Division of Infectious Diseases

M4 Students in our HIV Enhanced Education Track present Capstone Projects and Celebrate MATCH DAY!

The UNMC College of Medicine offers a unique Enhanced Medical Education Track (EMET) program which provides an opportunity for medical students to delve into particular disciplines of interest in the field of medicine throughout their four year degree program. Track students attend seminars, preceptorships and complete a research project culminating in a poster or conference presentation. The EMET program is co-directed by Drs. Sara Bares, Jasmine Marcelin and Nada Fadul.

Yesterday, on the eve of their Match Day, our two M4 Students, Bianca Christensen and Travis Schreier (under the mentorship of Dr. Susan Swindells and Dr. Sara Bares) presented their Capstone Projects at UNMC College of Medicine.

Today, after years of hard work, months of interviews, weeks of decision and the most anxiety-filled week of their lives, they found out where they will be spending the next few years of their lives as newly minted doctors.

Bianca’s project is a retrospective cohort study identifying the demographic features and virologic outcomes associated with health insurance enrollment among AIDS Drug Assistance (ADAP) participants in Nebraska. The study found that ADAP users who received insurance in addition to ART supply were more likely to achieve virological suppression than those who only received ART supply. She presented her capstone project at the the American Conference for the Treatment of HIV in Chicago in April 2018, and will be submitting her work for publication. You can read more information about Bianca hereBianca will be continuing her medical training in Boston with Pathology Residency at Massachusetts General! We wish her all the best!

Travis’ project looked at characterizing HIV practitioners’ recommendations regarding treatment as prevention, pre-exposure prophylaxis and condom use. The study found that most practitioners commonly or always recommend condoms despite the fact that most acknowledge the validity of data that successful treatment of HIV or use PrEP prevents transmission. Travis was the first author on the resulting paper entitled: “U.S. HIV practitioners’ recommendations regarding condom-free sex in the era of HIV pre-exposure prophylaxis and treatment as prevention“, published in Open Forum Infectious Diseases on February 21, 2019.   Travis will be staying here at UNMC to continue his medical training with a Pediatrics Residency!

Each year, our UNMC HIV clinic takes two medical students into the EMET track, and we look forward to working with them over the course of their undergraduate medical training to immerse them in HIV care and Infectious Diseases. We will soon be announcing our new M1 EMET students, who will start working with us over the coming summer.

Congratulations again to Bianca and Travis, we are proud of you! And congratulations to all M4s out there who found out where they matched today!

More information about the EMET program can be found here.


 

EMET Student Profile – Bianca Christensen

Our department is proud to participate in UNMC College of Medicine’s Enhanced Medical Education Track (EMET) program!  EMETs are enrichment opportunities to explore interdisciplinary fields of medicine with in small groups and with close faculty mentorship. Two students from each medical school class are selected to participate in our Comprehensive HIV Medicine EMET, a program that spans their four years in medical school and includes journal clubs, seminars, and clinical experiences culminating in a capstone project focused on an aspect of HIV care.  Today we’re excited to feature Bianca Christensen, an M4 completing her EMET experience!

What drew you to the HIV EMET program?

I have been interested in HIV since high school, and when I first learned about the HIV EMET program on my interview day at UNMC, I knew I wanted to apply for the program if accepted to UNMC. I wanted to learn more about the complexity of HIV, including both the social and biological factors involved in HIV medicine. The program also offered early clinical exposure, which introduced me to the role of the medical student on the patient care team.

What have you chosen to do for your capstone project?

My capstone project, a retrospective cohort study, sought to identify the demographic features and virologic outcomes associated with health insurance enrollment among AIDS Drug Assistance (ADAP) participants in Nebraska. I had the amazing opportunity to be mentored by Dr. Susan Swindells and to learn more about the impact of insurance enrollment on health outcomes (i.e. virologic suppression) for Nebraska ADAP recipients. It is well known that health insurance is associated with improved health outcomes, and that is no different for people living with HIV, but the relationship between ADAP-funded health insurance and virologic suppression hasn’t been well studied. My goal was to see if there was a difference between Nebraska ADAP participants that were enrolled in ADAP-funded health insurance and Nebraska ADAP participants that did not have health insurance but did receive ADAP-funded medications. Ultimately, I hoped my project would identify patients at risk for poor outcomes who may benefit from targeted outreach and increased support.

