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

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.

Wuhan virus

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.

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.

Summary

This health advisory notifies clinicians that influenza activity remains high in the United States. Ongoing elevated activity is due to influenza B/Victoria viruses, increasing circulation of influenza A(H1N1)pdm09 viruses, and low levels of influenza B/Yamagata and influenza A(H3N2) viruses. CDC’s influenza forecasts suggest that national influenza activity will remain elevated for several more weeks. Because influenza activity is elevated and both influenza A and B virus infections can cause severe disease and death, this health advisory also serves as a reminder that early treatment with antiviral medications improves outcomes in patients with influenza. Early treatment with antiviral medications is recommended for hospitalized patients and high-risk outpatients, including children younger than two years. Clinicians should continue efforts to vaccinate patients for as long as influenza viruses are circulating, and promptly start antiviral treatment of severely ill and high-risk patients with suspected influenza without waiting for laboratory confirmation.

Recommendations for Clinicians

1)  All People Six Months and Older Who Have Not Yet Received an Influenza Vaccine this Season Should Be Vaccinated Against Influenza. 

All available vaccine formulations this season contain A(H3N2), A(H1N1)pdm09, and B/Victoria virus strains.21 The 2019-2020 U.S. quadrivalent influenza vaccines contain these and an additional influenza B/Yamagata virus. CDC does not recommend one influenza vaccine formulation over another.

2)  All Hospitalized, Severely Ill, and High-Risk Patients with Suspected or Confirmed Influenza, Regardless of Influenza Vaccination Status, Should Be Treated with Antivirals As Soon As Possible After Onset of Illness Antiviral treatment is recommended as early as possible for any patient with suspected or confirmed influenza who—

  1. Is hospitalized. 
  2. Has severe, complicated, or progressive illness. This may include outpatients with severe or prolonged progressive symptoms or patients who develop complications such as pneumonia but who are not hospitalized.
  3. Is at high risk for influenza complications but not hospitalized. This includes—
  4. Children younger than two years. Although children younger than five years are considered at higher risk for complications from influenza, the highest risk is for those younger than two years.
  5. Adults 65 years and older.
  6. People with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), and metabolic (including diabetes mellitus) disorders.
  7. People with neurologic and neurodevelopment conditions, including disorders of the brain, spinal cord, peripheral nerve, and muscle, such as cerebral palsy, seizure disorder, stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury.
  8. People with immunosuppression, including that caused by medications or by HIV infection.
  9. Women who are pregnant or postpartum (within two weeks after delivery).
  10. People younger than 19 years who are receiving long-term aspirin therapy.
  11. American Indians and Alaska Natives.
  12. People with extreme obesity (i.e., body mass index is equal to or greater than 40).
  13. Residents of nursing homes and other chronic care facilities.

3)  Antiviral Treatment in Non-High-Risk Patients with Uncomplicated Influenza


Antiviral treatment can benefit other individuals with influenza. While current guidance focuses on antiviral treatment of those with severe illness or at high risk of complications, antiviral treatment may be prescribed for any previously healthy (non-high risk) outpatient with suspected or confirmed influenza who presents within two days after illness onset. Multiple randomized controlled clinical trials (RCTs) and meta-analyses of RCTs have demonstrated efficacy of early initiation of treatment (started within 48 hours of illness onset) with neuraminidase inhibitors in reducing duration of fever and illness symptoms by about a day compared with placebo in otherwise healthy children and adults with uncomplicated influenza.6,9 Clinical judgment—considering the patient’s disease severity and progression, age, likelihood of influenza, and time since onset of symptoms is important when making antiviral treatment decisions for outpatients who are not at increased risk for influenza complications.

4)  Choice of Antiviral Medication


Four influenza antiviral medications approved by the U.S. Food and Drug Administration (FDA) are recommended for use in the United States during the 2019-2020 influenza season.  Three drugs are chemically related antiviral medications known as neuraminidase inhibitors: oral oseltamivir phosphate (available as a generic version or under the trade name Tamiflu®), inhaled zanamivir (trade name Relenza®), and intravenous peramivir (trade name Rapivab®). These medications block the viral neuraminidase enzyme and have activity against both influenza A and B viruses.

