Infections caused by a type of bacteria resistant to multiple antibiotics are occurring more frequently in U.S. children and are associated with longer hospital stays and a trend towards greater risk of death, according to a new study published in the Journal of the Pediatric Infectious Diseases Society. Previously acquired mostly while children were already in the hospital, the new findings also suggest the infections--caused by bacteria from the Enterobacteriaceae family that are resistant to multiple drugs--may be spreading more often in the community.

"Antibiotic resistance increasingly threatens our ability to treat our children's infections," said study author Sharon B. Meropol, MD, PhD, of University Hospitals Rainbow Babies and Children's Hospital in Cleveland and Case Western Reserve University School of Medicine. "Efforts to control this trend are urgently needed from all of us, such as using antibiotics only when necessary, and eliminating agricultural use of antibiotics in healthy animals."

In the retrospective study, researchers analyzed data from 48 children's hospitals throughout the U.S., focusing on approximately 94,000 patients under the age of 18 who were diagnosed with Enterobacteriaceae-associated infections between 2007 and 2015. The proportion of these infections caused by bacteria that were resistant to multiple antibiotics increased from 0.2 percent in 2007 to 1.5 percent in 2015, a more than 700 percent increase in prevalence over the eight-year period.

Bacterial infections resistant to multiple drugs are especially concerning in children, for whom there are a limited number of stronger antibiotics currently approved for use compared to adults, putting kids at higher risk for worse outcomes. In the study, children with Enterobacteriaceae infections resistant to multiple antibiotics had hospitals stays that were 20 percent longer than patients with infections that were susceptible to antibiotics, the researchers found. The results also suggest a greater mortality risk among pediatric patients infected with the resistant strains, although the increased odds for death were not statistically significant.

Most of the resistant infections were present when the children were admitted to the hospital, suggesting the bacteria may be increasingly spreading in the community. Older kids, children with other health conditions, and those living in the Western U.S. were more likely to have the infections, the study found. The results build on previous research reporting rising rates of these infections in adults and outbreaks in hospitalized children, especially in less-developed countries in Latin America and Asia, where antibiotics are available over the counter.

Future research should focus on better ways to limit the transmission of resistant Enterobacteriaceae bacteria, including between hospitals and long-term care facilities and their communities, in addition to the development of new antibiotics that are safe and effective to use in children, Dr. Meropol said. "While the march of antibiotic resistance seems inexorable, informed and rigorous efforts to reverse this trend have been successful for other types of organisms, and are urgently needed within this context."

Fast Facts

  • Infections caused by a type of bacteria resistant to multiple antibiotics are increasing in U.S. children and are associated with longer hospital stays and a trend towards greater risk of death.
  • Caused by members of the Enterobacteriaceae family of bacteria that are resistant to multiple antibiotics, these infections may be increasingly spreading in the community, not just in hospitals.
  • Efforts to control rising antibiotic resistance, including the appropriate use of antibiotics in humans and animals, and the development of new antibiotics, are urgently needed.

###

Editor's Note: The study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. 

In August, 2008, UpToDate®, in conjunction with Texas Children’s Hospital, 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 program 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 30; awardees will be announced in June; and the subscriptions will start in July, 2017. 

Criteria

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

  • 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 to children 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.  Cells may be expanded as needed. 

Completed applications (as a word document) should be returned to Martin I Lorin, MD (This email address is being protected from spambots. You need JavaScript enabled to view it.) by May 30, 2017. Click here to download an application.

 

The first Antimicrobial Stewardship Research Workshop (ASRW) was held November 29-30, 2016, and was co-organized by Society of Healthcare Epidemiology of America, Infectious Diseases Society of America, Society of Infectious Diseases Pharmacists, Pediatric Infectious Diseases Society, and Centers for Diseases Control and Prevention and was supported by a grant from Merck. The audience was multidisciplinary with multiple backgrounds: teaching hospital, community, adult, pediatric, and industry. Additionally, the workshop had live following on Twitter, with the hashtag, #ASRW16.

The two-day workshop was filled with several topics, but gave a broad overview of the need for and challenges of studying antimicrobial stewardship. For the first half of the day, speakers set the stage of the antimicrobial stewardship research agenda: Drs. Lauri Hicks and Preeti Malani presented outpatient and inpatient stewardship research, respectively. For review of basic concepts of research, Dr. Ebbing Lautenbach provided an epidemiology toolbox presentation. Defining the right kind of question for research can be difficult and Dr. Vanessa Stevens walked the audience through various examples of good and bad research questions and the following presentation on the various areas of research in antimicrobial stewardship by Dr. Rebekah Moehring complemented it well. After this introductory morning, groups were encouraged to breakout and discuss different approached to a research question and included various themes, such as hospital vs. outpatient and internal vs. external funding of research.

For the second half of the day, the discussion focused further into the different aspects of research: Drs. Pranita Tamma and Jeffrey Linder presented on defining exposures, outcomes, and confounders of interest based on inpatient and outpatient settings, respectively. Dr. Marc Scheetz explained the nuances between research for generalized knowledge vs. quality improvement and assurances projects. The audience was introduced to how social sciences can be involved in antimicrobial stewardship, with Dr. Heather Reisinger giving an overview of implementation science and how the models may be able to be used in stewardship research. Dr. Stevens returned to discuss the pros and cons of health economics to evaluate stewardship programs and Dr. Julia Szymczak ended the evening with a vigorous reminder that there are many behavioral factors associated with antimicrobial prescribing and identification of these factors may help with implementation of stewardship interventions.

After a heavy first day, everyone returned bright-eyed for the second day, which was more concentrated on various strategies for evaluating antimicrobials stewardship interventions. Dr. Jessina McGregor explained the ins-and-outs of interrupted time series analysis and how they can be very helpful in evaluating programs; following that, Dr. Theoklis Zaoutis educated the audience of how the cohort design can be used for studying the impact of an intervention. Other assessment strategies were reviewed: Dr. Jonathon Edwards explained how the National Healthcare Safety Network (NSHN) will use the Antimicrobial Use and Resistance (AUR) report to benchmark antimicrobial usage through the standard antimicrobial administration ratio (SAAR), which was followed by Dr. Scott Fridkin’s presentation on what kind of metrics and comparisons should be used and how to include variation into assessment of programs.  Dr. Deverick Anderson highlighted the pitfalls of just relying on antimicrobial consumption as a metric and discussed how desirability of outcome ranking (DOOR) and response adjusted for duration of antibiotic risk (RADAR) may be able to shine more light on specific outcomes of interest.

After lunch, the final topic was to put all the different concepts together for a successful research program. Dr. Anderson returned to the stage to discuss the details needed for data management and common issues that arise when developing the components. Dr. Elizabeth Dodds-Ashley, Jeffrey Gerber, and Fridkin led an open discussion of different funding mechanisms for research in antimicrobial stewardship (NIH, AHRQ, professional societies, foundations, industry, etc.). Lastly, Dr. Malani wrapped up the workshop with a presentation on the importance of disseminating research and various mechanisms to maximize the audience reach.

Overall, the workshop seemed highly successful; the topics were broad which provided a great base for new researchers and reinforced concepts for more advanced researchers. Additionally, it provided concrete examples of multiple concepts that are used in antimicrobial stewardship research, as well as pitfalls in the current mechanisms of evaluation (e.g. duration of therapy) and areas in need of further development. The ASRW will continue to build, with projected meetings for 2017 (in Chicago) and 2018 (in Baltimore).

The Pediatric Infectious Diseases Society (PIDS) supports universal vaccination of children according to evidence-based policies as outlined by leading public health agencies and professional societies, including the Centers for Disease Control and Prevention (CDC), the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), the Infectious Diseases Society of America (IDSA), and many other reputable organizations.

