Discussion
This retrospective study showed that nebulized antibiotic treatment reduces the number of hospitalizations and length of stay in the intensive care unit in children with tracheostomy. There was also a significant reduction in bacterial load in tracheal aspirates cultures of these patients with nebulized antibiotic treatment.
Patients with long-term tracheostomies commonly become colonized with gram-negative bacteria that may increase the risk of exacerbations which may cause significant morbidity and mortality. Currently, there are no published guidelines for the diagnosis and management of respiratory infections and colonization in pediatric patients with long-term tracheostomies.
Although inhalation of antibiotics is an effective therapetic approach and used in many patients with persistent colonization due to gram-negative microorganisms, data is scarce for children with tracheostomies. Recently, two small case series suggested a benefit of nebulized antibiotics in tracheotomized patients with neurological impairment and frequent respiratory exacerbations17,18.
Colonization with gram-negative bacteria, predominantly with P. aeruginosa , are common in children with tracheostomy due to bypassing of defensive mechanisms of upper airways. Mc Caleb et al. evaluated the respiratory microbiology in children with tracheostomy in their study and demonstrated that 90% of the cohort (n=93) had P. aeruginosagrowth in the tracheal aspirate cultures3. Sanders et al. investigated clinical outcomes of chronic bacterial colonization of 185 children with tracheostomies. Gram-negative microorganisms especially P. aeruginosa were the most common identified microorganisms with a prevalence of 68%. They also showed that children with chronic colonization with gram-negative bacteria had worse clinical outcomes, such as an increase in the number of hospitalizations and length of stay in the intensive care unit4. In line with the other studies P. aeruginosa was the most commonly identified pathogen in our study; we isolated P. aeruginosa in 77% of our patients.
As reported in previous studies, the most common underlying comorbidity in children with tracheostomy were neurologic disorders in our study19,20. Fourteen of 22 children had a neurologic illnes, and additonal four children had a concomittan neurologic impairment such as hypotonia. Further, 90% of our patients suffered from swallowing-feeding problems, and gastroesophageal reflux. It is well known that children with neurologic impairment are at high risk for morbidity and mortality related to respiratory complications. In addition to insufficient cough effort, pulmonary micro-aspirations, and colonization with gram-negative bacteria especially with P. aeruginosa are the main causes of hospitalisations21-23.
Presence of chronic P. aeruginosa infection is associated with an increased morbidity and early mortality in CF patients and inhibition of chronic bacterial growth via long-term inhaled antibiotics has become a part of the standard care and increasingly used for children with other chronic respiratory diseases such as non-cystic fibrosis bronchiectasis24. However, to date, specific data are lacking about the indications, duration, and doses of the nebulized antibiotics in children with tracheostomy. Persistent colonization and high bacterial loads in the airways lead to chronic airway inflammation and cause exacerbations25. In this study, we found that nebulized antibiotics reduced the median number of hospitalizations in children with tracheostomy and persistent colonization. In addition, with a median treatment duration of 3 months (2-5 months), we observed a decrease in bacterial load, from 105 to 104 CFU/ml, as well as in the number of the patients with a colony count >105 CFU/ml. Eckerland et al. retrospectively evaluated the effect of nebulized tobramycin and colimycin in 20 patients with neurological disorders. After 12 months of treatment with nebulized antibiotics, they showed a decrease in the frequency of respiratory tract infections and the number of hospitalizations in the entire study group as well as tracheotomised patients (n=9). However, they did not evaluate the effect of the intervention on the bacterial load in that study10.
Plioplys AV et al. reported the results of cyclic monthly intermittent use of nebulized tobramycin in two tracheotomised patients with cerebral palsy and recurrent pneumonia. After 12 months, they showed a decrease in the number and length of hospitalizations due to pneumonia17. Crescimanno et al. evaluated the effect of nebulized colimycin in 15 patients with neurologic impairment and reported reduced number of infections and hospitalizations. After 15 months of nebulized antibiotic use, the bacterial burden also decreased in all patients receiving nebulized colimycin therapy18.
Duration of nebulized antibiotics in tracheotomised children varied from 2 weeks to 12 months in published studies and optimum dose was not clear10,11,17,18. Since there are no specific guidelines regarding the duration and the dose of nebulized antibiotics in tracheotomised children, we discontinued nebulized antibiotics in patients who had clinical recovery and when the colony count was lower than 105 CFU/L. Although we used nebulized antibiotics for a relatively short period, we observed notable improvements in clinical outcomes.
Nebulized antibiotics are generally well tolerated without any adverse effect10,18. In our study, no side effects such as respiratory symptoms caused by airway irritation or nephrotoxicity were observed.
Development of resistant microorganisms is a concern for long term inhaled antibiotics. Murray Mp et al. investigated the efficacy of nebulized gentamycin in adults with non-cystic fibrosis bronchiectasis in a randomized controlled trial. They used continuous twice-daily 80 mg nebulized gentamycin for 12 months. None of the patients had gentamycin resistance gram-negative microorganisms at the end of the study24. In our study gentamycin resistance was seen in nearly 30% of our patients which may be related to frequent use of antibiotics and hospitalizations.
Our study has some limitations. It is a retrospective, single-center study, with a small sample size. Another limitation is that we could not assess neurologic side effects of colimycin, and ototoxicity of gentamicin.
In conclusion, we showed that the use of nebulized antibiotics reduced the number of hospitalizations, length of stay in the intensive care unit, and bacterial load in children with persistent airway colonisation without significant side effects. Nebulize antibiotics are a reasonable treatment option for tracheotomized children with persistent colonization. Further prospective studies with larger study groups are needed to determine the main indications and the optimal duration and doses of the long-term nebulized antibiotic treatment in these patients.
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