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Division of Infectious Diseases

Pharm to Exam Table: Doravirine DRIVES the way to more ART options

The Department of Health and Human Services HIV guidelines panel currently recommends antiretroviral therapy (ART) consisting of two nucleoside reverse transcriptase inhibitors plus an integrase inhibitor for most treatment naïve HIV infected individuals1.  Prior to the advent of integrase inhibitors, the utilization of non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimens had been common.   Both efavirenz and rilpivirine had been commonly used although both NNRTI’s present some challenges.  Efavirenz related neuropsychiatric adverse effects and drug metabolism enzyme induction properties present challenges for its use.  Rilpivirine has been shown to be less efficacious in naïve patients with baseline viral loads greater than 100,000 copies per milliliter or CD4 counts less than 200/cmm.  In addition, patients requiring a proton pump inhibitor cannot use rilpivirine due to its need for an acidic environment to be absorbed.  An NNRTI without similar restrictions may be beneficial.

Doravirine (DOR) is a novel NNRTI that provides a similar efficacy for the treatment of HIV infection with activity against HIV variants that are resistant to efavirenz (EFV) and rilpivirine (RPV).  Doravirine offers a better safety profile without neuropsychiatric adverse effects, minimal drug-drug interactions and is unaffected by food intake and need for an acidic absorption environment.  In August, 2018, doravirine was approved by the FDA for use and will be available solely (Pifeltro™) or as a single tablet regimen (Delstrigo™) in combination with lamivudine (3TC) and tenofovir disoproxil fumurate (TDF).

Two phase III trials, DRIVE-AHEAD and DRIVE-FORWARD, provided the basis for FDA approval.  The summary of these trials follows.

DRIVE-AHEAD2: A randomized, double-blind, phase III trial compared doravirine to another NNRTI, efavirenz. Adults with HIV-1 infection naïve to ART, HIV RNA >1,000 copies/ml, and CD4 >100/mm3 were randomized to receive DOR 100mg with 3TC 300mg/TDF 300mg or EFV 600mg with TDF 300mg/emtricitabine (FTC) 200mg. The primary endpoint of the study measured virologic response with the proportion of patients achieving HIV RNA <40 copies/ml at week 48. Comparisons between each arm were similar, 77% in DOR arm vs. 78% in EFV arm, demonstrating non-inferiority. Clinical adverse events deemed drug-related were reported in 31% of patients in DOR arm and 56% in EFV arm.  Dizziness (6.5% DOR vs. 25% EFV) and abnormal dreams (5.6% DOR vs. 14.8% EFV) had the largest variation between the two groups. Only one emergent NNRTI mutation arose to the DOR group, K101K/E mutation, which causes intermediate resistance to RPV and low-level resistance to EFV.

DRIVE-FORWARD3: A randomized, controlled, double-blind, phase III, non-inferiority trial compared doravirine to ritonavir-boosted darunavir, a protease inhibitor. Adults with HIV-1 infection naïve to ART, with plasma HIV RNA >1,000 copies/ml were screened and randomized to receive DOR 100mg or DRV 800mg/RTV 100mg (DRV/r), in combination with either TDF/FTC or ABC/3TC based on investigator choice. The proportion of patients that achieved plasma HIV-1 RNA <50 copies/ml at week 48 defined the primary endpoint of this trial. Doravirine showed non-inferiority to ritonavir boosted darunavir, with 84% in DOR arm vs. 80% in DRV/r arm achieving success with HIV RNA <50c/ml at week 48. Clinical adverse events due to drug therapy were reported in 31% in DOR and 32% in DRV/r group, with diarrhea comprising 5% of DOR patients vs. 13% of DRV/r patients. Lab abnormalities were similar between the two regimens, except LDL-cholesterol increases in <1% of DOR patients vs. 9% of DRV/r patients. Resistance testing was performed in 15 protocol-defined virologic failure (PDVF) patients, and within this group no emergent mutations to DOR were found. One case of resistance was found in a patient that discontinued treatment because of non-compliance at week 24, thus was not included in the PDVF category, encompassing resistance to DOR (V106I, H221Y, F227C) and FTC (M184V).

In summary, doravirine paired with 3TC/TDF demonstrates similar efficacy to regimens anchored by efavirenz or ritonavir boosted darunavir at week 48 in HIV infected treatment naïve patients.  Doravirine demonstrated an acceptable tolerability and safety profile with very little treatment emergent ART resistance mutations.  Studies investigating a switch to DOR/3TC/TDF in virologically suppressed experienced patients (DRIVE-SHIFT) and in ART naïve patients with NNRTI transmitted resistance are currently ongoing.  However, comparisons of doravirine based regimens versus any of the currently recommended INI based regimens is unknown.