PIDS stands behind the overwhelming scientific evidence showing that vaccines do not cause autism. It is dangerous to perpetuate this myth and doing so is likely to result in harm to our children from vaccine-preventable diseases. Statements by those claiming a connection between vaccines and autism with no scientific basis should be recognized as fraudulent and misleading. The false link between autism and vaccines was first popularized by Dr. Andrew Wakefield, a British physician who falsified data and later profited from his false theory. Dr. Wakefield’s work was proven to be fraudulent, his medical license was revoked, and he has been discredited by leading medical societies and medical journals.

Vaccines provide tremendous health benefits to individuals and to society. PIDS calls on our government leaders to recognize the overwhelming evidence showing the outstanding safety of childhood vaccines and to avoid the temptation to equate anecdotes with scientific evidence. We further call on our government leaders to avoid providing a hint of legitimacy to myths such as this one for which there is no scientific evidence. To do so will unnecessarily endanger the lives of American children.

###

The Pediatric Infectious Diseases Society (PIDS) is the world’s largest professional organization of experts in the care and prevention of infectious diseases in children. PIDS membership includes leaders in clinical care, public health, academia, government, and industry who advocate for the improved health of children nationally and globally. The Society fulfills its mission through research, advocacy, guideline development, fellowship training, continuing medical education, its support of immunization practices in children, and The Journal of the Pediatric Infectious Diseases Society, its quarterly peer-reviewed publication. To learn more about PIDS, visit www.pids.org and follow PIDS on Facebook and Twitter.

 

If it has seemed like you’ve been seeing more cases of antibiotic-resistant Pseudomonas aeruginosa over the past few years, the study by Logan and colleagues suggests you may be right.  This retrospective study used data from the Surveillance Network Database to describe the epidemiology of Pseudomonas aeruginosa isolates from children and trends in antibiotic resistance from 1999-2012. This national network of clinical microbiology laboratories included data from 300 US hospitals diverse in location, size, and patient population. The analysis included isolates from children 1-17 years of age without a known diagnosis of cystic fibrosis. Per the definition by the Centers for Disease Control and Prevention, multidrug-resistance (MDR) was defined as nonsusceptibility to agents in 3 of the following 5 antimicrobial classes: cephalosporins, β-lactam/β-lactamase-inhibitor combination, carbapenems, fluoroquinolones, and aminoglycosides. Carbapenem-resistance (CR) was nonsusceptibility to at least 1 of the 3 agents in the cabapenem class (imipenem, meropenem, or doripenem).

The authors report a number of interesting findings. First, among 77,349 P. aeruginosa isolates included in the analysis approximately 20% were MDR, 11% were CR, and 8.4% were both MDR and CR. The highest proportions of MDR and CR P. aeruginosa isolates were from inpatient settings (especially those in an ICU), respiratory sources, and children 13-17 years old. Second, the overall trends indicate significant increases in both MDR and CR among P. aeruginosa isolates in the US. During the 13.5 year study period, the proportion of MDR isolates increased from 15.4% to 26% and the proportion of CR isolates more than doubled from 9.4% to 20%. This trend was observed in nearly all age categories and patient locations, the only exception being children 13-17 years old in an inpatient setting. As shown in figure 1, there were steady increases seen from 2010-2012 in both MDR and CR isolates. 

Finally, when examining resistance to individual antibiotics, rather than classes of antibiotics, some location-specific differences were seen. In the inpatient setting during the latter years of the study (2008-2012) the highest rates of resistance were seen to doripenem (27.6%), gentamicin (26.1%), cefepime (19.7%), ceftazidime (18.0%), and levofloxacin (16.9%). However, during the same time period in the outpatient setting the highest resistance rates were seen to gentamicin (28.4%), amikacin (21.8%), tobramycin (17.3%), ciprofloxacin (13.6%), and levofloxacin (13.1%). Additionally, significantly increasing resistance during the entire study period was seen to gentamicin and piperacillin-tazobactam in both inpatient and outpatient settings.

As noted in the manuscript, the reason for increasing rates of antibiotic resistance among P. aeruginosa isolates is likely multifactorial, with antibiotic usage, device usage, and increasing numbers of medically complex children all potentially playing a role. Given the limitations of the database, the authors were unable to differentiate colonization from infection and with respiratory isolates being the most common, some of these may represent colonization in patients with tracheostomy and/or ventilator dependence. Unfortunately, the Surveillance Network disbanded after 2012 so this study does not include data beyond 2012, which may be helpful in determining the impact of more widespread pediatric antimicrobial stewardship efforts. Despite the limitations, these findings highlight the importance of continued efforts in antimicrobial stewardship, as well as vigilance in infection prevention and control efforts to hopefully slow the spread of drug-resistant organisms.

Logan LK, Gandra S, Mandal S, Klein EY, Levinson J, Weinstein RA, Laxminarayan R. Multidrug-and Carbapenem-Resistant Pseudomonas aeruginosa in Children, United States, 1999–2012. Journal of the Pediatric Infectious Diseases Society. 2016 Nov 16

In the November 22/29, 2016 issue of JAMA, PIDS president Janet Gilsdorf, MD, FPIDS wrote a thoughtful and poignant reflection on how, and whether, we can achieve appropriate balance as practicing physicians (pediatric infectious disease physicians, in her and my case) between our work lives and our home lives. As a father of two children, ages 4.5 and 8 years, and as the spouse of another academic pediatric subspecialist (my wife is a PICU attending at my institution), I found myself nodding in agreement as I read Dr. Gilsdorf’s words—smiling in knowing sympathy in some places, and crying at others. She captures the true travails of attempting to balance a busy and diverse academic medical workload with some semblance of family time.

My own children have long asked why it is that daddy is always home at night while mommy has to be on call (an advantage of the peds ID lifestyle), or why daddy is always paged during dinner, and in the car, and at bedtime (the perils of the ID lifestyle), while mommy has more free attention at home. The choices we make, from which subspecialty to which subfields and career paths within that, as Dr. Gilsdorf rightly points out, do not and cannot occur in a vacuum. Our children and spouses see what we do, how we act, the choices we make (whether we feel they are, or not, they are choices), and respond to them. Thankfully, my own kids seem fairly well-adjusted about it and Dr. Gilsdorf can also say hers did relatively well, with some caveats. All told, there are success stories.

But as Dr. Gilsdorf points out, these successes are not by chance and are not without choice and sacrifice. It is, as they say, not possible to have your cake and eat it too. You cannot be the perfect parent and the perfect academician. You can, as she paraphrases Winnicott, be a ‘good-enough parent’. And I’ll add here, you can actually choose to be a good-enough physician as well. The work-life balance question is so stressful for us because we all want to succeed, to be the best we can be, to achieve. For some that is possible and easy, for some that is possible but harder, and for some, that may not be possible, or even the balance they hope to achieve at all. A chaotic household with multiple caretakers but a triumphantly successful academic career could easily become a more ordered, calmer household with more consistent caretakers and a solidly ‘fine’ career. Neither is superior when examined in isolation, despite our professional biases. Every one of us, as a parent and as a physician, must find our own path. As Dr. Gilsdorf herself writes, “We had our own equation for success as physician-parents, or, rather, we had an equation that we invented…” We must try our best to balance our own equation according to what makes us and our family happy, and then hope that it might just be good enough.

Greetings from the PIDS leadership! We were delighted to see the large and engaged turnout at the recent PIDS Business Meeting during IDWeek in New Orleans. Our society is growing in both numbers and impact, and our new organization chart reflects the wide variety of our activities. We encourage our members to participate in our many committees and task forces (note: apply for committee membership upon the solicitation that occurs every summer and apply for all that interest you.)

At IDWeek a number of important issues were discussed, including:

Recognition of the excellent research by our members

  1. 2016 Distinguished Research Award –Samuel Katz, MD
  2. The Caroline B. Hall Lectureship in Pediatric Clinical Research – Octavio Ramilo, MD
  3. The Caroline B. Hall Clinically Innovative Research Award –Jeffrey Gerber, MD, PhD
  4. PIDS Poster Awards
    1. David Griffith, MD
    2. Sarah Labuda, MD
    3. Liset Olarte, MD
    4. Nicole Poole, MD
    5. Emily Souder, MD

Introduction of the new PIDS Education and Research Foundation web-site

The Foundation, a separate legal entity from the Society, manages donations and gifts to the Society and distributes the research and training awards. We welcome your financial support.