How do you think your experience will shape your practice of medicine in the future?

Although I may not interact directly with patients living with HIV in my future practice as a pathologist, my experience in the HIV EMET has provided me with the tools necessary to address the stigma surrounding HIV. I hope to practice in the global arena, specifically in resource-limited regions with underserved populations. When working with these populations, it is essential to understand not only the medical environment but also the social aspects related to disease. My experience in the HIV EMET has provided me with priceless tools to integrate these two components of patient care. I have also valued working with professionals from all threads of the HIV management web: physicians, social workers, pharmacists, nurses, researchers, advanced practice providers, clinical study coordinators, and community organizations. Observing and experiencing the seamless integration of all of these professions has given me the skills to work as an effective team member.

Bianca presented her capstone project at the The American Conference for the Treatment of HIV in Chicago in April 2018, and she will also present her poster at the M4 EMET Capstone Fair on March 14th.  Congratulations, Bianca!

CROI 2019 – The Official UNMC ID Guide of Where We Will Be!

 

CROI 2019 is here and we want to be sure YOU know where to find us in Seattle. Below is the list of faculty presentations and posters from our Division. Find us on Twitter @UNMC_ID 

Content courtesy #CROI2019 http://www.croiconference.org/sites/default/files/uploads/croi2019-program-and-information.pdf 

Oral presentations:

Tuesday March 5 2019 (Oral Abstract O-05 STRANGE BEDFELLOWS: STIs, CONTRACEPTION, AND TRIALS OF HIV TESTING Room 6AB 10:00 AM – 12:00 PM)

Abstract 51: DOUBLE-DOSE LEVONORGESTREL IMPLANT DOES NOT FULLY OVERCOME INTERACTION WITH EFAVIRENZ
Kimberly K. Scarsi, Lauren Cirrincione, Shadia Nakalema, Kristin Darin, Ian Musinguzi, Isabella Kyohairwe, Pauline Byakika-Kibwika, Andrew Owen, Lee Winchester, Anthony Podany, Susan E. Cohn, David Back, Courtney V. Fletcher, Marco Siccardi, Mohammed Lamorde

Abstract 52: PHARMACOGENETICS WORSENS AN ADVERSE ANTIRETROVIRALHORMONAL CONTRACEPTIVE INTERACTION
David Haas, Yoninah S. Cramer, Catherine Godfrey, Susan L. Rosenkranz, Francesca Aweeka, Baiba Berzins, Robert Coombs, Kristine Coughlin, Laura E. Moran, David Gingrich, Carmen D. Zorrilla, Paxton Baker, Susan E. Cohn, Kimberly K. Scarsi, for the AIDS Clinical Trials Group A5316 Study Team

Wednesday March 6 2019  10am-12pm (Oral Abstract O-07 TB: FROM CONTACT TO CURE AND BEYOND Room 6AB)

Abstract 82: EARLY BACTERICIDAL ACTIVITY OF HIGH-DOSE ISONIAZID AGAINST MULTIDRUG-RESISTANT TB
Kelly E. Dooley, Sachiko Miyahara, Florian von Groote-Bidlingmaier, Xin Sun, Richard Hafner, Susan L. Rosenkranz, Eric Nuermberger, Laura E. Moran, Kathleen Donahue, Susan Swindells, Andreas H. Diacon, for the ACTG A5312 Study Team

Wednesday March 6 2019, (Oral Abstract O-08 HEPATITIS C: NOW YOU SEE ME; SOON YOU WON’T Room 6C 10:00 AM – 12:00 PM)

Abstract 87: A PHASE 1 STUDY OF LEDIPASVIR/SOFOSBUVIR IN PREGNANT WOMEN WITH HEPATITIS C VIRUS
Catherine A. Chappell, Elizabeth E. Krans, Katherine Bunge, Ingrid Macio, Debra Bogen, Kimberly K. Scarsi, Leslie A. Meyn, Sharon L. Hillier

Wednesday March 6 2019,Oral Abstract O-10 NEW OPTIONS AND OPPORTUNITIES IN PrEP Auditorium – 4AB

