Division of Infectious Diseases

SHEA Journal Club Review: “Not Throwin’ Away My Shot”: Early data for COVID-19 vaccination in previously infected healthcare workers and solid organ transplant recipients

Reviewed by Erica Stohs MD, MPH, University of Nebraska Medical Center, Omaha, NE; and Hannah Imlay MD, MS, University of Utah Health, Salt Lake City, UT (originally posted for SHEA Journal Club)

As more vaccinations are completed worldwide, specific vaccine strategies and outcomes among special patient populations are newly available. Two populations of interest include vaccinees with previous COVID-19 and those with a history of a solid organ transplant.

First, among vaccinees who previously had COVID-19, two studies published in The Lancet investigated whether one or two doses of an mRNA vaccine are sufficient and necessary. Both studies were conducted among health care workers (HCWs) in the United Kingdom.

One study used serology, live virus neutralization (in a subset), and T-cell enzyme ELISpot assays to measure vaccine responses after a single dose of BNT162b2 (Pfizer) vaccine among 72 HCWs, 21 (29%) of whom had evidence of previous SARS-CoV-2 infection (16 with baseline serology positive, 5 with T-cell responses to non-spike antigens). Anti-spike titers after a single dose of vaccine were significantly higher in patients with prior natural infection than infection-naive patients. T-cell responses followed a similar pattern. A different study examining vaccine responses among HCWs with previous COVID-19 included 51 patients – 24 had a previous mild or asymptomatic SARS-CoV-2 infection, 27 had remained seronegative throughout and were considered infection naive. All patients received a dose of the BNT162b2 (Pfizer) vaccine and were tested 19-29 days later. Among infection-naïve patients, anti-S titers after one dose were comparable to anti-S titers in patients with previous natural infection. Among those with a previous SARS-CoV-2 infection, vaccination increased anti-spike titers substantially. These two studies suggest that a single-dose strategy for immune competent patients with previously diagnosed SARS-CoV-2 may be acceptable although duration of immunity was not evaluated. Conversely, they highlight the importance of the second dose to develop robust immunity in those who are infection-naïve.

Second, preliminary data have now been generated regarding the response to the first dose of mRNA vaccination among solid organ transplant recipients (SOTRs).

SOTRs were not included in previously existing mRNA COVID-19 vaccine studies but are at increased risk for severe COVID-19 illness. SOTRs receiving mRNA COVID-19 vaccines between mid-December and early February were recruited to measure antibody response 14-21 days after receipt of vaccination. A total of 436 SOTRs were included with a median age of the cohort was 56 years; median time from transplant was 6.2 years. Humoral antibody response was seen in only 17% (76 of 436) at a median 20 days after vaccination. Anti-metabolite maintenance immunosuppression, increased age, and receipt of BNT162b2 (Pfizer) vaccine were associated with decreased response. Importantly, what remains unknown is humoral response after full vaccination and effectiveness in preventing symptomatic COVID-19 illness. However, based on low responses following the first mRNA administration, SOTRs are likely to require, at minimum, a full course of mRNA vaccination rather than stopping at a single dose.

References:
Prendecki M, et al. “Effect of previous SARS-CoV-2-infection on humoral and T-cell responses to single-dose BNT162b2 vaccine.” The Lancet 2021;EPub.
Manisty C, et al. “Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals.” The Lancet 2021;EPub.
Boyarsky B, et al. “Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients.” JAMA 2021;EPub.

New Faculty Spotlight – Dr. Daniel Brailita

Background: I was born in Bucharest, Romania and completed Medical School there. I trained in Internal Medicine and Infectious Diseases in Texas, finishing as chief resident at Texas Tech and chief fellow at UT Southwestern in Dallas. I moved to Nebraska in 2007 where I helped building the first ID practice encompassing Central Nebraska and Tri-Cities area. My family and I enjoyed the Nebraska Nice community as the kids grew up. I helped with State Health Department projects as well as served in local Health Department Board. I joined UNMC ID Division in January 2021 and I am looking forward to our expansion of Community ID and Telehealth services.

Why UNMC:

UNMC is something that any Nebraskan is very proud of, and a best place to work and give back to the community. It has gained National and even International recognition in several areas, including the ID Department and Biocontainment unit.

What about ID makes you excited?