View this advisory in its entirety here:  CDC Advisory

Download the IDSA Flu Practice Guidelines

REQUEST FOR APPLICATIONS

Ralph D Feigin, MD, UpToDate® Pediatric Subscription Awards

Background

UpToDate®, in conjunction with Texas Children’s Hospital, has established a series of pediatric subscription awards in honor of Dr Ralph David Feigin, who had been Editor-In-Chief of the Pediatrics Section of UpToDate since its inception in 1999.  The award grants up to six, three-year subscriptions to UpToDate®  to physicians, other health care providers, or health care facilities that provide care to underserved or low-income children and who could not otherwise afford the subscription.  The deadline for applications is May 31. Awardees will be announced in June, and the subscriptions will start in July, 2020.

Criteria

Applicants must meet all four (A, B, C, and D) of the following qualifications. 

  1. Practice or teach in low-income or medically underserved areas.

A low-income or medically underserved area is defined as meeting any one of the following:

      1) a rural area more than 50 miles from the nearest city with a population of 400,000 or more and more than 50 miles from a medical school

      2) a practice in which 50% or more of the patients are uninsured, are insured by a governmental program or are identified as minorities

      3) a community or area designated by a governmental agency or governmental representative as medically underserved or qualifies as a health professional shortage area

      4) a low-income country as designated by the WHO 

Deliver health care or health education to children and their families

Do not currently have access to UpToDate® and are unable to afford the initial one-year subscription of approximately $500 and the approximately $400 yearly renewal fee.

Have access to a computer with internet capability.

Application Process

Applicants should complete the application below electronically and submit as a word document.  Cells may be expanded as needed.

Completed applications (as a word document) should be submitted to Martin I Lorin, MD (This email address is being protected from spambots. You need JavaScript enabled to view it.) by May 31, 2020. (Application

 

PIDS Journal Club, December 2019

 

Immune Monitoring of CMV After Transplantation? Refinements in Our Approach Are Necessary.

Reviewing: Paouri B et. al., “Quantiferon-Cytomegalovirus Assay: A Potentially Useful Tool in the Evaluation of CMV-Specific CD8+ T-Cell Reconstitution in Pediatric Hematopoietic Stem Cell Transplant Patients”, Ped. Transplant., 20181

Background

Despite improvements in the detection and management of cytomegalovirus (CMV), morbidity and mortality remain significant in the transplant population. Methods that might improve risk stratification, that might reduce drug toxicity and that might reduce levels of drug resistance are necessary to improve management. Reconstitution of CMV specific immunity in hematopoietic stem cell transplant (HSCT) patients has been associated with control of and protection against CMV reactivation and disease. In this paper, the investigators evaluated the clinical utility of using CMV specific cell mediated immune responses to predict CMV DNAemia in pediatric HSCT patients. 

Methods and Results

Thirty-seven pediatric HSCT patients were followed prospectively. Weekly CMV PCR was performed to look for DNAemia until day 100 and then if clinically indicated. The Quantiferon-CMV assay was performed prior to transplant, early after transplant and at days 30, 90, 180, 270, and 360 after transplant.

The principle behind the Quantiferon-CMV is identical to the Quantiferon-TB. Whole blood is placed in separate tubes with a negative control, a mitogen positive control, and specific CD8 stimulating peptides. After incubation, interferon gamma is measured and can be reported as qualitatively positive, negative, or indeterminate or as a quantitative result. Production of interferon gamma acts as a surrogate for stimulation of CD8 specific T cells, in this case, to CMV.

Prior to transplant, 17 (46%) patients were negative by Quantiferon-CMV, 12 (32%) patients were indeterminate, and 5 (14%) were positive. There was no correlation between pre-transplant cell mediated immunity (CMI) and CMV DNAemia at < 30 days post-transplant. CMV DNAemia occurred in 51% of patients with half of those episodes occurring at < 30 days presumably before full engraftment. Fifteen of these DNAemic patients (40% of total cohort) developed immunity at an average of 82 days’ post-transplant. In those who developed immunity, later reactivation of CMV was lower (15% vs. 53%) than in those who did not develop immunity. In this cohort, acute graft versus host disease (GVHD) did not alter the recovery of CMV immunity.

Critique

The percentage of indeterminate results was high in this cohort and may reflect disease state or conditioning regimen for transplant, as over 50% of the indeterminate samples were drawn in the 1-3 days after transplant. In addition, this method is probably not helpful in the early post-transplant period at least for those with an HSCT. It should, however, be more useful in those receiving a solid organ transplant (SOT) as pre-existing immunity remains after conditioning. The technique appears to have merit and may be useful in the future once larger prospective studies are undertaken.

