Division of Infectious Diseases

Virtual IDWeek – A First, and Memorable Experience

by UNMC ID First Year Fellow Dr. Jonathan Ryder

My first experience with IDWeek was nothing like I expected it to be (given its virtual nature), yet it provided a fantastic experience, full of learning opportunities from the world’s experts. First, I will comment that we are fortunate at UNMC infectious diseases fellowship to be provided protected time to attend IDWeek as first year fellows. Being able to access a highly educational event pays dividends down the road by hearing from content experts and seeing previews of novel diagnostics and antibiotics.

IDWeek 2020 kicked off with Fellows’ Day, in which we were able to learn about how other fellows cope with the COVID-19 pandemic, how the job market is shaping up in these unprecedented circumstances, and listen to some truly unusual and challenging cases from other fellows. The next day of IDWeek included the 24-hours of COVID-19 Chasing The Sun event, a whirlwind of COVID-19 information. Listening to Dr. Fauci speak was an amazing opportunity as well as learning about summaries of treatment options and controversies of transmission routes.

The rest of the week allowed for attendance of sessions electively to our areas of interest. My favorite sessions were on infectious complications in people who use intravenous drugs, the risk of infective endocarditis in bacteremia, and AmpC beta-lactamases. UNMC’s own Dr. Mark Rupp gave an enthralling SHEA lectureship that is highly recommended. I spent a lot of time learning about staphylococcal bacteremia and endocarditis, as these were areas I have encountered frequent questions as a first year fellow.

Overall, IDWeek 2020 was a success, even with it being my first virtual conference. The sessions had amazing speakers with high yield content. The part that I missed out on the most was opportunities for networking, arguably the most valuable part of a conference. I wish I could have met future mentors and other ID fellows. However, I was quite impressed with the organization and efficiency of the virtual conference. I look forward to attending ID Week 2021 in San Diego (hopefully) next year!

LIVE from #IDWeek2020, it’s UNMC ID!

IDWeek is our premier Infectious Diseases conference, and we are excited about it all year long. This year the anticipation is no different, although the conference itself will be very different because of COVID-19. This year is completely virtual, with a full 24hrs of #ChasingTheSun COVID coverage starting October 21, 2020. Many presentations are pre-recorded so we can access them at our leisure; posters are virtual with recorded voice-overs; there will be live Q&A with presenters throughout the week; and a few live sessions not to be missed! With thousands of registrants, our social media feeds are sure to be filled with #IDWeek2020 and we are here for it!

We want you to know where you can find UNMC ID faculty and trainees this week presenting and moderating, and follow us on twitter at @UNMC_ID!

Oral Presentations

Check out our posters

Presenter(s): Andrew Watkins, PharmD; Trevor Van Schooneveld MD; Scott Bergman, PharmD: Use of a Novel Clinical Decision Support Tool for Pharmacist-Led Antimicrobial Stewardship in Patients with Normal Procalcitonin

Presenter(s): Mark Ridder MD (2nd Yr Fellow); Kelly Cawcutt MD: The Buck Stops Here. PICC Line Utilization: Stewardship Is Not Only About Antimicrobials Any More

Presenter(s): Brett Young PharmD (Pharmacy Resident); Scott Bergman, PharmD; Nico Cortes-Penfield MD; Trevor Van Schooneveld, MD; Bryan Alexander, PharmD: Evaluation of addition of outpatient parenteral antimicrobial therapy and orthopedic ID resources to transitions-of-care outcomes

Presenter(s): Claire Ferguson (Medical Student); Scott Bergman, PharmD; Jennifer Cavalieri; Mark Rupp, MD; Trevor Van Schooneveld, MD; Salman Ashraf MD: Assessment of the Long-Term Effects of Training Consultant Pharmacists to Promote Antimicrobial Stewardship in Long-Term Care Facilities

Co-Author: Nico Cortes-Penfield MD: Impact of #idjclub, a synchoronous twitter journal club, as a novel Infectious Disease education platform

Co-Author: Jasmine Marcelin, MD: In their own words: a Qualitative Analysis of Factors Contributing to Gender Bias in Academic Advancement in Infectious Disease

Presenter(s): Mackenzie Keintz MD (IM Resident); Jasmine Marcelin, MD, Bryan Alexander PharmD, Trevor Van Schooneveld MD, Scott Bergman PharmD, Erica Stohs MD: Impact Of Clinician Specialty on the Use of Oral Antibiotic Therapy for Definitive Treatment of Uncomplicated Bloodstream Infections

Co-Author: Jonathan Ryder (1st yr ID Fellow): A Retrospective Cohort Study of Treatment Patterns and Clinical Outcomes in Patients with COVID-19

Co-Author: Jasmine Marcelin MD: Equity in academic advancement: findings from an IDSA-sponsored survey of infectious disease physicians

Presenter(s): Bryan Alexander PharmD; Trevor Van Schooneveld MD; Scott Bergman PharmD; Nico Cortes-Penfield MD: Significant Institutional Cost Savings from OPAT-Facilitated Discharge for Patients with Challenging Situations

Presenter(s): Clayton Mowrer MD (2nd Yr ID Fellow); Erica Stohs MD, Trevor Van Schooneveld MD: Evaluation of Surgical Site Infections in Solid Organ Transplant Recipients with Beta-Lactam Allergies

