News

JPIDS Accepted for MEDLINE Indexing

THE PEDIATRIC INFECTIOUS DISEASES SOCIETY IS PLEASED TO ANNOUNCE:
The Journal of the Pediatric Infectious Diseases Society has been accepted for MEDLINE indexing!

Read more: JPIDS Accepted for MEDLINE Indexing

Square Peg, Round Hole – Fitting ID Physicians in Productivity Compensation Models

About a week ago, I sat down to fill out my annual review at the academic institution where I work. As part of this, I listed the goals I would like to attain over the coming year. Each goal is assigned a category, and while some categories are easy to fill, such as academic research, the "clinical productivity" category remained blank. I struggled to identify my goal in this area.

The changing landscape of medicine has resulted in various compensation mechanisms for physicians, such that models once seen mainly in private practice are bleeding into academic institutions. This results in changes in how physicians are paid as we move toward models that align targets for volume and quality. As a pediatric ID physician, I normally do not give much thought to the number of patients that I see when I am in clinic or on service – that may need to change soon. Now that our hospital has moved to a primarily Relative Value Units (RVU) productivity based system, I must now think about numbers, complexity, and time. This feels foreign to me, as I picked a career I loved without much thought or consequence of these real life issues of "compensation" and "benchmarking." Pediatric ID is not traditionally seen as "revenue generating" compared to other specialties1. This bodes for particular concern for cognitive specialties limited by referrals and with few, if any, profitable procedures.

The major models by how pediatric ID physicians are compensated are varied and changing2. Pure 100% salary based (hospital funded) positions are increasingly rare. Instead, there may be any range of seemingly complex models currently in practice: grant funded, production (RVU) based, quality benchmarking, internally funded positions (such as directorships, chairs, fellowship coordination), hospital system efforts (such as antimicrobial stewardship, infection control, and OPAT) – and any combination of these such that salaries are often patched together. A growing number of Pediatric ID physicians are also in hybrid positions, commonly hospitalist, ER/urgent care, even primary care. Others may be the shared pediatric ID physician among several hospitals in a given area.

Significant work is being done by both adult and pediatric ID societies regarding the value of the ID physician,3,4 the ramifications of which we hope will translate into some protection from these new compensation models that are emerging. I spoke with Dr. Julia Szymczak regarding her abstract presented as a platform at PAS this year, titled: "Beyond the RVU: Exploring the Value of a Cognitive Pediatric Subspecialty." She conducted interviews with key stakeholders, including hospital administrators, surgeons, subspecialists, and pediatric infectious disease physicians, at 5 different hospitals across the country to explore and understand the value of a pediatric infectious disease physician to a healthcare organization. Several domains of how we are valued were recognized. Unfortunately, many of these areas escape capture by current measures that administrators use to justify the finances needed to retain a pediatric infectious diseases physician (manuscript forthcoming).

We, as a group, know we are important. Papers have been written about the value ID physicians add to patient care and a health system5-8. Additionally, Szymczak et al. demonstrated that others know our value too9. Why are we struggling to translate value into sustainable positions and comparable salaries? That is a bit more nebulous to answer but one we wish to make progress toward. In the meantime, there are some actionable items now, several of which Dr. Szymczak captured in her study and have been discussed in recent literature and on the IDSA website, such as maximizing our billing and coding efforts, most of which are likely time based, to ensure that we don't miss out on giving ourselves value for the time we spend with patients9, 3. Thinking about creative ways to expand referral bases through telemedicine10 or contracting to offer phone consultations are also ongoing efforts.

Other interventions may require a system based approach: negotiate with our hospital administrators and local insurance providers regarding bundling of payments, or fund programs like OPAT via the surgical specialties that use it the most. We must be adept in the language of what hospital administrators want to hear (Triple Aim?! Hospital Strategic Plan?! I'll show you how our work meets these and more!). Advocating for increased hospital funded time to sustain system efforts like infection control and other programs may be helpful when we share with each other how we do this in our respective institutions and how successful (or unsuccessful) we have been.

And while we are doing this, I do think we must move away from the stigma that we are a "revenue losing" specialty by developing ways to better capture how much money we SAVED a hospital or health system. For example, the undocumented and uncompensated work that we often undertake includes curbside consults from our colleagues and phone calls from outside physicians and providers, recently highlighted by Dr. Paul Sax's blog11. Creating and validating tools to measure the time and activities we do to prevent a hospitalization or readmission or that could be handled through an outpatient visit will be extremely helpful. Personalizing system based efforts, such as the impact of hospital based guidelines or outbreak management and translating that into cost-savings may also be a worthy effort.

The RVU system is here at my institution. And while things may change in another few years when reimbursement strategies are overhauled yet again, this has been a valuable time for me to think about these issues, which will likely follow us through the years.

For now, in the blank box for clinical productivity goals on my annual review, I've written:

  • Know and understand the strategic plan and priorities for my institution
  • Work with coders to determine if I've been appropriately billing, and if not, improve on this
  • Begin to engage colleagues to better understand how others are faring at their respective institutions to see where value has been recognized.

I'll let you know how I fare in a year! -- Louise Vaz, MD, MPH

References:

  1. Rochlin JM, Simon HK. Does fellowship pay: what is the long-term financial impact of subspecialty training in pediatrics? Pediatrics. 2011 Feb; 127(2):254-60.
  2. Castle VP, Gilsdorf JR. Assessing the value of pediatric consultation services as bundled payments evolve: infectious diseases as a model. J Pediatr. 2014 Oct;165(4):650-1
  3. Infectious Disease Society of American. Value of ID specialists' toolkit. Website: http://www.idsociety.org/Value_ID_Specialist/ Accessed 6/14/2015.
  4. Gilsdorf, J. Presidents' Letter http://www.pids.org/news/460-pids-president-letter.html Accessed June 15, 2015.
  5. Fariñas MC1, Saravia G, Calvo-Montes J, et al. Adherence to recommendations by infectious disease consultants and its influence on outcomes of intravenous antibiotic-treated hospitalized patients. BMC Infect Dis. 2012 Nov 9;12:292.
  6. Honda H, Krauss MJ, Jones JC et al. The value of infectious diseases consultation in Staphylococcus aureus bacteremia. Am J Med. 2010 Jul;123(7):631-7.
  7. McQuillen D, Petrak R, Wasserman R et al. The Value of Infectious Diseases Specialists: Non–Patient Care Activities. Clin Infect Dis. 2008 47 (8): 1051-1063.
  8. Petrak RM, Sexton DJ, Butera ML, et al. The value of an infectious diseases specialist. Clin Infect Dis. 2003 Apr 15;36(8):1013-7.
  9. Szymczak J, Lee GM, Woods C et al. Beyond the RVU: Exploring the Value of a Cognitive Pediatric Subspecialty. Presented as Platform. Pediatric Academic Societies Meeting 2015, San Diego CA. April 25. Abstract No. 1180.8.
  10. Kahn, J. Virtual Visits — Confronting the Challenges of Telemedicine. N Engl J Med 2015; 372:1684-1685.
  11. Sax, P. Seriously, How much would you pay for a curbside consult? http://blogs.jwatch.org/hiv-id-observations/index.php/seriously-how-much-would-you-pay-for-a-curbside-consult/2015/04/22/ Accessed June 15 2015.

PIDS Announces Commitments to Antibiotic Stewardship at White House

The Pediatric Infectious Diseases Society (PIDS) is proud to stand with more than 150 organizations and key stakeholders in making strong commitments to improving the appropriate use of antibiotics. Announced at today's White House Forum on Antibiotic Stewardship, the commitments highlight the importance of using antibiotics wisely to help slow the emergence of resistant bacteria, preserve the efficacy of existing antibiotics, and limit the spread of resistant infections.