Abstract 103: LYMPHOID TISSUE PHARMACOKINETICS OF TENOFOVIRALAFENAMIDE VS -DISOPROXIL FUMARATE
Courtney V. Fletcher, Ann Thorkelson, Kayla Campbell, Lee Winchester, Timothy Mykris, Jon Weinhold, Jodi Anderson, Jacob Zulk, Puleng Moshele, Siri Jorstad, Anthony Podany, Jason V. Baker, Timothy Schacker

Wednesday March 6 2019, 10am-12pm (Oral Abstract O-13 ANTIRETROVIRAL CLINICAL TRIALS AND RESISTANCE Room 6AB)

Abstract 139: LONG-ACTING CABOTEGRAVIR + RILPIVIRINE AS MAINTENANCE THERAPY: ATLAS WEEK 48 RESULTS
Susan Swindells, Jaime-Federico Andrade-Villanueva, Gary J. Richmond, Giuliano Rizzardini, Axel Baumgarten, Maria Del Mar Masia, Gulam Latiff, Vadim Pokrovsky, Joseph M. Mrus, Jenny O. Huang, Krischan J. Hudson, David A. Margolis, Kimberly Smith, Peter E. Williams, William Spreen

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Themed Discussions 

Wednesday March 6 2019: TD-08 WEIGHT GAIN DURING ART Room 6AB 1:30-2:30PM

Abstract 669: RISK FACTORS FOR EXCESS WEIGHT GAIN FOLLOWING SWITCH TO INTEGRASE INHIBITOR–BASED ART
Jordan E. Lake, Kunling Wu, Kristine M. Erlandson, Sara H. Bares, Paula Debroy, Catherine Godfrey, John R. Koethe, Grace A. McComsey, Frank J. Palella, Katherine Tassiopoulos

Abstract 673: THE IMPACT OF WEIGHT GAIN AND SEX ON IMMUNE ACTIVATION FOLLOWING INITIATION OF ART
Sara H. Bares, Laura M. Smeaton, Vincent Vu, Beth A. Zavoda-Smith, Sarah E. Scott, Catherine Godfrey, Grace A. McComsey

Abstract 518 IMPORTANT SEX DIFFERENCES IN OUTCOMES FOR INDIVIDUALS PRESENTING FOR THIRD-LINE ART
Catherine Godfrey, Michael D. Hughes, Justin Ritz, Robert Gross, Robert A. Salata, Rosie Mngqibisa, Carole Wallis, Mumbi Makanga, Marije Van Schalkwyk, Mitch Matoga, Courtney V. Fletcher, Beatriz Grinsztejn, Ann Collier, for the ACTG 5288 Team

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Poster Presentations:

Tuesday March 5 2019, 2:30-4pm (P-N1 WEIGHT GAIN DURING ART Poster Hall – 4EF )

Abstract 669: RISK FACTORS FOR EXCESS WEIGHT GAIN FOLLOWING SWITCH TO INTEGRASE INHIBITOR–BASED ART
Jordan E. Lake, Kunling Wu, Kristine M. Erlandson, Sara H. Bares, Paula Debroy, Catherine Godfrey, John R. Koethe, Grace A. McComsey, Frank J. Palella, Katherine Tassiopoulos

Abstract 673: THE IMPACT OF WEIGHT GAIN AND SEX ON IMMUNE ACTIVATION FOLLOWING INITIATION OF ART
Sara H. Bares, Laura M. Smeaton, Vincent Vu, Beth A. Zavoda-Smith, Sarah E. Scott, Catherine Godfrey, Grace A. McComsey

Tuesday March 5 2019, 2:30-4pm: (Poster P-U3 SOMETHING’S MISSING; CONTRACEPTION AND HIV Poster Hall – 4EF )

Abstract 1010: PHARMACOKINETIC AND PHARMACOGENETIC ASSESSMENT OF ART AND CONTRACEPTIVE IMPLANTS
Randy Stalter, Jared Baeten, Kimberly K. Scarsi, Bani Tamraz, Katherine Thomas, David Erikson, Jairam Lingappa, Kavita Nanda, Athena Kourtis, Rena Patel, for the Partners PrEP Study Team

Tuesday March 5 2019, 2:30-4pm: (Poster P-R5 EPIDEMIOLOGY OF TREATMENT AND SURVIVAL Poster Hall – 4EF )