Conclusions 

Immune monitoring of CMV may help with stratifying patients for episodes of reactivation, as those who recovered CMV immunity were less likely to reactivate in this cohort. However, since most episodes of CMV reactivation occurred before immune reconstitution was expected, the clinical utility of this assay may be limited in HSCT patients to post engraftment. However, CMV immunity prior to transplant in those receiving a SOT, may also predict who will be more likely to control DNAemia. A prospective trial is underway in adult patients (NCT02538172) 2

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

Author

Marc Foca, MD

Columbia University Irving Medical Center, New York, NY USA

Peer Reviewers

Joshua Wolf MBBS, PhD, FPIDS, FRACP, St. Jude Children’s Research Hospital, Memphis, TN

Sanjeev Swami MD, The Children’s Hospital of Philadelphia, Philadelphia, PA

References 

  1. PaouriB, Soldatou A, Petrakou E, Theodosaki M, Tsentidis C, Kaisari K, Oikonomopoulou C, Matsas M, Goussetis E. Quantiferon-Cytomegalovirus assay: A potentially useful tool in the evaluation of CMV-specific CD8+ T-cell reconstitution in pediatric hematopoietic stem cell transplant patients. Pediatr Transplant. 2018 Aug;22(5):e13220. doi: 10.1111/petr.13220. Epub 2018 May 18. 
  1. Clinical Trials.gov. Cell Mediated Immunity for Prevention of CMV Disease.

https://clinicaltrials.gov/ct2/show/NCT02538172. Sept. 2015. Accessed Dec. 2019

Journal of the Pediatric Infectious Diseases Society

NEWS RELEASE

Influenza can be especially dangerous for children, who are at greater risk for serious complications from the illness, including hospitalization and even death. Yet child care centers in the U.S. rarely require children or the adults who care for them to be vaccinated against flu, according to a new study published in the Journal of the Pediatric Infectious Diseases Society.

At the United Nations General Assembly meeting in New York City on September 23, 2019, the Center for Disease Control hosted the Antimicrobial Resistance Challenge: A night celebrating antimicrobial resistance fighters. The venue brought together representatives from various organizations and institutions engaged in the fight against antimicrobial resistance, including PIDS, and showcased artwork bringing attention to the fight against antimicrobial resistance. The event premiered the film “Antimicrobial Resistance Fighters,” which was directed by Michael Wech and introduced by Dame Sally Davies, the Chief Medical Officer for England and Chief Medical Advisor to the UK government.

This powerful and well-made documentary highlighted individual stories to explain the threat of antimicrobial resistance to the general public. One such story featured Mr. David Ricci, a white American young man who spoke passionately at the event about his journey combating an infection that he contracted while living in Calcultta, India. In 2011, Mr. Ricci worked as a volunteer at an orphanage for children living with HIV/AIDS, when he barely survived a horrific accident in which he was struck by a train, his bones and muscles crushed as he was dragged under. The film showed footage of the location where the accident took place, alongside piles of waste and trash where volunteers pulled him out from under the train. At a local clinic his leg was sawed off above the knee at the bedside without anesthesia. He was transferred to a hospital where he underwent multiple surgeries. Brief footage in the film flashed images of his initial wound against the backdrop of the grounds of his accident.  Mr. Ricci flew back home to the U.S. two weeks after the accident where he was cared for at the University of Washington Medical Center in Seattle. He was found to have a wound infection caused by multiple bacteria that harbored the New Delhi metallobetalactamse-1 enzyme. Dr. John Lynch, the infectious diseases physician caring for him at the University of Washington, explained that after several antibiotics failed, they ultimately treated Mr. Ricci’s infection with colistin and a series of surgical debridements.

Mr. Ricci, who is now a patient advocate and antimicrobial resistance fighter, described his body’s reaction to each dose of colistin as feeling like his organs were being eaten away. Later in the film, another story unfolds describing the use of colistin in agriculture. Mr. Ricci comments that despite the toxic effects that colistin had on his body, the effectiveness of this last line drug against his multi-drug resistant infection saved his life. He acknowledges that he is alive because the bacteria causing his infection were still susceptible to colistin. He expresses his astonishment that our society could allow widespread agricultural use of colistin that would threaten its effectiveness.

