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

MRSAMRSAin patients with CFin patients with CF

Effect on lung functionEffect on lung functionand what we can do about it……and what we can do about it……

Kate Amond , MS, RN, BSNKate Amond , MS, RN, BSN

CF and resistant bacteriaCF and resistant bacteria

Age expectancy now >37 yrs oldAge expectancy now >37 yrs old Medical providers now using more antibiotics Medical providers now using more antibiotics

with patients with CF than years past.with patients with CF than years past. Care has shifted over the years from mostly Care has shifted over the years from mostly

inpatient care to mostly outpatient careinpatient care to mostly outpatient care Increasing prevalence of resistant bacteria with Increasing prevalence of resistant bacteria with

increased antibiotic use.increased antibiotic use.

MRSAMRSA

Currently about 18.9% of people with CF Currently about 18.9% of people with CF have MRSAhave MRSA

Most common ages 11-17yrsMost common ages 11-17yrs Which means it is OUR job to eradicate it!Which means it is OUR job to eradicate it!

MRSA is unique from other bugs-MRSA is unique from other bugs- It can spread from healthy people without It can spread from healthy people without

CF to people with CFCF to people with CF This is different from This is different from Pseudomonas Pseudomonas

aeruginosa aeruginosa and and Burkholderia cepaciaBurkholderia cepacia..

Increasing prevalence of community Increasing prevalence of community acquired strainsacquired strains

2 studies2 studies 1. Ren, C.L., Morgan, W.J., Konstan, M.W., 1. Ren, C.L., Morgan, W.J., Konstan, M.W.,

Schechter, M.S., Wagener, J.S., Fisher, K.A., Schechter, M.S., Wagener, J.S., Fisher, K.A., et al (2007). et al (2007). Presence of MRSA in Presence of MRSA in Respiratory Cultures from CF patients is Respiratory Cultures from CF patients is associated with lower lung functionassociated with lower lung function.. Pediatric PulmonologyPediatric Pulmonology, 42(6), 513-518., 42(6), 513-518.

2. Dasenbrook, E.C., Merlo, C.A., Diener-West, 2. Dasenbrook, E.C., Merlo, C.A., Diener-West, M., Lechtzin, N., & Boyle, M.P. (2008). M., Lechtzin, N., & Boyle, M.P. (2008). Persistent MRSA and rate of FEV1 decline Persistent MRSA and rate of FEV1 decline in Cystic Fibrosisin Cystic Fibrosis.. American Journal of American Journal of Respiratory and Critical Care Medicine,Respiratory and Critical Care Medicine, 178(8), 178(8), 814-821.814-821.

PrevalencePrevalence

1995- only 0.1% of patients reported to CF 1995- only 0.1% of patients reported to CF registry had respiratory tract cultures + for registry had respiratory tract cultures + for MRSAMRSA

2001- 7.3% of patients were MRSA +2001- 7.3% of patients were MRSA + Now about 18.9%Now about 18.9%

LIMITED DATA ON IMPACT MRSA HAS ON LIMITED DATA ON IMPACT MRSA HAS ON CLINICAL STATUS AND LUNG FUNCTION IN CLINICAL STATUS AND LUNG FUNCTION IN PTS WITH CFPTS WITH CF

Ren et al studyRen et al study

Hypothesis: Hypothesis:

Presence of MRSA in respiratory cultures from Presence of MRSA in respiratory cultures from CF patients would be associated with more CF patients would be associated with more severe disease than that seen in patients with severe disease than that seen in patients with methicillin sensitive S. methicillin sensitive S. aureusaureus (MSSA). (MSSA).

Used data from Epidemiologic Study of Cystic Used data from Epidemiologic Study of Cystic Fibrosis (ESCF) allowing a large sample sizeFibrosis (ESCF) allowing a large sample size

<18 yrs old<18 yrs old

Number (%)Number (%)

>18 yrs old>18 yrs old

Number (%)Number (%)

All agesAll ages

Number (%)Number (%)

MSSAMSSA

1,394 (90)1,394 (90) 232 (84)232 (84) 1,626 (89)1,626 (89)

MRSAMRSA

163 (10)163 (10) 45 (16)45 (16) 208 (11)208 (11)

TOTALTOTAL

1,5571,557 277277 1,8341,834

Ren et al (2007)Ren et al (2007)

In children and adults whose resp. cultures In children and adults whose resp. cultures yielded only S. aureus, those with MRSA yielded only S. aureus, those with MRSA had significantly lower mean FEV1 than had significantly lower mean FEV1 than those with MSSA.those with MSSA.