Drug-resistant infections are responsible for at least 23,000 deaths and 2 million illnesses in the U.S. each year, according to the Centers for Disease Control and Prevention. Yet studies suggest that up to half of all antibiotic use in people, including children, is unnecessary or inappropriate, contributing to rising rates of resistance as effective treatment options for resistant infections dwindle.

"As a leading organization of physicians, scientists, and other professionals dedicated to treating and preventing infections in children, effective antibiotic stewardship has been a PIDS priority for several years," said PIDS President Janet R. Gilsdorf, MD, FPIDS. "We are thrilled to join with the other organizations and stakeholders at this forum today in making important commitments to improve the appropriate use of antibiotics."

Among these is continued support for the Annual International Pediatric Antimicrobial Stewardship Conference, jointly sponsored by PIDS and Children's Mercy Hospitals and Clinics in Kansas City, Missouri. Now in its sixth year, the conference will bring together medical professionals June 4-5 to discuss how to develop and maintain effective stewardship programs. Other PIDS commitments announced today include:

  • Supporting efforts to identify best practices for improving antibiotic use in the care of children in hospitals and outpatient settings.
  • Collaborating and partnering with other key organizations on provider education, the development of clinical practice guidelines, and other areas.
  • Supporting research on rapid diagnostics to improve antibiotic use and patient outcomes.
  • Advocating for the appropriate use of antibiotics in the agriculture industry.

A full list of PIDS commitments announced at the White House is available online: http://www.pids.org/component/content/article/8-content/content/466-pids-commitments.html.

"Antibiotic resistance is a serious and growing threat to public health and to our pediatric patients," said Jason Newland, MD, MEd, FPIDS, chair of the PIDS Pediatric Committee on Antimicrobial Stewardship and PIDS' representative at today's forum. "Using antibiotics wisely to preserve their effectiveness is a key part of the broader, multi-disciplinary approach we need to combat this problem. It will take all of us working together to meet this challenge."

A recognized leader in the field of antibiotic stewardship and another PIDS member also attending the forum, Theoklis Zaoutis, MD, MSCE, FPIDS, noted the high stakes involved. "Antibiotics are a precious, lifesaving, and limited resource," Dr. Zaoutis said. "Unless we do more to use this resource judiciously and take additional actions to address resistance in a comprehensive way, our patients' lives are at risk from these resistant infections."

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About PIDS

PIDS membership encompasses leaders across the global medical, 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, including links to additional reliable sources of information about antibiotic resistance, visit http://www.pids.org/resources/antibiotic-resistance-resources.html

President's Letter: The Future of Pediatric Infectious Diseases

"Freedom from infections for all children through excellent clinical care, research, education, and advocacy"

This is the vision of the Pediatric Infectious Diseases Society, built on the guiding principles of our Founding Fathers (and Mothers). To this end, the Society has realized significant accomplishments over the past two years under David Kimberlin's outstanding and insightful leadership.

So, where do we go from here?

In the past month, the Society has reviewed the priorities of the members as revealed in the most recent Needs Assessment survey. Based on those results, we have established five pillars upon which to build the activities of the Society over the next two years and, through the Strategic Planning exercise during the recent PAS meeting, developed strategies to strengthen these pillars.

Pillar 1: Value of Infectious Diseases to Hospital Systems

As health care in the United States moves from fee-for-service to contract-based reimbursement for clinical services, the value of our expertise in meeting the goals of hospital systems, in both financial and clinical outcomes, will be paramount. Led by Dr. Julia Szymczak, a post-doctoral fellow in medical sociology, the Society's Value of Pediatric ID as a Subspecialty subcommittee has completed a qualitative, focus-group based study of five pediatric inpatient units and will publish the results soon. In addition, the Journal of the Pediatric Infectious Diseases Society will soon publish a systematic review of pediatric antibiotic stewardship programs, accompanied by an editorial, and Dr. Theo Zaoutis' group is conducting a quantitative study of the outcomes of patients with and without PID consultations. Materials from these efforts will be available to members as they educate their health systems about the value of our clinical services.

Pillar 2: Recruitment of Future ID Pediatricians

This was not a good year for the ID match, either for adult or pediatric training programs. Only 41% of PID participating training programs and 45% of certified positions in PID filled. The Needs Assessment survey identified three priorities in meeting this challenge: (a) Increase the awareness of the value of PID consultations, (b) Increase efforts to achieve compensation equal to other subspecialties, which is directly related to (a), and (c) Increase awareness of career choices for PID trainees. Over the next two years, our Society will work with IDSA to better understand and reverse the recent trend away from infectious diseases among young physicians and will develop materials for training programs to educate their students, residents, and ID trainees about the wide variety of professional opportunities for pediatricians with ID expertise.

Pillar 3: Training and Guidance for PID Fellows

Our fellows are our future and, since its inception, the Society has been devoted to facilitating the education of new ID pediatricians. The top four priorities identified in the Needs Assessment survey regarding fellowship training are: (a) Develop training opportunities for the care of the immunocompromised host, (b) Develop training opportunities related to antibiotic stewardship, (c) Enrich research opportunities, and (d) Provide career guidance. The Society will meet these priorities by continuing to support/endorse courses on transplant infectious disease, HIV pediatric disease, and related topics in conjunction with the St. Jude/PIDS Pediatric Infectious Diseases Research Conference and the annual International Pediatric Antibiotic Stewardship Conference held at Children's Mercy Hospital in Kansas City, Missouri. In addition, the Society and its Foundation will continue to provide research awards to promising fellows and to support the St. Jude/PIDS Pediatric Infectious Diseases Research Conference in its highly valuable career development sessions.

Pillar 4: Research Activities Related to Pediatric Infectious Diseases

Developing new understanding of microbes and their disease-causing processes as well as evaluating the most effective means for diagnosing, treating, and preventing infections has been a cornerstone of the Society since its very beginnings. And yet, lack of research funding was identified in the Needs Assessment survey as the third greatest concern among our members. Almost 40% of respondents felt Society resources should be devoted to identifying key national research priorities in PID and lobbying for federal action and funding, which is a major activity of the Research Affairs Committee. Further, almost 80% of respondents indicated they are interested in participating in PID-related clinical multicenter studies. The future is bright for our members in these activities and the Research Affairs Committee will assist in identifying and coordinating such opportunities.

Pillar 5: Engagement of New and Established PIDS Members

Our Society is rich with members who generously contribute their time and expertise to its many activities. And yet, the Needs Assessment survey revealed that only 55% of respondents feel engaged with PIDS activities. This, actually, isn't bad for a professional society, but we can do better. Over the next two years, the Society will continue to encourage its members to participate in our important activities. What can you do? For starters:

  1. Maintain your membership by paying the annual PIDS dues
  2. Volunteer for committee membership. If your first request cannot be honored, reapply next year. And the next.
  3. Respond to the next Needs Assessment survey so we know what is most important to you.
  4. Attend meetings sponsored by PIDS
  5. Participate in PAS and IDWeek programs sponsored by the Society
  6. Read, promote, and submit your best scientific work to the Journal of the Pediatric Infectious Diseases Society
  7. Serve as an enthusiastic role model for undergrads, medical students, and residents as they refine their career choices
  8. Respond to calls for congressional support letters sent by IDSA and the AAP on issues related to PID. Congressional aides tell us these really matter.

With great enthusiasm, I look forward to working with you as, together, we shepherd our specialty and our Society solidly into the future.