 “Antimicrobial Resistance Fighters” was powerful, and will raise awareness to the general public about the global threat of antimicrobial resistance. The film is an example of what events like the AMR Challenge strives to accomplish by bringing together advocates in the fight against antimicrobial resistance from all disciplines, reminding us that we must work together to share our experiences and expertise. 

By Rana Hamdy; Newsletter Edition 9.23.19

To learn more about PIDS AMR efforts, visit our Antibiotic Resistance page here.  U.S. Antibiotic Awareness Week is being observed November 18-24, 2019.

Dropulic LK,  et.al.  A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection. J Infect Dis 2019;220:990.

 

Background

Both genital and oral herpes simplex virus (HSV) infections are common throughout the world.  Most infections are asymptomatic but many produce painful ulcerations that often recur.  Further, neonatal HSV infections produce a severe disease while genital HSV-2 infections are a major risk factor for the acquisition and transmission of HIV.

Methods and results

In this manuscript the authors describe the initial clinical evaluation of a replication defective herpes simplex virus vaccine.  A replication defective vaccine is one in which one or more essential genes have been deleted so the vaccine virus, which is grown in a cell line that provides the missing gene product(s),  can infect a cell but the virus produced is non-infectious because of the deletions.  Thus, another term used is a single cycle vaccine.  This is one of several new approaches to vaccine development discussed briefly below.

The vaccine HSV529 (HSV-2 dl5-29), a double deletion of  HSV-2 UL5 and UL 29, was evaluated in 60 healthy adults in a double blind study of participants who were either seronegative for HSV1 and HSV-2, or positive for either HSV-1 or HSV-2 or both.  The vaccine was provided in a 3 dose schedule administered IM at 0,1 and 6 months. Safety and both antibody and T cell responses were quantified.

The overall safety profile of the vaccine was acceptable although mild to moderate local reactions were common (89%).  There was no significant difference compared to placebo recipients in unsolicited adverse events.  A fourfold increase in neutralizing antibody titers was induced in 11 of 14 HSV seronegative participants after the third dose and titers remained elevated at 6 months. For those HSV seropositive, there was a mixed response but none of the recipients had a 4 fold increase.  There was also some evidence of T cell induction but CD8 responses were weak in seronegative participants and were even less for seropositive subjects.  CD4 responses were higher than CD8 for both groups.

Discussion

This is an interesting time for HSV vaccines.  The recent failure of a prophylactic (to prevent disease and persistent infection) monovalent glycoprotein D (gD) vaccine to protect against HSV-2 (1) and the sub optimal but significant decrease in recurrent HSV-2 disease and shedding by a bivalent therapeutic vaccine (to decrease recurrent disease and shedding in those already infected) (2) has led many to believe that a successful vaccine must present more HSV antigens.  Hence the development of this replication defective candidate as well as live attenuated vaccines that have deleted neuroinvasive HSV proteins (3,4) in order to present more HSV antigens.  On the positive side the prophylactic gD2 candidate did protect against HSV-1 genital disease and infection (1) and established a correlate of protection (5) providing encouragement to the field.  Similarly, the therapeutic vaccine established a proof of concept for therapeutic vaccines.  The vaccine evaluated in the current manuscript offers advantages to the subunit vaccines evaluated previously, in that it presents all the HSV antigens to the immune system.  However, it remains unclear as to whether a single round of virus replication will be sufficient to induce long lasting protection.  Also of interest, similar approaches have recently been used for cytomegalovirus (CMV) vaccines after the partial success of a monovalent glycoprotein B CMV vaccine (6).  Thus both replication defective (7) and live attenuated vaccines (8) are being developed.

Stay tuned for results of upcoming clinical trials for these and other herpes virus vaccines.

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

References

  1. Belshe RB, Leone PA, Bernstein DI, et.al. Herpevac Trial for Women. Efficacy results of a trial of a herpes simplex vaccine. N Engl J Med. 366:34; 2012.
  2. Bernstein DI, Flechtner JB, McNeil et.al. Therapeutic HSV-2 vaccine decreases recurrent virus shedding and recurrent genital herpes disease. Vaccine.  37:3443; 2019.
  3. Bernstein DI, Pullum DA, Cardin RD, et.al.  The HSV-1 live attenuated VC2 vaccine provides protection against HSV-2 genital infection in the guinea pig model of genital herpes. Vaccine. 37:61; 2018
  4. Richards AL, Sollars PJ, Pitts JD, et.al.  The pUL37 tegument protein guides alpha-herpesvirus retrograde axonal transport to promote neuroinvasion. PLoS Pathog. 13: e1006741; 2017.
  5. Belshe RB, Heineman TC, Bernstein DI, et.al. Correlate of immune protection against HSV-1 genital disease in vaccinated women. J Infect Dis. 209:828; 2014.
  6. Bernstein DI, Munoz FM, Callahan ST, et. al.  Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial. Vaccine.34:313; 2016
  7. Adler SP, Lewis N, Conlon A, et.al.  Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects. J Infect Dis. 220:411; 2019
  8. Hansen SG, Marshall EE, Malouli D, et.al. A live-attenuated RhCMV/SIV vaccine shows long-term efficacy against heterologous SIV challenge. Sci Transl Med. Jul 17;11; 2019.