Seeing a very ill patient getting better and getting back to his normal life. The detective work. The feeling you can solve a puzzle that is not system specific or straightforward. And the opportunities that will come in the field as we transition to genomic and individualized medicine.

Tell us something interesting about yourself UNRELATED to medicine

I enjoy officiating at USA Swimming, High School meets and participated in National Meets. I enjoyed volunteering at Omaha Olympic Trials and this city puts up the best meet in the world.

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UNMC ID at SHEA 2021 – Where to Find Us!

The SHEA 2021 Spring conference is here and this is your guide on where to find our UNMC ID team presenting throughout the conference, starting with pre-conference workshops. And yes, there is still time to sign up and attend!

Lectures/Workshops

Pre-Conference Workshop: Sharing Our Science: Using Modern Means to Get Your Message Out There; Using Twitter to amplify your research and messages – by Marcelin & Cawcutt April 13, 1-330PM

Session Title: Being an Equity Ally in Infection Prevention; Being an active and effective anti-racism all – Marcelin; Gender equity in academic medicine and infection prevention – Cawcutt; Wednesday April 14 from 4-530PM

Abstract Presentations:

ABSTRACT 106:Knobmanship: Dialing Up Understanding of VAE Triggers. Hinkle, Rupp, Cawcutt

ABSTRACT 102: COVID & VAE Discordance. Hinkle, Rupp, Cawcutt

Follow the conference on Twitter using the hashtag #SHEASpring2021 for meeting updates & highlights.

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Why I Love ID – Dr. Richard Hankins

It has been a hot minute since we had a chance to share the perspective of our faculty on why they love ID. Dr. Hankins was able to share as a fellow, but now shares his updated reasons from the perspective of a junior faculty member.

“When thinking of why I love infectious diseases, I always find a multitude of reasons, and just seem to come up with more over time. 

I think infectious diseases appeals to life-long learners.  We get the opportunity to learn about patients, but at the same time get to learn about many different microorganisms.  As new microorganisms present themselves, we have to be ready to learn about them.  While its always interesting to see what is coming down the road, I also enjoy looking at the history of medicine and how infectious diseases impacts the world around us.  Whether it was the Haitian Revolution, the French invasion of Russia, or current day COVID-19, the impact of infectious diseases is quite astonishing. 

Infectious Disease physicians also get the opportunity to assist in cases where nobody is quite sure what is going.  I think the work up of a fever of unknown origin is always exciting because everything is relevant and we have to really get to learn about patients’ day to day life in order to figure out what is going on.

This seems like a list I could continue about, and I’m sure if you ask me tomorrow I’d have a few new reasons as well.”

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Changing the Culture of Culturing

Originally written by Dr. Cawcutt and posted on IDSA Journal Club

Despite a recommendation from the Surviving Sepsis Campaign (SSC) to procure blood cultures within the first hour after sepsis recognition, implementation of this practice been suboptimal. This prompted the implementation of routine blood culture obtainment in non-elective intensive care unit (ICU) admissions, whether infection was suspected or not, for all adult patients at a single center in the Netherlands.

In a before-and-after study from this center including patients admitted from January 2015 to December 2018, automatic orders for blood cultures were implemented immediately on ICU admission in January 2017. End points studied included the number of positive blood cultures, with subsequent determination if these were contaminants or true bloodstream infections (BSIs), along with the rate of vancomycin use based on the blood culture results.

Cultures obtained on ICU admissions increased from 32.3% to 84.5% after implementation, with an increase in diagnosed BSIs from 95 (5.4%) to 154 (8.2%) and a relative risk (RR) of 1.5 (95% confidence interval [CI] 1.2-2.0; P = 0.0006). This resulted in a number needed to culture of 17 for detection of one additional BSI.  From a contamination standpoint, there was a noted increase from 2.3% and 9.6% with an increased RR of 4.3 (95% CI 3.0-6.0, P < 0.0001). The vast majority (94.4%) of BSIs were discovered in patients presumed to have infection based on the ordering of empiric antibiotics. Of significant interest, despite the increased culture obtainment and positive cultures, utilization of vancomycin did not increase within this before-and-after study.

