photo Dr. Kris Bryant

Message from Dr. Kris Bryant, PIDS President

Now, more than ever, the world needs pediatric infectious diseases specialists. Your energy in taking care of patients. Your expertise in developing infection prevention and treatment protocols. Your creativity in designing studies to understand the pathogenicity of the virus and its impact on children, and developing new diagnostics.

To those of you who have been working on the frontlines of the pandemic, especially those of you in Washington, California and New York, please let us know how we, as your friends and colleagues, can support you from afar. Please let us know how the Society can support you.

I believe PIDS can play a vital role in facilitating an exchange of information about COVID-19 between experts in our field. On March 18th, a presentation originally scheduled for the St. Jude/PIDS conference was presented as a webinar. Dr. Mark Denison presented "Learning from SARS-COV-2". He was joined by Dr. Janet Englund ("The Seattle Flu Study") and Dr. Hana Hakim ("Infection Control of Coronavirus"). A recording of the webinar can be found on the PIDS website. A special thank you to St. Jude Children's Research Hospital for their ongoing support of PIDS and the PID community.

PIDS Connect is a place to share policies and general strategies that you have found effective in your respective hospitals and communities. Many thanks to colleagues in Seattle who have taken a lead in this area and have been making their policies readily available to all. I am thrilled to announce that Janet Englund and members of Seattle Children's team have organized a special COVID-19 Webinar for Grand Rounds and will be sharing this via Webex next Thursday, March 26 at 11 am ET/8 am PT. Presenters include:

  • Dr. Ruth McDonald, MD, Nephrology, Seattle Children's
  • Dr. Alpana Waghmare, MD, Infectious Diseases, Seattle Children's
  • Dr. Tony Woodward, MD, MBA, Emergency Medicine, Seattle Children's
  • Dr. Danielle Zerr, MD, MPH, Infectious Diseases, Seattle Children's
  • Moderator: Dr. Kristina Toncray, MD, Hospital Medicine, Seattle Children's

I hope many of you will join us on Thursday. I anticipate the recorded presentation will be available online. Click here for more details.

In closing, I am going to state the obvious. This is an incredibly exhausting, stressful time. The following cartoon was created by Signe Wilkinson, a cartoonist at the Philadelphia Inquirer and Daily News. Signe is a friend and colleague of Jonathan Zimmerman, the husband of our Secretary-Treasurer Susan Coffin. Jonathan contacted Signe and asked for permission to share the cartoon widely and Signe graciously agreed. As Jonathan noted, "There are a huge number of people who need to see this and feel the sense of encouragement and support for the hard work they are doing and the even harder work to come."

See it online at: https://www.inquirer.com/health/coronavirus/coronavirus-healthcare-workers-hospitals-social-distancing-medicine-20200317.html.

I also encourage you to read the text of an Op-Ed below published in USA Today. I have removed the author's name from this communication at his wife's request. She generously noted, "This is not about me. This is about all of us."

Feel free to reach out to me with questions, concerns, and requests. We will try to keep the work of the Society moving forward, recognizing that many of you have no spare minutes in your day.

As best you can, take of yourselves.

Kris

The real heroes among us

I recently read that Penguin is rushing to publish a reprint of the English translation of "The Plague," the 1947 Albert Camus novel about an Algerian town decimated by a deadly infection. Earlier this month, the book sold out of stock on Amazon. Purchases of the Italian version have tripled; so have sales of the book in France, where Camus wrote it in the waning days of World War II.

That's because of the coronavirus crisis, of course, which made me dip into my wife's tattered copy of "The Plague." And that's where I recognized her.

My wife, that is.

She's too modest to be named here, but suffice to say that she is a physician at a major hospital in our area. Her job is to help prevent and treat infections, both at the hospital and in our broader community.

Since the crisis began, she has been working 16 to 18 hours a day. She has arranged coronavirus tests for hospital staff and others. She has advised doctors — at her institution, and elsewhere — about how to care for infected patients, and how to see that they do not infect others. And she has worked with state and local government officials to control the outbreak.

That means talking or texting on the phone, from dawn through the wee hours of the night. It means listening to all of the requests that come in, and carefully addressing each one. It means consoling people who are panicked, and getting people who are too casual to step it up.