Author

David Bernstein MD (Cincinnati Children’s Hospital Medical Center)

Peer Reviewers

Sandra L Arnold MD (Le Bonheur Children’s Medical Center)

Christine Salvatore MD (Komansky Children's Hospital)

l

IDSA, the Society for Healthcare Epidemiology of America, and the Pediatric Infectious Diseases Society were recently awarded a contract from the Centers for Disease Control and Prevention to continue the Leaders in Epidemiology, Antimicrobial Stewardship, and Public Health (LEAP) Fellowship through the 2020-2021 academic year.

The LEAP Fellowship is a 1-year funded training program, aimed at developing late-stage ID trainees and early-stage ID physicians into health care leaders capable of working as clinical partners to local and national public health agencies.

Applicants are being sought for the LEAP program for the upcoming 2020-2021 academic year. Application criteria are still being finalized; however, preliminary criteria are as follows:

  • Applicants must be physicians between their first year of ID fellowship and up to two years post fellowship.
  • Applicants must be associated with an Infectious Diseases training program, and with a health care facility with robust antibiotic stewardship, infection control, and/or hospital epidemiology programs.
  • Applicants must have or be in the process of establishing a relationship with state or local health departments.

Final application instructions and criteria will be sent out in late 2019. The most up-to-date information can be obtained by visiting IDSA’s LEAP Fellowship webpage or by contacting LEAP Fellowship Program Manager Michele Wagner, at: This email address is being protected from spambots. You need JavaScript enabled to view it..

Dr. Kris Bryant

It is the season to be grateful and I’m making a list.

First, I am thankful and incredibly honored to serve as the next President of the Pediatric Infectious Diseases Society.  Our society has been fortunate to have a history of strong and innovative leadership.  Paul Spearman is both a mentor to me and a tough act to follow!  I’m looking forward to growing initiatives that he championed around member engagement and advocacy.  I couldn’t ask for better partners than President-elect, Buddy Creech, and Secretary-Treasurer, Susan Coffin.

I am thankful for our hardworking and resourceful staff, Executive Director, Christy Phillips, and Marketing and Communications Manager, Winter Harris.  It is a little mind-boggling to consider that PIDS and the PIDS Foundation are run with a permanent staff of two.  Fortunately, we have dozens of dedicated volunteers who do much of the work that supports our strategic aims.  In the coming year, I hope to bring you a formal strategic plan that will help us prioritize our work and potentially grow our resources.

Finally, I am thankful to be able to work in this profession.  I always tell trainees that I have the best job in the world.  One of the things I appreciate about this field, is that my “best” job doesn’t necessarily look like your “best” job.  As pediatric infectious diseases specialists, some of us work in large academic medical centers.  Others work in smaller community hospitals.  Some of us are employed by industry or public health partners.  Some of us move our field forward by leading NIH-funded research labs and others advance the field through clinical trials (or contribute data to multi-center clinical trials).  We are educators.  We are policymakers.  We are entrepreneurs.  In future newsletters, I plan to highlight the breadth of opportunity and talent in our profession with profiles of members who work in a variety of settings.  Yes, I hope this sort of storytelling will be valuable as we think about how best to recruit trainees to our fellowship programs.  I also hope to “introduce” you to fellow Peds ID specialists that maybe you haven’t had a chance to meet in person, or perhaps I'll help you learn something about a longtime colleague that you didn’t know.  I also want to make it clear—if it wasn’t already—that all are welcome in PIDS.

As 2019 draws to a close, if you have ideas for me, questions or concerns to share, please reach out.  We have some exciting projects on the horizon… but more about those next time.

Kris

 

PIDS Journal Club, September 2019

Oral linezolid for routine treatment of uncomplicated Staphylococcus aureus bacteremia? Not ready yet.