Journal of the Pediatric Infectious Diseases Society: reminder from Dr. Theo Zaoutis, Editor-in-Chief

  1. Encourage your institution to subscribe to JPIDS 
  2. Send your manuscripts to JPIDS. Your excellent science makes our journal and our Society strong.

Results of the IDSA fellows’ survey, 2016 (note: small numbers of PID trainees)

  1. Trainees state they like their jobs and love PID, are generally happy with their careers and work-life balance, and would do it all again (and encourage others to join them in PID)
  2. Trainees have concerns that include the perception of limited job availability, less than ideal compensation in our field, and a gender discrepancy in compensation (note: we need to understand this one better)

PID Recruitment: What we know about recruitment to Infectious Diseases (from the IDSA survey of Bonura et al CID 63:155, 2016):

  1. Career decision-making for ID physicians is a two-step process, beginning during the early medical school years (motivated by emotional connectivity) then modified during residency (motivated by pragmatism).
  2. Intellectual stimulation of ID is seen as a positive
  3. M1, M2 microbiology courses focused on concept development over memorization are favored
  4. Interest in ID is strengthened by:
    1. Confidence in microbiology knowledge
    2. Exposure to ID
    3. Attendance at ID conferences
    4. Strong, enthusiastic ID mentors (Note: nobody wants to follow in the footsteps of a complainer).
  5. Detractors from ID include:
    1. Salary
    2. Perceived limited job availability
    3. Lure of primary care (note: this is more relevant to adult ID; for peds, it may be the lure of hospital medicine)

PID Recruitment: What we can do?

  1. Participate in Med School microbiology courses, emphasize pediatric illnesses and patients, and move the course toward concepts and away from memorization
  2. Facilitate medical student attendance at PID meetings
  3. Serve as enthusiastic mentors for med students/residents
  4. Consider establishing medical student ID interest groups with adult ID

We hope to see you at the PAS meeting, May 6-9, 2017, in San Francisco and at IDWeek, October 4-8, 2017, in San Diego.

Janet R. Gilsdorf, MD, FPIDS
President, Pediatric Infectious Diseases Society

Antibiotics are fundamental to modern medicine. They are essential to treat a wide spectrum of infections from routine streptococcal throat infections to life-threatening sepsis and to prevent infections in patients undergoing surgery and chemotherapy. However, the spread of antibiotic-resistant bacteria has placed the world on the precipice of what public health leaders call a "post-antibiotic" era in which even simple surgical procedures could be complicated by deadly infections. In the United States alone, at least two million Americans acquire a serious antibiotic-resistant infection each year, with an estimated 23,000 deaths as a direct result.1

All antibiotic use carries a risk of contributing to the development of antibiotic resistance. Additionally, although antibiotics are generally safe, these drugs also carry risks for individual patients. For example, antibiotics can cause adverse events ranging from minor side effects to serious allergic reactions and antibiotic use increases the potential for a patient to develop an infection caused by Clostridium difficile (C. diff), which can sometimes cause life-threatening diarrhea. A recent estimate found that nearly half a million Americans contracted a C. diff infection in 2011, resulting in 15,000 deaths. 2 Because of these risks to both individual patients and to the public health, antibiotics should only be used when indicated.

In 2015, the White House released a goal to reduce inappropriate antibiotic use in outpatient settings by 50 percent by the year 2020. 3 Outpatient use accounts for the majority of antibiotics prescribed for humans in the United States. While it is known that antibiotics are often used inappropriately, the amount of outpatient antibiotic use that is inappropriate and amenable to reduction needs to be quantified.

Over the past year, the Centers for Disease Control and Prevention (CDC) and The Pew Charitable Trusts undertook efforts to quantify the potential for reducing inappropriate outpatient antibiotic use in the United States. In support of this effort, Pew convened a panel of experts, including experts from the CDC, to set a baseline of antibiotic prescribing in the United States and establish condition-specific targets for reduction of unnecessary outpatient antibiotic prescribing. Based on current prescribing data, these experts determined that at least 30 percent of overall antibiotic use in outpatient settings is unnecessary. 4 In order to meet the White House goal of a 50 percent reduction in inappropriate use, total outpatient antibiotic prescribing in the United States would need to fall 15 percent by 2020. The majority of this reduction would come from reducing unnecessary use of antibiotics for acute respiratory conditions. These conditions account for 44 percent of antibiotic prescriptions in outpatient facilities, and half of these prescriptions are unnecessary.

As representatives of a range of health care providers and public health officials, we recognize that antibiotic resistance is a major threat to public health and commit to collective action to address this challenge by ensuring the appropriate use of these critical therapies. In support of national targets, our organizations commit to work in partnership with our members to expand current antibiotic stewardship efforts, fill research gaps around effective interventions for improving prescribing habits, and help our members use antibiotics appropriately in outpatient settings. These coordinated efforts will help preserve these life-saving therapies for the good of all of our patients.

Click here to view the statement online and download pdf copy.


1 U.S. Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United States, 2013, accessed Nov. 12, 2014, http://www.cdc.gov/drugresistance/threat-report-2013

2 Fernanda C. Lessa et al., "Burden of Clostridium difficile Infection in the United States," New England Journal of Medicine, 372 2(2015): 825-834, doi: 10.1056/NEJMoal408913.

3 The White House, National Action Plan for Combating Antibiotic-Resistant Bacteria, March 2015, accessed July 27, 2015, https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf

4 This goal specifically targets a reduction in unnecessary antibiotic prescribing, and does not include goals aimed at improving antibiotic selection. Ensuring the appropriate antibiotic is chosen for a particular condition is another critical aspect of antibiotic stewardship.

Impact of Matrix-Assisted Laser Desorption and Ionization Time-of-Flight and Antimicrobial Stewardship Intervention on Treatment of Bloodstream Infections in Hospitalized Children.

As a result of growing antimicrobial resistance worldwide, the promotion of judicious use of antibiotics1 has become increasingly important. In the health care setting, antibiotic stewardship programs (ASPs) aim to achieve excellent clinical outcomes while at the same time minimize toxicity, reduce costs, and decrease unnecessary exposure to broad spectrum antibiotics, thus limiting selection for antimicrobial resistant strains2,3.

At the same time, exciting advances in detecting antimicrobial resistant pathogens from clinical specimens are in development. The manner by which hospitals and microbiology labs are able to use this technology to drive patient care is highlighted by the study by Malcolmson and colleagues, reported in the JPIDS early web release on June 23rd 4.

Malcolmson et al report their experience in optimizing antimicrobial therapy at their institution after implementation of a new Matrix – Assisted Laser Desorption and Ionization Time of Flight (MALDI-TOF) mass spectrometry system. A MALDI-TOF mass spectrometry identifies microorganisms down to subspecies level. In simple terms, bacteria or yeast are selected from a culture plate or broth cultures and transferred to a target plate that lyses the organisms with solvents. The lysate is then run through the MALDI-TOF, which compares the subsequent spectral profiles of a number of bacterial components to those in a database for organism identification. Compared to traditional methods, which rely on bacterial growth characteristics and phenotypic criteria in biochemical reactions, long incubation times, and intensive personnel time, the MALDI-TOF can be an accurate, rapid, and inexpensive way to identify bacteria, fungi, and mycobacteria. Limitations of MALDI-TOF reflect the accuracy of identification with a small inoculum, the need to run susceptibilities separately, and the difficulty of separating closely related species (such as S.pneumoniae, S. mitis, and S. oralis). Within the last five years, MALDI-TOF has emerged as an important diagnostic tool in clinical microbiological laboratories5–7.

