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Division of Infectious Diseases

VAE – A Perpetual Prevention Problem

Ventilator-Associated Events (VAEs) were adopted by the National Health Safety Network (NHSN) in 2013, and have subsequently been associated with worse patient outcomes. However, the shift to VAE has left controversy as to both its value, and how best to prevent it.

Recently, Zhu et al published a large study focused on risk factors and outcomes from VAEs. This study again demonstrated worse outcomes for those with VAEs. Yet, again despite a large cohort of patients, we lack the causality needed to understand how to improve VAEs, and subsequent patient-centered outcomes, beyond simply avoiding mechanical ventilation.

Drs. Cawcutt and Van Schooneveld published a related commentary in Infection Control and Hospital Epidemiology entitled Caution, Not Causality: The Limitations of Risk Factor & Outcome Research on Ventilator-Associated Events, highlighting many of the issues that plague research on VAEs – from the limited data on VAE-related outcomes, to the multifactorial etiologies of VAE (not all VAE’s are related to pneumonia), and finally, the limitations of retrospective research providing associations, but not causality, for VAE’s amongst adult patients on mechanical ventilation.

VAE’s do seem to matter for patient outcomes, justifying the surveillance and metrics. But, we lack adequate understanding on most effective preventative strategies. With the recognition that VAEs may not be infectious, evidence-based, holistic approaches to best practices for mechanically ventilated patients are needed.

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UVGI N95 Decontamination – a Method to Extend the Supply of N95 Respirators in Time of Emergency

Outbreaks due to respiratory viruses pose a unique threat to health care as they require often significant amounts of personal protective equipment. Based upon previous modeling of severe influenza pandemics, the need for N95 filtering face piece respirators (FFRs) would range between 1.7 and 7.3 billion FFR’s, however there were only an estimated 60 million FFRs available at the time of the onset of the COVID-19 pandemic [1].

Given this known threat and likely shortfall of FFRs, work has been done to evaluate the efficacy and safety of maximizing the use of FFRs in the context of pandemic situations. Strategies have included prolonged use, as well as decontamination and reuse which may be employed in the context of FDA issued emergency use authorization. This paper is an overview of decontamination strategies as well as the particular data supporting the evidence for decontamination and reuse at the Nebraska Medical Center with the use of ultraviolet light germicidal irradiation (UVGI).

Findings of this review include that multiple strategies may be employed dependent upon resources and requirement for facilities, and that UVGI is a feasible and effective strategy for large-scale decontamination and reuse of FFRs with recognition of certain limitations. Advantages of UVGI include a generally low resource requirement with high output for reuse of FFRs with evidence for efficacious decontamination for many target pathogens (including many respiratory viruses), and evidence for efficacy in particular for 3M 1860, 1870, and 1870+ N95 respirators. However, limitations include strap integrity reduction over multiple irradiation cycles and the use, thus limiting the total number of cycles for FFR decontamination and reuse and the inability to apply UVGI to all N95 respirators.

UVGI decontamination can safely be used in times of emergency to extend the supply of N95 respirators. However, each N95 respirator model is different and the efficacy of UVGI decontamination should be confirmed for each model before broad application. In addition, manufacturer’s recommendations for single use should be reinstituted when adequate supplies of FFRs are available. A more sustainable approach to respiratory protection with the use of elastomeric respirators or powered air purifying respirators (PAPRs) should also be considered. Finally, it is important to recognize that PPE is but one intervention in a fully functional respiratory protection plan that includes engineering and administrative controls.

For more information, click here for the article.

1) MillsD,Harnish DA, Lawrence C, Sandoval-PowersM, Heimbuch BK. Ultraviolet germicidal irradiation of influenza-contaminated N95 filtering facepiece respirators. Am J Infect Control. 2018;46(7):e49–55. https://doi.org/10.1016/j.ajic.2018.02.018.

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COVID Vaccine Trial – Update & Future Adolescent Opportunities

The University of Nebraska Medical Center and Nebraska Medicine are participating in an international clinical trial to evaluate the safety and effectiveness of Novavax COVID-19 vaccine for adults. 

Novavax vaccine is a protein-based vaccine from the coronavirus spike protein and is adjuvanted with saponin-based Matrix-M™ to enhance the immune response and stimulate high levels of neutralizing antibodies. It does not contain live virus, it cannot replicate, nor cause COVID-19.

Initially in the trial, two of three participants received vaccine and one of three received placebo. At this point, participants who first received the vaccine will receive placebo, and participants who received placebo first will now receive the vaccine. This crossover design ensures the administration of active vaccine to all participants in the trial. Crossover participants will remain blinded to their courses of treatment to preserve the ability to assess efficacy of the Novavax vaccine. All participants will be followed for up to two years to monitor the safety and durability of the protection from the vaccine.

The company is now expanding the vaccine trial to include adolescents. If you would like to be notified about the opportunity to participate in the adolescent trial, you can email us at unmcvaccine@unmc.edu

Dr. Diana Florescu is leading the UNMC Novavax trials

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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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