Abstract 916: LOW RATE OF SEX-SPECIFIC ANALYSES IN CROI PRESENTATIONS IN 2018: ROOM TO IMPROVE
Monica Gandhi, Laura M. Smeaton, Christina Vernon, Eileen P. Scully, Sara Gianella, Selvamuthu Poongulali, Anandi N. Sheth, Marije Van Schalkwyk, Karin L. Klingman, William R. Short, Valarie S. Opollo, Susan E. Cohn, Kimberly K. Scarsi, Rosie Mngqibisa, Elizabeth Connick

Abstract 518: IMPORTANT SEX DIFFERENCES IN OUTCOMES FOR INDIVIDUALS PRESENTING FOR THIRD-LINE ART
Catherine Godfrey, Michael D. Hughes, Justin Ritz, Robert Gross, Robert A. Salata, Rosie Mngqibisa, Carole Wallis, Mumbi Makanga, Marije Van Schalkwyk, Mitch Matoga, Courtney V. Fletcher, Beatriz Grinsztejn, Ann Collier, for the ACTG 5288 Team

Wednesday March 6 2019: Poster P-B6 HIV AND THE REPRODUCTIVE TRACT Poster Hall – 4EF 2:30 PM – 4:00 PM

Abstract 241 HIV-SUPPRESSED PATIENTS’ PLASMA AND SEMEN EXOSOMES CONTAIN PROTECTIVE LEVELS OF ART
Jennifer L. Welch, Jack T. Stapleton, Hussein Kaddour, Lee Winchester, Courtney V. Fletcher, Chioma M. Okeoma

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Congratulations to all of our UNMC ID faculty presenting at #CROI2019! Check out their oral and poster presentations and share your thoughts with us on Twitter @UNMC_ID


 

UNMC appreciates our residents!

This month, UNMC is hosting two events to recognize our hard working residents!

On February 22nd, the UNMC chapter of the Gold Humanism Honor Society (GHHS) participated in National Thank a Resident Day, an event designed to shed light on how vital the house staff are to healthcare institutions both in providing outstanding healthcare as well as teaching medical students. Says Connor Mullhall, the M4 who organized this year’s event, “We are very appreciative of our residents and are so excited to have an opportunity to share that appreciation with them.”

“Thank a Resident Day” ready to thank residents!

The UNMC chapter of GHHS hand-wrote “thank you” notes to all 514 Nebraska Medicine residents, delivered Eileens Cookies, and organized and hosted an appetizer and milkshake event open to all UNMC residents. The thank you notes included the poem shown in this article’s feature image, written by Dr. Kelly Cawcutt in February 2018.

Residents enjoying GHHS’s event on 2/24

On February 28th, UNMC and Nebraska Medicine are also hosting a House Officer Appreciation Day!  Members of UNMC leadership shared statements of gratitude for the hard work and dedication of our residents here in the UNMC newsroom.

Residents are at the heart of our institution, working tirelessly to ensure our patients receive the best care and train students who aspire to be like them some day. At these events we celebrate the hard work they do every day.  Thank you to our residents for their compassionate care, dedication to our patients, and education of our students!

What to Expect in Antimicrobial Stewardship…Shorter is Better, Of Course!

The following was previously posted by Dr. Marcelin to SHEA Journal Club published online in February 2019.

Electronic clinical decision support tools and rapid diagnostic testing have significantly impacted the way we practice Infectious Diseases. Despite these scientific gains, Antimicrobial Stewardship still requires an understanding of the behavioral science of prescribing. Prior studies have demonstrated that antibiotic prescribing may be influenced by specific behavioral interventions, such as peer comparison, or “nudge” theory.

The Study

Yadav et al. conducted a quasi-experimental quality improvement study to determine the impact of implementing an “Expected Practice” (EP) method to alter antibiotic prescribing practices towards favoring shorter duration of therapy (DOT). This method leverages the prescriber’s desire to meet their own institutional expectations, which may be viewed as more authoritative than external medical society guidelines. The authors chose DOT as the endpoint because clinicians were concerned about potential poor outcomes with shorter DOT.

The EP document included a wealth of evidence supporting shorter treatment durations for the uncomplicated infections, including urinary tract infections (UTI, 1-5 days), pyelonephritis (5-7 days), skin/soft tissue infections (SSTI, 5-6 days), community-acquired pneumonia (CAP, 5 days), and ventilator-acquired pneumonia (VAP, 7 days). The authors already had an established antimicrobial stewardship program, whose practices did not change during the study, with the exception of implementing procalcitonin testing.