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

Milestones, Millennials, and Metrics, Oh My!

Out with the old, and in with the new! The wheel of the academic calendar is about to turn once again, with graduations planned for those fellows finishing training and taking exciting new faculty roles at home or at other institutions, and preparations made for orientation of shiny new fellows in one month's time. This June every Pediatric Infectious Diseases program is required to report on its fellows for the second time using the ACGME milestones, a set of evaluation tools intended to provide finer detail in assessing each trainee's progress toward competence and independent practice. As we bless the abilities of the outgoing fellows and the next wave of fellows prepares to embark on the intellectual adventure that is fellowship, it seems a perfect time to ruminate on the ever-shifting landscape of Pediatric Infectious Diseases.

We don't often think about generational differences in our training environment, but they are certainly there. The tools, attitude, and practice of the emeritus professor will undoubtedly differ from those of the sprightly new fellow. Many of those retiring from practice are baby boomers; many of those starting training are millennials. What are we losing as one generation moves on, and what are we gaining as the other enters our field? How do these changes specifically affect us in Infectious Diseases?

Baby boomers are traditionally described as having a very strong work ethic and going the extra mile, being loyal to their employers, building on consensus leadership, and being oriented toward service and the larger mission of their work. As they retire, we are losing master clinicians whose dedication and ideas have markedly improved our field and advanced scientific understanding over their careers.

These losses are balanced against what we gain from our new trainees. Millennials have grown up in a world of big data and instant gratification, they expect respect, and they are the most highly educated generation to date. These traits – which could be seen as negative – may stand to improve our field yet further. Millennials are focused on making a contribution with their efforts and are goal-oriented. Their facility with technology allows them to multi-task better than the rest of us. They love continuous feedback, and they find new, entrepreneurial solutions to problems. For example, an Orthopedics resident here at the University of Washington who knew how to write computer code decided to create a program for collecting ACGME milestone evaluations that could be easily accessed on his attendings' smartphones, and is now sharing his program with other specialties. Through their ingenuity, the millennials can even make mundane required reporting feel entertaining. Millennials want variety and fun at work, they prize diversity and work-life balance, and they want to participate in a global community. Doesn't sound so bad, does it?

As we go to upload our ACGME milestones reports, we should ask our trainees how to use, gather, display, and understand the data we've generated. The milestones really are a new experiment in how best to train physicians, and we would all do well to enlist the help of our clever trainees in figuring out how to collect and utilize them best. And while we lose the retiring experts who provide our expert consensus around clinical care, we can use this as an opportunity to move away from older, bad habits that are hard to break (such as use of IV antibiotics when oral ones will do) and instead embrace the newest in evidence-based medicine that the millennials may end up finding and teaching us. After all, at the rate articles are published in PubMed, if you read just one new journal article a day in 2014, you would be about 3,200 years behind in your reading at the end of the year. We are inundated with data, from a fellow's progress in the ACGME milestones to the trend in a patient's C-reactive protein; keeping up with medicine is difficult today, but the millennials are poised to make it easier. If we can be open-minded in our conceptions of Infectious Diseases careers, there is no doubt that the millennials will harness their skills and the current abundance of data to combat infections in ways we never imagined. - Matthew Kronman, MD

Are oral antibiotics really safer than intravenous antibiotics?

Pediatricians like antibiotics. Of the top ten medications prescribed to children, five of them are antibiotics accounting for over a quarter of outpatient prescriptions in children [1]. On average, there are 1365 prescriptions of antibiotics written per 1000 children less than 2 years of age [2]. A main driver for the large number of antibiotic prescriptions is the perception that oral antibiotics are largely safe drugs. The prevailing thought is that there is little downside of antibiotic usage due to their large therapeutic window. Of course, for those of us who care for children who require long courses of antibiotics, we know that these are not benign drugs. We've all seen the complications of prolonged therapy, even oral therapy, including allergies, neutropenia, hepatotoxicity, Clostridium difficile, and the development of antibiotic resistance. However, there is a paucity of data to confirm the dangers of prolonged oral antibiotics in children. In the current issue of the Journal of the Pediatric Infectious Diseases Society, Olson et al aim to determine the rate of adverse events from both parenteral and oral antibiotic use [3].

There has recently been increased scrutiny into the practice of long-term intravenous antibiotic therapy. The complication rate of antibiotics administered via peripherally-inserted central catheters (PICC lines) has been documented to be as high as 30% [4]. Because of this, there has been a push for early transition from intravenous to oral antibiotics in treating conditions that require prolonged antibiotics such as osteomyelitis [5]. The discussion is often framed as getting the patient off the more dangerous IV form of antibiotics and transitioning to the "safe" oral formulation. Intrinsic to this discussion is the assumption is that there are few risks to prolonged oral antibiotics, which may not be the case.

In this retrospective cohort study, Olson and colleagues reviewed charts of all patients seen in the Pediatric Infectious Diseases clinic at their tertiary care center who had received more than 14 days of antimicrobial therapy. Although they documented a lower catheter-related adverse event rate than others (13%), they reported a 31.9% overall adverse event rate for long-term antibiotic usage with similar rates between intravenous and oral antibiotic courses. Serious adverse events were seen more commonly in intravenous antibiotic usage but still occurred in 7.8% of patients receiving oral antibiotics. These included allergic reactions, neutropenia, renal, and liver abnormalities. Most striking was that 31.1% of reported adverse events were deemed severe enough to result in a change in medication. These data support the practice of close follow-up of all children receiving prolonged antimicrobial therapy regardless of whether it is administered via central catheters or by mouth.

Unfortunately, there are likely a large number of children who are discharged on prolonged antibiotics who may never be seen by an infectious diseases specialist and who may not have adequate follow up by other providers in a timely fashion. Given the high rate of adverse effects, this may lead to premature discontinuation or intermittent usage of antibiotic therapy, which could lead to treatment failure or the development of antimicrobial resistance. Although in this situation we cannot directly influence the care of children we do not consult on, we can continue to communicate to colleagues that antimicrobial treatment, even oral antibiotics, require a constant evaluation of the risks and benefits of continued therapy.

"Give enough but not too much. And we'd be happy to follow that patient in Peds ID clinic." -- David K. Hong, MD

REFERENCES

  1. Chai G, Governale L, McMahon AW, Trinidad JP, Staffa J, Murphy D. Trends of outpatient prescription drug utilization in US children, 2002-2010. Pediatrics. 2012;130(1):23-31. PubMed PMID: 22711728.
  2. Hicks LA, Taylor TH, Jr., Hunkler RJ. U.S. outpatient antibiotic prescribing, 2010. N Engl J Med. 2013;368(15):1461-2. PubMed PMID: 23574140.
  3. Olson SC, Smith S, Weissman SJ, Kronman MP. Adverse Events in Pediatric Patients Receiving Long-Term Outpatient Antimicrobials. Journal of the Pediatric Infectious Diseases Society. 2015;4(2):119-25.
  4. Barrier A, Williams DJ, Connelly M, Creech CB. Frequency of peripherally inserted central catheter complications in children. Pediatr Infect Dis J. 2012;31(5):519-21. PubMed PMID: 22189533. Pubmed Central PMCID: 3329567.
  5. Keren R, Shah SS, Srivastava R, et al. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute osteomyelitis in children. JAMA Pediatr. 2015;169(2):120-8. PubMed PMID: 25506733.

The Disconnect Between Perception, Ability and Personal Agency

There is a vast crevasse between what healthcare workers (HCWs) perceive to be the problem and what they will do to overcome it.