Presenter(s): Wilfredo Lopez (medical student); Sara Bares MD; Nada Fadul MD: Lung Cancer Screening in at-risk patients with HIV in a Midwestern Clinic

Co-Author: Trevor Van Schooneveld: #BeASteward: Transforming Infectious Diseases Fellows Into Antimicrobial Stewards Using the IDSA Antimicrobial Stewardship Curriculum

Presenter(s): Jasmine Marcelin MD; Kelly Cawcutt MD: Trends in Speaker Representation at the Infectious Diseases Society of America (IDSA) ID Week Conference, 2013-2019

Presenter(s): Casey Zelus MD (1st yr ID Fellow); Andre Kalil MD; Trevor Van Schooneveld MD; Jasmine Marcelin MD; Kelly Cawcutt MD: Pneumonia due to Co-Infection in the ICU: Detection and Clinical Significance

Congratulations to all of our presenters, and we hope everyone enjoys #IDWeek2020!

Welcoming our New Infectious Diseases PGY-2 Pharmacy Resident

We are excited to welcome Molly Miller PharmD as a new PGY-2 in our ID Pharmacy Residency Program! She’s the second ID Pharmacy resident we have had and a fantastic addition to our team! Read on to learn a little more about her…

Tell us about the position you recently started
I recently started as a second-year pharmacist resident specializing in infectious diseases. This year I will dive deeper into the complexities of infectious diseases and their treatments through rounding with the inpatient infectious diseases consult services (including general, orthopedic, oncology, transplant, and pediatric infectious diseases), acting as part of the Antimicrobial Stewardship Program, and participating in various outpatient and outreach activities, including HIV clinic, the Outpatient Parenteral Antimicrobial Therapy (OPAT) program, and community outreach stewardship.

Tell us about your background
I grew up in rural Nebraska on an acreage with my family (and lots of farm animals) and graduated from Arlington High School. I completed my undergraduate degree in chemistry at the University of Nebraska-Lincoln and went on to obtain my Doctor of Pharmacy degree from the University of Nebraska Medical Center. I completed my Post Graduate Year 1 (PGY1) pharmacy residency at Nebraska Medicine. You could say I bleed Husker red.

Why did you choose to come work at UNMC
My training as a student and as a PGY1 pharmacy resident at Nebraska Medicine ignited my passion to continue my training as a PGY2 infectious diseases resident. The program here provides an excellent learning environment with the variety of ID consult teams and diverse patient populations. Here, I get to be an integral part of a rounding consult team and to work with some of the top infectious diseases clinicians in the nation who care not only about providing extraordinary patient care, but also about teaching and developing the next generation of infectious diseases clinicians. I also find the opportunity to train in an IDSA-designated Antimicrobial Stewardship Center of Excellence extremely valuable, as I have a strong passion for antimicrobial stewardship. The excellent preceptors and family atmosphere provided by the program create an unmatched environment in which to learn and grow, and I consider it the utmost privilege to have the opportunity to complete my training here. There truly is no place like Nebraska.

What makes you excited about working in ID
My passion for infectious diseases pharmacy has grown undeniably strong throughout my pharmacy training. I am fascinated by the complexity of infectious diseases and the associated treatment modalities. Each patient case is a unique puzzle to solve with many different pieces to carefully consider and fit into place. The field will constantly evolve as drug-resistant infections continue to emerge, necessitating the generation of new strategies and medications to treat these serious infections. This creates endless opportunities for pharmacists to exercise and develop their ingenuity and critical thinking skills, which I find extremely exciting.

Tell us something about yourself that is unrelated to medicine
I am an animal lover and enjoy spending time visiting my family and all the animals on my parents’ acreage on my free weekends. Someday I hope to have as many animals of my own (good thing my husband is a veterinarian), but for now we just have a mini Australian shepherd named Bella and an orange tabby cat named Boo.

Learn more about the Nebraska Medicine ID Pharmacy Residency Program here

#PharmToExamTable: Treatment of Clostridioides difficile infection in adults: What is the evidence supporting a tapered vancomycin regimen?

This is a continuation of this month’s #PharmToExamTable question about C. difficile treatment, answered by Andre Wilt, PharmD 2020 Graduate of UNMC College of Pharmacy, who is now a pharmacy manager at PharmScript

(Reviewed by Scott Bergman PharmD and Andrew Watkins PharmD)

In the last blog post published on September 8, 2020, we reviewed the The Infectious Disease Society of America (IDSA) recommendations for diagnosis and treatment of non-severe Clostridioides difficile infection (CDI), severe CDI, fulminant CDI, and recurrent CDI. In this post, we evaluate the evidence to support the recommendation for use of a tapered oral vancomycin regimen for recurrent CDI.

The first evidence for an oral vancomycin tapered regimen was reported by Tedesco et. al in a 1985 observational report.6-7 This retrospective case series included 22 patients with 17 having a baseline of ≥3 CDI relapses. The patients were subject to an oral vancomycin regimen similar to the one eventually recommended in the IDSA guidelines consisting of 125 mg twice daily for 7 days, 125 mg once daily for 7 days, 125 mg once every 2 days for 7 days, then 125 mg every 3 days for 14 days. All patients were diarrhea-free within 72 hours of completion and relapse free at a mean of 6 months.

