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.