Reviewing: Willekens R, et al, “Early oral switch to linezolid for low-risk patients with Staphylococcus aureus bloodstream infections: a propensity-matched cohort study”, Clin Infect Dis, 20181

Background

Management of apparently uncomplicated Staphylococcus aureus bacteremia (SAB) is challenging because relapse is common, probably related to unrecognized deep-seated infection .2 As oral antibiotic therapy is increasingly used for bloodstream infections, oral treatment for SAB is under consideration.3 In the pediatric world, infectious diseases physicians report using oral therapy for bacteremic osteomyelitis, but not proven SAB without a bony focus.4 This study, by Willekens et al, evaluated the effectiveness of oral linezolid, a highly bioavailable anti-staphylococcal antibiotic, to complete treatment of SAB in adults after initial parenteral therapy.1

Methods and Results

This was a subgroup analysis of a prospective observational cohort study comprising adults with SAB; it included participants judged to be at low risk of complications who received either entirely parenteral antibiotics or were switched to oral linezolid after 3-9 days of parenteral therapy at treating clinician discretion. The primary outcome was relapse of S. aureus infection within 90 days, and secondary outcomes included length of hospital stay (LOS), and 14- or 30-day mortality. A propensity score-matched sub cohort matched linezolid-treated participants with the two “most similar” parenteral-treated participants.

A total of 152 participants were identified (45 linezolid and 107 parenteral therapy); 135 were included in the propensity-matched sub cohort. Participants were treated for a median of 15 days in each group. Risk factors for treatment failure (e.g. chronic renal failure, risk factors for endovascular infection, unknown BSI source, sepsis and ICU admission) were much more common in the parenteral therapy group, even after propensity score matching. Although not statistically significant, patients who received oral linezolid were slightly less likely to have relapse of infection (RR 0.5; P=0.9) or to die by 14 days (RR ∞; P=0.2) or 30 days (RR 0.17; P=0.08). They did have significantly shorter median LOS (8 vs. 19 days; P<0.01). The authors concluded that treatment of SAB in selected low-risk patients with an oral switch to linezolid after initial parenteral therapy yielded similar clinical outcomes as parenteral therapy.

Critique

The main problem with interpreting this study is the possibility of indication bias.5 Clinicians appear to have been more inclined to give conservative (parenteral) therapy to participants at higher risk of treatment failure; there are differences in baseline characteristics and 14-day mortality (before any likely effect of the treatment). The authors did attempt to address this with propensity score matching but, because they had only a small group of potential matches and did not require close matching, the groups remained very different. Propensity score matching relies on selecting a comparator group that is similar to the intervention group.6 Other issues include unknown applicability to pediatric patients and to other special populations such as patients with neutropenia or other immunocompromise.

Conclusions

The study does not prove that oral linezolid is as safe and effective as parenteral therapy for treatment of SAB, since the patients receiving oral linezolid might have had a better chance of success.  It may provide some justification for occasional use following a short course of IV therapy, and sets the stage for a prospective randomized non-inferiority study (e.g. NCT01792804)7, but I will wait for those results before routinely using oral linezolid as completion therapy for uncomplicated SAB.

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

Author

Joshua Wolf MBBS, PhD, FPIDS, FRACP

St. Jude Children’s Research Hospital, Memphis, TN, USA 

Peer Reviewers

Sandra L Arnold MD (Le Bonheur Children’s Medical Center, Memphis, TN, USA)

Suchitra Rao MBBS, MSCS (Children’s Hospital Colorado, Aurora, CO, USA)