The second report of evidence for a tapered vancomycin regimen was published by McFarland et. al in 2002. This retrospective case series studied 163 patients with 29 and 7 cases attributed to tapered and pulsed oral vancomycin regimens, respectively. The study population had a mean baseline of 3.2 prior CDI episodes. Patients were subject to receive low, medium or high doses of either metronidazole or oral vancomycin. Patients with treatment failure were subject to a subsequent tapered or a pulsed regimen with the same antibiotic. Statistically fewer recurrences occurred in the oral vancomycin tapered [9/29 (31%), p = 0.01] and pulsed [1/7 (14.3%), p = 0.02] regimens compared to medium dose (1-2 g/day) oral vancomycin alone [10/14 (71.4%)]. Additionally, fewer occurrences occurred in the tapered and pulsed regimens compared to the low dose (<1 g/day) oral vancomycin regimen [26/48 (54.2%)] and high dose (≥2 g/day) oral vancomycin regimen [9/21 (42.9%)].

Additional evidence for tapered oral vancomycin regimens from observational studies were reported by Bakken in 2014 and Sirbu et. al in 2017. The prospective case series from Bakken studied 25 patients using a tapered and pulse vancomycin or metronidazole regimen in addition to lifeway kifer, a fermented dairy product containing probiotics. The study population had a mean baseline of 4 CDI relapses. The 21 patients subject to an oral vancomycin taper and pulse planned over 8 weeks had a regimen consisting of: 125 mg every 6 hours for 14 days, 375 mg every 72 hours for 14 days, 250 mg every 72 hours for 14 days, then 125 mg every 72 hours for 14 days. Of the patients receiving vancomycin, 17 (81.0%) were cured and remained diarrhea-free at least 9 months after intervention.

The retrospective case series from Sirbu et. al studied 100 patients using two different tapered and pulsed oral vancomycin regimens. The study population had a mean baseline of 3.15 prior CDI episodes. Both study groups were subject to oral vancomycin four times daily for 10-14 days followed by tapering to twice daily dosing for 7 days, once daily dosing for 7 days, then every other day dosing for at least 2 weeks. One treatment group was subject to additional dosing every 3 days for at least 2 weeks. Patients who received dosing every other day plus additional dosing every 3 days had higher cure rates [52/64 (81.1%)] compared to patients who only received every other day dosing [22/36 (61.1.%)]. There was a higher cure rate in patients with ≤2 prior CDI episodes [56/71 (81.1%)] compared to those with >2 prior CDI episodes [18/29 (62.1%)].

Evidence in a randomized controlled trial for tapered oral vancomycin was reported by Hota et. al. This prospective, open-label study evaluated 30 patients subject to treatment with vancomycin plus either a taper and pulse or a fecal transplant. The study population had a baseline of ≥2 prior CDI episodes. Both study groups were initially treated with oral vancomycin 125 mg four times daily for 14 days. One group received a fecal transplant enema 48 hours after discontinuing vancomycin, while the other group was given a vancomycin taper and pulse regimen consisting of: 125 mg twice daily for 7 days, 125 mg once daily for 7 days, 125 mg every other day for 7 days, then 125 mg every 3 days for 7 days. The primary outcome was recurrence of symptomatic, laboratory-confirmed CDI within 120 days of the intervention. More patients experienced CDI recurrence in the fecal transplant group [9/16 (56.2%)] than in the vancomycin taper group [5/12 (41.7%)], which correlated to a 43.8% and 58.3% resolution in symptoms, respectively.

The current data from four observational studies and an open-label clinical trial supports recurrent CDI success rates ranging from 58-100% when using oral vancomycin tapered and pulsed regimens. Dosing regimens from these studies were adopted in the IDSA guidelines for recurrent CDI. However, for recurrent CDI episodes, the IDSA classifies the strength of vancomycin tapered and pulsed regimens as weak with a low quality of evidence. These recommendations were based on the limitations of data being primarily from observational studies and small sample sizes of patients. In the future, more randomized controlled trials with larger sample sizes should be conducted to compare with the evidence presented in the previous studies. Overall, evidence supports the use of vancomycin taper regimens in recurrent CDI.

References
1. Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L, eds. Pharmacotherapy: A Pathophysiological Approach, 10th ed. New York, NY: McGraw-Hill; 2017.
2. Lamont JT, Kelly CP, Bakken JS (2018). Clostridioides (formerly Clostridium) difficile infection in adults: Clinical manifestations and diagnosis. UpToDate. Retrieved March 22, 2020.
3. Lamont JT, Kelly CP, Bakken JS (2020). Clostridioides (formerly Clostridium) difficile infection in adults: Treatment and prevention. UpToDate. Retrieved March 22, 2020.
4. McDonald LC, Gerding DN, Johnson S, et. al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):1-48.
5. Tedesco FJ, Gordon D, Fortson WC. Approach to patients with multiple relapses of antibiotic-associated pseudomembranous colitis. Am J Gastroenterol. 1985;80(11):867-868.
6. McFarland LV, Elmer GW, Surawicz CM. Breaking the cycle: Treatment Strategies for 163 Cases of Recurrent Clostridium difficile Disease. Am J Gastroenterol. 2002;97(7):1769-1775.
7. Murphy MM, Patatanian E, Gales MA. Extended duration vancomycin in recurrent Clostridium difficile infection: a systematic review. Ther Adv Infectious Dis. 2018;5(6):111-119.
8. Bakken JS. Staggered and Tapered Antibiotic Withdrawal with Administration of Kefir for Recurrent Clostridium difficile Infection. Clin Infect Dis. 2014;59(6):858-861.
9. Sirbu BD, Soriano MM, Manzo C, et al. Vancomycin Taper and Pulse Regimen with Careful Follow-up for Patients with Recurrent Clostridium difficile Infection. Clin Infect Dis. 2017;65(8):1396-1399.
10. Hota SS, Sales V, Tomlinson G, et al. Oral vancomycin Followed by Fecal Transplantation Versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection: an Open-label, Randomized Controlled trial. Clin Infect Dis. 2017;64(3):265-271.

