Division of Infectious Diseases

Do you really need to test the poo? Diagnostic stewardship for (outpatient) diarrheal illness

Rapid molecular testing has changed the landscape of diagnostic approaches to many infectious disease syndromes, including diarrheal illnesses. These panels typically have the capacity to diagnose multiple organisms in one test. The FilmArray gastrointestinal pathogen panel (BioFire) tests 22 stool pathogens. Despite the impact of improved clinical efficiency, these tests are often expensive, especially in the outpatient setting, but the convenience of a comprehensive testing panel can lead to unnecessary testing.

Recent IDSA guidelines on management of diarrheal illness only recommends rapid diagnostic testing in patients who are immunocompromised or those with fever, severe diarrhea, abdominal pain, bloody stools. Clark et al. sought to validate these recommendations in the outpatient setting by evaluating the yield of the molecular testing, and clinical outcomes.  In this retrospective study, 629 patients were included in the analysis, and over two-thirds of patients had a duration of diarrhea greater than 14 days.

Given the possibility of asynchronous testing without face-to-face encounter, physical exam findings were not included in assessment, only documentation of patient-reported abdominal pain. Only 20% of the specimens actually had pathogens detected, and were clinically relevant in only 5% of patients (19/107 in immunocompromised patients vs 14/522 immunocompetent patients, p<0.001).

The authors validated that the IDSA guideline-based criteria had a sensitivity of 97% (95% CI 84.2-99.9), specificity of 33.9% (95% CI: 30.1-37.8), negative predictive value of 99.5% (95% CI: 97.3-100.0), and a positive predictive value of 7.5% (95% CI: 5.2-10.4). They found that application of these testing criteria would have avoided testing in 32% of patients, and avoided unnecessary antibiotics) in 23% of patients.

The authors concluded that duration—based criteria for testing stool is not warranted, however given the higher prevalence of clinically relevant pathogens in immunocompromised patients (who may demonstrate fewer systemic symptoms), broadly testing in this patient population is reasonable. C. difficile was not included in this study, and guidelines recommend two-step testing for C. difficile infections (rather than single-step PCR, as would be the case for this panel).

The retrospective nature and absence of clear physical exam findings limit the findings. Nevertheless, this study emphasizes the opportunity for diagnostic stewardship to decrease inappropriate testing without significant clinical penalty, and identifies immunocompromised patients as a valuable subgroup where less restricted use of this test for diarrhea is reasonable.

Citation: Stephen D Clark, Michael Sidlak, Amy J Mathers, Melinda Poulter, James A Platts-Mills, Clinical yield of a molecular diagnostic panel for enteric pathogens in adult outpatients with diarrhea and validation of guidelines-based criteria for testing, Open Forum Infectious Diseases, ofz162, https://doi.org/10.1093/ofid/ofz162


 

 

Dr. Elizabeth Schnaubelt promoted to Lieutenant Colonel in the US Air Force

Please join us in extending congratulations to Dr. Elizabeth Schnaubelt for her promotion to Lieutenant Colonel (Lt Col).  This is a very significant achievement that is given in recognition of a military officer’s expertise, professionalism, and leadership abilities.  Here is a little bit of background on Lt Col Schnaubelt’s role here, and how she found her way to Omaha:

Dr. Schnaubelt joined the UNMC/Nebraska Medicine team last summer when she was assigned as the inaugural medical director for the U.S. Air Force Center for Sustainment of Trauma Readiness Skills (C-STARS) Omaha. C-STARS Omaha’s mission is to advance the readiness skills and competency of U.S. Air Force (USAF) medical personnel so they can provide safe and effective care for patients who have contracted or may have been exposed to highly hazardous infectious diseases.  To accomplish the C-STARS Omaha mission, Dr. Schnaubelt and her team also work closely with the Nebraska Biocontainment Unit.  In addition to her significant responsibilities as the C-STARS Omaha medical director, Dr. Schnaubelt carries a substantial clinical load, attending on the General Infectious Diseases and Orthopedic Infectious Diseases services in the UNMC ID Division, and fully participates in the clinical and educational missions of UNMC.