I have observed all of this effort with enormous admiration, and also with a touch of envy. I take my own job seriously, but nothing I do will ever be as significant as what she is doing right now. She is not just my wife. She's my hero.

But if you used that term to describe her — and if she found 10 free seconds to reply —she would scoff at it. She's not some rugged surgeon or emergency-room doctor like you see on the TV melodramas, saving lives between commercials for car insurance and laundry detergent.

Yet that's also what makes her an actual hero, not a Hollywood one. The real heroes among us don't command our attention. They work behind the scenes, making sure that everything around us works as well.

Do we have the right protocols in place for handling the sick? Do we have enough masks, and gloves, and hand sanitizer? And is our staff trained to use them? Not sexy stuff, and not something that most people ever think about. But my wife does.

She's not alone, of course. By now, you've surely read about the nursing home in Kirkland, Washington, that was ravaged by coronavirus. But you probably haven't read about the nearby hospital, where everyone shifted into high gear.

Engineers mobilized to seal off rooms so contaminated air would not escape. Sanitation crews worked overtime to clean every space. And with protective helmets in short supply, nurses put sanitary pads inside them to provide extra insulation. These people are the real heroes, precisely because they don't see themselves that way.

And that's also how they resemble Bernard Rieux, the doctor who narrates "The Plague." As bodies pile up around him, Rieux works tirelessly to aid the sick and dying. But he rejects all the fancy talk about sacrifice and selflessness, which doesn't really matter when you've got a plague going on.

"This whole thing is not about heroism," Rieux tells a friend. "It's about decency. It may seem a ridiculous idea, but the only way to fight the plague is with decency."

The friend asks him what "decency" means. "In general, I can't say," Rieux replies, "but in my case I know that it consists of doing my job."

When this crisis has passed, there will be another, and then another. My wife will be there, working with quiet decency to protect the rest of us. This whole thing is not about heroism, for her. She's just doing her job.

Greetings,

Now is the time when we traditionally begin promoting IDWeek 2020 and registration for members. However, these are unprecedented and unpredictable times, as you and your colleagues in the ID community are on the frontlines of the COVID-19 pandemic.

coronovirus illustration

PIDS continues to work to provide links to COVID-19 resources. Our sources include those provided by the U.S. Centers for Disease Control and Prevention, the American Academy of Pediatrics, the Society for Healthcare Epidemiology of America, and the Infectious Diseases Society of America. See COVID-19 Resources

President Trump Must Invoke Defense Production Act Now for Medical Supply and Equipment Production

Infectious disease and HIV physicians, healthcare epidemiologists and other medical professionals on the frontlines defending our country from COVID-19 urgently need equipment and supplies to protect themselves, identify infections, treat patients, and save lives. In health settings across the country, we are confronting shortages of essential equipment—including viral culture swabs, gloves, masks, eye protection, gowns and ventilators—that we need now to diagnose and treat patients and to maintain a healthy and sufficient workforce in the face of this fast-moving and destructive virus.

The Publications Committee, consisting of 17 members (including three PIDS fellows) and jointly led by the PIDS Past President Paul Spearman and the past Past President Janet Gilsdorf, is charged with developing, overseeing, and promoting the Journal of the Pediatric Infectious Diseases Society (JPIDS), the scientific journal owned by the Society.  We meet annually at IDWeek and hold several telephone conferences each year.  In conjunction with the Editor-In-Chief (Theo Zaoutis), the Associate Editors, the editorial board, and the publisher (Oxford University Press) of JPIDS we monitor its publishing and financial performance.  

Members of the Committee, as well as the Society at large, are encouraged to develop and identify financial supporters for potential supplements (which advantage the Society financially) and to submit outstanding scientific papers to the Journal.  Further, members are reminded that accepted articles are citable even before they are assigned to an issue of JPIDS. 

Recent Committee-endorsed activities of the Journal include the uneventful move to online-only publication and to bi-monthly issues.  Further, the latest impact factor of 2.443 is strong evidence of the Journal’s success.  With input from Oxford University Press, we continue to monitor the cOAlition S initiative and its Plan S movement toward universal open access of scientific journals and its potential impact on the Journal. 