References:

  1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Department of Health and Human Services. March 2018. Available at: http://aidsinfo.nih.gov/contentFiles/AdultandAdolescentGL.pdf.  [Accessed 4 September 2018].
  2. Orkin C, Squires KE, Molina JM, et al. Doravirine/lamivudine/TDF is noninferior to efavirenz/emtricitabine/TDF in treatment naïve adults with HIV-1 infection: week 48 results of the phase 3 DRIVE-AHEAD study. Clinical Infect Dis. (Submitted).
  3. Molina JM, Squires K, Sax P, et al. Doravirine versus ritonavir-boosted darunavir in antiretroviral naïve adults with HIV-1 infection (DRIVE-FORWARD): 48-week results from a randomized, double-blinded, phase 3, non-inferiority trial. Lancet HIV 2018; 5e211-e220.

Content provided by Kelsey Christensen, 4th year PharmD Candidate, and Josh Havens PharmD, Specialty Care Clinic Pharmacy Coordinator

Update for HIV Care Providers and Educators Revived and Reinvigorated!

Content written by Nikki Regan, APRN

After a several year hiatus, the UNMC HIV Update conference was back and better than ever.  The conference planning committee at the UNMC/Nebraska Medicine Specialty Care Clinic started organizing this event over a year ago.  “The interest was definitely there,” said Ann Fitzgerald, APRN at the clinic and AIDS Education and Training Program Director for Nebraska. “In the past we have had about 80 attendees. This year’s conference brought in over 100 participants, and according to our live polling, 40% of them were first-time attendees.”

The attendees were from diverse backgrounds, including social workers, nurses, advance practice providers, physicians, pharmacists, dentists and public health workers, with some people travelling over 50-100 miles to attend.

The HIV Update conference was jam-packed with hot topics, focused on a multidisciplinary approach to care.

  • Dr. Sara Bares kicked the morning off with a review of new and upcoming approaches for the management of HIV. She shared information about the updated treatment guidelines, as well as new FDA approvals and other treatment options coming down the pipeline, such as long-acting injectable ARV therapy.
  • Dr. Mark Malliard shared the joy and new-found simplicity of treating Hepatitis C–“You will cure their Hepatitis C, and your patients will love you.”
  • Dr. Jasmine Marcelin gave a moving presentation on the history and persistence of disparities in healthcare for people living with HIV, especially people of color. She urged the audience to move the focus from equality to equity, and ultimately—social justice.
  • Josh Havens, PharmD, discussed Pre-Exposure Prophylaxis (PrEP) for HIV negative patients and encouraged providers who aren’t yet providing PrEP to consider doing so. Unfortunately, there are few providers in the area who are prescribing PrEP at this time.
  • Dr. Jean Amoura deciphered terminology and care considerations related to transgender care.
  • Dr. Susan Swindells, Kim Scarsi, PharmD, and Precious Davis, MSN, opened up discussion of several case-based scenarios to demonstrate how the inter-professional team can work together to meet the needs of complex patients.
  • Dr. Mario Sanchez and Dr. Alex Dworak, from One World Community Health Center, teamed up to highlight the importance of addressing mental health and substance abuse disorders. Their advice for uncovering these comorbidities: “Ask. Then be prepared for the answer.”
  • Daniel Cobos, RN, MPH and Nikki Regan, APRN, wrapped up the day with an entertaining debate regarding condoms. Cobos argued that in the era of U=U and PrEP, condoms are outdated. Regan noted the increase prevalence of other STIs, as well as the underlying complexity of U=U, and suggested we “keep condoms in the conversation”.

Community partners, including Douglas County Health Department and Charles Drew Health Center, were also on hand to promote their services and interact with providers.

The Planning committee would like to thank all of their sponsors and partners for the event, including the Midwest AIDS Training & Education Center, and the Nebraska Ryan White Part B program.  The committee would also like to thank Deanna Hansen, Deb Justesen and Sara Weber for their hard work in keeping the conference running smoothly throughout the day. You can find more quotes, photos, and audience reactions to the day on Twitter: #UNMCHIV2018, and be sure to follow @UNMC_ID to be the first to hear about future conferences!

An Empiric Nudge in the Right Direction

The following review was originally posted by Dr. Marcelin to the September 2018 SHEA Journal Club and featured on Medscape’s SHEA Expert Commentary earlier this month. 

Use of empiric antimicrobial treatment in acute care settings is often the result of the “diagnosis momentum” heuristic, wherein the antibiotics started in one location for “sepsis” are continued for several additional days after transfer to a second location. Vancomycin remains one of the most commonly prescribed inpatient antibiotics, despite a decline in prevalence of invasive MRSA infections. The authors of the first article “Rate of positive cultures necessitating definitive treatment in patients receiving empiric vancomycin therapy” compared the rate of actual positive culture requiring vancomycin to the rate of vancomycin use in a single-center retrospective observational study. The majority of these infections were SSTIs, bacteremia and pneumonia.

Concern for MRSA is likely the driver of overuse of vancomycin, yet this organism was confirmed in only 8.4% of the positive cultures. Over the three-month period studied, only 11% of 1662 patients on vancomycin had a positive culture necessitating vancomycin use as definitive therapy.  This means that up to 90% of patients on empiric vancomycin can likely be safely de-escalated, especially after 48 hrs. of negative cultures.  However, convincing prescribers to discontinue presents a separate challenge for Antimicrobial Stewardship Programs (ASP).