Overall, this study suggests that automatic ordering of blood cultures for all non-elective ICU admissions may improve adherence to SSC recommendations in a clinical setting with pre-existing suboptimal adherence, thereby detecting more clinically relevant BSIs. The counterbalance of increased contamination rates with cost of laboratory evaluation and the lack of change in vancomycin use (given multidisciplinary discussions regarding cultures) may not be generalizable and would require monitoring if implemented elsewhere. (Verboom et al. Crit Care Med. 2021;49(1):60-69.)

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Beating Biofilms

By: Kelly Cawcutt, MD, MS, FACP, FIDSA. Originally posted with CloroxPro, linked below.

Biofilms play an important role in the development of hospital-acquired infections (HAIs). In my line of work, I’m often reminded of their presence when handlining central venous catheters or endotracheal tubes, but biofilms can also be present on any environmental surfaces. Biofilms are defined as a complex collection of microorganisms that attach to a surface and create a surface specific ecosystemic on that surface (known as an extracellular polymeric substance [EPS]). Given the complexity, and strong adherence to surfaces, biofilms result in a perpetual conglomerate of microorganisms that may be impossible to fully eradicate, resulting in a difficult, albeit often underestimated cause of infections in healthcare.

Given the increase usage of ventilators for the treatment of severe COVID patients, I thought now was a particularly good time to drive awareness about this complex, Jello-like matrix filled with micro-organisms such as bacteria.

Biofilms contribute to many infectious diseases. Some classic examples are endocarditis, prosthetic joint infections and Clostridioides difficile (C. diff) along with device-related infections such as central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs) and ventilator-associated pneumonia (VAP), among others. In the era of COVID-19, the impact of biofilms on HAIs may be more prominent due to the high device utilization in the intensive care units (ICUs) and long length of stays.

Considering the impact of biofilms, there are many details to consider. First, given the capacity for biofilms to form on any surface, preventing microorganisms from attaching to a surface is a key intervention. The prevention of infection is multifaceted, and echoes the importance of infection control measures such as hand hygiene, device stewardship, aseptic technique, maintenance of devices and equipment, and environmental cleaning. Beyond this, patients may have additional risk factors that contribute to their likelihood of biofilm development which can include diabetes, kidney disease and immunosuppression. The risk factors are associated with decreased innate immune responses that normally fight the development of biofilms, so when a disease impacting the innate immune system is present, there is less of our individual capacity to prevent the build-up of that ‘gunk’ on my patient’s endotracheal tube. Recognizing the role comorbid conditions, especially those that are very common (like diabetes and kidney disease) may play in such infections is essential as we strive to beat biofilms and prevent HAIs.

There are many human pathogens that are described to comprise, and grow within, biofilms can result in infection, including, but not limited to, Staphylococcus aureus, Pseudomonas aeruginosa, Legionella pneumophila. Candida species, including both Candida albicans and Candida auris (C. auris), are known to also cause biofilms. The known presence of these organisms has resulted in innovative devices, such as central venous catheters, impregnated with antimicrobial agents to prevent microbial attachment to the catheter, and therefore biofilm development. Such catheters have demonstrated decreases in HAIs, specifically in this scenario, CLABSI.

Although individual patient infection control measures must be followed, environmental sources of biofilm cannot be ignored. One specific rising concern in the infection control world is C. auris, which was first detected in 2009, and subsequently has spread throughout the world. Infections secondary to C. auris are significant due the life-threatening nature of these infections, combined with both the resistance to several antifungal medications and the capacity to spread within healthcare facilities. C. auris has been described to cause surface biofilms in patient rooms that may be difficult to eradicate, therefore be a conduit for infections. C. auris may be contracted from a patient, or their environment (including equipment that may be used for multiple patients), in as little as 4 hours, therefore effective disinfection is critical. Chlorhexidine-based regimens for patient asepsis may not be as effective as povidone iodine and environmental disinfectants, such as ethyl alcohol and quaternary ammonium, may be less effective than hydrogen peroxide or sodium hypochlorite. We must understand which infection control strategies, including the chemicals used, are effective against pathogens, or we will miss the opportunity to prevent HAIs!

Beyond the patient and physical environment, biofilms with infectious pathogens (such as Pseudomonas aeruginosa and Legionella pneumophilia) can form in water sources and clear guidance exists from the CDC on how to assess, and decrease the risk, of water-based biofilm as a source for transmission of infection within hospitals. Examples of where such biofilms could occur is within faucets, ice machines, showers, toilets and drains.