The Society’s contract with Oxford University Press ends December, 2020, and as we consider a renewed contract, the Committee is working closely with our publications consultant Dr. Morna Conway to examine new models of our financial relationship with the publisher that will result in a higher net monetary return to PIDS, a simplified structure that reduces the administrative burden on PIDS, and increased protection from risk for PIDS.  Toward this end, we plan to hold a JPIDS strategy meeting with Dr. Conway at PIDS headquarters in April. 

IDSA, SHEA and PIDS Announce 2020-2021 LEAP Fellowship Awardees

IDSA, SHEA and PIDS are pleased to announce the 2021 awardees of the Leadership in Epidemiology, Antimicrobial Stewardship, and Public health (LEAP) Fellowship.  Currently in its second iteration, the LEAP Fellowship is a $100,000 training award competitively granted to four promising young infectious diseases physicians.  Funded by the Centers for Disease Control and Prevention, this fellowship aims to foster the next generation of Infectious diseases leaders in public health, hospital epidemiology and antimicrobial stewardship, giving them the hands-on experience they’ll need to lead and collaborate across these disciplines of healthcare.

Awardees

Angela “Holly” Villamagna, MD, Oregon Health and Science University

Leap Fellowship Project: Beyond coronavirus: establishing best practice guidance and assessing acceptability of international travel screening in Oregon acute care hospitals. 

Partner Health Department:   Oregon Health Authority

Sophie Katz, MD, Vanderbilt University Medical Center

Leap Fellowship Project:  Creating a Sustainable and Scalable Outpatient Antimicrobial Stewardship Intervention in a High-Prescribing State: Development of Provider Feedback Reports and Academic Detailing Strategies through User Centered Design.

Partner Health Department:  Tennessee Department of Health

Do Young Kim, MD, Rush University Medical Center

LEAP Fellowship Project:   Building Hospital Organizational Capacity and Knowledge to Control Candida auris (BLOCK-CA).

Partner Health Department:  Chicago Department of Public Health 

Daniel Dodson, MD, University of Colorado

LEAP Fellowship Project:  Improving assessment and implementation of antibiotic stewardship: a partnership between state public health, academic medicine, and community hospitals.

Partner Health Department:  Colorado Department of Public Health and Environment

The LEAP Fellowship will commence July 1, 2020 and last one year.  The Fellowship is for early career infectious diseases physicians - those in their second or third year of fellowship or up to two years post fellowship.  For those interested in future years of the LEAP Fellowship, please visit https://idsociety.org keyword “LEAP Fellowship” for the most up-to-date information.

Coronavirus disease-19 (COVID-19) cases continue to climb in the US and abroad. At least twenty-two states have announced confirmed cases, and several states report community transmission. The Centers for Disease Control and Prevention have predicted that widespread transmission of COVID-19 in the United States is likely to occur.  Our members are actively engaged in the identification of potential patients, hospital preparedness, and coordination of the public health responses.  We have an incredible group of experts who bring essential expertise to the table.

In the face of what expert are calling a public health emergency, cancellations of long-anticipated meetings have been necessary. Earlier this week, out of an abundance of caution, the difficult decision was made to cancel the St. Jude/PIDS meeting. As noted in an email to attendees earlier this week, leaders wanted to avoid unnecessary exposures to the immunocompromised children of St. Jude.   Today, the Society for Healthcare Epidemiology of America’s Board of Trustees unanimously decided the 6th Decennial International Conference on Healthcare Associated Infections will no longer occur March 26 – 30, 2020, recognizing that many of the participants "have a substantial role in addressing COVID-19 globally." 

PIDS is committed to supporting members engaged in combatting the COVID-19 outbreak.  Please join us for a 90-minute presentation on COVID-19 by PIDS member Dr. Mark Denison on Friday March 13 from 12:00-1:30pm EST.  Dr. Mark Denison is an internationally recognized virologist whose laboratory studies the model coronavirus, mouse hepatitis virus (MHV), to understand the replication, cell biology, and protein functions of coronavirus. Over the last two decades, the Denison Laboratory has been called upon to define the replication of SARS coronavirus (SARS-CoV), MERS coronavirus (MERS-CoV), and the newly emergent SARS-CoV-2. Dr. Denison and his team have played an integral role in developing virus mutants as live virus vaccine candidates and characterized the potential effect of novel antiviral compounds in disrupting replication and pathogenesis of coronaviruses. The goal of this talk will be to review what we know about COVID-19 infections, the biology of SARS-CoV-2, potential therapeutic interventions, and future needs.  Additionally, don't forget to read Dr. Stanley Plotkin’s article in JPIDS, “The New Coronavirus, the Current King of China”.  