#PharmToExamTable: Treatment of Clostridioides difficile infection in adults: Guideline review

This month’s #PharmToExamTable question was answered by Andre Wilt, PharmD 2020 Graduate of UNMC College of Pharmacy, who is now a pharmacy manager at PharmScript

(Reviewed by Scott Bergman PharmD and Andrew Watkins PharmD)

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea in healthcare settings. The pathogenesis of CDI begins as an ingestion of toxigenic C. difficile spores which colonize the colonic microbiota (flora). Exposure to antibiotics, particularly clindamycin, fluoroquinolones, and cephalosporins leads to a disruption of the normal colonic microbiota. This disruption causes C. difficile overgrowth and production of exotoxin A and B, leading to manifestations of diarrhea and inflammation of the colon (colitis). CDI is defined as 3 or more unformed stools within 24 hours, during or after antibiotic use, that presents with diarrhea, fever, leukocytosis or abdominal pain. Diagnosis includes the presence of symptoms, a stool test positive for C. difficile toxins or detection of toxigenic C. difficile. CDI severity can range from mild to moderate (non-severe), severe and fulminant colitis (severe with complications). Common risk factors for CDI and recurrent episodes include antibiotic usage, advanced age and gastric acid suppression. The most important initial step in treatment is to discontinue offending antibiotic agents. However, after discontinuing the offending agents, treatment regimens for CDI include oral vancomycin, fidaxomicin, metronidazole and fecal microbiota transplantation specific to severity and recurrence.

Non-severe CDI is clinically defined as leukocytosis with a white blood cell (WBC) count of ≤15,000 cells/mL and an absolute serum creatinine level <1.5 mg/dL. The Infectious Disease Society of America (IDSA) recommends treatment of an initial non-severe CDI episode with either oral vancomycin 125 mg given four times daily for 10 days or fidaxomicin 200 mg given twice daily for 10 days. Alternatively, IDSA recommends treatment with oral metronidazole 500 mg three times daily for 10 days only if access to vancomycin or fidaxomicin is limited.

Severe CDI is clinically defined as leukocytosis with a WBC count of >15,000 cells/mL and an absolute serum creatinine level ≥1.5 mg/dL. For both non-severe and severe CDI, the serum creatinine values are based on absolute values and not in comparison to baseline values, as these are not always available. These criteria do not perform well in patients with chronic kidney disease and as a result further validation is needed. Similar to non-severe CDI, IDSA recommends treatment of an initial severe CDI episode with either oral vancomycin 125 mg given four times daily for 10 days or fidaxomicin 200 mg given twice daily for 10 days.

Fulminant CDI is clinically defined as the presence of hypotension or shock, ileus (intestinal obstruction/immobility) or toxic megacolon. The IDSA preferred regimen for an initial fulminant CDI episode is vancomycin 500 mg four times daily by mouth or nasogastric tube. Alternatively, rectal administration of vancomycin can be considered if ileus is present. Additionally, IDSA recommends the administration of intravenous metronidazole 500 mg three times daily with either oral or rectal vancomycin, especially with the presence of an ileus.

The IDSA guidelines reflect the use of a tapered and/or pulsed vancomycin regimen for the treatment of recurrent CDI. Tapered vancomycin regimens include dosing up to four times daily with a decrease in dosing frequency over several weeks. Pulsed vancomycin dosing regimens include a single dose given every 2-3 days for up to 2-8 weeks. The treatments can be performed in sequentially with a tapered regimen followed by pulsed dosing . The process of a tapered and/or pulsed vancomycin regimen is intended to target the elimination of C. difficile spores. The cycle of increasingly long antibiotic-free periods allows spores to germinate and the pulses of antibiotics eliminate newly germinated vegetative cells.

The IDSA recommends three separate treatment strategies for the first recurrent CDI episode. If metronidazole was used for the initial episode, treatment with the standard CDI regimen of oral vancomycin is recommended. Similarly, if vancomycin was used for the initial episode, treatment with the standard fidaxomicin regimen is recommended. If vancomycin was used for the initial episode, a prolonged taper and pulsed oral vancomycin regimen is recommended. The dosing regimen is as follows: oral vancomycin 125 mg four times daily for 10-14 days, oral vancomycin 125 mg two times daily for 7 days, oral vancomycin 125 mg once daily for 7 days, and then oral vancomycin 125 mg once every 2 or 3 days for 2-8 weeks.

The IDSA preferred treatment for two or more recurrent episodes is a fecal microbiota transplantation. Alternative treatments include again include a tapered and pulsed vancomycin regimen, or a course of vancomycin followed by a “chaser” of oral rifaximin or fidaxomicin.
Evidence for the treatment of CDI using a vancomycin tapered regimen was only studied for recurrent CDI in the primary literature. These included 4 observational studies and 1 clinical trial.

The next blog post will review the evidence to support using tapered oral vancomycin regimens for treatment of recurrent CDI.

