Division of Infectious Diseases

Pharm to Exam Table: Monoclonal Antibodies Make Their Way into HIV Treatment

Pharm to Exam Table: Clinical Pharmacology/Antimicrobial Updates – Trogarzo® (ibalizumab-uiyk), a new monoclonal antibody treatment approved for multi-drug resistant HIV-1

 On March 6th 2018, the Food and Drug Administration approved a new monoclonal antibody called ibalizumab-uiyk, marketed under the tradename Trogarzo®. Ibalizumab-uiyk (IBA) is an intravenous treatment administered every two weeks. It is intended for use in combination with other antiretrovirals (in an optimized background regimen), for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection, failing their current antiretroviral regimen.(1)

IBA is a humanized long-acting IgG4 monoclonal antibody that prevents attachment of the HIV-1 molecule to CD4+ T cells by changing the conformation of the CD4+ T cell receptor while preserving the function of the cell.  These functions classify IBA as an entry inhibitor.(1,3,4) Other previous entry inhibitors are enfurvitide (fusion inhibitor) and maraviroc (CCR5 antagonist). 

The FDA approval was based on results of study TMB-301 (N=40), an open-label study that investigated the antiviral activity and safety of IBA when administered with an optimized background regimen (OBR) in treatment-experienced patients with multi-drug resistant HIV-1. The study followed patients prospectively over 24 weeks after dosing them with IBA and their OBR.  At day 14, 83% of patients achieved at least a 0.5 log10 (roughly 70%) viral load reduction from baseline seven days after receiving the IBA loading dose. By week 25, the mean change from baseline viral load was -1.6 log10 with 55% of participants having a ≥1 log10 reduction in viral load. The most common drug-related adverse reactions (incidence ≥ 5%) were diarrhea (8%), dizziness (8%), nausea (5%) and rash (5%). Serious adverse events were reported in 23% (9/40) of participants and of these only one was considered drug-related (immune reconstitution inflammatory syndrome, IRIS).(1,2,4)

IBA is the first monoclonal antibody entry  inhibitor approved for HIV infection. Given its unique properties, tolerable safety profile, lack of drug-drug interactions or antiretroviral cross-resistance, IBA offers an attractive antiretroviral option for adjunct treatment of multi-drug resistant HIV-1 infection in combination with an Optimized Background Regimen.

References
1 Trogarzo ® [package insert]. TaiMed Biologics USA Corp., Irvine, California; 2018 
2 TaiMed Biologics Inc. Ibalizumab Plus Optimized Background Regimen in Patient With Multi-Drug Resistant HIV. Available from: https://clinicaltrials.gov/ct2/show/NCT02475629
3 Iacob S A, Iacob D G. Ibalizumab targeting CD4 receptors, an emerging molecule in HIV therapy[J]. Frontiers in microbiology, 2017, 8: 2323.
4 Lewis S et al. Long-acting ibalizumab in patients with multi-drug resistant hiv-1: a 24-week study. CROI, 2017 (Poster).

Images courtesy the Department of Health and Human Services AidsInfo website HIV/AIDS glossary on CCR5 Antagonists and Fusion Inhibitors.

Thanks to Chao Fu, UNMC PharmD candidate 2018 for providing concept for content.

Tune into this AMAZING Podcast : The Hot Zone: Biocontainment with Dr. Hewlett

 

Dr. Angela Hewlett recently was interviewed via podcast for a Travel Medicine show regarding biocontainment, including how to treat and handle highly infectious agents(yes, including Ebola). The blog posts include everything from what biocontainment is to worse case scenarios and other unique aspects of preparing for, and providing care for, people with these types of infections. The namesake for this podcast is a book regarding origins of the Ebola virus (this link is informational only, there is no benefit, financial or otherwise, to Dr. Hewlett or anyone involved with this blog post in regards to sales or sharing of this book).

You can access this podcast at: http://travelmedicinepodcast.squarespace.com/

 

Interested in learning more about Biocontainment?

Check out our the National Ebola Training and Education Center and the Nebraska Medicine Biocontainment Unit.