The International Affairs Committee and other PIDS members are preparing a compilation of the experience of COVID-19 in children to serve as a resource and advocate for the inclusion of children in research related to this pathogen. Materials will be posted soon. We encourage you to share resources developed by your respective hospitals or state health departments on PIDSConnect. It is also an excellent place to pose questions to other members about hospital or community preparedness activities. 

Finally, our partner societies have shared some excellent resources available here: IDSASHEA, and AAP.

 

Dr. Anthony Flores completed his undergraduate degree at the University of Wyoming.  He received his MD, PhD (Microbiology), and MPH (Epidemiology) from the University of Rochester School of Medicine and Dentistry and moved to Houston, TX in 2006 for his pediatric residency followed by ID fellowship at Baylor College of Medicine and Texas Children’s Hospital.

Currently, Dr. Flores is Associate Professor at McGovern Medical School of the University of Texas Health Sciences Center at Houston.  He is an attending physician in the Division of Pediatric Infectious Diseases at Children’s Memorial Hermann Hospital and MD Anderson Cancer Center in Houston, TX.  In addition, Dr. Flores is a member of the Center for Antimicrobial Resistance and Microbial Genomics where his laboratory studies the epidemiology and molecular pathogenesis of groups A and B streptococci.

Dr. Flores was a former recipient of the Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation and maintains a strong interest in improving diversity in science and medicine. In Dr. Flores’ words,

“Improving diversity in our workforce will lead to diversity of thought and ultimately enhance the care we provide to children.”

The Pediatric Infectious Diseases Society is committed to inclusion, diversity, access, and equity (IDA&E) at all levels within the society.  It is critical that the diversity of our membership reflect that of the patients, families, and communities we collectively serve through health care, research, education, and advocacy. We know we have opportunities: a recent report in the Journal of Infectious Diseases on workforce diversity indicated that <20% of the PIDS membership self-reported as underrepresented minorities (Asian, Black/African American, or Hispanic/Latino) and 45% as women (https://academic.oup.com/jid/article/216/suppl_5/S606/4160395).  Using the broader definition of “historically disadvantaged background,” including LGBTQ, socioeconomically disadvantaged, or first-generation college educated to gauge membership diversity, we are not more diverse.

PIDS is recruiting members to join an Inclusion, Diversity, Access, and Equity Task Force. The group’s initial charge will include:

  • Articulate IDA&E principles for our society
  • Review existing policies, practices and processes to identify where we have opportunities to improve and/or implement best practices related to IDA&E
  • Identify strategies to increase under-represented populations among those pursuing careers in pediatric infectious diseases
  • Create a Strategic Roadmap to determine if the identified goals are being met

While this is work that will require broad engagement from society members, we are looking for members to initially serve on the task force. Dr. Anthony Flores has agreed to lead this initiative, with support from Dr. Tina Tan. You can read about Dr. Flores in this month’s member spotlight here.  Dr. Tan is Professor of Pediatrics at the Feinberg School of Medicine, Northwestern University, a pediatric infectious diseases specialist at the Ann & Robert H. Lurie Children’s Hospital of Chicago, and the Chair of the IDSA Diversity, Inclusion and Equity Task Force. 

As you know, PIDS has 6 strategic aims: 

Aim 1: To promote the Value of ID to the healthcare system.

Aim 2: To recruit and train top talent into Pediatric ID Fellowship Programs.

Aim 3: To advance ID science and advocate for support for research in ID.

Aim 4: To engage PIDS membership through innovative programs and services.

Aim 5: To advance clinical care in ID, including appropriate antimicrobial use and childhood vaccinations.

Aim 6: To promote the success of JPIDS. 

I am not proposing to make inclusion, diversity, access, and equity our 7th strategic aim. Rather, our goal is to ensure the principles of IDA&E are inherent in each of our aims, and in all of the activities and interactions internal and external to our society.