Lt Col Schnaubelt began her military career as a Cadet at the United States Air Force Academy with hopes of flying fighter jets.  Her focus quickly changed after a visit to Haiti where she realized that her true passion was a career in medicine.  After the academy she attend medical school at Loyola University Chicago. Dr. Schnaubelt completed her internal medicine residency at Wright State University, and infectious diseases fellowship at San Antonio Military Medical Center. Following her medical training, she was deployed to Afghanistan, and was then assigned to Landstuhl Regional Medical Center in Germany.

Landstuhl Regional Medical Center (LRMC) is the largest U.S. medical treatment facility outside of the United States.  In additional to providing medical care to U.S. personnel in Europe, LRMC is uniquely positioned to treat the most critically ill patients who are evacuated from Iraq, Afghanistan, and countries in Africa.   While at Landstuhl, Lt Col Schnaubelt was recognized as the top field-grade (e.g., senior level) physician in the USAF when she earned the USAF Clinical Excellence Award in 2015. This award recognized her work as the infectious diseases medical lead on a team that developed contingency plans for treating and managing Ebola infected patients evacuated through Europe, from Africa.

Following her assignment in Germany, Dr. Schnaubelt was selected as an Epidemic Intelligence Service (EIS) officer and served in the Global Tuberculosis Prevention and Control branch at the Centers for Disease Control and Prevention in Atlanta, GA.  As an EIS officer she traveled and worked internationally as part of an effort committed to reducing the burden of TB in the world by conducting innovative, impactful and programmatically relevant research, and by providing technical assistance to national TB programs while working directly with country-level Ministries of Health.   Her international work included projects in China, Lesotho, Malawi, Namibia, Uganda, and Vietnam.   Upon completion of her EIS assignment, Dr. Schnaubelt relocated to Omaha for her current position.

Congratulations, Dr. Schnaubelt, on a well-earned promotion, recognizing your talents and long list of accomplishments.  We appreciate you and thank you for your service, as both a military officer, and an UNMC ID faculty member.

Nadal Fadul, MD on Why I Love ID

Why I love ID and UNMC:

The strong commitment to serving the community, the great opportunities provided to faculty; and my former colleague, Salman Ashraf, who is very happy here!  I chose ID because my passion is taking care of people living with HIV, however, I enjoy all of ID and the intellectual challenge it poses.

Something about myself unrelated to my work:

I enjoy reading and writing poetry in Arabic.

 


 

The Antimicrobial Stewardship Program: Keeper of the S. aureus bacteremia Checklist Manifesto

Staphylococcus aureus bacteremia (SAB) is a serious and sometimes devastating infection. There are established guidelines for optimal management, and more recently, numerous studies have shown the benefits of Infectious Diseases consultation, including improving guideline-adherent management, and reducing hospital stays, 30-day readmissions, and in-hospital mortality. Pharmacist-driven initiatives embedded within the Antimicrobial Stewardship Program (ASP) have also been shown to improve quality of care for patients with SAB.

In this study, Remtulla et al. described the impact of combining unsolicited prospective audit and feedback (PAF) a standardized SAB bundle on SAB management. ASP pharmacists used the SAB bundle once per patient, to make PAF recommendations to teams whose patients developed SAB. The SAB patients were identified to the ASP by twice-daily microbiology laboratory emails, only during normal business hours on non-holiday weekdays. The SAB checklist recommendations included ID consultation, repeat blood cultures, empiric therapy recommendation (vancomycin unless MSSA known), echocardiogram, duration of therapy guidance, and source control recommendations.

In their analysis of 199 patients, PAF recommendations were accepted at a rate of 92.6%, and 44% of the recommendations were for ID consultation. SAB bundle adherence increased from 29.0% to 72.8% (p<0.001) in the intervention group, with statistically significant (p<0.001) increases in ID consultation (56.5% vs 93.4%), guideline-adherent therapy (83.9% vs 99.3%), echocardiography (72.6% vs 95.6%), and duration of therapy (87.0% vs 100%). Reductions in 30 day readmission and 30 day mortality rates were not statistically significant, likely owing to the small study size.

Implementation of this SAB bundle seemed to augment the impact of ID consultation, because even in the intervention groups without ID consultation, the adherence to the bundle elements approached that of the pre-intervention groups with ID consultation.