In the second article, “Microbiology Comment Nudge Improves Pneumonia Prescribing”, the authors capitalized on the fact that perhaps most decisions to start empiric vancomycin/piperacillin-tazobactam in setting of pneumonia occur in the context of concern for unidentified MRSA or Pseudomonas aeruginosa. Even with negative cultures, are prescribers continuing these antibiotics because of a fear that these bacteria are lurking in the cultures, but missed by the microbiology lab? In active stewardship education, we can tell people “the likelihood that MRSA or pseudomonas is going to be present in a person without specific risk factors is low”. In a complex patient care scenario however, prescribers can talk themselves into the possibility of these bacteria being present even when it highly unlikely. What if the micro lab could say unequivocally that these organisms were absent; would that change practice?

In this quasi-experimental study conducted within a 4-hospital system in Detroit, the microbiology lab cultured respiratory specimens of individuals being treated for pneumonia. The lab made a simple modification to their reporting system for normal “commensal respiratory flora” (which included growth of Neisseria, Corynebacterium and Streptococcus, with no dominant growth of any single organism). The lab added the statement: “No S. aureus/MRSA [methicillin-resistant Staphylococcus aureus] or P.[Pseudomonas] aeruginosa” to the report, and the ASP provided a brief education to prescribers.  

After this behavioral nudge was implemented, prescribers were 34% (p<0.01) and 5.5-fold more likely to de-escalate antibiotics than when the report only stated “commensal respiratory flora”. Additionally, with fewer vancomycin/piperacillin-tazobactam combination days of therapy (DOT), they noted a 17% reduction in acute kidney injury (p<0.03) even after adjusting for severity of illness with APACHE II or Charlson comorbidity index scores.  The DOT of MRSA and antipseudomonal therapy was reduced from 7 to 5 days (P<0.01). The authors do not state how long their lab took to finalize cultures, but assuming at least a preliminary result of the “commensal respiratory flora” comment nudge in 48 hrs. even the intervention arm had room for earlier de-escalation, with a median empiric DOT of 5 days. Multidrug-resistant organisms (MDROs) were not generally prevalent in either group, however there was a significant difference in development of subsequent MDROs after the culture result nudge (8% vs 1%, p=0.035). Despite these significant stewardship outcomes, however, no effect on mortality, development of Clostridium difficile infection, or change in length of ICU/hospital stay was observed.

Behavioral nudges use positive reinforcement and indirect messaging to influence decision-making, and exist in many areas of our clinical environment already. Many microbiology labs already include resistance markers in the rapid diagnostic test results, which serve to passively guide prescribers to appropriate antibiotic choices. As ASPs aim to collaborate with prescribers to change behaviors, these behavioral nudges can be a useful low-effort/high-yield tool to further assist with antibiotic de-escalation, even in critically ill patients.

References:

Dustin Waters and Joshua Caraccio Rate of positive cultures necessitating definitive treatment in patients receiving empiric vancomycin therapy. Infection Control & Hospital Epidemiology, Volume 39, Issue 8 August 2018 https://doi.org/10.1017/ice.2018.123

Mary Musgrove et al.  Microbiology Comment Nudge Improves Pneumonia Prescribing. Open Forum Infectious Diseases, Volume 5, Issue 7, 1 July 2018, https://doi.org/10.1093/ofid/ofy162

Dancing with the Doctors – An Event for Child Life 

This is a theme the pediatric patients are used to: bright lights and surrounded by doctors while their families are anxiously waiting nearby hoping for the best.  This time, the patients and doctors will meet outside of the Medical Center and their hospital gowns will be replaced with ballroom gowns.

Under the coaching of Vintage Ballroom instructor, Rebekah Pasqualetto, three pediatric patients are teaming up with the doctors’ who saved them to put on the biggest performance of their young lives. The dancing isn’t easy. Between school, doctor appointments, and daily lives the girls dedicated two months to learning three styles of dance: Rumba, Merengue, and Country Swing. Each song matches the personality of each child. 11-year old Daisy likes to dance with her friends to the latest pop hits. 12-year old Maura has dance training from previous years of ballet. Even with surgery restrictions, Maura is adamant about performing a trick on the dance floor. 12-year old Raeleigh loves fashion, she is very considerate of others. Raeleigh will be joined on the dance floor by her younger sister Addisyn who suffers from watching Raeleigh undergo treatment.

The girls will not be partnered up with strangers. They will be dancing with their doctors and they love it. Unfortunately, years of medical experience do not transfer to dancing. The doctors – Alan Langnas, David Mercer, James Ford, and Sachit Patel – also need to train at Vintage Ballroom to prepare for the show.