This is particularly pronounced in the field of infection control. To give but one example, 44% of cases that occurred during the outbreak of severe acute respiratory syndrome (SARS) in 2003, despite the implementation of SARS-specific infection control directives, involved HCWs. When 15 HCWs of those affected were interviewed, eight were aware of a breach in infection control precautions, only nine reported receiving formal infection control training, 13 were unsure of how to properly don and doff personal protective equipment (PPE), and six reused items that had been potentially contaminated by a SARS patient.

The reuse of items after exposure to a SARS patient, the inconsistent use of PPE, and the awareness of half of the interviewed HCWs of a breach in infection control precautions, reflect the ongoing challenges of enforcing infection control. The focus of Fierro et al's publication in the most recent issue of JPIDS explored exactly why HCWs followed infection control and prevention guidelines or not. In the study, the authors surveyed several hundred HCW in the ambulatory setting regarding barriers to use of PPE when pertussis is suspected. Only 70% of clinical HCWs reported mostly or always wearing PPE when caring for a patient with suspected pertussis, while <30% reported wearing PPE for a patient with any respiratory symptoms.

Interestingly, HCWs identified three factors that were independently associated with PPE use: perceived availability of PPE (adjusted OR 5.41), knowledge and skills to improve PPE use (adjusted OR 4.62), and personal agency (adjusted OR 3.18). HCWs felt they would be 5.4 times more likely use PPE if masks were more available near the patient's exam room. So how is it that, when the authors placed masks in more accessible locations to increase the availability and use of PPE, that there was no substantial change in usage?

Perceived availability, ability and personal agency remained just that, a perception. This correlates with the HCW's belief that improving their own use of PPE was nearly a nonissue (adjusted OR 0.16). Like those who were aware of a breach in wearing PPE or with other infection control measures, HCWs did not allow their awareness of the precautions to lead to adopting them. Perhaps what the SARS case series demonstrates is that, even when battling an infectious pathogen that led to 774 fatalities worldwide, the implementation of infection control precautions in the face of severe and potentially fatal illness is still not enough to change behavior. Fierro et al. demonstrates this similarly, in the context of resurging pertussis epidemics across the country that place the youngest and vulnerable among us at most risk. We may have to rely on more than belief in one's ability and personal agency to create a sea change in the daily aspects of our practice. - Pui-Ying Iroh Tam, MD

References

Ofner-Agostini et al. Cluster of cases of severe acute respiratory syndrome among Toronto healthcare workers after implementation of infection control precautions: a case series. Infect Control Hosp Epidemiol 2006 May;27(5):473-8.

Fierro et al. Barriers to the use of PPE to prevent pertussis exposures in a pediatric primary care network. J Pediatr Infect Dis Soc 2015;4(1):49-56.

Digital Epidemiology and Harnessing Big Data for Infectious Diseases and Public Health

Written by: Christina Gagliardo, MD, FAAP

HealthMap
ProMed-mail
Global Public Health Intelligence Network (GPHIN)
Google Flu Trends

These are a few web-based systems which have contributed to technological improvements in surveillance capacity for significant public health events such as infectious disease outbreaks. These entities collect information and perform syndrome surveillance on specific diseases drawing from sources such as web-based queries, systems such as community-health based reporting with mobile phones, social media, and local news. When used in combination, detection of diseases and outbreaks is more timely and sometimes more sensitive than traditional surveillance systems (1-4). Examples include the Ebola outbreak starting in 2014 and several polio outbreaks in 2013 and 2014 where digital reports generated through these informal surveillance channels often preceded official reports (such as by WHO). For polio, digital surveillance reports were available 14.6 days (range 0-40 days) earlier than official WHO reports (4).

Another online surveillance tool, Google Flu Trends (GFT), was launched in 2008 and was intended to supplement traditional surveillance systems such as that done by CDC to monitor influenza. GFT analyzed Google search queries of influenza-like illness and symptoms and were able to improve early detection of influenza outbreaks one to two weeks ahead of CDC reports. GFT worked well to predict influenza outbreaks in the 2007-2008 flu season as well as during the 2009 H1N1 outbreak (5). In later years, however, it was noted that GFT grossly overestimated flu prevalence and predicted double the amount of doctor's visits than CDC surveillance (6-8). A proposed solution was to combine CDC data with GFT-derived information that was "recalibrated" to be more reliable, with the thought that when used in combination, performance would be better than GFT or CDC alone. This is in line with the original proposed intention of GFT: to be used as a "'complementary signal', rather than a stand-alone forecasting tool" (9).

The exponential increase in the use of social media, such as Twitter, provides another potential opportunity to perform public health surveillance and create predictive models. Once group successfully used Twitter data to show that CDC influenza-like illness rates correlated to the rate of Tweets of influenza infection, and predicted influenza two to four weeks sooner(10). The New York City Department of Health and Mental Hygiene validated their model and showed a strong parallel to local influenza activity as well (11).

A leading researcher in the field of digital epidemiology is Marcel Salathé, PhD. His study showed a correlation between CDC-estimated vaccination rates by region and geo-spatial vaccine sentiments as expressed on Twitter (12). When simulating an infectious disease outbreak, he showed that grouped negative sentiments about vaccines lead to clusters of unprotected people, which increased the likelihood of an outbreak in that area.

Analyzing big data generated through social media to perform "digital epidemiology" and surveillance continues to be enhanced and developed. Eventually it may be a reliable tool which we can easily access to perform infectious disease surveillance on a large scale and more relevant to our everyday practice, on the local level. It is an emerging field with huge amounts of untapped utility and the potential for collaboration between science, medicine, public health, and technology.

References:

  1. Hulth A, Gustaf R, Annika L. Web queries as a source for syndromic surveillance. PLoS One 2009; 4: e4378.
  2. Freifeld CC, Chunara R, Mekaru SR, et al. Participatory epidemiology: use of mobile phones for community-based health reporting. PLoS Med 2010; 7: e1000376.
  3. Barboza P, Vaillant L, Le Strat Y, et al. Factors influencing performance of internet-based biosurveillance systems used in epidemic intelligence for early detection of infectious diseases outbreaks. PLoS One 2014;9: e90536.
  4. Anema A, Kluberg S, Wilson K, Hogg R, Khan K, Hay S, Tatem A, Brownstein J. Digital surveillance for enhanced detection and response to outbreaks. www.thelancet.com/infection Vol 14 November 2014
  5. Ginsberg J, Mohebbi MH, Patel RS, Brammer L, et al. Detecting influenza epidemics using search engine query data. Nature. 2009 Feb 19;457(7232):1012-4. doi: 10.1038/nature07634.
  6. Lazer, David; Kennedy, Ryan; King, Gary; Vespignani, Alessandro (14 March 2014). "The Parable of Google Flu: Traps in Big Data Analysis". Science 343 (6176): 1203–1205. doi:10.1126/science.1248506.
  7. Lazer, David, Ryan Kennedy, Gary King, and Alessandro Vespignani. 2014. "Google Flu Trends Still Appears Sick: an Evaluation of the 2013‐2014 Flu Season". Copy at http://j.mp/1m6JBX6 
  8. Butler, Declan (13 February 2013). "When Google got flu wrong". Nature 494: 155–156. doi:10.1038/494155a.
  9. Lohr S. Google Flu Trends: The Limits of Big Data. 3/28/14. NY Times. http://bits.blogs.nytimes.com/2014/03/28/google-flu-trends-the-limits-of-big-data 
  10. Paul MJ, Dredze M, Broniatowski D. Twitter Improves Influenza Forecasting. PLOS Currents Outbreaks. 2014 Oct 28. Edition 1. doi: 10.1371/currents.outbreaks.90b9ed0f59bae4ccaa683a39865d9117
  11. Sills J. Twitter: Big Data opportunities. Science, Letters. http://www.cs.jhu.edu/~mpaul/files/science_letter_twitter.pdf 
  12. Salathe´ M, Khandelwal S (2011) Assessing Vaccination Sentiments with Online Social Media: Implications for Infectious Disease Dynamics and Control. PLoS Comput Biol 7(10): e1002199. doi:10.1371/journal.pcbi.1002199
  13. Costello, V. Researchers Changing the Way We Respond to Epidemics with Wikipedia and Twitter. PLoS Blogs. Jan 2015. http://blogs.plos.org/plos/2015/01/researchers-changing-way-respond-epidemics-wikipedia-twitt/ 

 

Cultivating Interest in Pediatric ID: Is Timing Everything?