 


 

Nebraska Antimicrobial Stewardship Summit: A Step Forward in Fighting Antibiotic Resistance

The CDC estimates 30% of all antibiotics prescribed in outpatient setting in the US are unnecessary. Similarly 30% of antibiotics used in hospitals are estimated to be unnecessary or incorrectly prescribed. Inappropriate antibiotic prescribing in long-term care facilities have been found to be even higher in some studies (up to 75%). Improving antibiotic use is essential in the fight against antibiotic resistance. In the US, more than 2 million illnesses are caused by antibiotic resistant bacteria, leading to 23,000 deaths annually. Antibiotic use is also strongly associated with C. difficile infection which is another major public health threat. C. difficile infections are responsible for 250,000 illnesses requiring hospitalization or affecting already hospitalized patients and leads to 14,000 deaths each year in the US.

Antibiotic use in Nebraska is reported to be higher than the national average. Prescribing providers and healthcare institutions in Nebraska realize the need to pay attention to this important issue. Our colleagues at Nebraska Antimicrobial Stewardship Assessment and Promotion Program (ASAP) with the support of Nebraska DHHS Healthcare Associated Infections (HAI) prevention team have been working with various healthcare facilities across Nebraska to improve antibiotic prescribing. There are many other organizations in the state collaborating with the Nebraska DHHS HAI team and Nebraska ASAP for the same goal. It is quite evident that healthcare facilities and prescribing providers are on-board in promoting appropriate antibiotic use in the state and developing antimicrobial stewardship programs (ASP) in their facilities. However, they need some support and guidance on best implementation strategies and effective use of the resources.

In order to meet the needs of healthcare facilities and prescribing providers in the state, Nebraska DHHS HAI team and Nebraska ASAP partnered with various local and regional organizations to organize a summit on antimicrobial stewardship. Nebraska Antimicrobial Stewardship Summit will be held on Friday June 1, 2018 in La Vista, NE. Many well known national and regional subject matter experts will be speaking at the summit. They will describe the rationales for developing ASP across the healthcare continuum. They will also outline simple strategies for ASP implementation in a variety of healthcare settings and share available resources to facilitate the process. There will be a networking session during the lunch, where attendees can find out how various organizations in the state can help them successfully implement ASP in their facilities.

The Nebraska Antimicrobial Stewardship Summit will be very helpful for any healthcare workers who are thinking about or already working on promoting appropriate antibiotic prescribing at their healthcare facility. Join us in the fight against antibiotic resistance! Register for the Summit at https://www.unmc.edu/cce/catalog/clinicmed/ne-as-summit/index.html. Follow @UNMC_ID on twitter for updates on #NebStewardSummit2018.

 

Content provided by Dr. M Salman Ashraf, Associate Professor, Division of Infectious Diseases, Department of Internal Medicine, Co-Medical Director, Nebraska Antimicrobial Stewardship Assessment and Promotion Program; Medical Director, Nebraska Infection Control Assessment and Promotion Program

 

Precious Davis, BSN, MSN on Why I Love ID

Why I Love ID:

“Before beginning nursing school, I always had a strong desire to give back to my community by educating and bringing awareness to the high STD rates in Douglas County. Throughout my career, I encountered some setbacks because of lack of enough work or educational experience to work in the field. While finishing my Masters Degree earlier this year, an HIV Case Management position became available, I jumped at it. Lo and behold, here I am today at the Specialty Care Clinic!  I am now able to collaborate with organizations within the community on patients referred to our clinic. What I love most about ID is being able to share my own personal experiences with patients that are receiving STD treatment and those from my community that need encouragement and reinforcement of compliance.”

-Precious Davis, BSN, MSN

See more about UNMC ID here.


 

Going Global for Biopreparedness – International Workshop on High-Level Isolation

Preparedness for outbreaks of infectious diseases is a critical, global issue, and several physicians from the UNMC Division of Infectious Diseases and other team members from the Nebraska Biocontainment Unit organized and participated in the International Workshop on High-Level Isolation in late April  The conference, which was held at the National Institutes of Health (NIH), was hosted by the National Ebola Training and Education Center (NETEC), Johns Hopkins Center for Health Security, National Institutes of Health, Centers for Disease Control (CDC) and the Assistant Secretary for Preparedness and Response (ASPR).

