Discussion
Tracheostomy and ventilator-dependent children are frequently prescribed
broad spectrum empiric antibiotics for illnesses7; 11;
12. Frequent and prolonged use of antibiotics is associated with
emergence of antibiotic resistance in numerous patient
populations13-15, but there is a paucity of data
specific to tracheostomy and ventilator-dependent children. Our study
found that increased antibiotic usage and episodes of hospitalization
put these patients at risk of MDROs. Other studies have found
respiratory tract MDROs increase the risk of complications1; 8; 9; 16, but we did not find that our participants
had more complications following MDRO detection.
We had a higher rate of MDROs in our patient population compared to
other studies of tracheostomy and ventilation-dependent
children15. 76% of our participants had at least one
respiratory tract culture with a MDRO. Our participants were
predominantly dependent on mechanical ventilation (93%) which could
explain the higher rate of MDROs in our group15; 17;
18. MRSA was the most common MDRO within our patient population with
49% of participants positive. This was consistent with a recent
publication by McCaleb et al. that found a similar rate of MRSA within
their single center study of pediatric tracheostomy
patients19. S. aureus and Pseudomonas
aeruginosa are the most commonly cultured organisms from tracheostomies
of pediatric patients8; 9; 18; 19. Russell et al.
found that tracheostomies in pediatric patients increase risk of
Gram-negative organisms such as P. aeruginosa but not S.
aureus 8 . It is suspected that organisms found in the
normal flora of the respiratory tract, like S. aureus , are
protective against lower respiratory tract infections but organisms such
as Pseudomonas disrupt the normal flora which can lead to more
infections 20. Gram-negative organisms are clearly
associated with an increased risk of lower respiratory tract infections,
but it is less clear if MRSA cultured from the airway represents
colonization versus evidence of a lower respiratory tract infection.
We found that frequent hospitalizations and antibiotic usage increased
the risk of MDRO in the respiratory tract of technology-dependent
children. It has been shown that hospitalizations and prior antibiotic
usage were independent risk factors for lower respiratory tract MDROs in
adults, but has not been well described in children15. We also found that both intermittent antibiotic
usage and chronic antibiotics increased risk of MDRO. We did not find
that there was an independent effect from type of chronic antibiotic
used, inhaled or oral, on risk of MDRO positivity. The literature is
unclear about emergence of antibiotic resistance with inhaled
antibiotics. Long term use of inhaled antibiotics in cystic fibrosis
patients increases the mean inhibitory concentration (MIC) over time but
does not affect the clinical efficacy of antibiotic
treatment21-23. Furthermore, inhaled antibiotics in
cystic fibrosis have not been found to select for intrinsically
resistant organisms 21-23. This differs from a review
by Laska et al. which demonstrated that use of inhaled antibiotics
increased the risk of resistant organisms in patients with
bronchiectasis24. There remains little literature
describing emergence of antibiotic resistance with inhaled antibiotics
in the pediatric tracheostomy and ventilator-dependent population.
Our study did not find having an MDRO increased the risk of
complications including number of hospitalizations, ED visits, or
antibiotic usage compared to those without MDRO. This finding contrasts
several papers that found having resistant Gram-negative bacilli orPseudomonas to be a risk factor for increased length of stay,
increased number of lower respiratory tract infections, and mortality1; 8; 9; 16. In our analysis without MRSA,
Gram-negative bacilli were the most common type of resistant organism
cultured. We did not find an increased risk of complications following
MDRO positivity with the exclusion of MRSA from our analysis. We found
that participants received more outpatient antibiotics after MDRO
positivity compared to prior to MDRO positivity using a pair-wise
comparison of these groups. This increased use of antibiotics could be
evidence of more frequent respiratory tract infections following MDRO
detection. It has been shown that specific organisms such as P.
aeruginosa , Enterobacteriaceae, or Acinetobacter baumannii in
tracheal cultures are associated with an increased number of lower
respiratory tract infections 7; 8. The increased use
of antibiotics seen following MDRO detection in our group may also
represent physicians having a lower threshold to treat with antibiotics
when an MDRO is found. Even when an MDRO is cultured from the
respiratory tract it is hard to determine if the organism represents
colonization or a true infection. One of the challenges in treating
tracheostomy-dependent children is defining true infection and treating
appropriately.
There are several limitations to this study. Our study is a single
center retrospective chart review, so the data are less generalizable.
This study is also limited by a relatively small sample size which may
lead to underpowered statistical analyses. There is considerable
variability in care provided including when tracheal aspirate cultures
were obtained, when antibiotics were used, and thresholds for hospital
admission. Data were limited only to what could be accessed in our
electronic health medical record. We aimed to maximize the data
collected for each patient by manually extracting data instead of using
automated data collection software.
Despite these limitations our study offers insight into a less-studied
pediatric technology-dependent patient population. Tracheostomy and
ventilator-dependent children represent a group of patients with complex
medical needs and high health care utilization. Respiratory tract
infections including tracheitis and pneumonia are the most common cause
of hospitalization within this population3-5. There
are no guidelines published for treatment and management of respiratory
tract infections in this patient population. Broad spectrum empiric
antibiotics are frequently used to treat respiratory tract infections in
these children but could increase risk of MDRO acquisition. Our study
suggests that more antibiotic usage and hospitalizations may increase
risk of MDRO positivity. This specific group of patients could benefit
from increased antibiotic stewardship focus with a tailored antibiotic
strategy. Additional studies are needed to help develop guidelines for
treatment of respiratory tract infections in tracheostomy and
ventilator-dependent children with the goal of minimizing the emergence
of MDROs.
Acknowledgments : We thank Hongjie Gu, MS and Michael
Wallendorf, PhD who provided statistical analysis through Division of
Biostatistics at Washington University School of Medicine.