Discussion
There is substantial variability in the surveillance and management of children with tracheostomy. Clinical guidelines are lacking in several aspects of tracheostomy care, including outpatient management of respiratory infections. Hospitalizations for these patients are lengthy, costly and common. To our knowledge, this is the first study to describe the outpatient treatment of respiratory infections, as well as to examine the impact of hospitalizations on children with long term tracheostomy.
In this study, we retrospectively analyzed whether hospitalization rates due to LRTI in patients with tracheostomy were affected by outpatient treatment methods of either receiving only increased AWC or receiving an antibiotic in addition to increased AWC. We found that those who received only AWC did not have significantly higher odds of hospitalization within 28 days of treatment, compared to those who received an antibiotic. This data indicates that there may be no advantage to prescribing antibiotics. Antibiotics can be costly, can induce bacterial resistance and can have systemic side effects, even in the case of inhaled tobramycin as renal failure and ototoxicity have been reported 6-8.
We identified no studies that evaluated the same interventions and outcome. However a study by Zhu 4 investigated hospitalizations due to ambulatory care sensitive conditions (ACSCs) which were defined as conditions for which good outpatient care could potentially prevent the need for hospitalization or for which early intervention could prevent complications. They found the most frequent and costly ACSCs that lead to hospitalization were bacterial pneumonia and tracheostomy infection. This study, along with our study where we found that patients called frequently for respiratory concerns and were treated often for these illnesses, indicates a need to identify optimal treatments to effectively treat LRTIs at home.
As noted earlier in the study, inhaled tobramycin was the most commonly prescribed antibiotic. Anecdotally, many parents prefer inhaled tobramycin due to its localized activity and fewer systemic side effects such as diarrhea and abdominal upset. In the absence of evidence based guidelines for treatment of LRTI in this patient population, antibiotic choice was determined by previous respiratory culture results, patient/parent preference, accessibility to and availability of the medication, insurance coverage and affordability. The intravenous form of tobramycin for inhalation is not widely available in outpatient pharmacies, with enteral antibiotics often being prescribed in its place.
Despite minimal data, treatment of LRTI is often based on previous cultures or most common bacteria cited in the literature (P. aeruginosa and MRSA)5. In agreement with previous studies, we found P. aeruginosa to be the most commonly isolated pathogen on respiratory cultures 9,10. This is in part due to the tenacious nature of Pseudomonas which strongly adheres to the tracheal mucosa 9. Though there is conflicting evidence, several authors have shown MRSA to also be prevalent in tracheal cultures, second to P. aeruginosa9,10. Nevertheless this was not the case with our study where S. maltophilia was actually more common than MRSA.
The cystic fibrosis (CF) literature has demonstrated an association between P. aeruginosa acquisition and increased pulmonary exacerbation rates, declining lung function and greater mortality11-13, as well as shortened survival in those with MRSA 14. The acquisition and outcomes of eradication of P. aeruginosa and MRSA in pediatric patients with tracheostomy remains unclear though a retrospective study by Russell15 showed that acquisition of P. aeruginosa was associated with significantly increased odds of readmission for respiratory tract infections within 12 months of discharge from the tracheostomy placement hospitalization.
While obtaining routine respiratory cultures is the norm in patients with cystic fibrosis16,17, there is no evidence showing the benefit of collecting surveillance respiratory cultures in healthy patients with tracheostomy. Biofilm is known to develop in tracheostomy tubes as soon as 7 days after tracheostomy tube change or initial placement 18 and results in subsequent bacterial colonization of the airway. Cline et al19showed that bacteria and antibiotic sensitivity can change between consecutive respiratory cultures and thus use of prior cultures was of limited benefit for choosing antibiotic therapy in treating exacerbations. In addition, reports have shown that colonization without infection is common and there are no good methods for distinguishing colonization (which may not require treatment) from overt infection that requires intervention 20,21.
Nevertheless, many practitioners use prior respiratory cultures as a guide for treatment of LRTI5. However, despite the prevalence of S. maltophilia in our patients’ respiratory cultures, trimethoprim-sulfamethoxazole was not prescribed as often as would be expected. This could be because S. maltophilia may not have grown on the most recent culture and so was not thought to be the cause of the current LRTI. We also think it could be due to previous findings showing that most children with tracheosomy will acquireP. aeruginosa10,15 and would benefit from anti-pseudomonal targeted therapy. A recent study 22evaluated treatment of S. maltophilia in children with tracheostomy and acute respiratory illness. They found no difference in the amount of time to return to respiratory baseline after treatment targeting S. maltophilia with trimethoprim-sulfamethoxazole versus those who were also S. maltophilia positive but did not receive targeted treatment. This study shows there may be no benefit of targeted treatment of S. maltophilia in this group, but more rigorous evaluation is needed.
There were several limitations to this study. This is a retrospective study, so we cannot ascribe causality to interventions for LRTI. Our sample size was small and does not preclude type II error, i.e., that antibiotics are effective in reducing LRTI hospitalizations in children with tracheostomy. Additionally, most of the patients were young and received a tracheostomy for prematurity and neuromuscular disease. Further study is required for children over 6 years of age as well as patients with other indications for tracheostomy.
We accounted for four confounders that we thought most impacted outcomes including lower odds of hospitalization if patients were recently hospitalized; however there were other confounders that we did not evaluate such as socioeconomic status, smoke exposure at home, daycare or school attendance and home nursing since this data was missing or incomplete. Cristea et al 23 showed that chronically ventilated children who lived in lower ZIP code- based annual household income areas had higher mortality.
Next, several patients also received treatment outside of Riley Hospital (such as antibiotics for LRTI from primary care provider) and we were only aware of these treatment episodes if parents called our clinic to report it. Our study was focused on chronically ventilated patients as these patients were more likely to be treated solely within our hospital system compared to patients who were not chronically ventilated, ensuring that we were less likely to miss any episodes of LRTI. It is reasonable to assume that we underestimated the number of treatment episodes given outside of Riley Hospital considering it was easier to see the local pediatrician than our outpatient clinic for a sick visit either due to distance or sick visit availability. Similarly, patients were sometimes hospitalized outside of Riley Hospital. We were only aware of the hospitalizations if discharge paperwork was sent to us and so the number of hospitalizations was also likely underestimated. Our analysis does not account for adherence to the prescribed treatments. Diagnosis of LRTI lacks consistency owing to various definitions of infection and treatment recommendations, further complicating decision to treat with antibiotics 24,25.