Please consider applying for the taskforce here.

Kris 

 

Dear All – 

St Jude and PIDS leadership have made the difficult decision to cancel the upcoming St. Jude/PIDS Conference due to the increasing spread of COVID-19.   This decision was made after several days of deliberation with the conference organizers, PIDS leadership, and the St. Jude Infection Prevention Team.  Out of an abundance of caution, we want to avoid unnecessary exposures to the immunocompromised children of St. Jude; moreover, there is simply no effective way to rapidly screen for the virus and attendees will be travelling from international and national sites, which further confuses risk calculation. 

We know that this decision will affect you all in a number of ways, but we trust that you understand that this is an evolving issue that requires utmost caution. For those who submitted abstracts for presentation, please know that we still plan to publish these in their entirety in an upcoming issue of JPIDS. If you have any other questions or concerns, please feel free to reach out to our PIDS staff at This email address is being protected from spambots. You need JavaScript enabled to view it..

PIDS will continue to update our membership on COVID-19 developments. We wish you all the best as you care for your local communities and advance research on this and other microbes that threaten pediatric health.

Onward and upward,

Elaine and Buddy

Greetings from the PIDS Communications Committee! Our committee oversees and coordinates communications within PIDS, between PIDS and other organizations with shared missions, and between PIDS and the public.  This includes the PIDS website, PIDS Connect, PIDSNews, and social media.  We also evaluate marketing materials, as well as other potential communication vehicles, in meeting the needs of the membership and develop recommendations for future means of communication. This Spring, we will be working with PIDS leadership and staff to develop a new PIDS website to better meet your needs.  Additionally, we will focus our efforts on increasing membership engagement on PIDS Connect, promoting pediatric ID, and PIDS efforts on social media.

If you have questions or suggestions on how our committee can better serve you, please contact Rebecca Wallihan at This email address is being protected from spambots. You need JavaScript enabled to view it.

Thank you,

PIDS Communications Committee

The LEAP Fellowship application deadline has been extended until Monday, February 24th at Midnight Pacific Time.  There is still time to start an application today and this will give those in the process a little more time to complete.

The LEAP Fellowship is a 12 month funded program for early career ID physicians or physicians currently in ID fellowship (MD or DO).  Its purpose is to train ID physicians how to be medical leaders that can bridge the gap between clinical healthcare and public health departments, with a focus on preventing healthcare-associated infections (HAI) and antimicrobial resistance (AR). The program is led by IDSA, SHEA and PIDS, and is funded by the CDC.  This years’ LEAP Fellowship commences July 1, 2020 and carries a $100,000 award for the academic year.

Visit the IDSA website page for more information,  including eligibility      requirements and application materials at www.idsociety.org/LEAPfellowship

 

If you have any questions or concerns, please reach out to Michele Wagner, MPH, LEAP Program Manager, at This email address is being protected from spambots. You need JavaScript enabled to view it. or by phone at 202-462-2618.

I am pleased to share our inaugural Member Spotlight, featuring Sabah Kalyoussef, DO. My hope is that the Member Spotlight will foster connections between PIDS members and highlight the diversity of work that we do as pediatric infection diseases specialists.

Kris

Sabah Kalyoussef, DO is a Volunteer Clinical Assistant Professor at Rutgers-Robert Wood Johnson Medical School. She is an Attending in the Division of Pediatric Infectious Diseases and Division of Hospital Medicine at the Children’s Hospital at Saint Peter’s University Hospital in New Brunswick, NJ.

Dr. Kalyoussef received her undergraduate degree in Biological Sciences from Rutgers, The State University of New Jersey.  She obtained her osteopathic medical degree at Rowan University School of Osteopathic Medicine.  Dr. Kalyoussef then completed her residency at the Children’s Hospital at Saint Peter’s University Hospital and fellowship in Pediatric Infectious Diseases at the Children’s Hospital at Montefiore.  Her research interests include latent tuberculosis infection and pediatric sepsis.

As a part-time pediatric hospitalist, Dr. Kalyoussef has a strong interest in family-centered rounds, resident education and performance improvement projects.  Dr. Kalyoussef serves on the PIDS Education Committee.