International Workshop on High Level Isolation participants, representing 14 countries around the world

Representatives from high-level isolation units from 14 countries around the world convened to share experiences and discuss issues like high level isolation unit design, clinical care and personal protective equipment in an interactive forum.   This international collaboration provided opportunities for the sharing of information and networking that are of utmost importance to enhance global preparedness for highly hazardous communicable diseases.

Getting ready to learn during the meeting.

To learn more about the Nebraska Biocontainment Unit, visit www.nebraskamed.com/biocontainment

To learn more about the National Ebola Training and Education Center, visit www.NETEC.org

 

 


 

Happy Administrative Professionals Day!

If you work in an office at all, chances are you have come into contact with an Administrative Professional.  The impact of an Administrative Professional on their office team has been compared to glue or paperclips that keep the office together. Our Administrative Professionals are an integral part of our group here at UNMC ID.  Sure, they help with things like setting up meetings, lectures, organizing receipts and appointments; but the best part of our people here are the intangibles. These individuals are so well integrated into our daily routines that it can be easy to take them for granted, but if they are absent for some reason, it becomes more obvious to us how much we rely on them for our days to go smoothly. In addition to the administrative duties, our Administrative Professionals are like family. They routinely visit our faculty and fellows to say hi, to check in with us to make sure we are staying sane, help new faculty and staff get acclimated, organize collections of food and money to help our colleagues in the division during difficult times, celebrate our birthdays and achievements, and give hugs or hold our hands when we have losses or disappointments. They do all of these things without ever asking for recognition.

It is sometimes easy to get caught up in the moment of “special days”, and it is wonderful to lavish gifts and flowers on those who tirelessly strive to preserve our routines at  work.  However, we should all develop the habit of thanking our Administrative Professionals EVERY DAY, not just on this one day, because if you really think about it, without them, our worlds at work might truly fall apart.

To our own Administrative Professionals in the UNMC ID Division: Deanna Hansen, Deborah Justesen, Sandy Nelson, Jonathan Nguyen and Regina Shumaker, and to ALL Administrative Professionals in every professional setting: THANK YOU for all you do! 

World Meningitis Day 2018: #AllMeningitisMatters

It’s World Meningitis Day! #Meningitis affects more than 2.8 million people globally each year.  Meningitis can be a scary disease.  It can be contagious, debilitating, and even deadly.  That’s why it is important to understand what it is, how to recognize it and how to prevent it.

What is meningitis?

The meninges are a set of tissue membranes that line the skull and vertebral column, encasing the brain and spinal cord.  The primary function of the meninges is to protect the central nervous system. If these membranes becomes inflamed for any reason, this condition is called meningitis.

When should we suspect meningitis and how do we diagnose it?

Symptoms of meningitis can progress quickly over hours, or slowly over several days. Individuals with meningitis may complain of fever, headache, nausea, and neck pain or stiffness.  Bright lights or loud sounds may make them feel worse. Without treatment, these symptoms may progress to confusion, stupor, coma or even death.

When these symptoms are identified, medical professionals will obtain a lumbar puncture. This procedure helps to diagnose meningitis by obtaining a sample of fluid from around the spinal cord.  Specific tests should be ordered to look for evidence in the fluid of bacterial, fungal, viral, or even parasitic causes if history suggests.

What causes meningitis?

Viral Meningitis

  • Viral infections by far are the most common cause of meningitis. Enteroviruses are the most common virus identified but the list of viruses causing meningitis is long.
  • Some viral meningitis syndromes can be caused by viruses spread by mosquitoes in warmer weather (such as West Nile Virus)
  • Viral meningitis is typically less severe and most people get better on their own in 7-10 days
  • Some people receive antivirals like acyclovir while awaiting results of spinal fluid testing to rule out herpes simplex virus (HSV) infection
  • Vaccines exist for VZV, mumps, measles and rubella (MMR). These vaccines help prevent systemic disease from these viruses, and subsequently reduce the risk for developing meningitis.

