Atypical Bacteria and...Recurrent Respiratory Tract Infections< >From The Pediatric Infectious Disease Journal Role of Atypical Bacteria and Azithromycin Therapy for Children With Recurrent Respiratory Tract Infectionsi<

Authors: Susanna Esposito, MD; Samantha Bosis, MD; Nadia Faelli, MD; Enrica Begliatti, MD; Roberta Droghetti, MD; Elena Tremolati, MD; Alessandro Porta, MD; Francesco Blasi, MD; Nicola Principi, MD

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Pediatr Infect Dis J 24(5):438-444, 2005. © 2005 Lippincott Williams & Wilkins

Abstract and Introduction



Background: The aim of this study of 352 patients, 1-14 years of age, with acute respiratory infections and a history of recurrent respiratory tract infections (RRTIs), and 208 healthy subjects was to evaluate whether Mycoplasma pneumoniae and Chlamydia pneumoniae played a role in causing acute respiratory episodes among children with RRTIs and whether specific antibiotic treatment for these bacteria could improve the acute episodes and reduce recurrences.

Methods: The patients were blindly randomized to receive azithromycin (10 mg/kg/d for 3 days weekly, for 3 weeks) together with symptom-specific agents or symptom-specific agents alone. Acute M. pneumoniae and/or C. pneumoniae infection was diagnosed if the child had a significant antibody response in paired sera and/or if the DNA of the bacteria was detected in nasopharyngeal aspirates. Results: Atypical bacterial infections were identified for 190 patients (54.0%) and 8 healthy control subjects (3.8%; P < 0.0001). short term (1-month) clinical success was significantly more frequent among the patients who had received azithromycin together with symptom-specific agents than among those who had received symptom-specific agents alone, but the difference was significant only for the group of patients with atypical bacteria. in contrast, long term (6-month) clinical success was significantly more frequent among the patients who had received azithromycin in addition to symptom-specific agents, regardless of whether they experienced infections with atypical bacteria or other pathogens, although positive outcomes were significantly more frequent among those with atypical bacteria.

Conclusions: Atypical bacteria seem to play a role among children with RRTIs, and prolonged azithromycin therapy can significantly improve the acute episodes and reduce the risk of recurrences.


Taking in account the very low prevalence of atypical bacterial infections among our healthy control subjects, in comparison with the patients with a history of RRTIs, our results confirm that atypical bacteria play a role in causing both upper and lower respiratory tract infections among pediatric patients, with M. pneumoniae being more important. However, in addition to our previously published reports,[17-20,24-27] these data seem to indicate that infections caused by these bacteria may be associated not only with pharyngitis, acute bronchitis, wheezing and pneumonia but also with rhinosinusitis and croup, thus emphasizing that the entire respiratory tract can be infected.

This study adds additional information concerning the relationship between atypical bacteria and frequent recurrences of respiratory diseasesi, which was demonstrated previously only in some studies of patients with recurrent pharyngitis or recurrent wheezing.[23-25,27,33] However, considering that M. pneumoniae and C. pneumoniae may involve various sections of the respiratory tract, it is not surprising that at least some of the infections found among children with RRTIs can be caused by these pathogens. Because we found no seasonal differences in the incidence of M. pneumoniae and/or C. pneumoniae infections during the study period, it seems that atypical bacterial infections are not related to clear local outbreaks.

Because the infections diagnosed among children with RRTIs are usually considered to be of viral origin, it is suggested that they be treated only symptomatically.[4-6,12-14] However, our data not only indicate that the last episode of respiratory infection for children with a history of RRTIs may be associated with the presence of atypical bacteria in a significant number of cases but also show that prolonged macrolide treatment can favor the resolution of the acute episode and reduce the number of additional respiratory infections. These data are in agreement with those reported for children with recurrent wheezing associated with atypical bacterial infections,[23,27] and they suggest that macrolide treatment of M. pneumoniae and C. pneumoniae infections can significantly modify the clinical evolution of acute respiratory diseases in both the short term and the long term. Because 10-day antibiotic treatment is not always effective in eradicating atypical bacteria,[34,35] we chose a prolonged regimen of azithromycin for cases of suspected M. pneumoniae and/or C. pneumoniae infection, although in our study no presumption can be made with respect to eradication.

The short term evaluation of the effectiveness of azithromycin treatment among our study patients showed that the incidence of clinical success was significantly higher among the children who received azithromycin than among those who received symptom-specific agents alone, mainly because of the activity of azithromycin against atypical bacteria. The importance of the antimicrobial effect of azithromycin in the short term was supported by the fact that only patients with atypical bacterial infections received advantages from the administration of macrolides, whereas patients without atypical bacterial infections had similar outcomes regardless of the treatment group. In contrast, the long term efficacy of azithromycin, although greater among patients with atypical bacterial infections, was not related to the cause of the respiratory disease. The reduction in the number of new episodes of respiratory infection caused by M. pneumoniae and/or C. pneumoniae could again be attributed to the antimicrobial activity for atypical bacteria, but the favorable outcomes among patients without atypical bacterial infections might have been related to the antiinflammatory properties of macrolides. In this regard, it is thought that macrolides interact with the natural effectors involved in inflammationi, although the importance of this property has not yet been fully elucidated.[36,37] Although it is necessary to confirm our results with additional studies, our data suggest that a child with a history of RRTIs who is experiencing an acute episode of respiratory infection should be evaluated for infections caused by atypical bacteria and, when the results are positive, macrolide therapy should be considered to improve the course of the disease and to reduce the risk of recurrences.

Presented in part at the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, September 27-30, 2002.

Reprint Address Nicola Principi, MD, Institute of Pediatrics, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan, Via Commenda 9, 20122 Milan, Italy. Fax 39-02-50320226; E-mail:<