A hypothetical case of nasal microbiome transplantation Katherine P. Lemon, MD, PhD Institute & Boston Children s Hospital Mary-Claire Roghmann, MD, MS University of Maryland Microbiota-transplantation Working Group December 12, 2016
The Problem: repeated Staphylococcus aureus infections Child with a complex medical condition Dependent on a central venous catheter S. aureus (MSSA) brain abscess Later a S. aureus (MSSA) bacteremia S. aureus nasal & skin decolonization failed A third S. aureus (MSSA) infection
What next? Risk for repeat S. aureus infections Repeat decolonization, which might fail There is no vaccine against S. aureus
Staphylococcus aureus colonizes the human nose, skin and throat nostrils throat segments back of nose back of mouth lower throat Wertheim LID 2005 (rev) Mertz CID 2007
Staphylococcus aureus lives in the noses of ~25% of humans Colonization increases the risk of infection Gorwitz JID 2008
Most Staphylococcus aureus interactions with humans are harmless Harmless Infection
Staphylococcus aureus also causes infection Harmless Infection
Staphylococcus aureus kills up to 10,000 people per year in the U.S. CDC. Active Bacterial Core Surveillance Report, 2005-2011
S. aureus causes a range of infections Skin & soft tissue Bone Joint Blood stream Heart valve Pneumonia Medical devices
Some people experience repeated S. aureus infections USA300 clone of MRSA Reports of multiple recurrences Reports of multiple MRSA infections, e.g., SSTIs, within a household
Why are 75% of people are free of Staphylococcus aureus? and have a lower risk of infection
Our genetics has little influence on whether Staphylococcus aureus lives in our nose Andersen et al. JID 2012
other bacteria in the nose likely do Liu et al. Sci Adv 2015
Studies have identified bacterial genera/species inversely correlated with S. aureus Frank et al. PONE 2010 Wos-Oxley et al. ISME J 2010 Yan et al. CHM 2013
Can other members of the nasal microbiome keep S. aureus out? Benign or beneficial S. aureus
The Problem: repeated Staphylococcus aureus infections Child with a complex medical condition Dependent on a central venous catheter S. aureus (MSSA) brain abscess Later a S. aureus (MSSA) bacteremia S. aureus nasal & skin decolonization failed A third S. aureus (MSSA) infection
Hypothesis: the nasal microbiome can be replaced by one resistant to S. aureus Repeat decolonization to perturb the ecosystem Community will repopulate secondary succession Guide repopulation: Nasal Microbiota Transplant Donor: long-term S. aureus non-carrier Goal: to prevent S. aureus infection by eradicating S. aureus colonization
S. aureus nasal and skin decolonization First 5 days of every month for 3-4 cycles Topical antibiotic to both nostrils twice daily mupirocin Topical microbicide wash/bath once daily Chlorhexidine Dilute bleach Decolonize the household (all S. aureus carriers) Limit sharing of S. aureus via household surfaces (e.g., avoid sharing towels) e.g., Fritz et al. CID 2012
Risks of S. aureus decolonization Generally well tolerated Localized reaction to the topic mupirocin or microbicide Potential to select for resistant S. aureus Mupirocin resistance The protocol may fail
Theoretical Nasal Microbiota Transplant Harvest microbiota with nostril swab(s) Donor: healthy and repeatedly negative for S. aureus colonization for >1 year Nostril, throat, axilla, inguinal fold and maybe GI Swab the nostrils of the recipient immediately after decolonization protocol Topical decolonization only? Oral antibiotics included in the decolonization? What about other carriers in the household? How long to monitor for recurrence/reacquisition of S. aureus?
The Lemon Lab at Developing new and sustainable ways to manage the bacterial microbiome in the nose and on the skin to prevent and treat infections. Boston Children s Hospital
Discussion
Why study bacteria that live in noses?
Bacterial interactions with humans range from beneficial to harmless to infection Beneficial Infection (pathogen)
We think about nasal bacteria in terms of how they affect humans Commensal Harmless Mutualist Beneficial Pathobiont Can cause severe disease
What keeps Staphylococcus aureus behaving harmlessly? Harmless Infection
A systems level view of a complex microbial community (microbiota)
Goal: identify molecular mechanisms that drive community composition/function Metabolites or Signals Antagonism Synergy