Dr. Kalyoussef's own words about why she loves pediatric ID:

"I enjoy being a detective assigned to solve a mystery. ID processes can affect every organ system and require working with residents and staff to help my patients feel better!"

 

 

The Surviving Sepsis Campaign, an international group dedicated to improving prevention and treatment of sepsis, has now released its first international guideline specifically for management of sepsis and septic shock in children.

https://link.springer.com/article/10.1007/s00134-019-05878-6

This guideline represents contributions from 49 experts in infectious diseases, critical care, emergency medicine, evidence-based medicine and guideline methodology, as well as community representatives. The Pediatric Infectious Diseases Society provided a representative to the group who provided the perspective and expertise of pediatric infectious disease clinicians, and a focus on the importance of antimicrobial stewardship.

Infectious diseases expertise has been included in many recommendations, including considerations regarding choice of initial antibiotic therapy, identification of appropriate duration of therapy, importance of source control, and the relative importance of timely antibiotics in patients presenting with suspected sepsis. One novel recommendation is to permit a delay in administration of antibiotics for up to 3 hours for expeditious evaluation and diagnosis in patients with suspected sepsis but without shock.

The importance of antimicrobial stewardship has been emphasized throughout the guidelines, including in recommendations to evaluate the effect of sepsis-screening programs on inappropriate antibiotic administration, to perform expeditious evaluation of patients with suspected sepsis to allow responsible antibiotic use, choosing appropriately broad initial antimicrobial therapy, and identifying opportunities for discontinuation or targeting antibiotic therapy.

The Pediatric Infectious Diseases Society is proud to endorse these guidelines, which will improve the care of children with sepsis or septic shock around the world.

 

The Centers for Disease Control and Prevention (CDC) is closely monitoring an outbreak caused by a novel (new) coronavirus first identified in Wuhan, Hubei Province, China. Chinese authorities identified the new coronavirus, which has resulted in hundreds of confirmed cases in China, including cases outside Wuhan, with additional cases being identified in a growing number of countries internationally. The first case in the United States was announced on January 21, 2020. There are ongoing investigations to learn more.

Distributed via the CDC Health Alert Network
January 17, 2020, 2030 ET (8:30 PM ET)
CDCHAN-00426

Summary
The Centers for Disease Control and Prevention (CDC) continues to closely monitor an outbreak of a 2019 novel coronavirus (2019-nCoV) in Wuhan City, Hubei Province, China that began in December 2019. CDC has established an Incident Management System to coordinate a domestic and international public health response.

Coronaviruses are a large family of viruses. Some cause illness in people; numerous other coronaviruses circulate among animals, including camels, cats, and bats. Rarely, animal coronaviruses can evolve and infect people and then spread between people such as has been seen with Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) (https://www.cdc.gov/coronavirus/mers/index.html) and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) (https://www.cdc.gov/sars/index.html).

Chinese authorities report most patients in the Wuhan City outbreak have been epidemiologically linked to a large seafood and animal market, suggesting a possible zoonotic origin to the outbreak. Chinese authorities additionally report that they are monitoring several hundred healthcare workers who are caring for outbreak patients; no spread of this virus from patients to healthcare personnel has been reported to date. Chinese authorities are reporting no ongoing spread of this virus in the community, but they cannot rule out that some limited person-to-person spread may be occurring. China has reported that two of the patients have died, including one with pre-existing medical conditions. Chinese health officials publicly posted the genetic sequence of the 2019-nCoV on January 12, 2020. This will facilitate identification of infections with this virus and development of specific diagnostic tests.

Thailand and Japan have confirmed additional cases of 2019-nCoV in travelers from Wuhan, China. It is possible that more cases will be identified in the coming days. This is an ongoing investigation and given previous experience with MERS-CoV and SARS-CoV, it is possible that person-person spread may occur. There is much more to learn about the transmissibility, severity, and other features associated with 2019-nCoV as the investigations in China, Thailand, and Japan continue. Additional information about this novel virus is needed to better inform population risk.

This HAN Update provides a situational update and guidance to state and local health departments and healthcare providers that supersedes guidance in CDC’s HAN Advisory 424 distributed on January 8, 2020. This HAN Update adds guidance for evaluation of patients under investigation (PUI) for 2019-nCoV, prevention and infection control guidance, including the addition of an eye protection recommendation, and additional information on specimen collection.