Welcoming our New Infectious Diseases Fellows: Dr. Casey Zelus

We are excited to welcome Dr. Casey Zelus as a new fellow in our Infectious Diseases program! Read on to learn a little more about her…

Dr. Zelus…with a bagel she baked herself…that is as big as her face!

Tell us about the about the position you are starting
I just started a two year Infectious Disease Fellowship at UNMC, where I will get to explore the interaction between infectious microorganisms and the host immune system. Having recently finished my first month on UNMC’s busy inpatient General ID consult service – was a whirlwind! I’m thrilled with my decision to pursue ID and looking forward to the adventure.

Tell us about your background
I was born in Seattle Washington, but spent the first half of my childhood in Madison, Wisconsin before moving to Denver, Colorado. The allure of Los Angeles lead me to attend undergrad at Loyola Marymount University where I obtained my degree in biochemistry. After 5 years of LA traffic I moved to Omaha, Nebraska to attend Creighton Medical School which is where I ended up meeting my significant other. We couples matched into residency at UNMC and decided to stay in Omaha!

Why did you choose to come work at UNMC
Interestingly, I ended up coming to UNMC because they have a phenomenal Emergency Medicine Residency! My significant other enjoyed his away rotation in UNMC’s ED so much we ended up couples matching into their IM and ED residencies. Initially I thought I would pursue Rheumatology, but abruptly changed my mind after a phenomenal ID rotation my intern year. I subsequently rotated on ID two more times during residency and enjoyed working with the UNMC ID family so much I wanted to stay for fellowship.

What makes you excited about working in ID
I love playing the role of detective and ID is a constant stream of intellectual mysteries that need solving! As I became more involved, I started to realize the broader global implications and profound impact of infectious disease specialists – from combating rising resistance as an antibiotic steward to investigating global pandemics. Combine that with minimal midnight trips to the hospital and the ability to maintain work-life balance, and it was the right choice for me.

Tell us something about yourself that is unrelated to medicine
When I was trying to learn how to bake bread a few years back, I had a terrible time trying to figure out how to make sourdough (one of my favorites)! Finally after some YouTube videos and googling, it turns out I needed to make my own sourdough starter instead of a pack of yeast from the store! Mix some flour and water, then after a few days in a cupboard – voila! Your very own yeast starter. Caution: use a container much bigger than your initial mixture and give it plenty of room to grow, or risk some messy, yeasty clean up!

Learn more about the UNMC Infectious Diseases Fellowship here

Welcoming our New Infectious Diseases Fellows: Dr. Jonathan Ryder

We are excited to welcome Dr. Jonathan Ryder as a new fellow in our Infectious Diseases program! Read on to learn a little more about him…

Dr. Ryder exploring the Henry Doorly Zoo in Omaha, NE.

Tell us about the position you are starting
I am starting as a first-year infectious diseases fellow at University of Nebraska Medical Center (UNMC). I will be spending the next two years learning the vast field of infectious diseases through inpatient consultation and outpatient clinics. I will be learning how to improve human health by understanding the biology and pathophysiology of bacteria, viruses, fungi, and parasites as well as the pharmacology of antimicrobials.

Tell us about your background
I was born and raised in central Missouri, graduating from Jefferson City High School. I completed my Bachelor of Science in Biology and History at Truman State University in Kirksville, Missouri. During my time in college, I attended a summer research program at UNMC. I subsequently attended medical school at UNMC, graduating in 2017. I then left UNMC for Indiana University School of Medicine for internal medicine residency. Now, I have circled back for my third stent at UNMC for my infectious disease fellowship!

Why did you choose to come work at UNMC
As previously mentioned, I attended UNMC for medical school and prior to that, a summer research program in undergraduate training. I grew fondly of the city of Omaha during my time here, which I find to be an underrated gem in the Midwest. Omaha has many of the exciting features of a larger city, while having the convenience of a smaller town. Omaha has a great food scene, excellent amateur & college sports atmosphere, extensive bike & running trails, Broadway musicals, affordable cost-of-living, quick commutes, and of course, everyone loves the zoo! Along with Omaha being fun, my wife is also from Nebraska, so being closer to family & having job opportunities was important.

In my opinion UNMC is truly the star of Omaha. UNMC has a world class infectious diseases faculty with leaders in emerging infectious pathogens such as Ebola, biocontainment expertise, HIV treatment, antimicrobial stewardship, and more. The division has grown considerably and continues to do so, as does the entire UNMC campus, which always is adding new buildings!

Lastly, the fellowship program in infectious diseases at UNMC has amazing leadership with a well-balanced curriculum. There is strong emphasis in developing clinical skills while providing ample opportunities for research as well. There is training in general ID, solid organ transplant ID (including liver, kidney, heart, lung, and small bowel/multivisceral), oncology/hematopoietic stem cell transplant ID, orthopedic ID, HIV clinic, infection prevention, and antimicrobial stewardship. This breadth and depth of opportunities was hugely attractive to me for choosing UNMC.

What makes you excited about working in ID
The field of infectious diseases offers so many unique opportunities to me. First, I am quite inquisitive, and the field of infectious diseases challenges my curiosity each day. Infectious diseases is often consulted for some of the more complicated cases in the hospital that either have diagnostic dilemmas or therapeutic challenges. Second, there are many opportunities for practice modalities in infectious disease including academic, group practice, inpatient consultations, HIV clinician, transplant ID, antimicrobial stewardship, etc. The ability to have many options now and in the future allows career flexibility and opportunity. Finally, I truly find the diversity of infectious pathogens to be fascinating, especially the interactions of humans with their environment, ecological impacts of antimicrobials, and evolutionary mechanisms that effect human health.