Malcolmson’s paper capitalizes on the introduction of this technology at their institution to retrospectively capture outcomes of a new MALDI-TOF system for early identification of positive blood cultures. This coincided with the hospital’s new ASP. Using a quasi-experimental design, the pre-period was defined as October 2009 - July 2010, when positive cultures from the BACTEC machine were gram stained and sub-cultured for identification and occurred prior to the institution of an ASP. Results were entered into a lab system, with fax and phone call to the ordering unit or physician. This was compared to the post period between October 2013 to July 2014, when both the MALDITOF and ASP program were initiated. In the post period, an aliquot from the positive blood culture was run through their MALDI-TOF with results compared to the gram stain followed by the same notification system. The ASP included prospective audit and feedback by a clinical pharmacist who checked cultures and susceptibilities daily and communicated with the treating team about the management plan.

Charts were reviewed for patients with a positive blood culture for bacteria or yeast. Patients with contaminants and those with blood cultures positive prior to their admission were excluded. The primary outcome of interest was time to optimal therapy, defined as the number of hours from blood culture collection to time of antimicrobial with the narrowest effective spectrum. The study also measured the following secondary outcomes: time to effective therapy (defined in hours as the time from collection of the blood culture to time of first antimicrobial agent with known susceptibility), 30 day all-cause mortality, length of stay, readmission, and time to pathogen identification among others. The authors used descriptive statistics to describe outcomes during the two periods.

Results included 100 episodes of blood stream infections in the pre period and 121 in the post period. Minor differences were noted between the two periods but otherwise baseline demographics were similar. The main outcome of interest, time to optimal (narrowest) therapy, showed a significant reduction in the post period from 77 to 54.2 hours (p<0.001). While not statistically significant, time to effective therapy trended to improvement from 2.6 hours to 1.6 hours p=0.058. Time to organism identification was dramatically reduced from 43.7 hours to 18.8 hours (p<0.001). No other differences in outcomes were noted. In their subgroup analysis, gram negative bacteremia demonstrated statistically significant decreases in both time to effective and optimal therapy (2.0 to 0.7 hours and from 146.8 hours to 48 hours, p<0.001 respectively). Multidrug resistant gram negatives were identified more quickly (41.3 vs. 16.7 hours) and time to optimal therapy (149.5 hours vs. 16.0 hours) was decreased (p=0.002). ASP interventions included discontinuation of antimicrobials, tailoring to culture and susceptibility, and optimization of dose based on information garnered from the MALDI-TOF results. Specifically, ASP made 15 recommendations to broaden and 36 recommendations to narrow therapy. Other outcomes, including mortality, were not significantly different. Readmission numbers were very low across the study and C.difficile rates were not different in the periods.

While a single center study, Malcolmson et al demonstrated that the combined approach of an improved detection system and an effective ASP decreased time to optimal and, sometimes, effective antimicrobial therapy. This was particularly apparent for gram negative infections. It would have been interesting to quantify the added benefit of the ASP with these new technology platforms, but this could not be captured as both interventions were implemented nearly simultaneously. Additionally, the ASP in this institution did not operate round the clock daily, which could reflect additional lost benefits in time to optimal therapy.

With quicker and more accurate systems of microbial identification from various clinical sources, blood, tissue, CSF, etc. on the horizon, we may be better able to reduce unnecessary broad spectrum antibiotics and streamline empiric-to appropriate-antimicrobials more quickly. The MALDI-TOF system continues to be refined and other platforms, including those that are molecular based, such as Verigene, are already being utilized6,8,9. Growing numbers of antimicrobial stewardship programs across the country are demonstrating value by reducing antimicrobial use and improving quality of care.2,3 Enhanced technologies that allow for rapid identification of pathogens could have enormous promise within these programs. The sooner we know the organism and susceptibility, the faster informed interventions can take place.

References

  1. Spellberg B, Blaser M, Guidos RJ, et al. Combating antimicrobial resistance: policy recommendations to save lives. CID. 2011;52 Suppl 5(suppl 5):S397-428.
  2. IDSA. New Antibiotic Stewardship Guidelines Focus on Practical Advice for Implementation. Webpage. 2016.
  3. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. CID. 2016;62(10):e51-77.
  4. Malcolmson CNKHSKNSJTPRA. Impact of Matrix-Assisted Laser Desorption and Ionization Time-of-Flight and Antimicrobial Stewardship Intervention on Treatment of Bloodstream Infections in Hospitalized Children. JPIDS. 2016;June 23(epub ahead of print).
  5. Murray PR. What is new in clinical microbiology-microbial identification by MALDI-TOF mass spectrometry: a paper from the 2011 William Beaumont Hospital Symposium on molecular pathology. J Mol Diagn. 2012;14(5):419-23.
  6. Singhal N, Kumar M, Kanaujia PK, Virdi JS. MALDI-TOF mass spectrometry: an emerging technology for microbial identification and diagnosis. Front Microbiol. 2015;6:791.
  7. Bailey D, Diamandis EP, Greub G, Poutanen SM, Christensen JJ, Kostrzew M. Use of MALDI-TOF for diagnosis of microbial infections. Clin Chem. 2013;59(10):1435-41.
  8. Beal SG, Ciurca J, Smith G, et al. Evaluation of the nanosphere verigene gram-positive blood culture assay with the VersaTREK blood culture system and assessment of possible impact on selected patients. J Clin Microbiol. 2013;51(12):3988-92
  9. Bork JT, Leekha S, Heil EL, Zhao L, Badamas R, Johnson JK. Rapid testing using the Verigene Gram-negative blood culture nucleic acid test in combination with antimicrobial stewardship intervention against Gram-negative bacteremia. Antimicrob Agents Chemother. 2015;59(3):1588-95.

Grinsdale JA. Interferon-Gamma Release Assays and Pediatric Public Health Tuberculosis Screening: The San Francisco Program Experience 2005 to 2008.

Grinsdale et al. describe the experience of the San Francisco Department of Public Health’s (SFDPH) use of interferon-gamma release assays (IGRA) in a longitudinal retrospective pediatric cohort in a low TB-prevalence setting.

Latent tuberculosis infection (LTBI) was diagnosed in asymptomatic children with negative chest X-ray and positive QuantiFERON-TB Gold In-tube (QFT), regardless of tuberculin skin test (TST) results, if performed. A small subset of children with a prior or current positive TST and a negative QFT were treated for LTBI at the physician’s individual discretion. Indeterminate QFT tests were repeated and the subsequent test used to establish LTBI status, and for repeated indeterminate QFT tests, diagnosis of LTBI was based on the most recent TST result.

Inclusion criteria for the study were children <15 years of age with a QFT test performed March 1, 2005–December 31, 2008, with 1092 eligible children included. Children had varying risk factors for TB infection including contacts of active TB cases, immigrant children form high-prevalence TB countries who were also BCG vaccinated, and children born in the US being screened for school entry. The study population included 56 (5%) children <2 years of age and 292 (27%) < 5 years of age. QFT-negative/TST-positive discordant results were present in 158 (73%) of children.

976 (89%) of children in the cohort were not treated for LTBI, and observed for a median of 5.7 (range 4-7) years. No cases of active TB were seen in any untreated child during the 5587 person-years of follow-up, including among 146 TST-positive/QFT-negative children. Discordance between TST and QFT was most pronounced in BGC-vaccinated children born outside of the US who were <5 years old (93%) versus 73% in those > 5 years old, consistent with studies showing higher false positive TST results when BCG vaccine was given more recently. This highlights that widespread use of TST in foreign-born children inadvertently leads to increased and potentially unnecessary radiologic studies and LTBI treatment.

The findings of the study suggest that QFT has a high negative predictive value and supports use of IGRAs in screening BCG- and non-BCG vaccinated children, including those <5 years of age, and may prevent unnecessary imaging and treatment for LTBI in many children.