Results

In the 12 months after implementing EP, the average antibiotic DOT decreased by 10%, 11%, 11%, and 27% for UTI, SSTI, CAP and VAP respectively, with concomitant decreases in total antibiotic exposure measured in total milligrams administered. This impact was statistically sustained by the end of that year for UTI and CAP, but seemed to wane toward the end of the year for SSTIs and VAP.

The procalcitonin test that was also implemented during that period was associated with statistically significant increase of antibiotic dose exposure and DOT, which was thought to be due to patients with more complex illness having the test performed and subsequently requiring longer treatment durations.  Mortality was unchanged post-intervention.

Impact

The only condition in the EP where antibiotics were not recommended was asymptomatic bacteriuria, and though there is no way to be certain, it is possible that this particular recommendation contributed to the decreased DOT for UTI, by reducing the number of antibiotic starts for “UTI” that was really asymptomatic bacteriuria and didn’t require antibiotics at all. This study demonstrated that providing expectations of practice regarding specific conditions can have important clinical impact on prescribing.

The influence of this change goes beyond simple DOT or dose exposure, to other important factors not measured by this study, like impact on C. difficile infection rates, impact on antimicrobial resistance rates, reduction of antibiotic-related adverse drug events, hospital length of stay.

Citation

Kabir Yadav, Eriko Masuda, Emi Minejima, Brad Spellberg; Expected Practice as a Novel Antibiotic Stewardship Intervention, Open Forum Infectious Diseases, Volume 6, Issue 1, 1 January 2019, ofy319, https://doi.org/10.1093/ofid/ofy319

UNMC ID Fellow wins Internal Medicine Scientist Development Award

We are pleased to share that Dr. Richard Hankins, one of our senior ID fellows has been awarded the UNMC Department of Internal Medicine Scientist Development Award for 2019-2020.  This award will allow Dr. Hankins protected time to study optimization of CHG patient bathing as a method to prevent HAIs/pathogen transmission and pursue additional opportunities for career development. He will also be taking patient safety and performance improvement courses and start work for a masters degree. We asked Dr. Hankins to share his thoughts on this tremendous achievement. 

Since I started my infectious disease fellowship, I have always been interested in pursuing a career in academia.  Research, education, and teaching have always been interests of mine, but things at which I have constantly tried improve on.  Through fellowship I have tried to work on and obtain the necessary tools in order to improve my skill at becoming an independent researcher.  UNMC Infectious Diseases provided the option of a 3rd year of fellowship in order to perfect my skills as an academic clinical researcher in the field of infection control and antimicrobial stewardship.

One of the studies I will lead next year will be in assessing proper utilization of chlorhexidine. Chlorhexidine gluconate is a broadly active, biguanide antimicrobial disinfectant that appears to decrease hospital-acquired infections when it is used to bathe patients in intensive care units. However, it remains unclear what the best method is for applying CHG. We seek to evaluate two methods of CHG bathing 2% CHG impregnated cloths and 4% solution with regard to residual CHG skin concentration and quantitative skin microbial burden.

In order to provide me this opportunity the Internal Medicine department graciously awarded me the Scientist Development Award.  I am honored that they selected me, in order to provide me the opportunity to continue to developing my skills as a clinical researcher.  Beyond leading several studies in the upcoming year, I am looking forward to beginning work towards a Masters in Public Health with a focus in biostatistics, which I believe will further augment my training.

I’m incredibly excited for next year, and the opportunity that the UNMC Internal Medicine Department is providing for me with the Scientist Development Award.  I’m thankful that they selected me, but also thankful for all the help that the entire infectious diseases department provided me over the past year and a half.  My mentors Dr. Mark Rupp, Dr. Trevor Van Schooneveld, and Dr. Kelly Cawcutt have helped me immensely, in developing the skills necessary to take advantage of this opportunity. I know without all of their help I wouldn’t be in position to further launch my career.