Tell us something about yourself that is unrelated to medicine
I am unabashedly a huge professional football nerd and Kansas City Chiefs fanatic. You will find me on my couch screaming at the TV nearly every Sunday in the fall and on occasion tailgating with some BBQ. My wife and I are foodies who enjoy adventure and travel. I love to sit down with a good history book on a quiet evening. I am quite active on Twitter (I actually have 2 accounts, one for football and one for #IDTwitter), so follow me @JonathanRyderMD!

Learn more about the UNMC Infectious Diseases Fellowship here.

Our Fellowship Leaders can’t wait to review your applications!

Fellowship application season is open and as the leaders of our ID fellowship, we wanted to highlight some of the exciting aspects of our program. Our program and our division are growing. We began in 2011 with 2 fellows, grew to 4 in 2017, 5 in 2020, and are planning to expand to six fellows by 2021. Our faculty also continues to grow, as we now have 23 physician faculty and 4 full time ID pharmacists with diverse expertise. Dr. Trevor Van Schooneveld has been the Program Director and Director of the Antimicrobial Stewardship program. Dr. Zimmer is Associate Program Director and also the director of the Oncology ID program. This year we are looking forward to meeting you on our remote interviews via zoom!

First year fellow Dr. Casey Zelus teaching medical students about blood cultures

Fellows at UNMC enjoy a robust clinical experience that includes not only the typically complex patients seen at a tertiary referral center, but also includes extensive experience caring for immunosuppressed patients. In addition to our General ID service, where our fellows gain experience in teaching medical students and Internal Medicine residents, we have two separate immunocompromised services that care for oncology and solid organ transplant patients. We also have an orthopedic infectious diseases rotation where fellows gain experience managing these complex patients and work with faculty who have extensive experience in this area. We have expanded our ambulatory offerings with the creation of a non-tuberculous mycobacteria (NTM) clinic and a travel clinic. Fellows have the opportunity to spend time in the microbiology laboratory, as well as learn infection control and antimicrobial stewardship. The faculty at UNMC are nationally recognized experts in their field, and are also very approachable and devoted to the education and success of trainees. They have created extensive educational opportunities, covering topics from opportunistic infections in solid organ and hematopoietic stem recipients to emerging global pathogens and biopreparedness. Fellows gain knowledge in HIV/AIDS management working in our multidisciplinary HIV clinic which cares for over 1200 people with HIV. In addition to having access to world class ID expert antimicrobial stewardship, OPAT, and HIV pharmacists, our division also includes an ID pharmacy residency program and opportunities for research collaboration and rounding with pharmacy students, residents and faculty.

As new career opportunities develop for ID physicians, we have worked to provide our fellows with the skills to engage in these fields. UNMC ID fellows receive extensive experience in the area of infection control and antimicrobial stewardship. UNMC also offers the opportunity to stay for an option third year to further develop a research portfolio or pursue additional clinical expertise in subspecialty areas.

Recent graduate Dr. Raj Karnatak presenting his research

An important part of fellowship is developing skills in interpreting and performing research, and we provide our fellows with six months of mentored research experience centered on their career goals. A research committee assists fellows in mentor identification and project development. Fellows also participate in a week-long UNMC sponsored research training program, and typically present their work at national conferences like IDWeek and SHEA.

Our goal as program directors is to provide fellows with an educational experience that provides them with skills and knowledge to make them successful in whatever career path they choose. The opportunities available to ID physicians continue to expand and we hope you will consider UNMC ID. If you are interested in more information, please feel free to visit our website where you can check out a video to learn more about us. You can also contact us at the following:

Dr. Trevor Van Schooneveld
Program Director, Infectious Diseases Fellowship
Medical Director, Antimicrobial Stewardship Program
University of Nebraska Medical Center
985400 Nebraska Medical Center
Omaha, NE 68198-9400
Email: tvanscho@unmc.edu

Dr. Andrea J. Zimmer
Associate Program Director, Infectious Diseases Fellowship
Director, Oncology Infectious Diseases
University of Nebraska Medical Center
985400 Nebraska Medical Center
Omaha, NE 68198-9400
Email: andreaj.zimmer@unmc.edu

Welcoming our new Infectious Diseases Fellows: Dr. Laura Selby

We are excited to welcome Dr. Laura Selby as a new fellow in our Infectious Diseases program! Read on to learn a little more about her…

Dr. Selby enjoying the Henry Doorly Zoo!

Tell us about the position you are starting
I am starting a 2 year fellowship program to become a board certified Infectious Diseases physician. Infectious Diseases is a subspecialty of internal medicine that focuses on taking care of patients with complex infections, such as bacteremia (infections of the blood), HIV, tick borne illness, and now COVID-19.

Tell us about your background
I was born and raised in a small town in Oregon and grew up on a multigenerational farm. I completed my undergraduate degree in chemistry at Westmont College in Santa Barbara California. I returned to Oregon for medical school and residency in Internal Medicine at Samaritan Health Services, a small community based residency program in Corvallis, Oregon.