 

Written by: Saul Hymes, MD

Summary

In the June 2016 issue of the “Journal of the Pediatric Infectious Disease Society,” Jiménez-Truque and colleagues report the findings of their prospective longitudinal assessment of S. aureus colonization in student athletes [Jimenez-Truque 2016]. This prospective cohort study examined Vanderbilt University varsity athletes from August 2008 to April 2010. Nasal and oropharyngeal swabs were taken to assess for colonization with both MRSA and MSSA at enrollment and then monthly thereafter. Skin and soft tissue infections were monitored for and recorded. They enrolled 377 athletes and trainers, 224 of whom played contact sports (football, basketball, soccer, and lacrosse; defined using the AAP criteria) and 153 of whom played noncontact sports (cross country, tennis, golf, bowling, swimming, and baseball) or were trainers. Overall, 76.13% of athletes were colonized with S. aureus and 46.4% were colonized with MRSA on at least one occasion, but the prevalence of carriage was dynamic over time. Total S. aureus colonization rates ranged from 34% - 62% and MRSA rates ranged from 8% - 29%. Colonization rates were significantly higher in contact sports participants, ranging from 32% to 62% compared to 18% to 53% in non-contact participants. The colonization rate in the summer was significantly higher than that in the winter, with an OR for MRSA of 1.70 and for MSSA of 1.38. In their discussion, the authors note this was the largest prospective cohort to date of healthy college athletes. The study documented dynamic colonization that changed over the sports seasons, and overall demonstrated significant colonization rates, with real clinical implications, including an MRSA skin and soft tissue infection outbreak that occurred among the football team during their study period.

Commentary

I do not have to convince the readership of PIDSNews that antibiotic resistance is a problem. The CDC’s excellent 2013 threat report [CDC 2013] laid out the scope of the problem, and from the Joint Commission to the Centers for Medicare and Medicaid Services to the United States Executive Branch itself, official practice parameters and even mandates are starting to emerge to guide stewardship and other efforts to reduce antimicrobial resistance and infections with resistant organisms. And yet we don’t understand how best to manage and prevent these infections. While reducing antibiotic use is one key approach, understanding the dynamics of colonization with resistant organisms and how best to time (and where best to place) infection prevention efforts can be key for those organisms that are part of our commensal flora.

As the authors of the present study note, the leading cause of skin and soft tissue infections is S. aureus, a frequent skin and mucous membrane colonizer, with MRSA in particular both more virulent and harder to treat. In recent years MRSA infection rates are declining though the bulk of this is in hospital-acquired (HA) infections where a decline of 54.2% was observed between 2005-2011. Over the same period, only a 5% decline in community-acquired (CA) infections occurred [Dantes 2013]. Given this difference in the rates of decline, CA-MRSA infections are rapidly becoming the more dominant type and further contribution to our knowledge of community S. aureus colonization has the potential to further control these infections.

While the story of MRSA/MSSA infections or colonization in athletes is not a new one [Kazakova 2005], the present study contributes a number of novel findings to the field. First, its prospective nature allowed the authors to show a true seasonality to colonization, related to the particular sporting season. This is not surprising given differences in equipment use, close quarters in locker rooms, and training frequency that could allow for closer contact and spread of organisms, but having it tracked in this way may allow better resource allocation by sports teams. Currently, significant resources may be spent year round on cleaning equipment and on decolonization efforts for players. Armed with this data, programs may find that concentrating those efforts to just before the highest colonization season may be more cost-effective .

Additionally, this study further confirms that contact sports show a higher colonization risk, but it is interesting that it is still fairly high in the noncontact sports. One wonders if this is due to other modes of transmission/colonization, including cross-sports-team social gatherings, dorm living and other aspects of student life, or shared athletic facilities. This, too, is an avenue for further study, as the present study did not examine or control for these other factors. While doing so could be difficult, some form of social network tracking, as has been used for HIV transmission networks [Woodhouse 1994], could prove useful in future studies of this issue.

Finally, this study’s use of oropharyngeal swabs in addition to nasal swabs is of particular interest. The authors note they did not utilize groin or rectal swabs due to concerns of low participant acceptance of such procedures, which is reasonable. But as they show, even the dynamics of nasal vs. oropharyngeal colonization differed, with nasal carriage more common than oropharyngeal overall (31% vs 26%), but the addition of oropharyngeal swabs to nasal swabs increased the detection of S. aureus colonization by 12.4%. Clinically, a negative S. aureus swab from one site is not meaningful, and the same held true here. To truly track S. aureus or other commensal flora colonization, multiple swabs from at least a few if not all possible major sites of colonization should be used in order to maximize the accuracy of detection.

Overall the study adds to our knowledge of colonization dynamics in a population that is known to be at risk for S. aureus infection and to serve as a large reservoir of colonization. In addition, the study offers clear avenues for future research as well as ways to apply the results to day-to-day practice.

References:

  1. Jimenez-Truque N, Saye EJ, Soper N, Saville BR, Thomsen I, Edwards KM, Creech CB. “Longitudinal Assessment of Colonization With Staphylococcus aureus in Healthy Collegiate Athletes. J Pediatric Infect Dis Soc. 2016 Jun;5(2):105-13. Epub 2014 Nov 5.
  2. Antibiotic Resistance Threats in the United States, 2013. The Centers for Disease Control and Prevention, 2013. http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf 
  3. Dantes R, Mu Y, Belflower R, Aragon D, Dumyati G, Harrison LH, Lessa FC, Lynfield R, Nadle J, Petit S, Ray SM, Schaffner W, Townes J, Fridkin S, for the Emerging Infections Program–Active Bacterial Core Surveillance MRSA Surveillance Investigators. “National Burden of Invasive Methicillin-Resistant Staphylococcus aureus Infections, United States, 2011” JAMA Intern Med. 2013;173(21):1970-1978.
  4. Kazakova SV, Hageman JC, Matava M, Srinivasan A, Phelan L, Garfinkel B, Boo T, McAllister S, Anderson J, Jensen B, Dodson D, Lonsway D, McDougal LK, Arduino M, Fraser VJ, Killgore G, Tenover FC, Cody S, Jernigan DB. “A Clone of Methicillin-Resistant Staphylococcus aureus among Professional Football Players” N Engl J Med 2005; 352:468-475.
  5. Woodhouse DE, Rothenberg RB, Potterat JJ, Darrow WW, Muth SQ, Klovdahl AS, Zimmerman HP, Rogers HL, Maldonado TS, Muth JB, Reynolds JU. “Mapping a social network of heterosexuals at high risk for HIV infection.” AIDS 1994 Sep;8(9):1331-6.

Written by: Diana Yu, PharmD and Saul Hymes, MD

PIDS, as the premier national organization representing the care of and research into infectious diseases in infants and children, takes part in many conferences every year. At both IDWeek and PAS, PIDS organizes sessions and tracks—and those are well worth attending. But sometimes it’s the smaller meetings that can be the most worthwhile—the best balance of networking and education, especially for those in a particular subfield. Dr. Rana Hamdy wrote a few months earlier in these virtual pages about the PIDS-St. Jude’s annual research conference and what it offers in particular to fellows who would attend. Here we report on the 7th Annual International Pediatric Antimicrobial Stewardship Conference.

Led by Dr. Jason Newland and organized and sponsored by PIDS as well as Children’s Mercy in Kansas City, this conference continues to be a tremendous resource for those already working in the field of stewardship and, for the first time this year, is explicitly aimed as a resource for those new to stewardship as well. The conference attendees are a nearly equal mix of pharmacists and physicians, mirroring the close collaboration between those two positions in stewardship programs nationwide. And while the conference attendance is growing every year, it remains a relatively small (think couple of hundred not couple of thousand) group and a single conference track, which makes networking and focus on content that much easier.

Indeed, networking and fostering collaboration across institutions is a key goal of the conference. The pre-conference began, as it has for the past few years, with a dinner Wednesday night and a meeting Thursday morning for representatives of institutions participating in the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) collaborative, a multi-center quality collaborative aimed at sharing data on antimicrobial resistance and stewardship with the goal of studying and possibly standardizing pediatric stewardship practices that work.