This is yet another study demonstrating the ease of implementation of checklists/bundles for improving quality of patient care. Other studies have shown that automatic ID consultation for SAB can lead to better patient outcomes. However, the resources needed for automatic consultation may not be available to all hospitals, and this study provides another pharmacist-driven protocol that can also improve outcomes. Further improvements in an approach like this should include a mechanism for weekend/holiday notification in the absence of pharmacist presence, or inclusion of rapid diagnostic testing such as detection of mecA gene to facilitate earlier definitive treatment during uncovered periods.

 

Citation: Shahileen Remtulla, Karen Zurek, Carlos Cervera, Cristina Hernandez, Mao-Cheng Lee, Holly L Hoang, Impact of an Unsolicited, Standardized Form–Based Antimicrobial Stewardship Intervention to Improve Guideline Adherence in the Management of Staphylococcus aureus Bacteremia, Open Forum Infectious Diseases, Volume 6, Issue 4, April 2019, ofz098, https://doi.org/10.1093/ofid/ofz098


 

Bryan Alexander, PharmD on Why I Love ID

Why I love ID:

I love academic medicine; working jointly with an interdisciplinary team of experts to sort out the most complex clinical cases excites me. There is no place in the region that fulfills each of the aspects of that statement better than Nebraska Medicine.

While more and more of the practice of medicine necessarily moves to the long-term management of chronic disease states, infectious disease is one area where we are routinely able to cure a patient’s medical condition and appreciate the satisfaction that can bring for them. Also, the pathogen-host-antimicrobial interaction is fascinating and unique in medicine from a pharmacotherapy perspective. Drug therapy can be complicated enough in other areas without the host and its associated resistance mechanisms further complicating things, which makes being an ID pharmacist very intellectually rewarding. Finally, microbes are some of the most diverse, important, and fascinating entities on our planet. There’s always so much more to appreciate and learn (or re-learn!).

I also love:

I’ve always loved music, but developed an particular appreciation for opera in high school, which I was able to foster while living in Chicago and Baltimore/D.C. during my university years. I then lived away from a city without access to live performances for about a decade and had two small children. Now having moved here and with children that are a bit older (7 and 4), my wife and I have been excited to attend Opera Omaha and share more aspects of our love for music with them.

 


 

When you see CRE: Add Equal Parts Antimicrobial Stewardship and Infection Control

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

Dealing with carbapenem resistant organisms presents both an antimicrobial stewardship and infection control problem. Richter et al. aimed to predict risk factors for carbapenem resistance among Gram-negative rods (CR-GNR). The authors were particularly interested in whether differences exist in risk factors for development of ertapenem-resistance (ER-GNR), versus resistance to antipseudomonal carbapenems (ACR-GNR). This was a retrospective study over a 6-year period (2011-2016) evaluating cultures from any source from a mixed patient population of patients with malignancy, transplant patients, and those in the ICU.  The final analysis included 14292 GNR isolates, with 274 ER-GNR (majority Klebsiella species) and 618 ACR-GNR (mostly Pseudomonas species), and both groups of CRE were more common in respiratory cultures.

Multivariate analysis identified predictors of ER-GNR including renal disease, admission from another healthcare facility, mechanical ventilation prior to culture, receipt of any anti-MRSA agents within 30 days, and receipt of carbapenems within 30 days. Both test and validation models had a reliable c-statistic of 0.74 and 0.73 respectively. Predictors of ACR-GNR were similar. However, instead of renal disease, male sex was another predictor of ACR-GNR, and the test and validation models had reliable c-statistics of 0.76 and 0.77 respectively. They then assigned points to these models to predict likelihood of development of resistance.

Despite limitations including missing data, the authors suggest their risk scores may be more accurate at predicting carbapenem resistance than antibiograms since they are dynamic and can be automated. Carbapenem resistance was effectively ruled out (<5% likelihood) at scores of <6 in the ER-GNR model and <4 in the ACR-GNR model. This scoring system could be useful in guiding empiric antimicrobial therapy when patients present with sepsis, but may be less useful for locations where resistant GNRs are less prevalent.