Children <18 yrsChildren <18 yrs FEV1 80.7% predicted (MRSA+ group)FEV1 80.7% predicted (MRSA+ group) FEV1 89.4% predicted (MSSA+ group)FEV1 89.4% predicted (MSSA+ group)

Adults >18 yrsAdults >18 yrs FEV1 60.9% predicted (MRSA+ group)FEV1 60.9% predicted (MRSA+ group) FEV1 70.4% predicted (MSSA+ group)FEV1 70.4% predicted (MSSA+ group)

Mean FEV1 by MSSA/MRSA Mean FEV1 by MSSA/MRSA status and agestatus and age

Ren et al, 2007Ren et al, 2007

Presence of MRSA was associated with:Presence of MRSA was associated with: Increased hospitalizationIncreased hospitalization Increased use of antibiotic use across all antibiotic Increased use of antibiotic use across all antibiotic

classes and modes of deliveryclasses and modes of delivery

When compared to pts with MSSA only, a When compared to pts with MSSA only, a significantly larger percentage of patients with significantly larger percentage of patients with MRSA only in resp cx were hospitalized and MRSA only in resp cx were hospitalized and received IV antibiotics during study period.received IV antibiotics during study period.

Percentage of patients hospitalized at least once by Percentage of patients hospitalized at least once by MSSA/MRSA status and ageMSSA/MRSA status and age

Ren et al, 2007Ren et al, 2007

Use of Inhaled Antibiotics in Use of Inhaled Antibiotics in patients with Staph aureuspatients with Staph aureus

Ren et al, 2007Ren et al, 2007

PathophysiologyPathophysiology It is possible MRSA persists in airway longer It is possible MRSA persists in airway longer

than MSSA because of increased survival in than MSSA because of increased survival in the presence of commonly used antibiotics in the presence of commonly used antibiotics in CF patients.CF patients.

Production of toxins or virulence factors Production of toxins or virulence factors specific to MRSA may mediate increased specific to MRSA may mediate increased airway inflammation, edema, and airway inflammation, edema, and hypersecretion. Virulence factors damage host hypersecretion. Virulence factors damage host tissue.tissue.

Some community acquired strains are known Some community acquired strains are known to have enhanced virulence factors compared to have enhanced virulence factors compared with nosocomial strains.with nosocomial strains.

ResultsResults

Results of this study are first to show Results of this study are first to show significant association between MRSA significant association between MRSA and more severe airflow obstruction in and more severe airflow obstruction in CF patients compared to those having CF patients compared to those having only MSSAonly MSSA

Results lead to speculation that MRSA Results lead to speculation that MRSA infection results in more severe airway infection results in more severe airway disease in CF compared to MSSA disease in CF compared to MSSA infection.infection.

Discussion of Ren et al studyDiscussion of Ren et al study

Cannot determine what proportion of MRSA Cannot determine what proportion of MRSA was community acquired or hospital acquiredwas community acquired or hospital acquired

Do not know if association between lower Do not know if association between lower FEV1 and MRSA occurs in patients who harbor FEV1 and MRSA occurs in patients who harbor other organisms such as Pseudomonas with other organisms such as Pseudomonas with MRSA. MRSA. Some studies suggest concomitant infection with Some studies suggest concomitant infection with

staph and pseudomonas may actually result in more staph and pseudomonas may actually result in more favorable prognosis, some say opposite.favorable prognosis, some say opposite.

Limitations continuedLimitations continued

Study only included data from year 2001. Study only included data from year 2001. Cannot rule out possibility that some of Cannot rule out possibility that some of

patients in MRSA only group acquired patients in MRSA only group acquired other organisms in a preceding year that other organisms in a preceding year that could have affected FEV1could have affected FEV1

Conclusions from Ren et alConclusions from Ren et al

The presence of MRSA only in respiratory The presence of MRSA only in respiratory cultures is associated with significantly cultures is associated with significantly more severe airflow obstruction more severe airflow obstruction compared with the presence of MSSA compared with the presence of MSSA only.only.

Which came first, the chicken Which came first, the chicken or the egg?or the egg?