With the chaos of interviews, rank lists, and Match Day complete, I have found myself reflecting on our successful resident recruitment season. In the nearly 120 interviews I conducted, I was struck by a few things. First, pediatrics has attracted some great medical students – smart, motivated, and well-rounded. Secondly, I was surprised by the number of applicants who had already decided on a subspecialty, or at least narrowed it down to 2 or 3. Finally, I was saddened by the paucity of students who had an interest in infectious diseases.

I was left pondering 2 questions: Why do these great applicants not include ID in their list of top career contenders? Are we targeting the wrong group with our recruitment efforts?

Let's face it, pediatric ID isn't as outwardly "sexy" as higher profile fields like oncology or cardiology. There aren't too many fundraisers for kids with infections and ID isn't ranked as a pediatric specialty in U.S. News and World Reports. And while I don't expect to draw the adrenaline-junkies away from the faster-paced procedure-based specialties, I heard more interest in other non-procedure based fields like endocrinology or genetics than ID. It's also true that pediatric ID isn't compensated as well as some of these higher profile or procedure-based specialties, but that answer seems too simplistic. Students interested in pediatrics are generally not motivated by money, so what has caused this dearth in interest?

One factor that is potentially missing is exposure. Based on studies analyzing the timing of post-residency career choices, it seems early exposure is key to sparking interest. For many pediatricians, their choice of career path is decided during medical school or very early in residency. In a survey-based study, Dattner and Ozuah reported 50% of PGY-1 pediatric residents had already decided on a career path. Moreover, Freed and colleagues reported over a third of pediatric subspecialists decided to pursue subspecialty training prior to even starting residency. However, our fellowship recruitment efforts tend to focus on residents, not students. Many medical students have limited clinical experience in pediatric ID. While they may get routine and repeated exposure to other pediatric subspecialties, we in ID are often limited to interacting with students only briefly during lectures or while making rounds on the consult service. So in order to ensure a steady stream of qualified physicians in pediatric ID, would we be better served by equally concentrating attention on medical students AND residents early in training?

Finally, interest in a specialty or patient population is typically the most important factor influencing a postresidency career. While we can't force interest, we can educate trainees about the diverse populations and career paths within pediatric ID. By exposing students to the breadth of clinical cases and opportunities, we can perhaps help foment greater interest in our field. We also cannot underestimate the positive influence of role models. Studies in many medical fields have shown that working with a highly (or poorly) rated faculty member influences students' likelihood of choosing that specialty. So we in the PIDS community must strive to cultivate interest, provide mentorship, and recruit qualified pediatricians early and often throughout the medical education journey. By: Rebecca Wallihan, MD

References:

Dattner, Laura, and P. Ozuah. "Career Decision-Making among Pediatric Residents." Medical Education Online North America 10 (2005): 1-6.

Freed, Gary L., et al. "Recently trained pediatric subspecialists: perspectives on training and scope of practice." Pediatrics 123.Supplement 1 (2009): S44-S49.

March 2015: JPIDS Article Review & Commentary

In the March 2015 issue of the Journal of the Pediatric Infectious Disease Society, Le Doare and colleagues report the findings of their systematic review of antibiotic resistance rates in gram-negative bacteria (GNB) in children with sepsis living in resource-poor countries. A systematic review of PubMed, Embase, and World Health Organization (WHO) databases was performed for studies on children with sepsis living in low- and middle-income countries. Ultimately 30 studies were included in the review, comprising 71,326 children. 7,056 (13.9%) of those had positive blood cultures and GNB's were isolated in 4710 (66.8%) of those. In general, antibiotic resistance to WHO first-line agents was widespread. In neonates, Klebsiella pneumoniae was the most common pathogen; in Asia, its median resistance to ampicillin was 94%, to cephalosporins 84%; and in Africa, 100% and 50% respectively. Rates for other enterobacteriaceae in the neonatal population were similar. In children, Salmonella was the most common organism and MDR Salmonella (resistant to amoxicillin, co-trimoxazole, and chloramphenicol) was widespread, though resistance rates varied wildly by region: 30% in Asia and 75% in Africa. The authors conclude that there is a need for better antimicrobial resistance (AMR) surveillance, which should then shape improved WHO guidelines that acknowledge prevalent resistance to previous first-line agents, together with improved stewardship and infection control.

Commentary

We are all acutely aware of the rising burden of antimicrobial resistance and morbidity and mortality caused by it. But the now-infamous 2013 CDC threat report [CDC 2013], outlining 23,000 deaths and 2,000,000 episodes of morbidity attributable to resistant infections, only applies to the United States, and is not based on pediatric-specific data. When we turn to look at the rest of the world, the burden of pediatric bacterial disease overall and that due to resistant organisms specifically is astounding. This study provides a much-needed examination of the epidemiologic characteristics of GNB sepsis and the resistance patterns of the causative organisms in resource-poor countries. As the authors note, bacteremia remains a leading cause of death in children and neonates worldwide, with an estimated 6% of neonatal deaths and 14% of all childhood deaths, making this a potent area for study.

There are two areas of their review worth examining in greater detail, the first of which is the sheer degree of resistance found. For those of us practicing pediatrics in the United States, while antimicrobial resistance is a problem, it is currently a surmountable one. A recent study by Pranita Tamma and colleagues [Tamma et al. 2013] found susceptibility rates for Klebsiella pneumoniae of 94% to 3rd-generation cephalosporins and 93% to gentamicin. But as the present study shows, the developing world is altogether different, with data there quite concerning. They found resistance rates that were of a similar magnitude to our susceptibility rates here. In Asia only 16% of K. pneumoniae isolates were susceptible to 3rd-generation cephalosporins and in Africa 50% were. Gentamicin susceptibility was similarly low, 32% in Asia and 46% in Africa. These particular agents are significant, as the WHO guidelines for neonatal and pediatric sepsis are largely similar to those in the United States, with a recommendation for ampicillin and gentamicin/3rd-gen cephalosporin or a 3rd-generation cephalosporin alone, depending on age. Currently, with those guidelines, 84% of the children with K. pneumoniae sepsis studied in this review would fail empiric therapy. If this data accurately reflects not just the populations of the papers analyzed, but indeed the larger population in the countries studied, current WHO guidelines may leave anywhere from 50-85% of patients with GNB infections completely untreated.