Why did you choose to come work at UNMC
I chose to come to UNMC for many reasons, but the primary reason was for the world class training they offer. I never imagined myself moving to Nebraska, but when I came to interview the faculty, facilities, clinical training opportunities, and friendliness of the department was something I couldn’t pass up. I am excited to spend two years training at UNMC and getting to care for Infectious Disease patients in the Omaha area.

What makes you excited about working in ID
Infectious Diseases is one of the few medical specialties that relies heavily on both cutting-edge medical testing but also on good old-fashioned history and physical exam. Taking time to talk to my patients, learning about their history, family, and activities often provides vital clues to the type of infections they are at risk for. At the same time, needing to understand the intricacies of the newest medical diagnostic technologies, makes infectious diseases a fast-paced and fascinating field.

I love getting to work as part of a multidisciplinary team to take care of the sickest patients in the hospital. Infections remains a leading cause of death in hospitalized patients in the United States and worldwide. Severe infections affect patients who are healthy and also those with every known chronic condition, so even while working as an ID physician, I still have to understand the pathology and pathogenesis of non-infectious conditions. As the current COVID-19 pandemic has shown, the areas of research for infectious diseases are endless, and I look forward to participating in research opportunities during my fellowship training and beyond.

Tell us something about yourself that is unrelated to medicine
As I have called the pacific-northwest home for most of my life, I love to camp and hike. My favorite place to hike in the country is Glacier National Park in Montana; the only downside is the high number of bears that share the trails. I am looking forward to exploring a new area of the country during my time at UNMC.

Learn more about the UNMC Infectious Diseases Fellowship here.

What is the optimal dosing of daptomycin for VRE bacteremia?

This month’s #PharmToExamTable question was answered by Xiaoxiao (Monica) Qi, PharmD 2020 UNMC graduate who is pursuing a PGY1 Pharmacy Residency at Avera McKennan Hospital and University Health Center in Sioux Falls, SD.
It was reviewed by:
Scott Bergman, PharmD, BCPS, BCIDP – Antimicrobial Stewardship Coordinator at Nebraska Medicine and Clinical Associate Professor at UNMC College of Pharmacy
Andrew Watkins, PharmD – PGY2 Infectious Diseases Pharmacy Resident at Nebraska Medicine

In healthcare settings, infections due to vancomycin-resistant enterococci (VRE) are commonly encountered. Up to 31% of all enterococcal isolates are vancomycin-resistant in U.S. hospitals(1-4). Bloodstream infection caused by vancomycin-resistant enterococci (VRE) has been associated with higher morbidity, mortality, and prolonged hospital stay(2). Given that very few antibiotics with activity against VRE have been evaluated in the treatment of bacteremia clinically, the options for VRE bloodstream infection are limited. Thus, vancomycin-resistant enterococcal bloodstream infections (VRE-BSIs) are uniquely difficult to treat (5). Currently, only linezolid is approved by the US FDA for treating such a condition, but it does have a few limitations: linezolid resistance has emerged; prolonged use can lead to thrombocytopenia; it’s mechanism of action is bacteriostatic and the clinical success rate of treating VRE bacteremia varies. Recent clinical studies have shown improved clinical and microbiologic outcomes associated with daptomycin over linezolid in VRE-BSI (6).

Daptomycin is an antibiotic that is approved by the FDA for the treatment of bacteremia and right-sided infective endocarditis caused by Staphylococcus aureus (7). Daptomycin exhibits concentration-dependent bactericidal activity against gram-positive pathogens. The pharmacodynamic parameters of such activities are maximum concentration (Cmax)/minimum inhibitory concentration (MIC) or area under the concentration-time curve (AUC)/MIC ratios.5 Although it is not approved by the FDA for the treatment of bacteremia caused by Enterococcus spp., it has both in vitro and in vivo activity against this organism. It could be used in certain conditions, such as prolonged VRE bacteremia endocarditis, where a bactericidal agent is preferred. The usual dose of daptomycin for MRSA bloodstream infections is 6 mg/kg/day (7). However, VRE isolates generally demonstrate MICs 2- to 4-fold higher than those of S. aureus (5). The susceptible breakpoint of daptomycin for Enterococcus spp. has been ≤4 mg/L compared to <1 mg/L for Staphylococci (1). In 2019, The Clinical and Laboratory Standards Institute (CLSI) revised the interpretive criteria of daptomycin for Enterococcus faecium to be called “susceptible dose-dependent” (SDD) at MICs ≤4 mg/L. This is because of the epidemiological profile of the organism, new PK/PD data, emergence of daptomycin-resistant Enterococci, and clinical studies that rendered the previous interpretation of susceptible no longer appropriate for this species. The susceptible dose-dependent (SDD) category is used when susceptibility of an isolate depends on the dosing regimen used (8). For E. faecium, an increased daptomycin dosage of 8–12 mg/kg/day is recommended to treat the organism since it has naturally higher MICs and the pharmacokinetics(PK)/pharmacodynamics (PD) of daptomycin can be optimized with peak serum concentrations increasing linearly with the dose.

