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Development of a Cystic Fibrosis-Specific Antibiogram in a Pediatric Health System

21 Sep 2020 4:58 PM | Anonymous

By: Jamie Sullivan and Brooke Jacobson, PharmD Candidates 2021, UMKC School of Pharmacy

Mentor: E. Claire Elson, PharmD, BCPPS; Children’s Mercy Kansas City

Introduction

Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by dysfunction in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. As a result, abnormal, viscous secretions primarily affect the gastrointestinal and respiratory system in people with CF.1 These secretions cause a complex respiratory triad of increased inflammation, obstruction, and infection that may eventually lead to bronchiectasis, parenchymal destruction, and increased morbidity and mortality.1

While there have been significant advances in therapies to treat the underlying cause of CF over the last decade, a major focus of treatment remains the prevention and treatment of acute and chronic infection in the airways.1 A mainstay of treating airway infections in CF is the utilization of antibiotic therapy. However, because CF individuals have altered airway pathophysiology and require increased treatment, individuals are at risk of resistant infections. A child with CF may develop chronic infections and become colonized with certain organisms such as Staphylococcus aureus and Haemophilus influenzae which eventually causes damage to the lungs.3 Consequently, this allows the introduction of more virulent pathogens such as Pseudomonas aeruginosa, Burkholderia species, Achromobacter, and Stenotrophomonas maltophila to infect the lungs of the individual. Because chronic infection with P. aeruginosa is associated with lung function decline and mortality in CF patients,3 utilization of antimicrobial stewardship in the early stages of CF is imperative for slowing the progression of disease.

In every patient, it is important to practice proper antimicrobial stewardship. Most institutions use an institutional-specific antibiogram to guide antimicrobial empiric therapy. However, this can be difficult in special populations like CF as most institutions do not include CF cultures in their antibiogram. Not having access to a CF-specific antibiogram can lead to inappropriate and improper antibiotic selection and potentially increased rates of resistance. Therefore, Children’s Mercy Kansas City (CMKC) Cystic Fibrosis Center developed a CF-specific antibiogram to guide antimicrobial selection and monitor changes in susceptibility patterns over time.

Methods

This was a single center, retrospective, observational study beginning in 2015 and extending to 2026. To conduct this study, approval was obtained from the Institutional Review Board. This report includes a five-year interim data analysis from 2015-2019. The primary objective was to develop a CF-specific antibiogram at CMKC in order to guide empiric antimicrobial selection and treatment. Secondary objectives included a comparison of the institutional antibiogram with the CF-specific antibiogram in order to characterize differences in susceptibilities and changes of susceptibility patterns over time. CF patient culture data collection started in 2015. All CF patient cultures, obtained by sputum or deep pharyngeal swab, obtained at CMKC were included in the CF antibiogram. Patients were identified via a microbiology report. The following data were collected: demographics, microorganism isolated, and susceptibility information. Susceptibility information was reported for methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PA), Achromobacter, Stenotrophomonas maltophila, and Burkholderia species. CMKC hospital-wide (HW) antibiogram and CF-specific antibiogram were compared. Descriptive statistics and Fisher’s exact test for categorical data were utilized for analysis.

Results

At CMKC, the CF-specific antibiogram has been reviewed and published from 2015-2019 in conjunction with the institutional antibiogram. The MSSA, MRSA and PA isolates collected from expectorated sputum or deep pharyngeal swab in the CF population were compared to the CMKC HW antibiogram.

Over the five-year period there was a total of 6864 cultures with MSSA and 3202 cultures with MRSA isolated in both CF and HW antibiograms. Overall, MSSA and MRSA CF isolates were less susceptible compared to HW isolates for every antimicrobial tested. Clindamycin was significantly less susceptible in the CF population compared to the HW population for MSSA (71% vs. 79%, p=0.25) and MRSA (39% vs. 83%, p<0.001). MRSA was found at a higher rate in the HW isolates compared to the CF isolates (33% versus 27.5%). These results are summarized in the table below.


PA was the most prevalent gram-negative isolate seen among CF cultures, with 480 isolates identified over the five-year period. The PA isolates were less susceptible in CF cultures than in the CMKC HW population for every antimicrobial tested. The difference was most significant for aminoglycoside antibiotics in the CF population compared to the HW population for amikacin (71% vs. 99%, p<0.0001), gentamicin (71% vs. 93%, p<0.0001), and tobramycin (87% vs. 97%, p=0.0165). These results are summarized in the table below.


Conclusion

Overall, gram-positive and gram-negative microorganisms isolated from CF cultures were less susceptible when compared to the CMKC hospital-wide antibiogram. Furthermore, there did not appear to be significant changes in susceptibility patterns throughout this five-year interim analysis. At CMKC, the CF-specific antibiogram will continue to be reviewed and published each year with our institutional antibiogram. It will continuously be utilized to guide empiric antibiotic therapy selection for individuals with CF. The development of a CF-specific antibiogram has important clinical implications to guide empiric antimicrobial selection, and its development will allow for monitoring of resistance trends over time.

References:

  1. Paranjape SM, and Mogayzel PJ. Cystic Fibrosis. Pediatrics in Review. 2014;35;194. DOI: 10.1542/pir.35-5-194.
  2. Bhagirath AY, Li Y, Somayajula D, et al. Cystic Fibrosis Lung Environment and Pseudomonas Aeruginosa Infection. BMJ Pulm Med. 2016; 16: 175. DOI: 10.1186/s12890-016-0339-5.
  3. Lyczak JB, Cannon CL, Pier GB. Lung Infections Associated with Cystic Fibrosis. Clin Microbiol Rev. 2002; 15(2): 194-222. DOI: 10.1128/CMR.15.2.194-222.2002.

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