The second significant finding of this study is the high variability in resistance seen among Salmonella isolates. In particular, the variability of MDR isolates is concerning. While the rates they report by region were 30% for Asia and Southeast Asia and 75% for Africa and the Middle East, when examined by country, anywhere from 30% to 100% of isolates were MDR. And this variability is an area where the WHO guidelines again unintentionally leave a hole: the WHO guidelines of first-line use of chloramphenicol will have wildly varied treatment efficacy among the different countries. Individual countries could in theory make their own treatment guidelines but in practice the nature of their designation as resource-poor makes this unrealistic, leaving wide potential for ineffective treatment of what the authors found was an extremely common organism. Moreover, the resistance mechanism is plasmid-mediated via the incH1 plasmid, at least in non-typhoidal strains. As we have seen with other newer emerging resistance mechanisms such as the NDM-1 New Delhi metalloprotease, spread of an MDR GNB is as easy as a plane flight and from there plasmids can jump promiscuously. So while resistance rates are varied between regions and countries currently, given time this resistance will only spread further.

As the authors themselves note, both the high rates of resistance and the high rates of variability require better monitoring to validate data across a more representative sample of countries and locales within those countries (nearly all the papers they reviewed were based on tertiary-care centers in larger cities). At a minimum this data would be used to implement new empiric treatment guidelines that more accurately reflect the realities of current resistance spectra. But as we are beginning to realize more here at home, some of the most cost-effective changes these countries can make are in improving infection control guidelines and implementing comprehensive antimicrobial stewardship. New or better drugs just may not be a reality and so making better, smarter use of the ones we do have could make all the difference. By: Saul Hymes, MD

References:

  1. Le Doare K, Bielicki J, Heath PT, Sharland M. Systematic Review of Antibiotic Resistance Rates Among Gram-Negative Bacteria in Children With Sepsis in Resource-Limited Countries. J Ped Infect Dis (2015) 4(1):11-20.
  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. Tamma PD, Robinson GL, Gerber JS, Newland, JG, DeLisle, CM, Zaoutis, TE, Milstone, AM. Pediatric Antimicrobial Susceptibility Trends across the United States. Infection Control (2013) 34(12): 1244 – 1251.

Measles: A Case of Déjà Vu All Over Again

Last January, I had the opportunity to share some thoughts on PIDS' role in combating vaccine-preventable diseases, focusing on vaccine advocacy, innovative studies of pathogenesis, high-quality epidemiologic studies, and rigorous clinical trials. Now, one year later, we are experiencing a measles outbreak in the US that has affected over 100 people in 14 states, most of which are linked to an exposure at a California amusement park. As the outbreak unfolds, we are reminded of the cardinal symptoms of measles, a disease that many practicing physicians have never seen; the efficient transmission of the virus to unvaccinated individuals; and the importance of PIDS' ongoing education and vaccine advocacy efforts.

As recently as the 1950s, measles was one of the most common childhood infections in the US. On average, about half a million cases, 50,000 hospitalizations, 1,000 cases of chronic disability, and 500 deaths were reported each year; however, due to underreporting, it is estimated that as many as 4 million cases occurred annually. In many ways, measles is a typical respiratory illness, leading to fever, cough, coryza, conjunctivitis, and malaise. Because of this, and because of the fleeting nature of pathognomonic Koplik spots, we must maintain a reasonably high index of suspicion, particularly in our unvaccinated patients, in order to identify measles cases promptly. When measles is suspected, providers should evaluate measles-specific serum IgM antibody and measles RNA by PCR from both the oropharynx and the urine.

The timely diagnosis of a case of measles is of critical importance, since a single measles patient will infect approximately 15 others in the absence of pre-existing immunity (R0~15), making measles the most easily transmitted virus on the planet (for comparison, smallpox R0~5, Influenza R0~3). Moreover, 90% of non-immune individuals will develop measles infection following close contact with an infected individual. Fortunately, the MMR vaccine is remarkably effective (~95% after one dose and 98-99% after 2 doses) in generating life-long, protective immunity. The MMR vaccine is also effective if administered within 72 hours of measles exposure and is recommended for infants as young as 6 months of age if exposure is likely (e.g., travel to an endemic area).

This effectiveness of the MMR vaccine in preventing measles infection is the foundation of measles eradication efforts, which have been highly successful in many parts of the globe. PIDS members continue to play key roles in this effort, leading clinical trials, conducting global epidemiology studies, and informing public policy decisions. It is now time, through our vaccine advocacy committee, training programs, and local media markets to redouble our efforts in reassuring parents and providers about the safety of MMR vaccine and the importance of vaccine coverage (>93% coverage is required in a community to disrupt transmission). For more information about the current outbreak and for general talking points about measles, please visit the PIDS website (www.pids.org).

The eradication of measles has been a daunting task; unfortunately, the eradication of misinformation and mistrust may be even more so. Allowing measles to resurface essentially turns back the pediatric clock by several decades, reintroducing morbidity and mortality that are a distant memory. Our job, as a society and as individual members, is to provide clear, trustworthy information to our trainees, our patients, and the general public in order to ensure these preventable outbreaks do not become the new epidemiologic norm. - by Buddy Creech, MD, MPH, FPIDS

Pediatric Infectious Disease Experts Urge Vaccination as Measles Outbreak Continues

As physicians, scientists, and other medical professionals dedicated to treating and preventing infections in children, the Pediatric Infectious Diseases Society (PIDS) remains extremely concerned about the current measles outbreak as it continues to unfold.

It has become clear that we are in the midst of a larger, very disturbing trend. Despite the fact that measles was eradicated from the United States 15 years ago, this country had 644 measles cases in 2014, more than in any year since 1994. 2015 is now on pace to well exceed that number.

The measles vaccine is a victim of its own success. Vaccination was so effective at eliminating this disease, and many other diseases, that younger generations do not appreciate or understand the severity of vaccine-preventable diseases. Instead, the focus now often lies on unfounded, disproven and discredited concerns regarding the safety of the vaccine. We know that parents want the very best for their children, and this includes keeping them safe from serious infections. It is a tragedy that some parents, often because of misinformation they may have received from friends, colleagues, or the Internet, are putting their children and others in harm's way by refusing to vaccinate.

The current measles outbreak, which has now affected more than 100 people and will likely continue to spread, was entirely preventable. As long as approximately 95 percent of a population is vaccinated, a potential outbreak from measles will be halted in its tracks. Most states exceed this level of coverage, in part due to school vaccination requirements, but an increasing number of states have regions where vaccination coverage falls well below this level. This is in large part due to personal belief exemptions or religious exemptions that allow parents, misled by false information, to avoid vaccinating their children.

States with areas where vaccination rates are lower can look to Mississippi, where strong immunization requirements have maintained high vaccine coverage levels among children. As PIDS President David W. Kimberlin, MD, FPIDS, told The New York Times this week, "That kind of strong approach is helpful for the health of children in America. I believe that that should be something we all work toward, that we all hold in the highest of value in terms of our prioritization."

Simply put: vaccines are safe, vaccines are effective, vaccines save lives. Children are being harmed by the growing trend of vaccine refusal. We strongly urge any parent who has a concern about the safety of a vaccine, including the MMR vaccine, to discuss these concerns with their child's medical provider as soon as possible. Similarly, we encourage all primary care providers to actively engage all parents in the discussion about vaccines, provide clear messaging about their safety and efficacy, and be transparent about the minimal risks. This outbreak can be stopped, and future outbreaks prevented, with adequate vaccine coverage.

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Pediatric Infectious Disease Experts Urge Vaccination as Measles Outbreak Continues (PDF)

Reflections on Spiraling Empiricism

Written by: Pui-Ying Iroh Tam, MD

Last month, I was asked to consult on antimicrobial management for a premature baby who had presumed necrotizing enterocolitis. The baby was transferred from an outside hospital after a suspected aspiration event, and on arrival was started empirically on clindamycin. Due to suspected sepsis in a premature infant, she was also started on ampicillin, gentamicin and fluconazole. When she developed respiratory distress and deteriorated, neonatologists broadened her ampicillin and gentamicin to vancomycin and cefotaxime. Despite this, she continued to be unstable and blood cultures became positive for MSSA. Gentamicin was added for synergy and after there was no clinical response or sterilization of blood cultures after 3 days, was then changed to rifampin.