The show is quite special. Dancers from across the country will file into the Hilton Double Tree Banquet hall for the Nebraska Dance Festival on October 20, 2018. The day-long event will be filled with hundreds of competitors trying to out-dance one another. You can find more details about the event at https://www.nebraskadancefestival.com/

Dr. Diana Florescu is coordinating the fundraiser with Child Life, Vintage Ballroom, and Nebraska Dance Festival. The organizers of Nebraska Dance Festival – Amanda & Ilya Reyzin and Igor Litvinov – are supporting Child Life Services from University of Nebraska Medical Center! Through their donation, they will share the gift of reading and spread some fun to pediatric patients at Nebraska Medicine. Hospitalization can be a scary and isolating experience for children and teens. Many of the kids are hospitalized for long periods of time – months or even years – due to the severity of their illnesses. Books and games will allow kids to experience normalcy, socialization, and continued growth and development while hospitalized.

Please come to encourage these amazing kids and watch our doctors perform! You can also support these amazing kids by donating at www.nufoundation.org to Nebraska Medicine Child Life Impact Fund (#01145270).

Content Provided By Ada Florescu

Follow @UNMC_ID at #IDWEEK2018!

IDWeek is here and we want to be sure YOU know where to find us! Below is the list of faculty presentations and posters from our Division. Please come visit us at IDWeek –  We would LOVE to meet you! 

Content courtesy of Sandy Nelson and the entire UNMC ID Division. 

Tuesday, October 2
Session: The Vincent T. Andriole ID Board Review Course
Session Title: Infections in Transplant
Presenter: Andrea Zimmer, MD
Session time: 8:00 a.m. – 5:00 p.m.
Session location: W 2005-2020

Thursday October 4
Meet-the-Professor Session
Session: Are You Ready? Outbreak Response Training
Presenter: Angela Hewlett, MD
Session time: 7:15-8:15 a.m.
Session location: S 152-154

Session: Cool Findings in Bacteremia and Endocarditis
Session Time: 11:30-12:45 p.m.
Session Location: W 2002
Presentation Title: The Effect of Insurance Coverage on Appropriate Selection of Hospital Discharge Antibiotics for Staphylococcus aureus Bacteremia
Authors: Mark E. Rupp, MD, Trevor Van Schooneveld, MD, FACP et al
Presentation Number: 158

Posters 12:30-1:45pm

Session: Antimicrobial Stewardship: Interventions Leveraging the Electronic Health Record
Presentation Title: Impact of a Best Practice Alert Linking Clostridium difficile Infection Test Results to a Severity-based Treatment Order Set
Authors: Trevor Van Schooneveld, MD, FACP, Scott Bergman, PharmD, FIDSA, FCCP, BCPS et al
Presentation Number: 178

Session: Antimicrobial Stewardship: Interventions to Improve Outcomes
Presentation Title: Respiratory Viral Testing is Associated with Lower Frequency of Antibiotic Prescribing for Acute Upper Respiratory Infections at a Large Ambulatory Cancer Center
Authors: Erica Stohs, MD, MPH et al
Presentation Number: 206

Session: Bone and joint Infections
Presentation Title: Effect of Previous Antibiotic Exposure on the Yield of Bone Biopsy Culture in Patients with Osteomyelitis
Authors: Paul Fey PhD, Angela Hewlett MD, Mark Rupp MD et al
Presentation Number: 291

Session: Fungal Disease: Management and Outcomes
Presentation Title: Breakthrough Pneumocystis jirovecii Pneumonia among Cancer Patients: Opportunity for Antimicrobial Stewardship?
Authors: Erica Stohs, MD, MPH et al
Presentation Number: 402

Session: Microbiome and Beyond
Presentation Title: Vancomycin is Frequently Administered to Hematopoietic Cell Transplant Recipients without a Provider Documented Indication and Correlates with Microbiome Disruption and Adverse Events.
Authors: Erica Stohs, MD et al
Presentation Number: 616

Friday, October 5

Posters 12:30-1:45pm

Session: Bacteremia and Endocarditis
Presentation Title: Bloodstream Infection Survey in High-Risk Oncology Patients (BISHOP) with Fever AND Neutropenia (FN): Predictors for Morbidity and Mortality
Authors: Alison G. Freifeld, MD, Andrea Zimmer, MD, et al
Presentation Number: 1016

Session: Diarrhea Diagnostic Dilemmas
Presentation Title: The Value of Hardwiring Diagnostic Stewardship in the Electronic Health Record: Electronic Ordering Restrictions for PCR-Based Rapid Diagnostic Testing of Diarrheal Illnesses
Authors: Jasmine R Marcelin MD, Caitlin N. Murphy PhD, Paul D. Fey PhD, Trevor C. Van Schooneveld MD (et. al)
Presentation Number: 1095

Session: Healthcare Epidemiology: Non-acute Care Settings
Presentation Title: Infection Control Risk Mitigation and Implementation of Best Practice Recommendations in Long-term Care Facilities
Authors:  Mark E. Rupp, MD,  Muhammad Salman Ashraf, MBBS et al
Presentation Number: 1236

Session: Healthcare Epidemiology: Non-acute Care Settings
Presentation Title: Frequently Identified Infection Control Gaps in Outpatient Hemodialysis Centers
Authors: Mark E. Rupp, MD,  Muhammad Salman Ashraf, MBBS et al
Presentation Number: 1239