Bacterial Meningitis

  • The most common bacteria responsible for meningitis are: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b (HiB), group B Streptococcus, and Listeria monocytogenes.
  • Some of these organisms, like Streptococcus pneumoniae and Neisseria meningitidis, can be found in the back of the nose and throat of perfectly healthy people. When they get into the wrong place, (i.e. the central nervous system) they start to become a problem.
  • It’s important to note that Meningococcal Meningitis caused by Neisseria meningitidis is not transmitted through casual contact and generally thought of as less contagious than the common cold or flu. However, those with close physical contact or anyone with exposure to an infected person’s saliva via a cough, sneeze or a kiss should be receive antibiotic prophylaxis and contact precautions should be taken
  • There have been outbreaks of bacterial meningitis due to serogroup B meningococcal disease, and meningitis vaccination is recommended for college students
  • If bacterial meningitis is suspected based on spinal fluid testing and presenting symptoms, healthcare professionals will prescribe antibiotics targeting the most likely organisms (empirically) until this information is confirmed.
  • Vaccines exist for Streptococcus pneumoniae, Neisseria meningitidis (may have some protection against gonorrhea as well!!) and Haemophilus influenzae B (HiB)  

Fungal Meningitis

  • Fungal meningitis is rare and usually associated with those with a weakened immune system, like persons living with HIV, cancer patients or transplant recipients.
  • Fungal meningitis cannot be spread between individuals like bacterial meningitis; usually they occur if a person has been exposed to the fungus in the environment and subsequently develops a weakened immune system
  • The types of fungi called endemic fungi can be found in the soil of specific geographic regions. Cryptococcus can be associated with bird droppings. Histoplasma can be associated with bird/bat droppings and is most commonly seen in the Midwest near the Ohio and Mississippi rivers. Blastomyces is also common in soil from the Midwest, and Coccidioides is typically seen in the Southwestern US and South America.
  • A  recent multistate outbreak of fungal meningitis was associated with use of contaminated steroid epidural or paraspinal joint injections; many fungi were isolated in the outbreak, but the most commonly identified organism was Exserohilum rostratum.

 Parasitic Meningitis

  • Meningitis due to parasites is even more rare than fungal meningitis.
  • Some parasites can cause a type of meningitis called eosinophilic meningitis. These are Angiostrongylus cantonensis, Baylisascaris procyonis, and Gnathostoma spinigerum . People can be infected with these parasites by ingesting under-cooked food contaminated with their eggs.
  • Another type of parasitic meningitis is caused by an amoeba called Naegleria fowleri. This causes Primary amebic meningoencephalitis, which is a typically fatal brain infection. People are infected with this organism through contaminated freshwater when it enters the nose forcefully such as when swimming or diving in lakes or rivers, therefore consider plugging your nose as you enter the water if you dive or swim in freshwater.

Non-infectious Meningitis

  • These causes of meningitis include cancer, autoimmune disorders like lupus and drugs including non-steroidal anti-inflammatory medications and antibiotics.
  • Non-infectious Meningitis cannot be spread from person to person.

Treatment and Prevention of Meningitis

  • Think about meningitis if you or your loved one develops any of the symptoms described above.
  • Antibiotics are needed for bacterial meningitis, but do not help with other types of meningitis
  • The most effective way to prevent meningitis is through vaccination when available.
  • If you come into close contact with someone with a known case of bacterial meningitis, your doctor may prescribe you an antibiotic to help prevent you from developing bacterial meningitis too.
  • People who are at most risk for developing meningitis or complications include babies and elderly people, those with weak immune systems and people who do not have a functional spleen. These people should definitely be vaccinated if possible.

Take Away: Meningitis can be scary, so don’t be afraid to ask your local Infectious Diseases specialist for help!  Many of the worst cases can have good recovery if treated early and effectively.

Content courtesy Drs. Randy McCreery MD (IM PGY3, incoming UNMC ID Fellow), and Jasmine R Marcelin MD (UNMC ID Physician)


 

Happy Medical Laboratory Professionals Week!

Providing medical care for a single patient takes a village of health care professionals, and among these, we have some unsung heroes we would like to recognize this week – our Laboratory Professionals!

In Infectious Diseases, we rely heavily on our colleagues working in the lab, particularly in the microbiology lab. They process the cultures and tests to help us identify infecting organisms, determine which antibiotics will kill a certain bacteria, virus or fungus and help push medical care forward through research.  We simply could not do our jobs without all of their hard work, because, just as the hospital never sleeps, neither does the lab.