It is unclear if MRSA is simply a marker It is unclear if MRSA is simply a marker of more severe lung disease or an of more severe lung disease or an independent contributor to decline in lung independent contributor to decline in lung function.function.

Dassenbrook et al studyDassenbrook et al study

Hypothesis:Hypothesis: MRSA independently contributes to more rapid lung MRSA independently contributes to more rapid lung

function decline in individuals with CF.function decline in individuals with CF.

Rate of decline of FEV1 important outcome measurement Rate of decline of FEV1 important outcome measurement b/c:b/c:-it closely is related to morbidity and mortality in CF -it closely is related to morbidity and mortality in CF

-may allow better assessment of whether a pathogen is -may allow better assessment of whether a pathogen is only a marker of disease severity or an independent only a marker of disease severity or an independent contributor to loss of lung function.contributor to loss of lung function.

Dasenbrook cont.Dasenbrook cont.

Data taken from Cystic Fibrosis foundation Data taken from Cystic Fibrosis foundation patient registry (CFFPR)patient registry (CFFPR)

Data from 1996-2005Data from 1996-2005 Excluded individuals Excluded individuals

younger than 6 (unreliable PFT data)younger than 6 (unreliable PFT data) individuals older than 45 (mild phenotype)individuals older than 45 (mild phenotype) MRSA+ in first two yrs in cohort (to allow to MRSA+ in first two yrs in cohort (to allow to

adequately assess effect of new MRSA infection on adequately assess effect of new MRSA infection on lung function)lung function)

Distinguished difference between Distinguished difference between persistent MRSA and transient.persistent MRSA and transient. Persistent = 3 positive MRSA cultures (didn’t Persistent = 3 positive MRSA cultures (didn’t

have to be in a row)have to be in a row) Transient = just 1 or 2 MRSA cultures over Transient = just 1 or 2 MRSA cultures over

the course of study periodthe course of study period

MRSA status recorded every 3 monthsMRSA status recorded every 3 months

Of the 3,435 individuals who cultured Of the 3,435 individuals who cultured MRSA,MRSA, 49% demonstrated only transient MRSA49% demonstrated only transient MRSA 50% persistent MRSA50% persistent MRSA

Pts more likely to develop MRSA versus Pts more likely to develop MRSA versus stay negative if:stay negative if: Younger (mean 14 yrs old)Younger (mean 14 yrs old) Slightly better lung functionSlightly better lung function Was more likely to be colonized with Was more likely to be colonized with

Pseudomonas and MSSAPseudomonas and MSSA Pancreatic insufficiencyPancreatic insufficiency

FindingsFindings

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

Dasenbrook, 2008Dasenbrook, 2008

Findings, continuedFindings, continued

About ½ of individuals with CF who About ½ of individuals with CF who culture MRSA from the respiratory tract culture MRSA from the respiratory tract do so only transiently.do so only transiently.

34% one culture (1181 people)34% one culture (1181 people) 15% two cultures (522 people)15% two cultures (522 people)

Is there a way to determine which patients Is there a way to determine which patients will be transient and which will be will be transient and which will be persistent?persistent?

Findings, cont.Findings, cont.

An individual who cultured positive An individual who cultured positive MRSA in consecutive quarters went on to MRSA in consecutive quarters went on to develop persistent MRSA 81% of the develop persistent MRSA 81% of the time.time.

50% of patients that had their third 50% of patients that had their third positive MRSA culture within a year of positive MRSA culture within a year of their first MRSA culture.their first MRSA culture.

Dasenbrook, 2007Dasenbrook, 2007

Findings, contFindings, cont

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

UW studyUW study

29 total patients grew MRSA from 29 total patients grew MRSA from sputum at UW PPCsputum at UW PPC

Eradication protocol developed by Darci Eradication protocol developed by Darci Pfeil, NP, and Dr. RockPfeil, NP, and Dr. Rock

5 patients got MRSA protocol5 patients got MRSA protocol Triple antibiotic therapyTriple antibiotic therapy

PO Bactrim (Clindamycin, Rifampin, and nasal PO Bactrim (Clindamycin, Rifampin, and nasal Bactroban)Bactroban)

ResultsResults

Protocol given at first acquisition of Protocol given at first acquisition of MRSA starting 1/10/2005MRSA starting 1/10/2005