Session: HIV: Diagnosis and Screening
Presentation Title: Routine opt-out HIV screening and detection of HIV infection among emergency department patients
Authors: Nada Fadul, MD et al
Presentation Number: 1273

Session: HIV: Prevention
Presentation Title: Knowledge, Attitudes and Barriers of Pre-exposure Prophylaxis for HIV Infection Among Resident Physicians in Rural, Eastern North Carolina
Authors: Nada Fadul, MD et al
Presentation Number: 1289

Session: HIV: Prevention
Presentation Title: Acceptability and Feasibility of a Pharmacist-led Pre-exposure Prophylaxis Program in the Midwestern United States
Authors: Sara H. Bares, Joshua P. Havens, Kimberly K. Scarsi, Susan Swindells et al
Presentation Number: 1294

Session: Medical Education
Presentation Title: Antibiotic Prescribing Knowledge: A Brief Survey of Providers and Staff at an Ambulatory Cancer Center during Antibiotic Awareness Week 2017
Authors: Erica Stohs, MD, MPH et al
Presentation Number: 1302

Session: Respiratory Infections: Miscellaneous
Presentation Title: Impact of a Guidance Document, Order Set Changes and Physician Education on Antibiotic Prescribing in Acute Exacerbation of COPD
Authors: Scott Bergman, Trevor Van Schooneveld et al
Presentation Number: 1480

Session:Viruses and Bacteria in Immunocompromised Patients
Presentation Title: Bloodstream Infection Survey in High-Risk Oncology Patients (BISHOP) with Fever AND Neutropenia (FN): Correlation between Initial Empiric Antibiotic Regimen Correlation and Susceptibility Patterns
Authors: Andrea Zimmer, MD, Alison G. Freifeld, MD et al
Presentation Number: 1585

Saturday October 6
Session: Febrile Neutropenia
Session Title: Infections in Immunocompromised Hosts
Presenter: Alison Freifeld, MD
Session time: 10:30-11:45 a.m.
Session location: S 214-216

Posters 12:30-1:45 p.m.

Session: HIV: Sexually Transmitted Infections
Presentation Title: Assessment of Anal Papanicolaou Smear Screening and Follow-up Rates in Eastern North Carolina for HIV-Positive Patients who are Men who have Sex with Men
Authors: Nada Fadul, MD et al
Presentation Number: 2274

Session: Antimicrobial Stewardship: Non-hospital Settings
Presentation Title: Comparison of Antibiotic Use in Post-Acute and Long-Term Care Facilities Based on Proportion of Short Stay Residents Using a Long-Term Care Pharmacy Database
Authors: Philip Chung, PharmD, MS, BCPS, Scott Bergman, PharmD, FIDSA, FCCP, BCPS, Mark E. Rupp, MD, Trevor Vanschooneveld, MD,  Muhammad Salman Ashraf, MBBS et al
Presentation Number: 1837

Session: Antimicrobial Stewardship: Non-hospital Settings
Presentation Title: Digging Deeper: A Closer Look at Core Elements of Antibiotic Stewardship for Long-Term Care Facilities
Authors: Scott Bergman, PharmD, FIDSA, FCCP, BCPS, Philip Chung, PharmD, MS, BCPS, Mark E. Rupp, MD, Trevor Vanschooneveld, MD, Muhammad Salman Ashraf, MBBS et al
Presentation Number: 1838

Session: 222. Antimicrobial Stewardship: Potpourri
Presentation Title: Adherence to Practice Guidelines for Treating Diabetic Foot
Infections: An Opportunity for Syndromic Stewardship
Authors: McCreery R, Bergman SJ, Van Schooneveld TC
Presentation Number: 1874

Session: Healthcare Epidemiology: Device-associated HAIs
Presentation Title: Evaluation of a Midline Catheter Program and Effect on Central Line Associated Blood Stream Infections
Authors: Richard Hankins, MD; Mark Rupp, MD, Kelly Cawcutt, MD, MS et al
Presentation Number: 2096

Find us on Twitter @UNMC_ID; #UNMCID #IDWEEK2018

ID Pharmacist Scott Bergman (@bergmanscott) and our ID faculty #tweeterIDians Drs. Jasmine Marcelin (@DrJRMarcelin), Kelly Cawcutt (@KellyCawcuttMD), Nada Fadul (@fadul_nada), Salman Ashraf (@M_Salman_Ashraf), Erica Stohs @EStohs will be tweeting from the conference, so join us in the conversation!


 

Intensive Infection Control experience for UNMC ID Fellows

The Nebraska Medicine Infection Control and Epidemiology Department (IC&E) is well recognized for excellence. The department is staffed by 5 full-time Infection Preventionists (IP), a data analyst, and a staff assistant; Terry Michaels, manages the department. Dr. Rupp serves as the Medical Director and is assisted by Drs. Ashraf, Cawcutt, Marcelin, and VanSchooneveld as Associate Directors.

During the first 2 years of ID Fellowship, UMMC ID fellows have terrific opportunities to learn about infection prevention and the hospital infection control program. Each fellow has a month-long elective in infection control – during that month of intense study, they learn the nuts and bolts of hospital infection control. Working alongside experienced IPs and medical directors, ID fellows have hands on observation of infection surveillance, healthcare associated infection prevention efforts, and outbreak investigation.