Given the near impossibility of eradicating biofilms, further research into prevention of biofilms is of paramount importance. Specifically, the roles of antimicrobial impregnated devices and surfaces (such as the central venous catheter device mentioned above), and optimal patient asepsis and environmental disinfection. Our best offense continues to be adherence to infection control practices and engaging the entire healthcare team in the one-two punch required to beat biofilms. Our patients are depending on us!

Find the full original post here: https://www.cloroxpro.com/blog/infections-inside-out-beating-biofilms/

UNMC ID at #CROI 2021

Conferences may continue to look different due to the COVID-19 pandemic, but our ID faculty remain dedicated as ever to continuing to contribute to scientific knowledge and advancement of patient care. The Conference on Retroviruses and Opportunistic Infections (CROI) was held this year from March 6-10, and UNMC had several presentations. See below for the highlights and check out the conference for more details!

130 RIFAPENTINE +/– MOXIFLOXACIN FOR PULMONARY TUBERCULOSIS INPEOPLE WITH HIV April Pettit, Payam Nahid, Patrick P. Phillips, Andrew Vernon, Ekaterina Kurbatova, Rodney Dawson, Ian Sanne, Ziyaad Waja, Lerato Mohapi, Wadzana,Samaneka, John Johnson, Susan Dorman, Richard E. Chaisson, Susan Swindells, for TBTC Study 31/ACTG 5349 study team

178 ADVERSE PREGNANCY OUTCOMES AMONG HIV-INFECTED WOMEN EXPOSED TO ISONIAZID IN BRIEF-TB Amita Gupta, Michael Hughes, Jorge T. Leon-Cruz, Anchalee Avihingsanon, Noluthando Mwelase,Patrice Severe, Ayotunde Omoz-Oarhe, Gaerolwe Masheto, Laura Moran, Constance A. Benson,Richard E. Chaisson, Susan Swindells, for the ACTG 5279 BRIEF TB Trial

505 WEIGHT AND LIPID CHANGES IN PHASE 3 CABOTEGRAVIR AND RILPIVIRINE LONG-ACTING TRIAL Parul Patel, Ronald D’Amico, Shanker Thiagarajah, Sterling Wu, Emilie Elliot, Joseph W. Polli, Ojesh Upadhyay, Rodica Van Solingen-Ristea, Chloe Orkin, E. Turner Overton, Susan Swindells, Jean A. Van Wyk, Matthew Bosse, Vani Vannappagari

91 PK OF DOSE-ADJUSTED EMERGENCY CONTRACEPTION WITH EFV-BASED ART IN ACTG 5375 Kimberly K. Scarsi, Laura M. Smeaton, Anthony T. Podany, Maxine Olefsky, Elizabeth Woolley, Elizabeth Barr, Kayla Campbell, Sivaporn Gatechompol, Jeffrey Jeppson, Sajeeda Mawlana, Khuanchai Supparatpinyo, Catherine Godfrey, Susan E. Cohn, Rosie Mngqibisa, for the AIDS Clinical Trials Group A5375 Study Team

368 PHARMACOKINETICS OF 2 CONTRACEPTIVE IMPLANTS AMONG WOMEN ON RILPIVIRINE-BASED ART Shadia Nakalema, Catherine A. Chappell, Michelle Pham, Ritah Nakijoba,Leah Mbabazi, Pauline Byakika-Kibwika, Julian Kaboggoza, Stephen I. Walimbwa, Jeffrey Jeppson, Lee Winchester, Marco Siccardi, Courtney V. Fletcher, Kimberly K. Scarsi, Mohammed Lamorde

359 PERSISTENT HIV TRANSCRIPTION AND VARIABLE ARV LEVELS IN LYMPH NODES DURING ART Courtney V. Fletcher, Eugene Kroon, Timothy Schacker, Suteeraporn Pinyakorn, Nicolas Chomont, Suthat Chottanapund2, Peeriya Prueksakaew, Khunthalee Benjapornpong, Supranee Buranapraditkun, Jintanat Ananworanich, Sandhya Vasan, Denise C. Hsu, for the RV254/SEARCH 010 Study Group

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Combatting COVID-19 vaccine hesitancy among people with HIV

Nichole N  Regan, APRN-NP

Content written by Specialty Care Center Nurse Practitioner, Nikki Regan, APRN

The Nebraska Medicine Specialty Care Center provides primary and specialized care to over 1100 people with HIV (PWH) in the Nebraska and southwest Iowa region.