While the SHARPS meeting on Thursday morning was taking place and after a great Grand Rounds by Jason Newland on why antibiotic resistance (and thus stewardship) really matters, a new aspect of the official conference was introduced this year. Typically in past years the stewardship conference would begin at 1 PM, but this year a series of introductory talks were organized for Thursday morning for those new to stewardship—fellows, new PharmD’s, or those just starting a stewardship program. From speaking to a number of fellows and more junior attendees at the morning’s sessions, I learned that the sessions seemed extremely helpful, addressing some of the “why” and more broadly “how” of actually doing antimicrobial stewardship, before the rest of the conference dove deeper into details.

Thursday at lunch saw the 3rd meeting of the Pediatric Hematology-Oncology Stewardship Interest Group, or PHOASIG. Led by Dr. Josh Wolf of St. Jude, this group is organized around the idea that stewardship for patients with pediatric malignancies is fundamentally different from other stewardship areas and more data are needed to understand why and what the best approaches may be. Currently a number of multicenter collaborative research projects are in the works and those interested participants were encouraged to sign up for the email listserv.

Kicking off Thursday afternoon’s sessions, Dr. David Hyun of the Pew Foundation and Dr. Holly Maples of University of Arkansas reviewed recent publications in the primary literature on pediatric antimicrobial stewardship. Dr. Sarah Parker then spoke about the experience of starting and running a stewardship program at Children’s Hospital of Colorado. Their unique “Handshake Stewardship” program allowed them to get near universal buy-in and make stewardship an integral part of every team’s day. Then attendees heard the PIDS ASP fellowship award winners—Dr. Candace Johnson from Children’s Hospital of New York-Presbyterian on ASP activities in pediatric post-acute care facilities, Dr. Caroline Reuter on the role of MALDI-TOF and other rapid diagnostics on stewardship at Lurie Children’s Hospital in Chicago, and Dr. Matthew Thomas on a new smartphone-based antibiogram. The day ended with another new feature of the conference, a panel discussion with questions from the audience. This was a big hit. And before turning in for the evening, attendees were treated to an evening of beer and BBQ at the local Kansas City Boulevard Brewery. It was an evening of good food and good conversation.

On Friday, the second day of the conference, Dr. Eddie Stenehjem from Intermountain Healthcare began the morning by presenting the trials and tribulations of extending stewardship activities to smaller community hospitals within a healthcare system, suggesting that hospitals with fewer resources may need a “simpler” approach and accessibility to ID support. Dr. Ritu Banerjee from Mayo Clinic painted the evolving issues of multi-drug resistant Gram-negative infections, illustrating their increasing rates in children and the limited information on treatment options. Dr. Jonathan Beus from Children’s Hospital of Philadelphia highlighted how data will always be needed to evaluate stewardship efforts and to identify areas of opportunity. Finishing out the morning, Dr. Parker returned to discuss how business plans for stewardship can align with the health systems’ goals, including cost savings, safety, and regulatory requirements.

In the afternoon, Dr. Katherine Fleming-Dutra from the CDC discussed the methods and findings from the recent article released in JAMA about inappropriate antibiotic use in the outpatient setting. Oral abstract presentations from physicians and pharmacists included topics such as integrating rapid diagnostics, usage of clinical care guidelines for musculoskeletal and urinary tract infections, probiotic use to prevent C. difficile infection in hematology/oncology patients, and using electronic resources such as claims data to bolster stewardship efforts. Dr. Hyun returned to the podium to close out the final day of the meeting. He provided insight on the political landscape of antimicrobial stewardship; current challenges to meeting the requirements of the mandated stewardship policies and how the national action plan could affect different areas with limited resources.

All in all, it was, this year as it is every year, a wonderfully dense meeting. Attendees reported feeling that they not only had learned an incredible amount but that they now had a long list of even more articles and papers to review. But new collaborative connections were made, new stewardship programs received useful evidence and support and advice, and those who had not yet started a program came away with concrete notions of how and why to do so. For fellows not yet sure where in the world of Peds ID they are headed, the meeting was a valuable guide to what a career in stewardship can be like. Overall, nearly everyone seemed to enjoy themselves and were looking forward to the 8th annual meeting in 2017.

By Janet R. Gilsdorf, FPIDS, President, Pediatric Infectious Diseases Society

Our mission is noble: To enhance the health of infants, children, and adolescents by promoting excellence in diagnosis, management, and prevention of infectious diseases through clinical care, education, research, and advocacy.

Our progress in achieving the mission is strong and steady.

Pillar 1: Value of PID to health systems

The Society is committed to helping hospitals understand the value of our clinical services and, to that end, it has sponsored an interview-based study of perceptions of our value, which will soon be published, and a comparative study of clinical outcomes with and without PID consultation, which is in progress.

Pillar 2: Recruitment of future ID pediatricians

The Society is committed to maintaining a strong pipeline of PID practitioners and investigators and, thus, 1) is developing recruitment tools for use by fellowship programs, 2) is revising the career brochure, and 3) has produced a series of videos in which our members discuss their career choices. Check out the videos: https://www.youtube.com/watch?v=0Ykv-I7D6FY  
https://www.youtube.com/watch?v=0W2Z9tv9pVs

To engage residents and medical students in PID, the Society, under the leadership of Dr. Buddy Creech, submitted a grant to the NIH to support resident and student participation in the St. Jude/PIDS Pediatric Infectious Diseases Research Conference.

Pillar 3: Training and guidance of PID fellows

The Society continues support of our many fellow-directed resources and activities, such as the Fellows’ Survival Kit, Fellows’ Day at IDWeek, the St. Jude/PIDS Pediatric Infectious Diseases Research Conference and associated transplant ID symposium and HIV course, the Antibiotic Stewardship conference, and research awards, and is developing online educational modules for use in fellow education.

Pillar 4: Research activities related to PID

Research sits squarely at the core the PID Society. To further PID research, the Society is coordinating research opportunities through the PIDS Transplant Network and, NEW THIS YEAR, will offer two research awards for PID members through the generosity of the Pichichero Family Foundation.

Pillar 5: Engagement of new and established PIDS members

The Society membership is at an all-time high of 1340, and we are actively including more members and fellows in Society committees. The Social Media Task Force is engaging members and others in our activities through Twitter. We say hello to the newest members of the Board of Directors: Dr. Susan Coffin and Dr. Bonnie Maldonado, and a fond farewell to Dr. Kris Bryant, with heartfelt thanks for her valuable service on the Board.

Pillar 6: Growth of PIDS Education and Research Foundation

Do you know what PIDSERF is? If not, check it out: http://pidserf.org/about.html. This is the branch of the Society through which monetary gifts are transformed into research awards and educational endeavors for our members and fellows. This year, five awards will be given through PIDSERF. The Resource Development Committee is exploring additional avenues to enrich the PIDSERF award funds.

Pillar 7: Success of JPIDS

The Journal of the Pediatric Infectious Diseases Society is now indexed in PubMed and attracts manuscripts of important studies related to Pediatric Infectious Diseases from both national and international scientists. The success of the Journal translates into the success of the Society.

I look forward to meeting you at IDWeek in New Orleans from Oct 26-30, 2016.

Written by: Rana F. Hamdy, MD, MPH

On March 4-5, 2016, St. Jude Children’s Research Hospital hosted the 15th annual St. Jude/PIDS Research Conference. This two-day conference was held in the new Marlo Thomas Center for Global Education and Collaboration at St. Jude Children’s Research Hospital in Memphis, Tennessee and was attended by 145 participants. In contrast to the much larger IDSA and PAS annual meetings, this intimate venue facilitated meeting and networking with colleagues from across the country.