During the month rotation a small special project is also conducted and a specialized curriculum/lecture series is conducted. ID fellows are exposed to the infection control literature during a monthly infection control journal club in which they take turns critiquing recent publications along with IPs and faculty. The infection control experience is capped off by attendance of the SHEA/CDC basic course in Hospital Epidemiology. For the ID fellow interested in infection control as a career, opportunity for a third year of Fellowship directed toward specialized training in infection control and hospital epidemiology is encouraged.

Additional opportunities for experience and research in infection control is afforded through the CDC/Nebraska HHS-funded Infection Control Assessment and Promotion Program (ICAP) that is charged with improving infection control practices in health care settings (long-term care, critical access hospitals, acute care, dialysis units, ambulatory surgical centers, etc.) across the state of Nebraska. Learn more about the Nebraska ICAP directed by Dr. Salman Ashraf at https://icap.nebraskamed.com/

To learn more about individual infectious disease faculty working in infection control in the recent projects and publications, see the ID division website at https://www.unmc.edu/intmed/divisions/id/index.html

Content provided by Dr. Mark Rupp MD, Division Chief and Medical Director of Infection Control and Epidemiology

Allergy Emancipation

The following was originally posted to the Controversies in Hospital Infection Prevention Blog on 9/24/18 by Dr. Marcelin.

September 28, 2018 marks 90 years since Sir Alexander Fleming discovered penicillin as an effective antimicrobial which would soon save millions of lives. He warned soon afterwards that unless we used penicillin judiciously, we would see antibiotic resistance, and he was right. With decades of inappropriate antibiotic prescribing, we have dug ourselves a deep hole of antimicrobial resistance, and inaccurate penicillin allergies is but one shovel used to put us in this mess. How? Simple If/And/Then construct: IF unverified penicillin allergies lead to unnecessary/inappropriate use of broad-spectrum antibiotics which contributes to antimicrobial resistance, AND antimicrobial resistance is a public health problem, THEN unverified penicillin allergies are a public health problem.

In a single day on hospital service the Infectious Diseases consult team encountered a few patients with beta lactam allergies: one had developed significant angioedema in the last year with amoxicillin; another had developed a questionable rash on nafcillin therapy; a third recalled his mother telling him that he turned green after receiving oral penicillin as a child. Our approach: in the first case we avoided penicillin; in the second, we recommended a cephalosporin graded challenge which the patient tolerated; in the third, after detailed history we gave the patient full dose amoxicillin-clavulanate, he tolerated it well and he was able to discharge without IV antibiotics. These are fantastic cases for teaching purposes, but additionally, how exhilarating it is to liberate a patient from an irrelevant penicillin “allergy” and give them appropriate treatment upfront!

Penicillin allergies are frequently documented drug allergies in the hospital setting, with 10% of Americans reporting a penicillin allergy.  Some penicillin allergies are real. However, most penicillin allergies are either inaccurate or inconsequential, with only 1% of Americans actually demonstrating true allergy upon testing. Furthermore, most patients with true penicillin allergies lose hypersensitivity over time, and by 10 years after the event, 80% of patients are no longer penicillin allergic. Can you imagine if all potential food allergies were treated the same as penicillin allergies? People wouldn’t eat at all! Most people, if they have what they think might be a reaction to a food they like, might either try the food again or get tested to know for certain they cannot eat that food. But 50 years ago, if they had a rash that coincided with penicillin administration, it would never occur to them to try it again.

Once a penicillin allergy is listed in a patient’s record, they are more likely to receive inappropriate broad-spectrum antibiotics – a practice that can be both costly and have worse clinical outcomes.  Patients with methicillin-susceptible Staphylococcus aureus bacteremia treated with vancomycin instead of a beta-lactam have higher mortality rates than those receiving appropriate beta-lactam therapy. Patients undergoing surgery who receive alternative antibiotics for preoperative infection prophylaxis (due to reported penicillin allergies) have a 50% higher risk of developing a surgical site infection than those who appropriately receive beta lactam prophylaxis.

The Infectious Disease Society of America (IDSA) and Society of Healthcare Epidemiology of America (SHEA) recommend that patients with reported beta lactam allergy should undergo beta lactam allergy skin testing. Allergy verification and penicillin allergy skin-testing are becoming more recognized components of antimicrobial stewardship and de-labelling allergies can have significantly improved patient outcomes.  Following a simple algorithm can help to easily identify patients suitable for skin testing and could avoid almost 3 weeks hospitalization and 1000 days of second-line antibiotics. However in some situations or in low-resource settings, it may not be practical to perform skin testing on everyone who reports a penicillin allergy. In a previous blog post about beta-lactam skin testing I mused about whether better allergy histories are more bang for the buck, since a structured allergy history can potentially decrease inappropriate 2nd line antibiotic use by 26%.

