DISCUSSION
There are no peer reviewed publications regarding CF-specific
antibiograms. An abstract published in the proceedings from a conference
describes six-years of antimicrobial susceptibility data for MRSA, MSSA
and PA from two pediatric CF centers.10 Like the
current study, they found a higher proportion of MRSA in the HWA. PA
susceptibility was significantly decreased compared to the HWA at only
one CF site in the abstract. Generalizability is limited based on the
relatively small number of isolates analyzed and the susceptibility
information presented. The previous abstract and the current study
support the development and utilization of CF-specific antibiograms
within hospitals and CF care centers.
This study demonstrates that gram-negative and gram-positive
microorganisms were less susceptible in people with CF compared to a
hospital’s general population. The increased resistance seen in the CFA
is likely multifactorial, but may relate to increased antimicrobial
utilization as well as CF specific differences in airway pathophysiology
and microenvironment.1 The increase in antimicrobial
utilization is driven by systemic therapy for pulmonary exacerbations
and chronic maintenance medications with inhaled
therapy.2,4,13 CFTR dysfunction, airway surface liquid
abnormalities and impairment of mucociliary clearance result in
increased airway infection.4-7 Microorganisms that
infect the CF airway have innate and adaptive resistance mechanisms
resulting in decreased susceptibility to
antimicrobials.7 Alterations in pharmacokinetic
parameters of antimicrobials in people with CF require therapy
modification in order to achieve pharmacodynamic targets comparable to
healthy populations, resulting in even greater challenges in the
treatment of infection.9 Demographic information
related to the HWA was not obtained, future studies should characterize
other populations in order to determine susceptibility differences and
trends.
This study is unique in that it highlights the significant differences
between sputum and oropharyngeal swab isolates obtained from people with
CF. The isolates obtained from sputum were less susceptible than those
from oropharyngeal swabs. Multiple factors likely contribute to this
finding. Individuals with advanced lung disease are more likely to
expectorate sputum and typically have increased lifetime antibiotic
exposure, promoting resistance. Presumably, individuals with more
advanced age have correlating advanced disease and therefore are able to
expectorate sputum resulting in increased resistance. However, this is a
major limitation of the present study as age was evaluated as a total CF
population rather than culture source. Additionally, previous studies
have demonstrated the limitations of oropharyngeal sampling and the
challenges associated with this sampling method.8 For
the detection of PA, oropharyngeal sampling compared to bronchoalveolar
lavage fluid was more specific than sensitive. For individuals unable to
expectorate sputum, the false positive rate was consistently less than
10% resulting in a high negative predictive value for the presence of
PA in oropharyngeal sampling.13 However, sensitivity
was variable between 44-75% thus there is a lower positive predictive
value for PA in oropharyngeal sampling as well as in the identification
of other respiratory isolates.8,12-13
Other considerations related to the concordance of sampling includes
symptoms and the age of the individual.8,14 Despite
these limitations, the use of oropharyngeal swabs is standard practice
among young, non-expectorating children in CF Care Centers. This may
become increasingly relevant in the era of highly effective CFTR
modulator therapy, as more people with CF are healthier and unable to
produce sputum.15 Therefore, understanding the
differences in susceptibility between these isolate sources will be even
more important when making empiric antimicrobial selections.
This study was reassuring in that there did not appear to be any
clinically significant changes in percentage of susceptible isolates
during the five-year study period. However, limitations include not
standardizing for the number of cultures, source of the culture, or the
age of the population. Overall, this study supports the development and
sustainment of an institutional CFA.