Little is known about clinical outcomes in patients colonized with carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) who develop CP-CRE of a different genotype. Chen et al. conducted a retrospective cohort study of patients colonized with CP-CRE who went on to develop clinical infection. Of the 73 CP-CRE carriers who went on to develop infection, 65 developed clinical infection with the same CP-CRE genotype with which they were colonized. Eight developed clinical infection with a different genotype. After adjusting for age, severe clinical presentation and clinical isolate genotype, the authors found that patients whose clinical CP-CRE isolate was different from that with which they were colonized, had significantly increased mortality at 14 days (aRR, 6.36; 95% CI, 1.75–23.06; P = .005) and 30 days (aRR, 3.29; 95% CI, 1.22–8.90; P = .019).

This is a very small study in an area where the authors state the general prevalence of CP-CRE carriage is low, and clinical infection with a different genotype of CP-CRE was not common. However, it generates questions about current isolation practices for patients with CRE. Geographically cohorting patients with CP-CRE may help to reduce transmission to uncolonized patients, but this study raises the questions as to whether this practice may have unintended consequences of transmission of different CP-CRE genotypes between colonized patients, leading to worse outcomes.

References:
Stefan E Richter, Loren Miller, Jack Needleman, Daniel Z Uslan, Douglas Bell, Karol Watson, Romney Humphries, James A McKinnell; Risk Factors for Development of Carbapenem Resistance Among Gram-Negative Rods, Open Forum Infectious Diseases, Volume 6, Issue 3, 1 March 2019, ofz027, https://doi.org/10.1093/ofid/ofz027

 

Wen Kai Chen, Yong Yang, Ban Hock Tan; Increased Mortality Among Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Carriers Who Developed Clinical Isolates of Another Genotype, Open Forum Infectious Diseases, Volume 6, Issue 2, 1 February 2019, ofz006, https://doi.org/10.1093/ofid/ofz006

Congratulations to UNMC ID Faculty designated as Top Teachers for 2018!

After every rotation, medical students and Internal Medicine Residents at UNMC submit evaluations on their faculty members. The Department of Internal Medicine pools all of the evaluation data and designates the faculty with the top 33% of evaluation scores as “Top Teachers”.  For the year 2018, three of our Infectious Disease faculty members who attend on the General ID Service and participate in Medical Student Education were awarded this honor.

Meet our Internal Medicine 2018 Top Teachers from UNMC ID!

Dr. Sara Bares 

Assistant Professor of Medicine; Associate Director of the Specialty Care Clinic; Director of the UNMC COM HIV Enhanced Medical Education Track; Co-Director of UNMC COM Defenses & Invaders Microbiology Course

Dr. Jasmine Marcelin

Assistant Professor of Medicine; Associate Medical Director, Nebraska Medicine Antimicrobial Stewardship Program; Associate Medical Director, Nebraska Medicine Infection Control & Epidemiology; Co-Director of the UNMC COM HIV Enhanced Medical Education Track; Co-Director of Digital Innovation & Social Media Strategy for Division of Infectious Diseases

Dr. Trevor Van Schooneveld

Associate Professor of Medicine; Medical Director, Nebraska Medicine Antimicrobial Stewardship Program; Program Director, UNMC Infectious Disease Fellowship; Associate Medical Director, Nebraska Medicine Infection Control & Epidemiology

The UNMC ID Division would like to congratulate Drs. Sara Bares, Jasmine Marcelin, and Trevor Van Schooneveld for being awarded Top Teachers in 2018.

This is the 4rd Top teacher award for Dr. Bares, and 9th for Dr. Van Schooneveld. Dr. Marcelin received the award for 2018 in her first year of eligibility since joining the UNMC ID faculty. 

This is yet another testament to our Division’s commitment to Medical Education and growing the next generation of Infectious Disease Doctors!


 

UNMC ID Ebola Expert Dr. Angela Hewlett shares the Nebraska Experience

Dr. Angela Hewlett presented ‘Clinical Management of Ebola: The Nebraska Experience’ at Grand Rounds at the University of Wisconsin on Friday April 19th 2019.  Dr. Hewlett was invited by Internal Medicine Chief Resident Dr. Samantha Murray-Bainer as part of the University of Wisconsin Dream Speaker series, where each Chief Resident is given the opportunity to select a Grand Rounds speaker that has been influential to them.

We are thrilled to celebrate this honor with Dr. Hewlett, a testament to her expertise, influence and contribution to the field of Infectious Diseases and Biopreparedness.