There’s an age-old joke that if a team wants a detailed history on a patient, just consult ID. If our attention to detail is already expected, shouldn’t we feel empowered to take that allergy history and de-label the penicillin allergy?  Inpatient allergy consultations are difficult to coordinate when those divisions may be understaffed and allergists are busy with outpatient practices.  So how can we capitalize on their expertise when they can’t see the patient in the hospital? Simple: partner with them to create guidance for practice, utilize ordersets for allergy de-labelling and facilitate outpatient allergy evaluations after discharge.

In honor of Sir Alexander Fleming and National Penicillin Allergy Day, let us pledge to emancipate our patients from the fake allergies. Go on, get that detailed history! Get some penicillin skin testing! Do that graded challenge! Give that first line beta-lactam antibiotic! But for goodness’ sake when you do, please DELETE the allergy from the health record so that the ordeal does not have to be repeated!

UNMC ID Division Accolades!

Our Faculty at University of Nebraska Medical Center Division of Infectious Diseases have worked hard to maintain a strong academic presence at UNMC. We are a growing division, filled with faculty at all stages of their careers, and their collective academic prowess has our division leading the pack.  We are proud of our faculty and would like to share some of their accomplishments with our followers.

Dr. Angela Hewlett has been elected to the Executive Board of the Musculoskeletal Infection Society and will serve as MSIS President in 2020. She was recently an invited delegate at the International Consensus Meeting on Periprosthetic Joint Infection in Philadelphia, where experts in orthopedic infections from around the world (over 80 countries were represented) came together to develop a document based on the available scientific evidence and consensus when evidence is lacking, that can be used to improve the care of patients with musculoskeletal infections. Dr. Hewlett will be an invited speaker at #IDWeek2018 at the Meet the Professor Session on outbreak preparedness. She also published  the book,  Bioemergency Planning: A Guide for Healthcare Facilities.

Dr. Jasmine Marcelin was awarded the SHEA Race Against Resistance Scholarship, funding provided for a new Antimicrobial Stewardship clincian to learn more about the field. Dr. Marcelin partnered with Physicians Weekly to co-moderate two twitter chats on Minorities in medicine, and was recently featured on the cover of the July issue of Helio Infectious Diseases News in an article discussing Women in Infectious Diseases.

Dr. Susan Swindells was awarded the Department of Medicine Faculty Clinical and Educational Mentoring Award.

Dr. Trevor Van Schooneveld was recently named UNMC College of Medicine Resident Program Director of the Month in September (ID Fellowship Program Director)

CRE or not CRE: A Question of Risky Business and Notes from the Field

The following was originally posted by Dr. Marcelin to the August 2018 SHEA Journal Club 

Carbapenem-resistant Enterobacteriaceae (CRE) are not as prevalent in the United States as they are in the Eastern Hemisphere; however travel within our global village means creates opportunity for movement of these organisms to our region.  The following is a review of two studies on risk predictors for CRE and three “Notes from the field” investigations from the CDC.

 The Rapid Prediction of Carbapenem Resistance in Patients With Klebsiella pneumoniae Bacteremia Using Electronic Medical Record Data. Timothy Sullivan et al.   Open Forum Infectious Diseases, Volume 5, Issue 5, 1 May 2018

In this study, the authors created a model to predict the likelihood of carbapenem resistance (as defined by imipenem MIC ≥2μg/mL) in Klebsiella pneumoniae bacteremia. 613 individual cases of K. pneumoniae bacteremia occurred over a 4 year period, with a 10% imipenem-resistance rate. Logistic regression was used for the initial model development, which was subsequently re-validated using additional statistical methods.  The model included the following; colonization with imipenem-resistant Klebsiella pneumoniae, hospital location (ICU/med-surg vs low-risk units), age (>60yrs), total oral or intravenous antibiotic days of therapy (in the past 2 years) and inpatient days (in the past 5 years). The model correctly predicted imipenem resistance in 73% of cases, with a specificity of 59%; positive predictive value of 16% and negative predictive value of 95%. All culture data present in the EMR were available to the model, eliminating manual searches when making decisions about empiric therapy. The negative predictive value is high, but lack of generalizability could limit the clinical utility.

Using Patient Risk Factors to Identify Whether Carbapenem-Resistant Enterobacteriaceae Infections Are Caused by Carbapenemase-Producing Organisms Patricia Simmer et. al  Open Forum Infectious Diseases, Volume 5, Issue 5, 1 May 2018

In this brief report, authors identified risk factors for having a CP-CRE (as compared to non-CP-CRE). Their retrospective, single-institution cohort included 96 hospitalized individuals who had CRE over a one-year period, with an incidence of CRE that year of 4%. CP-CRE isolates (predominantly K. pneumoniae) were identified in 47% of the patients. They found that CP-CRE isolates were more commonly identified in patients with recent international healthcare exposure within six months (27% vs 2%; odds ratio [OR], 18.18; 95% confidence interval [CI], 2.26–46.53); and patients who were recently transferred from a post-acute care facility (31% vs 12%; OR, 3.39; 95% CI, 1.17–9.78). Considering the prevalence of CP-CRE in regions outside the United States, should we be more intentional about asking travel history when patients are being admitted to the hospital?