The conference began Friday morning with the “Frontiers in Infectious Diseases” symposium:

  • Dr. Joshua Wolf from St. Jude Children’s Research Hospital spoke on antibacterial prophylaxis in children with cancer, reviewing current practices and summarizing recent studies that provide guidance in antibacterial prophylaxis for children with acute myeloid leukemia, in particular.
  • Dr. Elaine Tuomanen introduced the next speaker, Dr. Manuel Amieva, noting that he was the first PIDS-St. Jude Postdoctoral Fellow. Now an
    Associate Professor of Pediatric Infectious Diseases and Microbiology & Immunology at Stanford University, Dr. Amieva used beautiful electron microscopy animations to show Helicobacter pylori‘s interactions with epithelial junctions.
  • Dr. Sing Sing Way, from Cincinnati Children's Hospital Medical Center, discussed the immunopathogenesis of prenatal infections, focusing on the role of T regulatory cells in pregnancy tolerance and susceptibility to infection in pregnancy.
  • Presenting remotely from Bethesda, MD, Dr. Barney S. Graham, from National Institutes of Health, presented “RSV Vaccine Development: A Time for Hope,” summarizing the results of historic RSV vaccine trials and new vaccine candidates.
  • Presenting the 2016 John H. Erskine Lecture in Infectious Diseases, Dr. Herbert “Skip” Virgin, IV, from Washington University School of Medicine, presented “Transkingdom Control of Immunity to Virus Infection”, elucidating the complex interactions between the gut virome, viral infections, and the human immune system.

In the afternoon, three PIDS and PIDS-St. Jude Fellowship Award Recipients presented their research in progress. Dr. Elisa Margolis, third year fellow at the University of Washington, presented “Finding the Needle: Microbiome Causality”; Dr. Laura Vella, third year fellow at The Children’s Hospital of Philadelphia, presented “Circulating T Follicular Helper Cells as a Periscope into the Lymph Node”; and Dr. James “Muse” Davis, third year fellow at the University of Wisconsin, presented “A Zebrafish Model of Cryptococcal Infection Reveals Distinct Roles for Macrophages and Neutrophils Responding to Spore and Yeast Forms.”

The day concluded with an impressive poster session with 30 posters representing 19 institutions and 4 countries. Best Poster Awards were awarded to Joy Hazelton, Diego Hijano, and Anita McElroy.

On Friday evening, St. Jude and PIDS hosted dinner at Itta Bena Restaurant – a hidden gem just above BB Kings Blues Club on Beale Street – for an evening of fine dining and live music in a relaxed atmosphere to enjoy the company of colleagues and friends.

The second day of the St. Jude/PIDS research conference began with the Keynote Address and Luminaries in Pediatric Infectious Diseases, followed by career development workshops tailored to fellow trainees.

Dr. Anne Schuchat, Principal Deputy Director for Centers for Disease Control and Prevention, delivered the conference’s keynote address, “Changing Practices and Paradigms: From Perinatal Infections to Pandemics and Beyond.” Dr. Schuchat told the public health stories of her involvement in interventions aimed to prevent Group B Streptococcus neonatal infections, the 2009 H1N1 influenza pandemic, and the Sierra Leone trial to introduce a vaccine against Ebola in 2014-2015.

Dr. Ann Arvin, Professor of Pediatrics at Stanford University, presented the Luminaries in Pediatric Infectious Diseases presentation: “Molecular Mechanisms of Varicella-Zoster Virus (VZV) Pathogenesis and their Clinical Implications”. Dr. Arvin presented her laboratory’s research elucidating the tropism of VZV for T cells and the molecular changes that induce trafficking to skin.

The focus of the conference then turned to career development. Dr. James E. Crowe, Jr, from Vanderbilt University, gave a personally reflective and philosophical presentation entitled “Core Capabilities for Successful Academic Medicine Careers,” inspiring participants to capitalize on their unique quirks and interests in the early stages of their careers.

Dr. Lara Danziger-Isakov (Transplant ID), Dr. Jason Newland (Antimicrobial Stewardship), Dr. Susan Coffin (Infection Control and Prevention), and Dr. Anne Schuchat (Public Health) comprised a group of impressive and inspiring panelists that displayed the breadth and diversity of career opportunities within pediatric infectious diseases. The panelists briefly summarized their career paths and what they love about their careers. The honest and inspiring discussion about career paths that followed was driven by questions from the audience, asked in-person by audience members as well as by Twitter.

Over lunch, there were multiple breakout sessions: NIH K Awards/Loan Repayment Program (led by Drs. Jim Cassat and Scott James), Negotiating Your First Job (led by Drs. Paul Spearman and John Williams), and Work/Life Balance (led by Drs. Lara Danziger-Isakov and Jason Newland).

The conference concluded with additional oral abstract presentations, including: “CMV Infection as a Cause of Fever and Morbidity Among Pediatric Cancer Patients on Maintenance Chemotherapy” (Dr. Paul Sue); “Intestinal Microbiome Alterations May Predict Infection Outcomes in Children with Acute Lymphoblastic Leukemia” (Dr. Hana Hakim); Neonates Fail to Mount a Mucosal Immune Response Against RSV Infection” (Dr. Diego Hijano); “Extended-Spectrum beta-lactamase-producing Enterobacteriaceae in Pediatrics (Dr. Jonathan Strysko); and “Fetal and Adult Progenitors Give Rise to Unique Populations of CD8+ T Cells” (Dr. Brian Rudd).

St. Jude and PIDS hosted yet another successful and well-attended research conference, providing the opportunity for each participant to present original research, to meet and learn from internationally renowned experts in pediatric infectious diseases, and to participate in focused career development workshops specifically tailored to pediatric infectious diseases fellows. From the perspective of a fellow trainee, attending the PIDS/ St. Jude Pediatric Infectious Diseases Research Conference was a high-yield experience to learn new science and to meet colleagues from across the country, opening doors for potential career opportunities and collaborations.

The next conference is scheduled for March 10-11, 2017 in Memphis, Tennessee. Funding is available from St. Jude for each institution to send one trainee and a junior faculty member.

Written by: Rana F. Hamdy, MD, MPH

On March 3, 2016, St. Jude and PIDS hosted the 3rd annual St. Jude/PIDS Pediatric Transplant ID Symposium. This one-day symposium was held the day prior to the St. Jude/PIDS Research Conference and brought together leaders in the field of pediatric transplant ID for presentations and discussions on topics related to infections in children undergoing hematopoietic stem cell or solid organ transplantation.

Highlights from the meeting included:

  • Dr. Sandy Feng, Professor of Surgery from the University of California San Francisco began the symposium with an overview of the immune system, immunosuppressive therapeutic agents, and their mechanisms of action, followed by a discussion of the feasibility of immunosuppressive withdrawal in liver transplant recipients.
  • Dr. Steven Holland, Chief of the Laboratory of Clinical Infectious Diseases at the National Institutes of Health, discussed the status of hematopoietic stem cell transplantation as a treatment option for primary immunodeficiency syndromes with myeloid defects including chronic granulomatous disease, Job’s syndrome, and GATA2 deficiency.
  • Dr. Michael Ison, Medical Director of the Transplant & Immunocompromised Host Infectious Diseases Service at Northwestern University Feinberg School of Medicine, described the epidemiology of diarrhea in transplant recipients and discussed the optimal diagnostic approach to these patients.
  • Dr. Brian Fisher, Assistant Professor of Pediatrics at The Children’s Hospital of Philadelphia, presented results from a multicenter clinical research study of the epidemiology and outcomes of respiratory viral infections in HSCT and SOT patients. Dr. Fisher discussed the process of establishing the infrastructure for performing large multi-center clinical epidemiology research studies in pediatric transplant patients, highlighting the opportunities that collaboration via the St. Jude/PIDS Transplant ID Symposium affords, and he invited any interested individuals to join the Transplant Research Network to discuss future opportunities for collaboration.
  • Dr. Theoklis Zaoutis, Professor of Pediatrics and Epidemiology and Chief of the Division of Infectious Diseases at The Children’s Hospital of Philadelphia, reviewed the epidemiology of invasive fungal infections (IFIs) in immunocompromised children; the diagnosis of IFIs, including the role of biomarkers; the evidence for antifungal prophylaxis among HSCT recipients and children with leukemia; and optimal treatment strategies for immunocompromised children with IFIs.
  • Dr. Gregory Storch, Professor of Pediatrics and Molecular Microbiology from Washington University School of Medicine, discussed emerging trends in diagnostic microbiology and the application of new diagnostic testing methods in managing infections in pediatric transplant recipients.
  • Dr. Michael Green, Professor of Pediatrics at Children’s Hospital of Pittsburgh, discussed the role of the Organ Procurement Transplant Network/United Network for Organ Sharing in protecting solid organ transplant recipients from unanticipated donor-derived infections.
  • Dr. Lara Danziger-Isakov, Professor of Pediatrics at Cincinnati Children’s Hospital Medical Center, discussed the components of a pre-transplant evaluation for identifying and mitigating the risk of post-transplant infections.
  • Drs. Hayley Gans and Gabriela Maron presented the top six papers in transplant ID in 2015-2016.