Here’s the link to Dr. Hewlett’s Grand Rounds presentation:

https://www.youtube.com/watch?v=5UuD5BJWyZY&list=PLdxJ3bo-hgxRcZ8JQAb8XATB4AElpqzXW&index=31

Photo: Dr. Samantha Murray-Bainer (Chief Resident), Dr. Angela Hewlett, and Dr. Elizabeth Trowbridge (Chair, Department of Internal Medicine), University of Wisconsin

Content courtesy: Dr. Hewlett

Does de-escalation of anti-MRSA therapy for culture-negative pneumonia affect patient outcomes?

Nosocomial pneumonia is a common hospital-acquired infection and has a high mortality rate in the critically ill.  Because drug-resistant bacteria like Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) are commonly responsible for these infections, guidelines recommend broad-spectrum empirical therapy that includes anti-MRSA coverage.  Treatment is ideally de-escalated and refined based on culture results.  However, culture negative infections leave a conundrum for clinicians who want to protect their patients but also minimize morbidity and inappropriate antimicrobial use.

Cowley et al. recently published a retrospective study in Chest evaluating the safety of anti-MRSA de-escalation by measuring 28-day mortality, hospital mortality, intensive care unit (ICU) and hospital length of stay (LOS), incidence of treatment failure, and incidence of acute kidney injury (AKI) in patients who were de-escalated compared to those who were not after negative culture result.  De-escalation was defined as transition to a narrower spectrum antibiotic (without MRSA coverage) within 4 days of culture. Of the 279 patients identified with culture-negative nosocomial pneumonia, 79% received vancomycin for MRSA coverage and 92% had some pseudomonal coverage in their empiric treatment.  Ninety-two met the de-escalation criteria.

The de-escalation group had a significantly higher incidence of chronic kidney disease at baseline, but the groups were otherwise well matched. There was no significant difference in 28-day mortality or treatment failure between the groups.  The de-escalation group had a shorter time to transfer out of the ICU and discharge, and they also experienced less AKI.

As Dr. Cawcutt wrote in her review, “De-escalation in culture-negative pneumonia may result in lower AKI and ICU and hospital LOS. There is clear potential benefit for patients and overall health care systems in advocating for earlier de-escalation, regardless of whether or not nares swabs were completed.”

This post is based on Dr. Cawcutt’s review in IDSA Journal Club, available here.  You can read the original article here.


 

Inter-Professional Relationships in HIV Pre-exposure Prophylaxis

We’re excited to feature a recent publication borne from student-faculty collaboration that highlights the importance of interdisciplinary care!

Dr. Jordan Broekhuis, the lead author, is one of our former HIV Enhanced Medical Education Track (EMET) students who is now a surgery resident at Beth Israel Deaconess.  He completed his EMET work here at UNMC under the mentorship of Drs. Sara Bares and Susan Swindells.  Their paper, “Midwest pharmacists’ familiarity, experience, and willingness to provide pre-exposure prophylaxis (PrEP) for HIV,” was published in PLoS One in November.  We recently talked to the authors about their work.

Could you give us a short summary of your work and what motivated you to conduct this study?

Pharmacists in Nebraska and Iowa were asked to complete a survey to gauge their familiarity, experience and willingness to provide HIV pre-exposure prophylaxis (PrEP).  PrEP  is underutilized and pharmacists could potentially play a role in expanding access to PrEP providers, especially in states such as Nebraska and Iowa where regulations support the implementation of collaborative practice agreements which allow for the delegation of responsibilities from the collaborating prescriber to the pharmacist.

What were some of your key findings?

While respondents had limited familiarity and experience with PrEP, most indicated a willingness to provide PrEP if given the opportunity to do so via a collaborative practice agreement and after additional training. 

What do you see as future directions for this research and pharmacist education around the use of PrEP?

This survey laid the groundwork for implementation of a pharmacist-led PrEP (P-PrEP) initiative here in Omaha.  We shared preliminary results of our P-PrEP project at IDWeek 2018 and hope to disseminate the final results soon.

You can read their full article here.  Interested in learning more about UNMC’s EMET program?  See our features of current and former EMET students and read more about the program here.


 

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