At the onset of the COVID-19 pandemic in March 2020, PWH expressed a variety of emotions and concerns. Most were afraid that their HIV status would increase risk of contracting COVID-19, or suffering from severe illness or death (based on early and limited data, it appears that PWH who are on effective therapy have the same risk for COVID-19 infection as people who do not have HIV). Our phones were overrun by patients cancelling appointments, strictly quarantining and afraid to leave their homes for any reason. Notably, many of our patients 55 years and older stepped forward, proud to be a symbol of survivorship, after experiencing the early HIV epidemic of the 1980s firsthand.

It is no surprise then that the advent and growing availability of COVID-19 vaccinations in 2021 has been met with a mix of emotions for PWH. Patients in general have expressed concern about the speed with which the Moderna and Pfizer vaccines were developed. The concept of mRNA delivery was previously unheard of to the general public. More specifically, our patients want to know if it is safe for them to receive the vaccine since they have HIV. Vaccine hesitancy may be higher among people of color, rooted in generations of structural racism resulting in medical mistreatment without proper informed consent. (Approximately one-third of patients at the Specialty Care Center identify as non-White). Finally, even patients who were eager to receive the COVID-19 vaccine were disappointed to learn that they will not be vaccinated in our clinic, since vaccinations are being managed by state and local health departments instead of hospitals and clinics.

The team at the Specialty Care Center has quickly mobilized a plan to promote acceptance of COVID-19 vaccinations for PWH in our community. Originating with the creation of a COVID-19 Task Force in January 2021, clinic champions have led several projects including the development of a COVID-19 FAQ handout for patients in both English and Spanish, a bulletin board in the patient waiting area displaying pictures and statements from staff as to why they chose to receive the vaccine, and a plan to actively discuss our recommendation to receive the COVID-19 vaccine with every patient in our care.

“Why I got the shot” vaccine bulletin board with testimonials from clinicians and staff at the specialty care center

With each clinic interaction, patients are offered assistance in pre-registering for the COVID-19 vaccine online, via www.vaccinate.ne.gov if they live in Nebraska. Patients from Southwest Iowa are also encouraged to contact their state and local health departments for direction. Additionally, clinic champions are contacting patients at home via telephone and One Chart Patient portal, and completing pre-registrations in that manner. Those patients 65 and older have been assisted with scheduling their vaccine appointment in their designated county of residence. Additionally, CARES Act funding has been earmarked to assist with transporting qualified patients to and from vaccine appointments.

This Nebraska Medicine FAQ site has more information about the COVID-19 vaccines.

Bottom line: people with HIV CAN and SHOULD receive the COVID-19 vaccine, in consultation with their clinician. To learn more, or to pre-register in the state of Nebraska, visit www.vaccinate.ne.gov.

Clinical Consequences of Contaminated Blood Cultures in Adult Hospitalized Patients at an Institution Utilizing a Rapid Blood-Culture Identification System

Dr. Mark Rupp; senior author and Division Chief for @UNMC_ID

Blood culture contamination results in prolonged hospital length of stay, inappropriate use of antibiotics, and increased cost as well as the associated adverse events such as falls, drug errors, and healthcare associated infections (adverse events that may occur during more prolonged hospital stay) and emergence of antibiotic resistance, C. difficile infection, and antibiotic side effects (adverse events associated with unnecessary antibiotic administration).

However, nearly all studies indicating the harm associated with blood culture contamination were performed in the era prior to the use of rapid, molecular-based blood culture identification systems. In many instances, with use of rapid blood culture ID systems, true pathogens can be differentiated from likely contaminants (e.g. Staphylococcus aureus versus coagulase-negative staphylococci) very quickly. The effect of rapid blood culture ID systems on the clinical importance of blood culture contamination is not well described.

Therefore, we performed a large retrospective cohort study comparing outcomes between hospitalized patients with blood culture contamination and those with sterile blood cultures – during a time period when a rapid blood culture identification system (Biofire FilmArray Blood Culture Identification) was in routine use.