References

  1. Willekens R, Puig-Asensio M, Ruiz-Camps I, Larrosa MN, Gonzalez-Lopez JJ, Rodriguez-Pardo D, et al. Early oral switch to linezolid for low-risk patients with Staphylococcus aureus bloodstream infections: a propensity-matched cohort study. Clin Infect Dis. 2018.
  2. Berrevoets MAH, Kouijzer IJE, Aarntzen E, Janssen MJR, De Geus-Oei LF, Wertheim HFL, et al. (18)F-FDG PET/CT Optimizes Treatment in Staphylococcus Aureus Bacteremia and Is Associated with Reduced Mortality. J Nucl Med. 2017;58(9):1504-1510.
  3. Hospenthal DR, Waters CD, Beekmann SE, Polgreen PM. Practice patterns of infectious diseases physicians in transitioning from intravenous to oral therapy in patients with bacteremia. Open Forum Infect Dis. 2019.
  4. Wood JB, Fricker GP, Beekmann SE, Polgreen P, Buddy Creech C. Practice Patterns of Providers for the Management of Staphylococcus aureus Bacteremia in Children: Results of an Emerging Infections Network Survey. Journal of the Pediatric Infectious Diseases Society. 2018;7(3):e152-e155.
  5. Walker AM. Confounding by indication. Epidemiology. 1996;7(4):335-336.
  6. Joffe MM, Rosenbaum PR. Invited commentary: propensity scores. Am J Epidemiol. 1999;150(4):327-333.
  7. ClinicalTrials.gov. Staphylococcus Aureus Bacteremia Antibiotic Treatment Options (SABATO). https://clinicaltrials.gov/ct2/show/NCT01792804?id=NCT01792804&rank=1&load=cart. Published 2013. Accessed September 16, 2019.

 

PRESS RELEASE

For Immediate Release: September 5, 2019

Contact: Christy Phillips, (703) 299- 9865, This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Pediatric Infectious Diseases Society Honors Six Distinguished Physicians, Scientists

The world's largest organization of professionals dedicated to the treatment, control and eradication of infectious diseases affecting children, the Pediatric Infectious Diseases Society, has honored six distinguished physicians and scientists from the United States and around the world who were elected this year to be fellows of PIDS. 

The designation “fellow” in PIDS honors those who have achieved professional excellence and provided significant service to the profession. “PIDS fellows are national and international leaders and experts in the field of pediatric infectious diseases. Their expertise touches the lives of children not only on those larger stages, but also at the local level in their hospitals, clinics, research labs, institutions, and communities,” said PIDS President Paul W. Spearman, MD, FPIDS. “Fellowship in PIDS is our way of recognizing these accomplished physicians, researchers, and scientists for their important contributions to our field.” 

Applicants for PIDS fellowship must be nominated by their peers and meet specified criteria, including continuing identification with the field of pediatric infectious diseases, national or local recognition, and publication of their work in strong biomedical journals. Nominees are reviewed and elected by the PIDS Board of Directors. Fellows of PIDS work in many different settings, including clinical practice, teaching, research, public health, and health care administration.

This year, the following individuals were honored as fellows of PIDS:

Nazha Abughali, MD, FPIDS

Ann Chahroudi, MD, PhD, FPIDS

Stephanie Fritz, MD, MS, FPIDS

David P. Greenberg, MD, FPIDS

Dean L. Winslow, MD, FPIDS

Joshua Wolf, MBBS, FPIDS

 

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About PIDS

PIDS membership encompasses leaders across the global scientific and public health spectrum, including clinical care, advocacy, academics, government, and the pharmaceutical industry. From fellowship training to continuing medical education, research, regulatory issues and guideline development, PIDS members are the core professionals advocating for the improved health of children with infectious diseases both nationally and around the world, participating in critical public health and medical professional  advisory committees that determine the treatment and prevention of infectious diseases, immunization practices in children, and the education of pediatricians. For more information, visit http://www.pids.org.

 

The PIDS Foundation Board of Trustees invites you to Party on the Potomac!  An evening of fun, fellowship and discussion of vaccine challenges in the 21st century.  Our guest speaker, Dr. Peter Hotez, will describe recent changes to the pediatric and adult vaccine schedules, focusing primarily on newer vaccine technologies and vaccine adjuvants and share common misconceptions regarding vaccine safety.  In addition to the mini-lecture, The PIDS Distinguished Physician and Young Investigator Awards will be presented.

Here are 5 reasons why should you attend:

  1. Meet your old Pediatric ID friends
  2. Make new Pediatric ID friends
  3. Share fond memories with PIDS members and other colleagues
  4. Network…for research ideas, for job opportunities, for FUN
  5. "Grab a prop and strike a pose” at the ID-themed photo booth

 

 
One more thing: we have some PIDS gear!  We will have PIDS-branded hats, water bottles, ties, and scarves available for a small donation to the PIDS Foundation. Please visit the PIDS booth or pick up your PIDS swag at the dinner celebration.

We hope to see you there!

Janet Gilsdorf, MD
PIDS Foundation Chair
 
Paul Spearman, MD
PIDS President
 
PIDS would like to thank our sponsors, Horizon Therapeutics, Karius, and Sanofi Pastuer, for their generous support.