The following snippets are Notes from the Field published in MMWR with new information about CRE organisms:

Verona Integron-Encoded Metallo-Beta-Lactamase–Producing Pseudomonas aeruginosa Outbreak in a Long-Term Acute Care Hospital — Orange County, Florida, 2017/MMWR Danielle Rankin, MPH et. al

The first VIM-producing Pseudomonas aeruginosa in Florida was detected in an outbreak of colonized patients at a long-term acute care hospital in Orange County. One patient was first identified in July 2017, followed by six additional patients identified in the subsequent months at the same facility. Only 2 isolates were closely related.

Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae from Less Common Enterobacteriaceae Genera — United States, 2014–2017/MMWR Maroya S. Walters, PhD et. al

CRE Surveillance by the Minnesota Department of Health revealed 20 CP-CRE from less common Enterobacteriaceae genera (i.e. not Klebsiella spp., Enterobacter spp. or E. coli). 7 IMP-producing Providencia rettgeri and 6 KPC-producing Citrobacter freundii predominated. Most patients with these isolates were currently hospitalized; two were previously hospitalized internationally in the last year.

Notes from the Field: Domestically Acquired Verona Integron-Mediated Metallo-β-Lactamase-Producing Enterobacteriaceae — Indiana, 2016–2017/MMWR DJ Shannon, MPH et. al

There is a question of possible regional emergence of VIM-producing CRE, with 7 patients & 9 isolates reported in Indiana between 2016-2017. One patient had three different VIM-CRE organisms isolated; all patients had prior overnight local hospitalizations and none had prior international travel within the past 6 months.


 

What’s all the buzz about West Nile Virus?

This summer, we have seen several cases of West Nile infection, prompting many questions related to the infection.

So, what’s all the buzz about West Nile? Drs. Jasmine Marcelin and Kelly Cawcutt compiled some answers to Frequently Asked Questions about West Nile.

What is West Nile Virus?  West Nile Virus is spread via mosquito bites.  Mosquitos get the virus by biting infected birds.  In North America, the virus causes disease seasonally from summer through fall, with peak infections occurring in August and September.  

Where can you get it? West Nile cases have been reported in all of the continental US states in the past, and most thus far in 2018. This year, as of CDC’s September 4 report, the leading states with cases of West Nile were North Dakota, Nebraska and South Dakota, respectively.

Who gets it? Anyone can get West Nile Virus. Besides mosquito bites, it has been spread through blood transfusions, organ donation, vertically from mother to fetus and via breast milk. Patients over age 60 are higher risk for developing infection, including serious complications.

What are the symptoms/signs of West Nile Virus infections? Most patients will not develop symptoms of infection, with only about 20% of patients falling ill. Symptomatic infection may include fever, muscle aches, headache, weakness or other nonspecific symptoms of a viral illness. According to the CDC, approximately 1 in 150 patients will develop severe, potentially fatal, infections from West Nile Virus.

Are we seeing more cases than usual this year? West Nile Virus infections vary year-to-year, but yes, there are more confirmed cases in Douglas County this year compared to last year (7 confirmed cases in 2017). In Nebraska, we already have seen more cases thus far than the entire season last year (79 cases and 4 deaths already compared to 68 cases and 2 deaths last year), but the season is not over.  Over the past several years, there are many seasons with much higher rates of infection in the state.

Is there more neuroinvasive disease than in the past? Neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis) occurred in about 46% of West Nile Virus infections over the past 18 years of surveillance. In the state of Nebraska, 42of the 79 cases of West Nile Virus infections this year have been classified as neuroinvasive. Nationally, of the 231 cases of West Nile Virus infections reported nationally to the CDC to date, 55% have been neuroinvasive cases. However, we are just at the peak of the season and will likely see more cases that are not neuroinvasive as the season progresses.

How do I test for it? Should I re-test? In general, diagnosis of West Nile Virus requires testing blood for antibodies to the virus. IgM antibodies present indicate a current or recent infection. If a person has neurologic symptoms (concerning for neuroinvasive disease), lumbar puncture is recommended with testing of the cerebrospinal fluid for West Nile IgM. If the initial IgM test is negative but suspicion for West Nile Virus is high, the antibody test should be repeated in 10 days (Convalescent testing), particularly if symptoms persist.

What is the treatment? The best treatment is time.There is no specific medication to treat infections due to West Nile Virus. Patients with this infection usually require symptomatic management, like fluids, supplemental oxygen, etc. Other treatments like antivirals, intravenous immunoglobulin (IVIG), or plasma exchange have not been proven to be beneficial.

Can it be prevented? There is no vaccine for West Nile Virus.  You can prevent West Nile infection by preventing mosquito bites. Use long sleeves, pants and insect repellents such as DEET or Picardin. Check out the EPA repellent information to help choose the best option here: https://www.epa.gov/insect-repellents/find-repellent-right-you

References:
https://www.cdc.gov/westnile/index.html 
https://www.cdc.gov/westnile/statsmaps/preliminarymapsdata2018/disease-cases-state-2018.html


 

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