1. MRSA in patients with CF Effect on lung function and what we can do about it…… Kate Amond, MS, RN, BSN

2. CF and resistant bacteria  Age expectancy now >37 yrs old  Medical providers now using more antibiotics with patients with CF than years past.  Care has shifted over the years from mostly inpatient care to mostly outpatient care  Increasing prevalence of resistant bacteria with increased antibiotic use.

3. MRSA  Currently about 18.9% of people with CF have MRSA  Most common ages 11-17yrs  Which means it is OUR job to eradicate it!

4.  MRSA is unique from other bugs-  It can spread from healthy people without CF to people with CF  This is different from Pseudomonas aeruginosa and Burkholderia cepacia.  Increasing prevalence of community acquired strains

5. 2 studies  1. Ren, C.L., Morgan, W.J., Konstan, M.W., Schechter, M.S., Wagener, J.S., Fisher, K.A., et al (2007). Presence of MRSA in Respiratory Cultures from CF patients is associated with lower lung function. Pediatric Pulmonology, 42(6), 513-518.  2. Dasenbrook, E.C., Merlo, C.A., Diener-West, M., Lechtzin, N., & Boyle, M.P. (2008). Persistent MRSA and rate of FEV1 decline in Cystic Fibrosis. American Journal of Respiratory and Critical Care Medicine, 178(8), 814-821.

6. Prevalence  1995- only 0.1% of patients reported to CF registry had respiratory tract cultures + for MRSA  2001- 7.3% of patients were MRSA +  Now about 18.9%  LIMITED DATA ON IMPACT MRSA HAS ON CLINICAL STATUS AND LUNG FUNCTION IN PTS WITH CF

7. Ren et al study Hypothesis: Presence of MRSA in respiratory cultures from CF patients would be associated with more severe disease than that seen in patients with methicillin sensitive S. aureus (MSSA). Used data from Epidemiologic Study of Cystic Fibrosis (ESCF) allowing a large sample size

8. <18 yrs old Number (%) >18 yrs old Number (%) All ages All ages Number (%) MSSA 1,394 (90) 1,394 (90) 232 (84) 232 (84) 1,626 (89) 1,626 (89) MRSA 163 (10) 163 (10) 45 (16) 45 (16) 208 (11) 208 (11) TOTAL 1,557 1,557 277 277 1,834 1,834 Ren et al (2007)

9.  In children and adults whose resp. cultures yielded only S. aureus, those with MRSA had significantly lower mean FEV1 than those with MSSA.  Children <18 yrs  FEV1 80.7% predicted (MRSA+ group)  FEV1 89.4% predicted (MSSA+ group)  Adults >18 yrs  FEV1 60.9% predicted (MRSA+ group)  FEV1 70.4% predicted (MSSA+ group)

10. Mean FEV1 by MSSA/MRSA status and age Ren et al, 2007

11.  Presence of MRSA was associated with:  Increased hospitalization  Increased use of antibiotic use across all antibiotic classes and modes of delivery  When compared to pts with MSSA only, a significantly larger percentage of patients with MRSA only in resp cx were hospitalized and received IV antibiotics during study period.

12. Percentage of patients hospitalized at least once by MSSA/MRSA status and age Ren et al, 2007

13. Use of Inhaled Antibiotics in patients with Staph aureus Ren et al, 2007

14. Pathophysiology  It is possible MRSA persists in airway longer than MSSA because of increased survival in the presence of commonly used antibiotics in CF patients.  Production of toxins or virulence factors specific to MRSA may mediate increased airway inflammation, edema, and hypersecretion. Virulence factors damage host tissue.  Some community acquired strains are known to have enhanced virulence factors compared with nosocomial strains.

15. Results  Results of this study are first to show significant association between MRSA and more severe airflow obstruction in CF patients compared to those having only MSSA  Results lead to speculation that MRSA infection results in more severe airway disease in CF compared to MSSA infection.

16. Discussion of Ren et al study  Cannot determine what proportion of MRSA was community acquired or hospital acquired  Do not know if association between lower FEV1 and MRSA occurs in patients who harbor other organisms such as Pseudomonas with MRSA.  Some studies suggest concomitant infection with staph and pseudomonas may actually result in more favorable prognosis, some say opposite.

17. Limitations continued  Study only included data from year 2001.  Cannot rule out possibility that some of patients in MRSA only group acquired other organisms in a preceding year that could have affected FEV1

18. Conclusions from Ren et al The presence of MRSA only in respiratory cultures is associated with significantly more severe airflow obstruction compared with the presence of MSSA only.

19. Which came first, the chicken or the egg?  It is unclear if MRSA is simply a marker of more severe lung disease or an independent contributor to decline in lung function.

20. Dassenbrook et al study  Hypothesis: MRSA independently contributes to more rapid lung function decline in individuals with CF. MRSA independently contributes to more rapid lung function decline in individuals with CF. Rate of decline of FEV1 important outcome measurement b/c: -it closely is related to morbidity and mortality in CF -may allow better assessment of whether a pathogen is only a marker of disease severity or an independent contributor to loss of lung function. -may allow better assessment of whether a pathogen is only a marker of disease severity or an independent contributor to loss of lung function.