From June 1, 2014 to December 31, 2016, 19,255 patients were admitted to the hospital who had blood cultures performed. After excluding pediatric age patients, patients with true bacteremia, patients with repeated admissions, and those with equivocal results, we analyzed outcomes in 11,010 patients with sterile cultures and 464 with contaminated cultures. Primary outcomes of interest were hospital length of stay and antibiotic use. Variables potentially affecting outcome were examined and included socio- demographic factors (age, gender, race, marital status, medical insurance status) and various comorbid conditions including smoking, alcohol use, BMI, COPD, CKI, cirrhosis, and diabetes. Additional factors examined included ICU stay, admission from the emergency department, and location of blood draw (peripheral vein versus central venous catheter).

Univariate and multivariate analysis was conducted using generalized linear models. Forward stepwise selection was utilized to create the final model and Akaike information criterion value was used to assess model fit.

Bottom line, after controlling for age, gender, race, BMI, comorbid conditions, and hospital factors, blood culture contamination was associated with nearly a full extra day (0.8 days) of hospital stay (P= 0.032) and nearly a full day (0.8 days) of unneeded antibiotics (P= 0.011).

Previous studies have noted the adverse effect of blood culture contamination on clinically important outcomes, and in general, previous investigators noted a greater effect then was noted in our study. The decreased negative effect may be due to the use of rapid blood culture identification systems and the presence of a robust antimicrobial stewardship program at our institution.

Therefore, despite the use of molecular-based rapid blood culture identification systems and well-functioning antimicrobial stewardship programs, blood culture contamination continues to adversely impact patient outcomes – resulting in significantly prolonged hospital stay and unnecessary use of antibiotics. Efforts to minimize blood culture contamination continue to be justified and needed!

Sidra Liaquat MBBS, MSc, Lorena Baccaglini PhD, DDS, Gleb Haynatzki PhD, DSc, Sharon J. Medcalf PhD and Mark E. Rupp MD

Infection Control & Hospital Epidemiology (2020), 1–7. doi:10.1017/ice.2020.1337

https://www.cambridge.org/core/journals/infection-control-and-hospital-epidemiology/article/abs/clinical-consequences-of-contaminated-blood-cultures-in-adult-hospitalized-patients-at-an-institution-utilizing-a-rapid-bloodculture-identification-system/F0B57309C6FB8464591E5CAC7E37C926

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https://twitter.com/UNMC_ID?ref_src=twsrc%5Egoogle%7Ctwcamp%5Eserp%7Ctwgr%5Eauthor

We are HIRING! Unique Community ID Opportunity Tailored to Your Professional Interests

Here @UNMC_ID we are always excited for the opportunity to grow our Division, and below you will find our announcement of a new position we have!

The Division of Infectious Diseases at the University of Nebraska Medical Center in Omaha, NE is recruiting a Community ID physician to join our growing faculty.  This opportunity can be customized to fit your professional interests – whether clinical, academic, research or combination at an internationally recognized ID program of excellence.

The Division is a robust group comprised of 26 ID physicians, as well as APP’s and clinical and research support staff. We provide full spectrum infectious disease care at our clinical partner, Nebraska Medicine.   Members of the department pursue specialty interests in all areas of infectious disease. We also have an academic mission with our fellowship program and graduate medical education. 

Opportunity Highlights:

  • Provide ambulatory tele-ID consultation services in several communities across Nebraska
  • Collaborative activities with the ICAP/ASAP Program to offer infection control and antimicrobial stewardship guidance to healthcare facilities across Nebraska
  • Inpatient and outpatient care
  • Abundant clinical opportunities and/or research with protected time and support

The successful candidate must be an MD/DO (or equivalent degree) who is board certified/eligible in Infectious Diseases with excellent clinical skills and enthusiasm for patient care, teaching, and/or clinical research. Our compensation package is extremely competitive.  In addition, comprehensive benefits and relocation assistance are offered. Academic rank is dependent on qualifications. Individuals from diverse backgrounds are encouraged to apply – https://unmc.peopleadmin.com/postings/53864

Learn more:

UNMC ID –  https://www.unmc.edu/intmed/divisions/id/index.html

ID blog – https://blog.unmc.edu/infectious-disease/feed/

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