Hence, when we first met this patient, she was on vancomycin, clindamycin, rifampin, cefotaxime and fluconazole.

Kim and Gallis first coined the phrase 'spiraling empiricism' back in 1989 with an article in the American Journal of Medicine titled 'Observations in spiraling empiricism: its causes, allures and perils, with special reference to antibiotic therapy [1].' Their term refers to the 'inappropriate treatment, or the unjustifiable escalation of treatment, of suspected but undocumented infectious diseases.'

Sound familiar? I faintly ridicule other specialties for committing this transgression, but whom of us in pediatric infectious diseases have not been seduced by the fallacies of antibiotic therapy? However, the implications of this practice – where over half of hospitalized patients receive antimicrobials [2], and where an estimated 50% of outpatient antimicrobial prescriptions are considered unnecessary [3] – is that we have also contributed to the growing problem of antimicrobial resistance. When the CDC published their first ever report in 2013 quantifying the extent of antimicrobial resistance, they estimated that at least 2 million people a year in the US become infected with antimicrobial resistant bacteria, and a minimum of 23,000 people die annually as a direct result of these infections [4].

These fallacies (I have bolded this word lest a reader skimming this should think I am detailing pearls of wisdom) are, as Kim and Gallis lists:

  1. Broader is better
  2. Failure to respond is failure to cover
  3. When in doubt, change drugs, or add another
  4. More disease(s), more drugs
  5. Sickness requires immediate treatment
  6. Response implies diagnosis
  7. Bigger disease, bigger drugs
  8. Bigger disease, newer drugs
  9. Antibiotics are non-toxic

Most illustrative is a recent case published in the New England Journal of Medicine [5]. A 14 year-old male with severe combined immunodeficiency status post two bone marrow transplants presented to a medical facility three times over a four month period with fever and headache. With an extensive negative infectious workup and low suspicion for bacterial meningitis, he was not given any empiric antimicrobials until his third presentation when he had interval development of status epilepticus and basilar leptomeningitis on MRI. Then he was given a series of empiric antimicrobials that physicians continued to add to and broaden when he did not respond. When next-generation sequencing analysis suggested neuroleptospirosis, his therapy was narrowed to penicillin, and the patient gradually recovered over the next seven days.

Of all the antimicrobials this patient needed, with all the technology that we could provide in the 21st century, the answer was the first antibiotic ever discovered. There is a beautiful simplicity to that which reminds one how much of clinical practice remains more of an art than a science.

And my premature baby on a veritable cocktail of antimicrobials? We optimized and simplified her therapy, cognizant of the perils of excessive and redundant antimicrobial use. After that I don't know, since I signed her out to the next attending. But I suspect all must have turned out well, since isn't ignorance bliss?

References

  1. Kim JH, Gallis HA. Observations on spiraling empiricism: its causes, allure, and perils, with particular reference to antibiotic therapy. Am J Med. 1989 Aug;87(2):201-6.
  2. CDC. Antimicrobial resistance – threat report 2013. http://www.cdc.gov/drugresistance/threat-report-2013/ Accessed 15 January, 2015.
  3. Fridkin S, Baggs J, Fagan R, Magill S, Pollack LA, Malpiedi P, Slayton R, Khader K, Rubin MA, Jones M, Samore MH, Dumyati G, Dodds-Ashley E, Meek J,Yousey-Hindes K, Jernigan J, Shehab N, Herrera R, McDonald CL, Schneider A, Srinivasan A; Centers for Disease Control and Prevention (CDC). Vital signs: improving antibiotic use among hospitalized patients. MMWR Morb Mortal Wkly Rep. 2014 Mar 7;63(9):194-200.
  4. Hicks LA, Taylor TH Jr, Hunkler RJ. U.S. outpatient antibiotic prescribing, 2010. N Engl J Med. 2013 Apr 11;368(15):1461-2. doi: 10.1056/NEJMc1212055.
  5. Wilson MR, Naccache SN, Samayoa E, Biagtan M, Bashir H, Yu G, Salamat SM, Somasekar S, Federman S, Miller S, Sokolic R, Garabedian E, Candotti F,Buckley RH, Reed KD, Meyer TL, Seroogy CM, Galloway R, Henderson SL, Gern JE, DeRisi JL, Chiu CY. Actionable diagnosis of neuroleptospirosis by next-generation sequencing. N Engl J Med. 2014 Jun 19;370(25):2408-17. doi: 10.1056/NEJMoa1401268. Epub 2014 Jun 4.

 

January 2015: JPIDS Article Review & Commentary

Written by: Matthew Kronman, MD, MSCE

Fisher BT, Sammons JS, Li Y, de Blank P, Seif AE, Huang Y, Kavcic M, Klieger S, Harris T, Torp K, Rheam D, Shah A, Aplenc R. Variation in Risk of Hospital-Onset Clostridium difficile Infection Across β-Lactam Antibiotics in Children With New-Onset Acute Lymphoblastic Leukemia. J Pediatric Infect Dis Soc. 2014;3(4):329-35.

Summary

In the December 2014 issue of the Journal of the Pediatric Infectious Diseases Society, Fisher, Sammons and colleagues report the findings of a large, multi-center retrospective cohort study of children with new-onset acute lymphoblastic leukemia (ALL) that aimed to determine the relative contributions of different β-lactam antibiotics to the risk of developing Clostridium difficile infection (CDI).

The authors employed the Pediatric Health Information System (PHIS) database, which includes pharmaceutical billing data and diagnoses for all children admitted to 43 freestanding children's hospitals. To decrease misclassification, the authors used previously well-validated definitions for both new-onset ALL cases (based on an ALL diagnosis and receipt of appropriate chemotherapy) and CDI outcomes (based on a CDI diagnosis and billing for C. difficile testing.)[1, 2] The PHIS data provided the authors with the ability to track antibiotic exposures to the day; the analyses were adjusted for age, race, gender, illness severity, days in the hospital, antibiotic receipt other than β-lactams, and admission hospital itself. The authors furthermore had the ability to adjust for other factors that could have been associated with CDI, such as use of proton pump inhibitors or use of an enteric feeding tube.

In their adjusted analyses, the authors found that the hazard for developing CDI increased by 5% (adjusted Hazard Ratio 1.05, 95% Confidence Interval 1.01-1.09) for each additional day subjects were exposed to anti-pseudomonal β-lactam antibiotics. This relationship held true for ceftazidime (5% increased hazard) and cefepime (7% increased hazard), but not for anti-pseudomonal penicillins such as piperacillin/tazobactam or carbapenems.

Commentary

There are three main reasons why we should take note of this study. First, this study backs up the antibiotic stewardship mantra "every dose counts" with hard data. Accounting for other confounding variables, every additional day of certain anti-pseudomonal β-lactam antibiotics added a 5% risk of developing CDI. This daily additional risk compounds rapidly: just 5 days of exposure to these antibiotics contributes an almost 30% increased risk of CDI. Remembering that these authors have previously demonstrated that hospital-onset CDI is associated with an almost 7-fold increase in mortality,[3] we can all use the present study to remind us not to put off until tomorrow stopping those antibiotics we could otherwise stop today.