Interspersed between the presentations were interactive breakout sessions built around case presentations, with lively discussions that provided an opportunity to explore variations in practice throughout the country.

A poster session also provided an opportunity to engage other symposium participants and learn about ongoing basic science, translational, and clinical research in pediatric transplant ID.

In total, 124 participants from 54 different institutions and 6 countries attended the St. Jude/PIDS Pediatric Transplant ID Symposium this year. Participants engaged with leaders in the field of pediatric transplant ID, discussed challenging cases and new research, and met colleagues from across the country, building new collaborations and networks. The next St. Jude/PIDS Pediatric Transplant ID Symposium will take place March 9, 2017 in Memphis, Tennessee.

Written by: Parvathi S Kumar MBBS, Andrés Alarcón MD

Since August 2015, a large outbreak of Lassa fever has devastated Nigeria, in West Africa. The index case of the current outbreak was reported from Bauchi in November, 2015.1 Secondary cases have been reported across 19 states in Nigeria. As of March of 2016, the Nigeria Center for Disease Control (NCDC) has reported a total of 254 cases (129 laboratory confirmed cases) and 137 deaths (suspected, probable and confirmed cases) with a case fatality rate (CFR) of 53.9%.2 The neighboring country of Benin detected an outbreak of Lassa fever on January 21st, 2016. Togo notified the World Health Organization (WHO) of its first 2 cases on March 9th 2016, and active surveillance of contacts are being monitored in Togo, Germany, and United States of America (USA). Currently, 2 secondary cases are being cared for in Germany and USA. The American citizen, a physician assistant is receiving care and treatment at Emory University Hospital in Georgia and is reportedly stable. The German patient who represents Europe's first case of locally acquired Lassa fever is being care for in Frankfurt, alongside four family members.

Typically, Lassa fever outbreaks have a low overall mortality rate of 1% with a mortality rate of 15-20% amongst hospitalized individuals.3,4 The unusually high CFR associated with the current outbreak is worrisome and remains unexplained. A heightened awareness resulting from the Ebola virus disease outbreak ravaging the area, coupled with the increasing capability to rapidly and accurately diagnose the condition may be contributing factors. Additionally, prior outbreaks may have been under reported when remote and rural areas of the country were primarily affected.

Lassa virus, an arenavirus, was first described in 1969, and named after the town in Nigeria where the first cases occurred.5 It is a zoonotic acute viral hemorrhagic illness lasting 1-4 weeks; endemic to West Africa, particularly Sierra Leone, Liberia, Guinea (Mano River region), and Nigeria. CDC estimates 100,000-300,000 Lassa virus infections in West Africa per year, with approximately 5,000 deaths.6 The neighboring countries of Benin, Togo, Ghana, and Mali report yearly outbreaks with peaks from December through February.7

The animal reservoir is a rodent of the genus Mastomys, commonly known as the “multimammate rat” that colonizes homes and peri-residential areas. The rodents once infected are typically asymptomatic; however, they can shed the virus in urine and droppings for a long time, possibly for the duration of its life time. Human infections result from direct contact with the rodent’s waste via inhalation or ingestion. Infection can also be acquired in the laboratory or through human to human transmission after exposure to the virus in the blood, tissue or secretions. Following an incubation period of 7-21 days, the infection results in severe hemorrhagic fever in 5-10% of the cases. Typically, the disease has a gradual onset, starting with fever, general weakness, and malaise. The symptoms are closely followed by pharyngitis, muscle pain, retrosternal chest pain, cough, bleeding from the mouth, nose, vagina or gastrointestinal tract, and the potential for associated hypotension and or sepsis.8 Recovery from a milder disease begins 8 to 10 days after disease onset with resolution of symptoms. Of importance, the disease is especially severe if acquired in the 3rd trimester of pregnancy resulting in more than 80% maternal mortality and fetal loss. Deafness secondary to sensorineural hearing (SNH) loss is a major morbidity associated with Lassa fever. It is estimated that SNH loss can occur in up to 25% of patients who survive the disease, making Lassa fever a major cause of deafness in endemic areas.8,9

Due to the increasing international travel and migration patterns, it is important to consider common and uncommon infectious etiologies of febrile illness in returning travelers to the USA or other non-endemic countries. In Lassa fever, ribavirin is most effective when given early in the disease and consideration should be made in consulting an infectious disease specialist to expedite potential compassionate use through the USA Food and Drug Administration (FDA) and Valeant Pharmaceuticals (Aliso Viejo, California). 10

If a case of Lassa fever is suspected, per CDC recommendations, it is prudent to immediately implement hospital infection-control policies, contact state and local health department for contact tracing, treatment recommendations, adherence to proper infection-control strategies, and proper diagnostic laboratory collection.12 Clinicians should notify local health authorities and CDC’s Viral Special Pathogens Branch immediately of any suspected cases of VHF occurring in patients residing in or requiring evacuation to the United States: 404-639-1115 or the CDC Emergency Operations Center at 770-488-7100 after hours.11

References

  1. Press Briefing on the Outbreak of Lassa fever in Nigeria by the Honourable Minister of Health. (Accessed March 25th 2016, at http://www.health.gov.ng/index.php/news-media/9-uncategorised/245-press-briefing-on-the-outbreak-of-lassa-fever-in-nigeria-by-the-honourable-minister-of-health.) 
  2. Lassa fever death rates in Nigeria higher than expected. (Accessed March 27th 2016, at http://www.cnn.com/2016/03/17/health/lassa-fever-outbreak-nigeria/.) 
  3. Ogbu O, Ajuluchukwu E, Uneke CJ. Lassa fever in West African sub-region: an overview. J Vector Borne Dis 2007;44:1-11.
  4. Centers for Disease C, Prevention. Imported Lassa fever--New Jersey, 2004. MMWR Morb Mortal Wkly Rep 2004;53:894-7.
  5. Frame JD, Baldwin JM, Jr., Gocke DJ, Troup JM. Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological findings. Am J Trop Med Hyg 1970;19:670-6.
  6. Lassa fever. (Accessed March 25th 2016, at http://www.cdc.gov/vhf/lassa/.) 
  7. McCormick JB, King IJ, Webb PA, et al. A case-control study of the clinical diagnosis and course of Lassa fever. J Infect Dis 1987;155:445-55.
  8. Cummins D, McCormick JB, Bennett D, et al. Acute sensorineural deafness in Lassa fever. JAMA 1990;264:2093-6.
  9. McCormick JB, Webb PA, Krebs JW, Johnson KM, Smith ES. A prospective study of the epidemiology and ecology of Lassa fever. J Infect Dis 1987;155:437-44.
  10. Lassa Fever in Nigeria. (Accessed March 26th 2016, at http://wwwnc.cdc.gov/travel/notices/watch/lassa-fever-nigeria.) 
  11. Imported Lassa Fever --- New Jersey, 2004. (Accessed March 26th 2016, at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5338a2.htm.)