, the beneficial effects were marginal; on average, the duration of need for supplementary oxygen and the length of hospital stay decreased by 1.5 days 1. As Tahan et al. 1 stated, respiratory syncytial virus bronchiolitis is the most common lower respiratory tract infection in infancy. Due to the harmful effects of large-scale antibiotic use in infants, macrolide treatment, even if associated with some anti-inflammatory or bronchial reactivity decreasing effects, should be restricted only to the cases with proven or presumptive atypical bacterial aetiology of infection.

REFERENCES

1. Tahan F, Ozcan A, Koc N. Clarithromycin in the treatment of RSV bronchiolitis: a double-blind, randomised, placebo-controlled trial. Eur Respir J 2007;29:91–97.[Abstract/Free Full Text]
2. Labro MT. Anti-inflammatory activity of macrolides: a new therapeutic potential?. Antimicrobial Chemother 1998;41:37–46.[CrossRef]
3. Culic O, Erakovic V, Parnham M. Anti-inflammatory effects of macrolide antibiotics. Eur J Pharmacol 2001;249:209–229.
4. American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics 2006;118:1774–1793.[Abstract/Free Full Text]
5. Crowcroft NS, Booy R, Harrison T, et al. Severe and unrecognised: pertussis in UK infants. Arch Dis Child 2003;88:802–806.[Abstract/Free Full Text]
6. Korppi M, Hiltunen J. Pertussis is common in non-vaccinated infants hospitalized for RSV infection. Pediatr Inf Dis J 2007; 26:316–318.
7. Kahane S, Greenberg D, Friedman M, Haikin H, Dagan R. High prevalence of "Simkania Z", a novel Chlamydia-like bacterium, in infants with acute bronchiolitis. J Infect Dis 1998;177:1425–1429.[Web of Science][Medline] [Order article via Infotrieve]
8. Greenberg D, Banerji A, Friedman M, Chiu C-H, Kahane S. High rate of Simkania negevensis among Canadian Inuit infants hospitalized with lower respiratory tract infections. Scand J Infect Dis 2003;35:506–508.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

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