Second, the present study should serve to remind us that what may appear to be routine practice changes in the Divisions we support may come with unintended consequences. The authors demonstrated that two cephalosporins – cefepime and ceftazidime – were associated with CDI in adjusted analyses while anti-pseudomonal penicillins were not. In the initial univariate analyses, the incidence rate ratio of CDI among those exposed to cefepime was more than twice that of those exposed to ceftazidime. We might consider ceftazidime, cefepime, and piperacillin/tazobactam as approximately equivalent selections for the empiric treatment of the febrile neutropenia so often seen in the ALL patients who were the subjects of this study. These data should remind us that even apparently small decisions such as deciding among these three agents should be weighed carefully, especially when institutional guidelines that might affect hundreds of patients are being developed and updated.

Lastly, we continue to learn slowly about our relationship with our gut microbiota. Large-scale epidemiologic studies such as this one can provide hints and clues as to the underlying biology of the diseases we examine. A meta-analysis demonstrated increased risks for community-onset CDI among those exposed to cephalosporins, monobactams, and carbapenems relative to those exposed to penicillins.[4] One might have supposed that agents with the largest breadth of anaerobic activity (such as piperacillin/tazobactam and carbapenems) were universally more likely to be associated with CDI, by substantially reducing the vast numbers of anaerobic commensal gut bacteria, allowing C. difficile the ecological space to grow logarithmically. Here, the authors demonstrate that piperacillin/tazobactam, despite its breadth of anaerobic activity, was not associated with CDI. Perhaps this finding can suggest testable hypotheses to further our understanding of how and why CDI develops in the first place.

In summary, Fisher, Sammons, and colleagues nicely demonstrated in this study the importance every additional day of antibiotics can hold. We have more to learn about CDI and how to prevent it, but in the meanwhile, we are better equipped to encourage our colleagues to stop unnecessary antibiotics as soon as possible.

References

  1. Fisher BT, Harris T, Torp K, et al. Establishment of an 11-year cohort of 8733 pediatric patients hospitalized at United States free-standing children's hospitals with de novo acute lymphoblastic leukemia from health care administrative data. Med Care 2014 Jan;52(1):e1-6.
  2. Shaklee J, Zerr DM, Elward A, et al. Improving surveillance for pediatric Clostridium difficile infection: derivation and validation of an accurate case-finding tool. Pediatr Infect Dis J 2011 Mar;30(3):e38-40.
  3. Sammons JS, Localio R, Xiao R, Coffin SE, Zaoutis T. Clostridium difficile infection is associated with increased risk of death and prolonged hospitalization in children. Clin Infect Dis 2013 Jul;57(1):1-8.
  4. Brown KA, Khanafer N, Daneman N, Fisman DN. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrob Agents Chemother 2013 May;57(5):2326-32.

JPIDS Article Review: The 100 Day Cough and the 50 day Positive PCR

Written by Chris Nyquist, MD, MSPH

"The lung is so irritated that every attempt to expel that which is causing the trouble...it neither admits the air or easily expels the air. For they are without this troublesome coughing for the space of 4 or 5 hours at a time, then this paroxysm of coughing returns, now so severe that blood is expelled with force through the nose and through the mouth."
1578 Pertussis Epidemic in Paris, Guillamaume de Baillou

The"100 day cough" described in the 1500's in England ultimately became known in 1679 as pertussis, "violent cough", courtesy of Sydenham (of Sydenham's chorea fame). In the 21st century we now have better diagnostic tools to identify pertussis, vaccines for pertussis and effective antimicrobials that should decrease the contagiousness of patients yet we continue to and increasingly have pertussis epidemics.

The CDC MMWR recently reported another pertussis epidemic in California. The number of reported cases in 2014 is surpassing the recent 2010 epidemic and represents the most cases reported in California in the last 70 years. The overall rate of pertussis in the population is 26 per 100,000 population with the highest incidence in infants younger than 1 year (174.6 cases per 100,000). This "new normal" makes the case for continued pertussis research rethinking what we know about pertussis epidemiology, testing and antibiotic use.

Stone et al describe a prospective cohort study conducted from July 2004 to August 2006 at Primary Children's Medical Center in Salt Lake City, Utah. The objective of the study was to better understand the length of time pertussis PCR (polymerase chain reaction) is positive in a patient with clinical pertussis. Children less than 18 years of age who were hospitalized with a positive B. pertussis PCR and met CDC laboratory confirmed definition of B. pertussis infection were defined as index cases. Associated cases were defined as close contacts with at least 7 days of unexplained cough illness. Subjects enrolled in the study had nasopharyngeal samples tested with pertussis PCR at baseline and then weekly for 3 weeks, then monthly or every other month, for 1 year from symptom onset until the samples yielded a negative result.

True B. pertussis cases were cases that had the first pertussis PCR positive or who met CDC clinical criteria for pertussis but had the initial sampling after 21 days of illness. Over half of the associated cases (close contacts) were PCR positive for pertussis. The final analysis included 31 PCR positive and 3 PCR negative subjects who were sampled after 21 days but met CDC clinical case criteria. Despite completing an appropriate course of antibiotics (14 days erythromycin or 5 days azithromycin) B. pertussis PCR results remained positive for a median of 58 days after symptom onset (range: 4 to 172 days). Half of the patients continued to have a positive pertussis PCR for greater than 50 days after the onset of symptoms, despite antibiotic treatment and clinical improvement.

What does this study mean for Pediatric Infectious Disease clinicians and Hospital Epidemiologists? How should we clinically use pertussis PCR? Does the prolonged presence of B. pertussis DNA beyond 21 days of illness or after completing recommended antibiotic treatment correlate with continued contagiousness of the patient and further transmission to susceptible hosts? How do we clinically use this information to improve patient care and public health?

Pertussis culture is the only 100% specific method for identification and is still the gold standard. PCR is now the preferred method of diagnosis in the clinical setting. Commercial serologic tests, although not yet standardized by the FDA, can be helpful for diagnosis later in illness or for epidemiologic studies although the interpretation of serology may be influenced by recent vaccination. A 2007 Cochrane review of antibiotic treatment for pertussis evaluated 10 trials published between 1969 and 2004 that described microbiologic eradication determined by pertussis culture. Meta-analysis of microbiologic eradication as an outcome in these trials was not possible because of the difference in type of antibiotics used.

For patients hospitalized with pertussis, the AAP Committee on Infectious Diseases Red Book ®, recommends standard and droplet precautions for 5 days after the initiation of effective therapy, or if appropriate antimicrobial therapy is not given, until 3 weeks after cough onset. In the early 1990s at Children's Hospital Colorado, we experienced healthcare associated transmission of pertussis from a hospitalized coughing patient who completed an appropriate course of antibiotics and was thus removed from droplet isolation. We subsequently tightened our restrictions and kept patients with pertussis in droplet isolation until the time of hospital discharge. Recently we relaxed our isolation policy and now allow hospitalized patients with pertussis who are hospitalized greater than 14 days and with two documented negative pertussis PCRs one week apart to be removed from droplet isolation. Further studies evaluating pertussis PCR may help provide an evidence basis for changes to recommendations regarding appropriate isolation practices.

Pertussis continues to be a 21st century problem. We need to clearly develop research to answer the old and new questions. Replication and expansion of this pilot study in the ambulatory setting may bring us closer to answering questions in the time of the pertussis "new normal."

Let's Set the Record Straight on the Influenza Vaccine

By: Rebecca Wallihan, MD

Between abundant vaccine myths and increasingly vocal anti-vaccine celebrities, it seems like an uphill battle each year to increase rates of influenza vaccination. This year we are faced with an additional challenge.

Read more: Let's Set the Record Straight on the Influenza Vaccine

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