Clinical criteria is available at https://www.cdc.gov/coronavirus/2019-nCoV/clinical-criteria.html. The criteria are intended to serve as guidance for evaluation.

Title: Fidaxomicin use for Clostridioides difficile in pediatrics: Is it all SUNSHINE and roses?   

Reviewing: Wolf J, Kalocsai K, Fortuny C, et al. Safety and efficacy of fidaxomicin and vancomycin in children and adolescents with Clostridioides (Clostridium) difficile infection: a phase 3, multicenter, randomized, single-blind clinical trial (SUNSHINE). Clin Infect Dis. 2019.

Author:                 Shaina Hecht, MD, Fellow, Infectious Diseases, Nationwide Children's Hospital Reviewers:                Sandra Arnold MD, MSc

Amanda Green MD

Background:

There is evidence that the incidence of Clostridioides difficile (CD, formerly Clostridium difficile) infection (CDI) in pediatrics is increasing, and has been associated with increased length of stay and increased risk of mortality in hospitalized children.  Although the majority of initial pediatric CDI cases are successfully treated, up to 40% of cases result in recurrence.  Fidaxomicin, a macrocyclic antibiotic, has been shown to be non-inferior to vancomycin for initial cure of CDI in adults, and significantly reduces the risk of recurrence.  A phase 2a pediatric study, published in 2018, showed a clinical response rate at end of treatment of 92% and a recurrence rate of 31% within 28 days after the end of treatment.  In the current study, the safety and efficacy of fidaxomicin compared to vancomycin was evaluated in pediatrics.

Methods and Results:

This study was a multicenter, investigator-blind, phase 3 trial that prospectively enrolled pediatric patients with non-severe CDI, and randomized patients to treatment with either fidaxomicin or oral vancomycin (2:1).  Diagnosis required diarrhea plus detection of toxin A/B or toxigenic CD in stool using at least one local diagnostic test.  One hundred forty-two patients (of 148 randomized), many of whom had at least one comorbidity, received treatment as allocated, and were followed for safety and efficacy until 30 days after the end of therapy (EOT).

The proportion of patients with confirmed clinical response (defined as clinical response at EOT, with no further requirement for CDI therapy at 2 days after EOT) was similar between patients in the fidaxomicin group and the vancomycin group.  However, there was a significantly higher incidence of recurrence in patients who received vancomycin compared to those who received fidaxomicin (29% versus 12%, respectively) resulting in greater global cure (no relapse within 30 days) with fidaxomicin (68.4%, 67/98) versus vancomycin (50.0%, 22/44) (adjusted treatment difference 18.8%; 95% CI 1.5%, 35.3%).  While not significant, the rate of global cure was higher in immunocompromised patients treated with fidaxomicin.  No serious adverse events were attributed to study treatments.

Critique:

This multicenter, randomized study showed a significantly higher global cure rate in patients treated with fidaxomicin compared to those treated with vancomycin.  Important limitations include enrollment of children < 2 years of age who are more likely to be asymptomatic carriers of toxigenic CD.  Additionally, diagnosis of CDI included PCR and ELISA- based testing, both of which can be positive in asymptomatic carriers.  Despite these concerns, fidaxomicin appears to be a safe and effective treatment option for children with CDI.

Conclusions:

While the study included children who may not have had true CDI, this study supports the safety and efficacy of fidaxomicin use in children and demonstrated a significantly higher cure rate at 30 days in non-severe CDI treated with fidaxomicin.  While the number needed to treat was low (5.3), given the high cost, fidaxomicin will likely be reserved for treatment of patients with a high risk of CDI recurrence, including those with cancer and other serious comorbidities.   Although not statistically significant, the finding of a higher rate of global cure in immunocompromised patients treated with fidaxomicin is promising, suggesting further studies are needed in this patient population. 

Share your thoughts about this review on our PIDS Connect community forum!

References:

  1. Wolf J, Kalocsai K, Fortuny C, et al. Safety and efficacy of fidaxomicin and vancomycin in children and adolescents with Clostridioides (Clostridium) difficile infection: a phase 3, multicenter, randomized, single-blind clinical trial (SUNSHINE). Clin Infect Dis. 2019.