Dr. Hankins’ main career and research mentors also weighed in on his award:

“Richard has been a real asset for our fellowship and it is very gratifying to see him succeed.  He has worked hard to grow as an Infectious Disease clinician and scientist and this award is validation of those efforts.  I am looking forward to working with Richard on his projects next year.”   – Dr. Trevor Van Schooneveld (ID Fellowship Program Director, Infection Control Associate Medical Director, and one of Dr. Hankins’ mentors)

“I have been a research and career mentor for Dr. Hankins starting in his final year of residency and through fellowship thus far, and supported his completion of several projects, presentations and manuscripts. Dr. Hankins has been motivated to create an academic, research career; with ongoing guidance, he will absolutely succeed in that role and I am pleased to play a part in his career development.” – Dr. Kelly Cawcutt (Infection Control Associate Medical Director, and one of Dr. Hankins’ mentors)

“This is a terrific honor for Rich and will enable him to join the ID division faculty as an instructor and devote significant time to career development. Rich’s research project will greatly expand our knowledge regarding this important infection prevention intervention, and take advantage of UMMC faculty development opportunities to hone his teaching and research skills.” – Dr. Mark Rupp (Infectious Diseases Division Chief, Infection Control Medical Director, and Dr. Hankins’ primary mentor)

Congratulations, Dr. Hankins! The entire UNMC ID Division is very proud!

How Can UNMC ID Help Support You In 2019?

We are excited to be closing in on our 2 year anniversary of our blog. With that anniversary, we have several positive changes coming for our team. Drs. Kelly Cawcutt and Jasmine Marcelin have been appointed Co-Directors for Digital Innovation & Social Media Strategy for the UNMC Division of Infectious Diseases. We also hired a fantastic Social Media Assistant, Hannah Tandon, a first year medical student at UNMC (see her recent introduction here).

We would like to take the time to thank all of our followers on Twitter, those who read and share our blog, and everyone who supports UNMC_ID’s digital footprint. As we are growing, it is time to assess ways to improve our blog and Twitter social media presence. We have provided a variety of different types of posts over the years, but we want to hear what content you would like to see more (or less) of going forward.

Please fill out this short, anonymous, survey to help us understand who our audience (our readers) is and how we can best support your needs going forward.  https://www.surveymonkey.com/r/8JHVRK2

Thank you!

 


 

Meet our new social media assistant: Hannah Tandon

Tell us a little about yourself. I grew up in Southern California but have been on the East Coast for the last six years.  I graduated from Amherst College in 2016, and I spent two years before medical school working as a post-baccalaureate Intramural Research Training Award fellow at the National Institutes of Health.  I managed chronic pain clinical trials, and I especially loved working with women with chronic pain, validating their experience, and facilitating meaningful care.  It was rewarding, especially in times like these, to be working on non-addictive strategies for chronic pain management.   This fall, I started medical school here at UNMC.

Why UNMC?  I spent the summer of 2015 working with infectious disease doctors Mark Rupp, Angela Hewlett, and Trevor VanSchooneveld, and it was that summer that clarified my desire to pursue a career in medicine.  It was the first time I saw people doing exactly what I wanted to do: provide patient care and lead clinical research teams. I’m so grateful to have the opportunity to pursue my calling in the place where I found it.

So does this mean you’re going to go into ID? I’m not sure!  The infectious disease department has certainly been a home for me, but I’m trying my best to keep an open mind.  I am very lucky to have many physician mentors who love their specialties and encourage students to follow their paths.  However, I think it’s one thing to observe others and another to provide care myself.  I am excited for next spring when I start my clinical rotations to get a better sense of what I am good at and enjoy.

Tell us something about yourself that isn’t related to medicine. I’ve been playing French horn for 10 years, and serendipitously UNMC started the Nebraska Medical Orchestra this year!  Playing music has always been my preferred way to relieve stress, and I enjoy meeting new people I wouldn’t otherwise encounter in my daily routine.


 

Prescribing in Pediatric Patients: Who is at Risk?

The following was previously posted by Dr. Marcelin to SHEA Journal Club published online in January 2019.

In the inpatient setting, much of the broad-spectrum antibiotic prescribing occurs in the context of the sepsis syndrome, where uncertainty leads to overly broad empiricism. Development of antibiotic-resistant Gram-negative rods (high-risk GNRs) may complicate empiric treatment choices, and in the pediatric population, delay in appropriate treatment can have a serious impact on morbidity and mortality. However, in some pediatric sepsis cases, bacteria may not even be the cause of illness, and antibiotics may be unnecessary.

