4. DISCUSSION
This systematic review summarises the current evidence base for the use
of antimicrobials in tracheostomy dependent paediatric patients. All 12
studies identified were retrospective cohort studies. These highlight
three core themes that should be the topic of future research: i) route
of antimicrobial administration (systemic versus topical); ii) the role
of cultures in guiding antimicrobial use; and iii) timing of
antimicrobial use (reactive versus prophylactic). All of which would
help clinicians optimise management for these children, reducing the
need for escalation of care and improving antimicrobial stewardship.
There is an urgent need for prospective, randomised controlled trial
evidence to address these issues and guide the management of this
vulnerable patient group.
Systemic antimicrobials are in routine use for tracheostomy associated
infections, with empirical treatment often aiming to coverPseudomonas and Staphylococcus as common causative
organisms. Although anti-pseudomonal antimicrobial usage has been
associated with increased hospital admission duration both on an
individual level29 and
hospital level28, this
likely reflects other clinical confounders such as their use in severe
infections. The relationship between longer hospital admissions and
hospital level prescribing rates may also represent poorer antimicrobial
stewardship leading to increased antimicrobial resistance.
Inhaled antimicrobial use is also widespread in the management of
tracheostomy associated infections; this is largely based upon
theoretical benefits, such as higher tracheal antibiotic concentrations
and reduced side effects. As well as extrapolation of evidence from the
management of adult ventilator associated pneumonia40, cystic
fibrosis41, and
non-cystic fibrosis bronchiectasis42.
Clearly, none of these populations represent children with tracheostomy
associated infections well due to differences in both pathology and
between children and adults, including physiology, anatomy, and risk
factor exposure profiles (such as smoking). Although nebulised
antimicrobials have been used in the treatment of respiratory illness
for over 70 years43,
further studies are needed to evaluate and compare alternate
antimicrobial use in children with tracheostomies 30.
Prophylactic inhaled antimicrobials are often used in clinical practice;
however, there is little international consensus on their use in
children with tracheostomies. To the best of our knowledge the only
guidelines endorsing their use in this patient cohort are by the
Brazilian Society of Paediatrics, specifically in the post-tracheostomy
period44.
Prophylactic antimicrobials have also been investigated in the context
of recurrent
LRTI34,36and persistent bacterial colonisation after LRTI33.
Indeed, the most recent British Thoracic Society guidelines support the
use of both enteral and inhaled antibiotics to reduce infection
frequency in individuals with learning disabilities suffering from
recurrent community acquired pneumonia45.
Although early evidence on prophylactic inhaled antibiotic use in
children with tracheostomies is promising, suggesting reduced frequency
of LRTIs and systemic antimicrobial use, it is very weak, limited to two
small retrospective cohort studies 30,31. Given the
already troubling prevalence of multidrug resistant organisms in this
population23,
randomised controlled trial evidence is needed to ensure this common
practice is actually beneficial and not detrimental to patients’ health.
Tracheal cultures are commonly obtained from paediatric tracheostomy
patients, with the aim of guiding subsequent antimicrobial therapy.
However, a positive culture alone is not diagnostic of infection.
Positive cultures may represent normal respiratory organisms or
colonisation of the respiratory tract, which is common after
tracheostomy. Yalamanchi et al. highlight this challenge of knowing
which culture results to act upon, reinforcing the need to interpret
culture results as part of a wider clinical assessment39.
Whilst Prinzi et al. demonstrated the potential harms of over-reporting
aspirate cultures, which can lead to unnecessary antimicrobial
exposure.37Further, Cline et al. demonstrate the danger of utilising historical
culture results to guide current treatment, which they estimate would
only be effective in half of
cases.38The increasing uptake of next generation sequencing techniques, which
are currently mainly limited to the research environment, may offer hope
for the future. Comprehensive profiling of microbial communities will
help us better understand the dynamic interplay between the tracheal
microbiome and host-immune
system.46,47In turn, improved understanding of what factors predispose individuals
to microbial dysfunction and subsequent infection could provide
alternatives to antimicrobial therapy to break the cycle of recurrent
infections25.
The data summarised here have four main overriding limitations. Firstly,
the populations studied were heterogeneous in terms of design,
intervention, and outcome measures, limiting their generalisability.
Secondly, there was no standardised definition of
tracheostomy-associated respiratory infections across different studies,
which often just reported clinical diagnosis, limiting their
comparability. Features of interest when comparing datasets include the
presence of positive tracheal aspirate cultures, radiographic changes,
changes in gas exchange, and other clinical features (such as cough,
sputum production, and pyrexia). Attention should be paid to infection
definition when designing future studies to support interpretability of
their results and subsequent meta-analysis. Thirdly, the small sample
size of these studies precludes subgroup analysis, compounding the first
two issues. Finally, all studies in our systematic review are
retrospective cohort studies, which by design provide low level evidence
for the efficacy of antimicrobial interventions. Prospective,
randomised, controlled studies are needed to guide clinical decision
making for this vulnerable patient cohort.