exclude: true --- background-image: url(img/cdc-aQOe0Ri267U-unsplash.jpg) background-size: cover class: middle left hide-count .fade-in[ # <span style='color:white'>The Death and Life of Bacterial Infections</span> ] .fade-in[ .callout-url-leftcorner[ <span style='font-size:0.75em;font-weight:bold;color:white'> Brendan J. Kelly, MD, MS Infectious Diseases & Epidemiology University of Pennsylvania </span> <span style='font-size:0.5em;font-weight:bold;color:white;'> 01 April 2021 </span> ] ] --- ## Healthcare Infections & Antibiotic Resistance .pad-left[ - **Healthcare-associated infections**: - ~ 1.7 million bacterial HAIs in US per year (1 in 25 US hospital patients) - ~ 100k deaths in US per year (5-10% absolute attributable mortality) - limit the success of surgery, cancer treatment, organ transplantation - HAIs drive an **epidemic of antibiotic resistance**: - 2.8 million antibiotic-resistant infections in US per year - 35,000 deaths from AR infections in US per year ] --- ## A New Paradigm for Bacterial Infection .pad-left[ - <u>High-throughput sequencing</u>: a new lens on complex microbial communities - <u>Fecal microbiota transplant (FMT)</u>: "ecobiotic" therapies exert large effects - **A new molecular epidemiology of infectious diseases:** - new <u>microbiome</u> measures & interventions - reframe familiar outcomes and exposures (e.g., antibiotics) - integrate methods and tools from microbial ecology - need for new modeling and computational approaches ] --- ## Mission .pad-left[ - International leadership in understanding complex microbial communities and their relationship to infectious diseases: - how are complex microbial communities best measured? - how is their behavior and relationship to disease best modeled? - how can they be altered to prevent and cure infectious diseases? - how can novel strategies address the epidemic of antibiotic resistance? ] --- class: full-screen hide-count <div class="grid-3-1"> <div class="extension-tile gridset-a animated flipInY"><div>Studies &<br>Key Findings</div></div> </div> --- layout: false class: full-screen hide-count <div class="grid-3-1"> <div class="extension-tile gridset-a"><div>Studies &<br>Key Findings</div></div> <div class="extension-tile gridset-b animated flipInX"><div>Methods<br>Resources &<br>Collaborations</div></div> </div> --- layout: false class: full-screen hide-count <div class="grid-3-1"> <div class="extension-tile gridset-a"><div>Studies &<br>Key Findings</div></div> <div class="extension-tile gridset-b"><div>Methods<br>Resources &<br>Collaborations</div></div> <div class="extension-tile gridset-c animated bounceInDown"><div>Future<br>Directions</div></div> </div> --- exclude: true layout: false class: full-screen hide-count <div class="grid-3-2"> <div class="extension-tile gridset-a"><div>Case from 1981</div></div> <div class="extension-tile gridset-b"><div>Prevalence</div></div> <div class="extension-tile gridset-c"><div>Incidence</div></div> <div class="extension-tile gridset-d animated fadeInRight"><div>Inference from<br>Exposures &<br>Outcomes</div></div> <div class="extension-tile gridset-e animated bounceInUp"><div>Relative Risk<br>&<br>Odds Ratios</div></div> <div class="extension-tile gridset-f animated slideInLeft"><div>Data Types<br>&<br>Distributions</div></div> </div> --- exclude: true class: full-screen hide-count <div class="grid-3-2"> <div class="extension-tile gridset-a animated flipInY"><div>Case from 1981</div></div> <div class="extension-tile gridset-b animated flipInX"><div>Prevalence</div></div> <div class="extension-tile gridset-c animated flipInY"><div>Incidence</div></div> <div class="extension-tile gridset-d animated flipInX"><div>Inference from<br>Exposures &<br>Outcomes</div></div> <div class="extension-tile gridset-e animated flipInY"><div>Relative Risk<br>&<br>Odds Ratios</div></div> <div class="extension-tile gridset-f animated flipInX"><div>Data Types<br>&<br>Distributions</div></div> </div> --- layout: false class: full-screen hide-count <div class="grid-3-1"> <div class="extension-tile gridset-a"><div>Studies &<br>Key Findings</div></div> <div class="extension-tile gridset-grey"><div>Methods<br>Resources &<br>Collaborations</div></div> <div class="extension-tile gridset-grey"><div>Future<br>Directions</div></div> </div> --- ## Studies & Key Findings .pad-left[ **Bacterial pneumonia during critical illness** - 3 prospective cohort studies (K23 NIAID, CDC BAA 2016, CDC BAA 2018) - respiratory microbiome → pneumonia; commensal bacteria reduce infection risk ] --- ## Studies & Key Findings .pad-left[ **Bacterial pneumonia during critical illness** - 3 prospective cohort studies (K23 NIAID, CDC BAA 2016, CDC BAA 2018) - respiratory microbiome → pneumonia; commensal bacteria reduce infection risk <hr style="background-color:#000000"> **<i>Clostridioides difficile</i> infection and colitis** - prospective cohort study (CDC BAA 2016): commensal bacteria reduce recurrence - randomized trial of fecal transplant (CDC - Lautenbach PI) ] --- ## Studies & Key Findings .pad-left[ **Bacterial pneumonia during critical illness** - 3 prospective cohort studies (K23 NIAID, CDC BAA 2016, CDC BAA 2018) - respiratory microbiome → pneumonia; commensal bacteria reduce infection risk <hr style="background-color:#000000"> **<i>Clostridioides difficile</i> infection and colitis** - prospective cohort study (CDC BAA 2016): commensal bacteria reduce recurrence - randomized trial of fecal transplant (CDC - Lautenbach PI) <hr style="background-color:#000000"> **COVID-19** - bacterial superinfection, antibiotic use and resistance (CDC - Lautenbach PI) - molecular epidemiology of SARS-CoV-2 ~ vaccination (Kelly PI, Wiebe Co-I) ] --- layout: false class: full-screen hide-count <div class="grid-3-1"> <div class="extension-tile gridset-grey"><div>Studies &<br>Key Findings</div></div> <div class="extension-tile gridset-b animated flipInY"><div>Methods<br>Resources &<br>Collaborations</div></div> <div class="extension-tile gridset-grey"><div>Future<br>Directions</div></div> </div> --- ## Methods, Resources & Collaborations .pad-left[ <u>Measurement</u>: **Director, Antibiotic Resistance Epidemiologic Studies (ARES) Laboratory** - bacterial culture, microbiome & whole genome sequencing - ARES lab investigators: Kelly / Lautenbach / David / Ziegler / Anesi - collaborations with microbiology (Bushman, Abt, Zackular) ] --- ## Methods, Resources & Collaborations .pad-left[ <u>Measurement</u>: **Director, Antibiotic Resistance Epidemiologic Studies (ARES) Laboratory** - bacterial culture, microbiome & whole genome sequencing - ARES lab investigators: Kelly / Lautenbach / David / Ziegler / Anesi - collaborations with microbiology (Bushman, Abt, Zackular) <hr style="background-color:#000000"> <u>Modeling</u>: **Multilevel Bayesian Regression for Microbiome Data** - collaboration with Dr. Jason Roy (DBEI → Rutgers University): mediation ] --- ## Methods, Resources & Collaborations .pad-left[ <u>Measurement</u>: **Director, Antibiotic Resistance Epidemiologic Studies (ARES) Laboratory** - bacterial culture, microbiome & whole genome sequencing - ARES lab investigators: Kelly / Lautenbach / David / Ziegler / Anesi - collaborations with microbiology (Bushman, Abt, Zackular) <hr style="background-color:#000000"> <u>Modeling</u>: **Multilevel Bayesian Regression for Microbiome Data** - collaboration with Dr. Jason Roy (DBEI → Rutgers University): mediation <hr style="background-color:#000000"> <u>Teaching</u>: **EPID 674: Measuring the Microbiome** - created & co-direct course (Dr. Kyle Bittinger, PCMP) ] --- layout: false class: full-screen hide-count <div class="grid-3-1"> <div class="extension-tile gridset-grey animated"><div>Studies &<br>Key Findings</div></div> <div class="extension-tile gridset-grey animated"><div>Methods<br>Resources &<br>Collaborations</div></div> <div class="extension-tile gridset-c animated flipInX"><div>Future<br>Directions</div></div> </div> --- ## Future Directions .pad-left[ **Bacterial pneumonia during critical illness** - integrate novel measures (resistome, virome) with modeling framework - visiting professorship University of Michigan ] --- ## Future Directions .pad-left[ **Bacterial pneumonia during critical illness** - integrate novel measures (resistome, virome) with modeling framework - visiting professorship University of Michigan <hr style="background-color:#000000"> **<i>Clostridioides difficile</i> infection and colitis** - methods of microbiome modification & new indications - appointed IDSA representative on AGA's FMT Steering Committee ] --- ## Future Directions .pad-left[ **Bacterial pneumonia during critical illness** - integrate novel measures (resistome, virome) with modeling framework - visiting professorship University of Michigan <hr style="background-color:#000000"> **<i>Clostridioides difficile</i> infection and colitis** - methods of microbiome modification & new indications - appointed IDSA representative on AGA's FMT Steering Committee <hr style="background-color:#000000"> **COVID-19** - spatial component to molecular epidemiology of infectious diseases - collaboration with Doug Wiebe & SpaceTimeEpi Group ] --- exclude: true layout: false class: full-screen hide-count <div class="grid-3-1"> <div class="extension-tile gridset-a animated flipInX"><div>Studies &<br>Key Findings</div></div> <div class="extension-tile gridset-b animated flipInY"><div>Methods<br>Resources &<br>Collaborations</div></div> <div class="extension-tile gridset-c animated flipInX"><div>Future<br>Directions</div></div> </div> --- class: hide-count background-image: url(img/cdc-aQOe0Ri267U-unsplash.jpg) background-size: cover .callout-url-bottom[ .fade-in[<span style="font-size:0.5em; color:white">slides ↓ </span>] <span style="link-color:white">[bjklab.org](http://www.bjklab.org)</span> ] --- exclude: true class: inverse, center, middle, hide-count <hr style="background-color:#1381B0"> .callout-url-middle[ <span style="font-size:0.5em; color:#1381B0">slides ↓ </span> ] .callout-url-bottom[ <span style="color:#1381B0">[bjklab.org](http://www.bjklab.org)</span> ]