Both in-vivo and in-vitro studies have demonstrated that using higher dosages of daptomycin increased both the degree and speed of bactericidal activity (1,5,7). One study compared in vitro activity of daptomycin at 6 vs. 10 mg/kg/day towards vancomycin-resistant Enterococcus faecium and showed that the higher dosage achieved a more rapid and greater reduction in bacteria (p 6 mg/kg) in two-hundred and forty-five patients were evaluated. Overall, 204 (83%) of all identified Enterococcus faecium were VRE. One-hundred and seventy-three patients (70.3%) had enterococcal bloodstream Infection. The median dose and duration of high dose-daptomycin was 8.2 mg/kg/day (IQR 7.7-9.7) and 10 days (IQR 6-15), respectively. The overall clinical success rate was 89% and microbiological eradication was observed in 93% of patients. This study showed that a high frequency of clinical success and microbiological eradication in patients treated with high-dose daptomycin for enterococcal infections, even in patients with complicated and difficult to treat infections. In terms of safety, no high-dose daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic (10).

Another retrospective cohort study on comparison of different doses for daptomycin has been done in patients hospitalized at Veterans Affairs facilities with VRE-BSI. Britt et al. compared standard-dose (6 mg/kg total body weight), medium-dose (8 mg/kg total body weight), or high-dose (≥10 mg/kg total body weight) daptomycin. A total of 911 patients were included (standard dose, n = 709; medium dose, n = 142; high dose, n = 60). Compared to high-dose daptomycin, both standard-dose and medium-dose daptomycin were associated with worse survival (adjusted HR [aHR], 2.58; P = 0.004). This association persists after adjustments of confounders. High-dose daptomycin was associated with significantly improved microbiological clearance. There was no difference in the risk of CPK elevation among the treatment groups. Despite the comparatively low number of patients that received high-dose daptomycin, the authors concluded that it was associated with improved survival and microbiological clearance in VRE-BSI (5).

A systematic review and meta-analysis was performed on the efficacy and safety of daptomycin versus linezolid in 2019. According to the sub-group analysis, high-dose daptomycin showed an increase in use from 6% in 2006 to 34% in 2012 and corresponding improved mortality benefits, which supports that a high-dose may be beneficial for the treatment of VRE bacteremia (11).

In conclusion, VRE isolates generally have MICs 2- to 4-fold higher than those of S. aureus and are now classified as “Susceptible Dose-Dependent” up to an MIC of 4 mg/L by the CLSI. Based on its concentration-dependent bactericidal activity, high-dose daptomycin (8-12 mg/kg) is needed to optimize pharmacodynamic (PD) parameters of Cmax and AUC over MIC. Current clinical data have shown that high-dose daptomycin is beneficial for the treatment of VRE bacteremia. Although high-dose daptomycin may raise a concern of more CPK elevation, it does not necessarily lead to more severe skeletal muscle toxicity or discontinuation of daptomycin.

References:
1. King EA, McCoy D, Desai S, Nyirenda T, Bicking K. Vancomycin-resistant enterococcal bacteremia and daptomycin: are higher doses necessary? J Antimicrob Chemother 2011 Sep 1;66(9):2112-8.
2. Sader HS, Jones RN. Antimicrobial susceptibility of Gram-positive bacteria isolated from US medical centers: results of the Daptomycin Surveillance Program (2007–2008). Diagn Microbiol Infect Dis. 2009;65:158-62.
3. Casapao AM, Kullar R, Davis SL, Levine DP, Zhao JJ, Potoski, B, et al. Multicenter study of high-dose daptomycin for treatment of enterococcal infections. Antimicrob Agents Chemother 2013 Sep 1;57(9):4190-6.
4. Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial Bloodstream Infections in US Hospitals: Analysis of 24,179 Cases from a Prospective Nationwide Surveillance Study. Clin Infect Dis 2004; 39: 309–17. https://doi.org/10.1086/421946
5. Britt NS, Potter EM, Patel N, Steed ME. Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients. Clin Infect Dis 2017;64(5):605–13.
6. McKinnell JA, Arias CA. Editorial commentary: linezolid vs daptomycin for vancomycin-resistant enterococci: the evidence gap between trials and clinical experience. Clin Infect Dis 2015; 61:879–82.
7. Daptomycin. [Clinical pharmacology]. Elsevier. Tampa (FL): Daptomycin indications. [cited 2020 Mar 13]
8. Satlin MJ, Nicolau DP, Humphries RM, et al. Clinical and Laboratory Standards Institute Subcommittee on Antimicrobial Susceptibility Testing and Ad Hoc Working Group on Revision of Daptomycin Enterococcal Breakpoints, Development of Daptomycin Susceptibility Breakpoints for Enterococcus faecium and Revision of the Breakpoints for Other Enterococcal Species by the Clinical and Laboratory Standards Institute, Clin Infect Dis 2020; 70:1240–46, https://doi.org/10.1093/cid/ciz845.
9. Akins RL, Rybak MJ. Bactericidal Activities of Two Daptomycin Regimens against Clinical Strains of Glycopeptide Intermediate-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus faecium, and Methicillin-Resistant Staphylococcus aureus Isolates in an In Vitro Pharmacodynamic Model with Simulated Endocardial Vegetations. Antimicrob Agents Chemother. 2001 Feb; 45 (2): 454-459.
10. Gonzalez-Ruiz A, Seaton A, Hamed K. Daptomycin: an evidence-based review of its role in the treatment of Gram-positive infections. Infect Drug Resist. 2016;9:47-58. https://doi.org/10.2147/IDR.S99046
11. Shi C, Jin W, Xie Y, Zhou D, Xu S, Li Q, et al. Efficacy and safety of daptomycin versus linezolid treatment in patients with vancomycin-resistant enterococcal bacteraemia: an updated systematic review and meta-analysis. J Glob Antimicrob Resist 2019 Oct 17.

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