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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