Download The Good, the Bad, and the Unknown: Exploring the CF Lung

Hot Topics in Antibiotic Management of
Pediatric CF Lung Disease
Mike Tracy, MD
Fellow, Pediatric Pulmonary
Overview
• Origins CF lung disease
• Conventional CF bacteria
• Treatment of 3 major CF bacteria
– Staphylococcus aureus
– Pseudomonas
– Non-tuberculous Mycobacteria
• Future of CF pulmonary infections
Origins of CF Lung Disease
Stolz et al, NEJM, 2015, 372;4
Origins of CF Lung Disease
Stolz et al. NEJM, 2015, 372;4
Prevalence of Conventional Respiratory
Bacteria by year in CF, 1988-2014
Annual Data Report 2014
CFF Patient Registry
Prevalence of Respiratory Bacterial
Organisms by Age in CF, 2014
Annual Data Report 2014
CFF Patient Registry
Airway Bacterial Changes over Time
Chmiel JF et al. Annal ATS 2014; 11(7):1120
Impact of Antibiotic treatment in CF
Antibiotic Era
1920
1930
1940
1950
1960
1970
1980
1990
2000
2010
24
22
Predicted
Median
Survival (US),
years
20
1965-1980:
Doubling of
predicted survival
18
16
14
12
10
1965
1970
1975
1980
1985
LiPuma, NACFC Plenary Session II, 2014
Patrick Flume (various sources)
Current Testing & Treatment
Insufficient
• Routine culture techniques easily identify only
~1% of known bacteria
– Limited use as most bacteria in CF lung exist in
biofilms
• When we identify & target conventional
pathogens:
– 25% of patients with pulmonary exacerbations do not
reach pre-exacerbation values in lung function
Sanders DB, et al. AJRCCM 2010;182(5):627
Chmiel JF et al. Annal ATS 2014; 11(7):1120
Staphylococcus aureus
• MSSA
• MRSA
• Many types infections
– Skin
– Bones
– Blood
– Lungs
Prevalence of Conventional Respiratory
Bacteria by year in CF, 1988-2014
Annual Data Report 2014
CFF Patient Registry
S. Aureus in CF by age
Annual Data Report 2014
CFF Patient Registry
Is S. aureus bad for people with CF?
• In children
– Increased inflammation
– Worse lung function decline
– Increased 10 yr mortality
• In older adolescents & adults
– Decreased 5-yr mortality
– Better lung function
– Lower risk exacerbations
Hoffman L, NACFC 2015
MRSA
Methicillin-resistant Staphylococcus aureus
• Chronic MRSA associated with worse outcomes
– Cause or marker?
• No conclusive studies for how to treat (or not to treat)
MRSA in CF
– Eradication Protocols
• Staph Aureus Resistance – treat or observe trial (STAR-too)
• So who and how do we treat?
Dasenbrook EC, et al. JAMA 2010;303:2386-2392
MRSA: Treatment
+ MRSA
New
Chronic
No Symptoms
• Eradication
protocol?
• None?
• Eradication
Protocol?
Mild Pulmonary
Symptoms
• Eradication
protocol?
• Oral antibiotics?
• Inhaled
antibiotics?
Acute Pulmonary
Exacerbation
• Oral/IV antibiotics
• Oral/IV antibiotics
Pseudomonas
• Common bacteria
• Opportunistic
• Many strains
– P. aeruginosa most common
• Spread by direct or indirect contact
• Initial colonization  how can we stop chronic
infection?
P. aeruginosa: CFF Guidelines 2014
• Recommendation 1
– Inhaled antibiotic therapy for the treatment of initial or
new growth of P. aeruginosa from an airway culture
– Inhaled tobramycin (300 mg twice daily) for 28 days
• Recommendation 2
– Recommends against the use of prophylactic
antipseudomonal antibiotics to prevent the acquisition
P. aeruginosa
Mogayzel PJ et al, AATS, 2014
P. aeruginosa by Age, 1988–2014
Annual Data Report 2014
CFF Patient Registry
P. aeruginosa: Initial Treatment
• No clear benefit of one treatment over another
– CFF recommends TOBI nebs as most studied
• Treatment is successful based on microbiology results
• Sustained eradication  less likely chronic infection
– Clinical long term benefit unclear
• Some groups less likely to clear
– Based on type of P. aeruginosa?
Mayer-Hamblett et al. CID 2015:61
Mayer-Hamblett et al. CID 2014:59
P. aeruginosa: Ongoing Research
• OPTIMIZE
– TOBI +/- Azithromycin
– Decrease pulmonary exacerbations?
• Torpedo-CF
– IV vs Oral antibiotics + Inhaled antibiotic (Colistin)
– Increase success of prolonged eradication?
Non-tuberculous Mycobacterium (NTM)
•
•
•
•
•
•
Major emerging pathway
“Cousins” to bacteria that cause TB
Opportunistic
>100 types NTM
Acquired from soil, dust, water
Person-to-person transmission may be
important
– Likely indirect, through environment
• Concern for accelerated decline in lung function
Mycobacterial species 2014
Annual Data Report 2014
CFF Patient Registry
New NTM Guidelines
Floto RA, et al. Thorax 2016;71:i1–i22
New NTM Guidelines: Screening
• Recommendation 2
– Cultures for NTM be performed annually in
spontaneously expectorating individuals with a stable
clinical course
• Recommendation 3
– In the absence of clinical features suggestive of NTM
pulmonary disease, individuals who are not capable
of spontaneously producing sputum do not require
screening cultures for NTM
Floto RA, et al. Thorax 2016;71:i1–i22
New NTM Guidelines: Diagnosis
NTM Pulmonary Disease (NTM-PD)
• Symptoms of NTM similar to other CF organisms
• A single positive culture of NTM does not
necessarily mean NTM-PD
– Need to rule out other common CF bacteria
– Need radiology studies, and repeat cultures
Floto RA, et al. Thorax 2016;71:i1–i22
New NTM Guidelines: Treatment
Floto RA, et al. Thorax 2016;71:i1–i22
Future of CF pulmonary infections
Bacteria
• Microbiome Many species
undetected
Fungi
• Aspergillus
• Interactions
with bacteria
Viruses
• Associated w/
30-40%
Pulmonary
Exacerbations
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