2-4 weeks after completion of triple 2-4 weeks after completion of triple antibiotic therapy, sputum cx done antibiotic therapy, sputum cx done If negative, three surveillance cxs done to If negative, three surveillance cxs done to

remove MRSA isolationremove MRSA isolation

ResultsResults

Protocol was successful 100% *of the Protocol was successful 100% *of the time at eradicating MRSAtime at eradicating MRSA All pts had negative cultures 6 months after All pts had negative cultures 6 months after

completion of protocolcompletion of protocol All pts had negative cultures 12 months after All pts had negative cultures 12 months after

protocolprotocol

3 patients received protocol as written3 patients received protocol as written 1 patient cultured MRSA+ in sputum at 1 patient cultured MRSA+ in sputum at

22ndnd surveillance culture surveillance culture Protocol given again (minus nasal Protocol given again (minus nasal

Bactroban)Bactroban) Cultures negative after 6 moCultures negative after 6 mo Cultures negative after 12 moCultures negative after 12 mo

1 patient received protocol but not until 1 patient received protocol but not until 5.5 months after 15.5 months after 1stst acquisition MRSA acquisition MRSA MRSA eradicated MRSA eradicated Culture negative at 6 monthsCulture negative at 6 months Culture negative at 12 monthsCulture negative at 12 months

14 patients who did NOT receive protocol 14 patients who did NOT receive protocol remained MRSA + during study periodremained MRSA + during study period

6 patients cleared the MRSA on their 6 patients cleared the MRSA on their ownown 4 of these only grew MRSA once4 of these only grew MRSA once 1 patient grew MRSA twice1 patient grew MRSA twice 1 patient grew > 4 times, but still cleared 1 patient grew > 4 times, but still cleared

spontaneously (will they stay neg?)spontaneously (will they stay neg?)

ResultsResults

1 patient had two positive cx then 1 patient had two positive cx then spontaneously cleared. Negative for 5 spontaneously cleared. Negative for 5 years, but now positive again.years, but now positive again.

Three patients excluded for incomplete Three patients excluded for incomplete datadata

So, …So, …

5 patients got protocol5 patients got protocol

6 patients cleared on their own6 patients cleared on their own

*need a longitudinal study with larger *need a longitudinal study with larger sample size*sample size*

Lessons learnedLessons learned

Importance of dictations and accurate Importance of dictations and accurate documentation!!!!documentation!!!!

Communication between PCP and PPC Communication between PCP and PPC provider crucialprovider crucial

If labs done at outside provider office, If labs done at outside provider office, need a lab that does MRSA culturesneed a lab that does MRSA cultures

Need faxed results of cultures to enter in Need faxed results of cultures to enter in our systemour system

Questions unansweredQuestions unanswered Which patients will be able to clear MRSA Which patients will be able to clear MRSA

on their own?on their own? Should MRSA be treated at first acquisition Should MRSA be treated at first acquisition

or wait to see if two or more cultures in a or wait to see if two or more cultures in a row grow MRSA?row grow MRSA?

Would there be a benefit to treating Would there be a benefit to treating persistent MRSA?persistent MRSA?

futurefuture

Limitations of UW study: Small sample Limitations of UW study: Small sample size!!!size!!!

Need for a multicenter study to increase Need for a multicenter study to increase sample size, therefore increasing validity.sample size, therefore increasing validity.

ReferencesReferences

Dasenbrook, E.C., Merlo, C.A., Diener-West, M., Dasenbrook, E.C., Merlo, C.A., Diener-West, M., Lechtzin, N., & Boyle, M.P. (2008). Persistent MRSA Lechtzin, N., & Boyle, M.P. (2008). Persistent MRSA and rate of FEV1 decline in Cystic Fibrosis. and rate of FEV1 decline in Cystic Fibrosis. American American Journal of Respiratory and Critical Care Medicine,Journal of Respiratory and Critical Care Medicine, 178(8), 814-821.178(8), 814-821.

Ren, C.L., Morgan, W.J., Konstan, M.W., Schechter, Ren, C.L., Morgan, W.J., Konstan, M.W., Schechter, M.S., Wagener, J.S., Fisher, K.A., et al (2007). M.S., Wagener, J.S., Fisher, K.A., et al (2007). Presence of MRSA in Respiratory Cultures from CF Presence of MRSA in Respiratory Cultures from CF patients is associated with lower lung function. patients is associated with lower lung function. Pediatric PulmonologyPediatric Pulmonology, 42(6), 513-518., 42(6), 513-518.