Thank you for all you do to help us provide excellent care for each and every patient we see!

 

Photos courtesy of Dr. Paul Fey. 


 

Headed to #ECCMID2018? UNMC ID will be there!

UNMCID is a versatile Infectious Diseases Division, with faculty active in multiple clinical/research pursuits. Some of our faculty are just returning from #SHEA2018 in Portland OR, and others are headed to Madrid Spain to participate in #ECCMID2018 this week from April 21-24. 

If you are going to be in Madrid this week, here’s where to find us at #ECCMID2018. Below is the list of faculty presentations, posters and moderated sessions from our Division.  Find us on Twitter @UNMC_ID ; #UNMCID

Click here for the ECCMID Conference Programme with interactive sessions and schedules. Find out more about #ECCMID2018 and the European Society of Clinical Microbiology and Infectious Diseases.

Poster Presentations

Sunday, April 22 2018 – 12:30-1:30pm

Session name: Bacterial infections in patients with cancer

  • Abstract number: 2926
    Title: Bloodstream infection survey in high-risk oncology patients (BISHOP) with fever and neutropenia (FN): clinical data
    Alison G Freifeld  MD, Andrea J Zimmer MD, Baddley JW; El-Boghdadly Z; Maziarz EK, Montoya JG, Rolston KV, Shoham S; Strasfeld LM; Young JH, Zhang Y, Meza J
  • Abstract number: 4157
    Title: Bloodstream infection survey in high-risk oncology patients (BISHOP) with fever and neutropenia (FN): microbiology data
    Rolston KV, Alison G Freifeld MD,  Andrea J Zimmer MD, Baddley JW; El-Boghdadly Z; Maziarz EK, Montoya JG, Shoham S; Strasfeld LM; Young JH, Zhang Y, Meza J

    Dr. Andrea Zimmer, Assistant Professor of Medicine, Oncology Infectious Diseases Faculty

    Dr. Alison Freifeld, Professor of Medicine, Oncology Infectious Diseases Director

Losing Ground Against Gonorrhea – The Rising Antibiotic Resistance

April is Sexually Transmitted Infection (STI) Awareness month  and there is a critical need to raise awareness toward preventing these infections in all our patients. In the past, most STIs were easily treated with readily available antibiotics, but unfortunately, the story of Gonorrhea has taken a turn down a frightening road.

Gonorrhea is the 2nd most commonly reported transmissible disease and therefore carries recommendations for annual screening among sexually active women < 25 years old and as needed screening for at-risk men and women with unprotected sexual encounters. Testing is simple and done with swabs or urine testing. Sexual partners within the last 60 days are at risk for infection and should be contacted and advised to seek medical care and presumptive treatment. The most recent CDC guidelines recommend treatment with both ceftriaxone and azithromycin, however, these options are starting to run out.

In late March, the UK reported a case of drug-resistant Gonorrhea acquired in southeast Asia that was resistant to, and failed treatment with, first line antibiotics (ceftriaxone and azithromycin) for Gonorrhea. Reports of ceftriaxone resistance have already been reported in several countries. The risk of the eventual emergence of untreatable Gonorrhea is real – and terrifying.

The CDC has been monitoring, and working to prevent, the evolution of drug-resistant Gonorrhea since the 1980’s but it appears we are losing the battle. Resistance has been increasing overtime, with the loss of fluoroquinolones already complicating our current treatment strategies. If cephalosporin and macrolide resistance increase in prevalence, the treatment options are dismal.

So, where do we go from here?

The threat of antibiotic resistance is ever-looming and prevention of the spread of this organism is crucial. Counseling patients on safe sex practices cannot be overemphasized in its importance. Following guidelines for screening, reporting and treating are critical to surveillance and in preventing accidently under-treatment which risks creating increasing resistance patterns. More research is needed on other treatment possible existing treatment options, development of new antibiotics and there may be some hope of future vaccine prevention of gonorrhea.

Wondering how you can help today? Help us raise more awareness of this critical issue – share this information and the above resources with patients, colleagues and on social media.  A healthier future for all demands action now.

 


 

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