Karsies et al. conducted a single-center retrospective cohort study to derive and validate a risk model that would predict likelihood of high-risk GNRs, with a goal to provide narrower empiric antimicrobials.  They defined high-risk GNRs as Pseudomonas spp., Acinetobacter spp., Enterobacter spp., Klebsiella oxytoca, Extended-spectrum Beta lactamase-producing organisms and other GNRs with reduced susceptibility to >1 antibiotic class.

Their institution’s baseline prevalence of these organisms was 25%. They used previously described cohorts from 2004 and 2007 for model derivation and created a new cohort for model validation (2014-2015) – both cohorts had over 500 infection episodes. Their previous study had established 10 candidate risk factors for high-risk GNRs, and the main outcome variable of this study was growth of any high-risk GNR from the sites sampled in individuals predicted to have growth.

Using a multivariable logistic regression, they examined variables that fit the model with at least a 95% sensitivity cutoff, and six factors fit in the model: hospitalization>48hrs, hospitalization within 4weeks, recent antibiotics, chronic lung disease, residence in chronic care facility and previous growth of high-risk GNRs. They then validated this in the second cohort, where individuals were considered high risk if they had one or more of the identified risk factors. The sensitivity was 96.4% and specificity 48% in the derivation cohort, and 93% and 51% respectfully in the validation cohort, with negative predictive values over 90% in both cohorts.

The size of the study and the pediatric focus are strengths, however, there was only an 8.5% relative risk reduction in unnecessary antipseudomonal antibiotics using six risk factors, as compared to without the model, using 10 factors. The risk factors that they identified are easily obtained, however may themselves not be independent of each other. Additionally, both groups had low baseline PRISM III scores, indicating that perhaps both groups of children were not as critically ill. A baseline high-risk GNR prevalence of 25 percent is alarmingly high and makes generalizability difficult without first doing a similar prospective study across multiple centers.

Reference: Karsies, Todd et al. “Development and Validation of a Model to Predict Growth of Potentially Antibiotic-Resistant Gram-Negative Bacilli in Critically Ill Children With Suspected Infection” Open forum infectious diseases vol. 5,11 ofy278. 24 Oct. 2018, doi:10.1093/ofid/ofy278

Baloxavir Marboxil for Uncomplicated Influenza – Worth the Cost?

Influenza season is in full swing and with that, the discussions surrounding treatment are heating up! Dr. Hankins, a second year ID fellow, led our recent journal club discussion on Baloxavir.

The New England Journal of Medicine article, Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents, discusses two randomized control trials, that were double-blinded for healthy outpatients with acute, uncomplicated influenza during the 2016-2017 influenza season. Phase II & Phase III trials reported. The primary outcome of both trials was time to alleviation of symptoms, with secondary outcomes of viral RNA titers, duration of virus detection, and resistance testing. The Phase II trial evaluated one time doses of baloxavir 10mg, 20mg and 40mg, vs placebo. The study evaluated adults in Japan who had a fever, at least one respiratory symptom, one systemic influenza symptom, and a positive rapid antigen test (the standard of care in Japan). The results of the phase II trial showed baloxavir significantly reduced time to alleviation of symptoms, with 54.2 hours in the 10 mg group, 51.0 hours in the 20 mg group, and 49.5 hours in the 40 mg group, compared to 77.7 hours in the placebo group.

The phase III trial evaluated baloxavir vs oseltamivir vs placebo, and used similar inclusion criteria, although it did not require a positive influenza antigen test, as this study was in the United States as well as Japan. It evaluated a one time dose of baloxavir 40mg or 80mg (decided by weight) vs oseltamivir 75mg BID for 5 days vs placebo. In the phase III Baloxavir successfully decreased time to alleviation of symptoms of approximately 1 day compared to placebo, but the time to alleviation of symptoms was comparable to oseltamivir. Viral load reduction appeared to be greater in the first few days, but then becomes equitable with oseltamivir. Plus, resistance to Baloxavir may increase to 10% after a single dose. Adverse events were similar in all groups.

Take-always: Baloxavir appears similar to oseltamivir for treatment of outpatient symptoms of influenza. Is there a possible utility for the viral load reduction of baloxavir in the inpatient setting, particularly among the immunocompromised or critically ill? Is the one-time dose of Baloxavir worth the cost given the no change in symptoms for outpatients? If we use it, will it only be short-lived given the higher rate of resistance that seems to evolve?

Will we prescribe it? The overall consensus seemed to be no; not if we can still use oseltamivir.