21. Dasenbrook cont.  Data taken from Cystic Fibrosis foundation patient registry (CFFPR)  Data from 1996-2005  Excluded individuals  younger than 6 (unreliable PFT data)  individuals older than 45 (mild phenotype)  MRSA+ in first two yrs in cohort (to allow to adequately assess effect of new MRSA infection on lung function)

22.  Distinguished difference between persistent MRSA and transient.  Persistent = 3 positive MRSA cultures (didn’t have to be in a row)  Transient = just 1 or 2 MRSA cultures over the course of study period  MRSA status recorded every 3 months

23.  Of the 3,435 individuals who cultured MRSA,  49% demonstrated only transient MRSA  50% persistent MRSA

24.  Pts more likely to develop MRSA versus stay negative if:  Younger (mean 14 yrs old)  Slightly better lung function  Was more likely to be colonized with Pseudomonas and MSSA  Pancreatic insufficiency

25. Findings  Persistent MRSA respiratory infection in individuals with CF aged 8 to 21 is associated, on average, with an increase in rate of decline in lung function or approximately 0.5 FEV1 % predicted per year.

26. Dasenbrook, 2008

27. Findings, continued  About ½ of individuals with CF who culture MRSA from the respiratory tract do so only transiently.  34% one culture (1181 people)  15% two cultures (522 people)  Is there a way to determine which patients will be transient and which will be persistent?

28. Findings, cont.  An individual who cultured positive MRSA in consecutive quarters went on to develop persistent MRSA 81% of the time.  50% of patients that had their third positive MRSA culture within a year of their first MRSA culture.

29. Dasenbrook, 2007

30. Findings, cont  FEV1 may not be as sensitive a marker of lung pathology in adults as in children, because it has been observed that adults with low absolute FEV1 demonstrate a slower overall rate of FEV1 decline and less variability in FEV1 with changes in lung health.

31. UW study  29 total patients grew MRSA from sputum at UW PPC  Eradication protocol developed by Darci Pfeil, NP, and Dr. Rock  5 patients got MRSA protocol  Triple antibiotic therapy  PO Bactrim (Clindamycin, Rifampin, and nasal Bactroban)

32. Results  Protocol given at first acquisition of MRSA starting 1/10/2005  2-4 weeks after completion of triple antibiotic therapy, sputum cx done  If negative, three surveillance cxs done to remove MRSA isolation

33. Results  Protocol was successful 100% *of the time at eradicating MRSA  All pts had negative cultures 6 months after completion of protocol  All pts had negative cultures 12 months after protocol

34.  3 patients received protocol as written  1 patient cultured MRSA+ in sputum at 2 nd surveillance culture  Protocol given again (minus nasal Bactroban)  Cultures negative after 6 mo  Cultures negative after 12 mo

35.  1 patient received protocol but not until 5.5 months after 1 st acquisition MRSA  MRSA eradicated  Culture negative at 6 months  Culture negative at 12 months

36.  14 patients who did NOT receive protocol remained MRSA + during study period  6 patients cleared the MRSA on their own  4 of these only grew MRSA once  1 patient grew MRSA twice  1 patient grew > 4 times, but still cleared spontaneously (will they stay neg?)

37. Results  1 patient had two positive cx then spontaneously cleared. Negative for 5 years, but now positive again.  Three patients excluded for incomplete data

38. So, …  5 patients got protocol  6 patients cleared on their own  *need a longitudinal study with larger sample size*

39. Lessons learned  Importance of dictations and accurate documentation!!!!  Communication between PCP and PPC provider crucial  If labs done at outside provider office, need a lab that does MRSA cultures  Need faxed results of cultures to enter in our system

40. Questions unanswered  Which patients will be able to clear MRSA on their own?  Should MRSA be treated at first acquisition or wait to see if two or more cultures in a row grow MRSA?  Would there be a benefit to treating persistent MRSA?

41. future  Limitations of UW study: Small sample size!!!  Need for a multicenter study to increase sample size, therefore increasing validity.

42. References Dasenbrook, E.C., Merlo, C.A., Diener-West, M., Lechtzin, N., & Boyle, M.P. (2008). Persistent MRSA and rate of FEV1 decline in Cystic Fibrosis. American Journal of Respiratory and Critical Care Medicine, 178(8), 814-821. Dasenbrook, E.C., Merlo, C.A., Diener-West, M., Lechtzin, N., & Boyle, M.P. (2008). Persistent MRSA and rate of FEV1 decline in Cystic Fibrosis. American Journal of Respiratory and Critical Care Medicine, 178(8), 814-821. Ren, C.L., Morgan, W.J., Konstan, M.W., Schechter, M.S., Wagener, J.S., Fisher, K.A., et al (2007). Presence of MRSA in Respiratory Cultures from CF patients is associated with lower lung function. Pediatric Pulmonology, 42(6), 513-518.