News

How Next Generation Sequencing is Changing Pediatric Infectious Diseases

Written by: Pia S. Pannaraj, MD, MPH

The technical advancement in microbial genomics is revolutionizing the field of infectious diseases.  The first complete genome sequence of a free-living organism, Haemophilus influenzae, was completed in 1995.  Since then, over 23,000 bacteria, 600 fungi and 4000 viruses have been sequenced. Most were completed in the last year and many more are in progress thanks to new high-throughput DNA sequencing technologies, a.k.a. Next Generation Sequencing (NGS).

Why is this exciting for pediatric infectious disease specialists?

NGS allows us to look at the complete DNA fingerprint of microbes with increasing speed and decreasing cost. We have deepened our ability to investigate outbreaks, detect antibiotic resistance genes, characterize difficult-to-culture organisms, and monitor host-microbe interactions at an unprecedented level of detail.

For example, the Centers for Disease Control and Prevention (CDC)'s PulseNet uses NGS to quickly detect multi-state foodborne outbreaks caused by Listeria, Escherichia coli, Salmonella and other dangerous bacteria. Bacterial cultures may take up to 3 days to grow in a laboratory while the foodborne pathogen continues to spread. NGS can determine information about the species, serovar, and subtype of bacteria within hours. This technology was used to determine the origin of a recent multi-state outbreak of Listeria in Hispanic-style cheese products. In March 2014, the Food and Drug Administration (FDA) suspended food production by Roos Food, Inc. after their cheese tested positive for a strain of Listeria indistinguishable from the outbreak strain. A 2011 multi-country outbreak of Shiga toxin-producing E. coli O104:H4 affected 4075 people, including 908 cases of hemolytic-uremic syndrome and 50 deaths. Researchers analyzed and published the complete genome mapping of the outbreak strain within 3 months of the outbreak's inception. A horizontal genetic transfer of a Shiga-toxin-encoding phage from an enterohemorrhagic E. coli onto an enteroaggregative E. coli strain resulted in an accumulation of synergistic virulence factors. Data sharing and open collaboration allowed researchers across the globe to analyze the outbreak strain with extraordinary speed.

Virulent pathogens – new and old – and increasingly multidrug resistant pathogens are becoming greater infection control challenges. In 2011, an outbreak of carbapenem-resistant Klebsiella pneumoniae affected 18 patients at the U.S. National Institutes of Health Clinical Center, 11 of whom died, despite early implementation of infection control procedures. Whole genome sequencing performed on patient and environmental isolates lead to the discovery that the index patient had left the hospital 3 weeks before the strain was isolated from another patient indicating that K. pneumoniae could silently colonize patients. Thus, effective surveillance protocols before isolation of multi-drug resistant strains were as important as infection control strategies after isolation.

The aggressive and highly lethal Ebola virus is an example of a pathogen that has been hard to study due difficulties in obtaining samples from remote areas where the outbreaks have occurred. Researchers are rapidly studying the current outbreak strain of the Ebola virus sequence to obtain insights on its origin, understand the virus' mutation over time, learn about the mechanisms underlying its pathogenicity, and determine how to design more sensitive and accurate diagnostic tests in the field. The current outbreak so far has caused 2,127 cases of disease and 1,145 deaths in Guinea, Liberia, Nigeria, and Sierra Leone.

Finally, sequencing technology has transformed our thinking about microbes on and in the human body. The human body contains over 100 trillion bacteria cells. We have just recently come to appreciate how these symbiotic microbes benefit us by breaking down our food, suppressing pathogenic bacteria, and nurturing our immune system. Multiple studies have revealed an intriguing association between the types and diversity of microbes in a child's gut and risk of asthma, diabetes, obesity, response to vaccines, and even behavior. Prospective studies in germ-free mice support these findings. What is important for pediatricians to know is that early exposures determine an infant's microbial composition as an infant. Mode of delivery, gestational age, breastfeeding vs. formula feeding, administration of antibiotics and the local environment all play a role in obtaining the "right" microbes. How do we know which are the "right" microbes? There is much more to discover, and NGS technology has opened the door to explore this question and many more.

The 5th Annual International Pediatric Antimicrobial Stewardship Conference

An Attendee's Perspective (and why all of you should go)
Written by: Saul Hymes, MD

Every year so many large conferences, courses, and annual meetings vie for our attention and our dollars.

Read more: The 5th Annual International Pediatric Antimicrobial Stewardship Conference

Does the Availability of Testing Improve Clinical Care?

Written by: Pui-Ying Iroh Tam, MD

Health outcomes for Americans have improved substantially over the last generation due to a number of factors including improved sanitation, vaccinations, increased education, and better health care.

Read more: Does the Availability of Testing Improve Clinical Care?

International Travel and Acquisition of Multidrug Resistant Organisms

Written by: Christina Gagliardo, MD

As pediatric infectious disease physicians, there are several key questions we all ask in order to obtain a thorough exposure history, including: "Do you have pets or animal exposures? Are your vaccines up to date? Have you ever travelled outside the country?" This last question has become increasingly important for several reasons which include ascertaining risk for tropical infections such as tuberculosis, malaria, typhoid, or dengue, vaccine-preventable illnesses such as polio and measles, but also to assess risk for colonization with multidrug resistant bacteria. A growing number of studies demonstrate acquisition of multidrug resistant bacteria during travel abroad. Likely every pediatric infectious disease physician has encountered an otherwise healthy child who is either colonized with, or has an infection from an extended spectrum beta-lactamase (ESBL) producing or other multidrug resistant organism (MDRO) with no discernible classic risk factors such as prior hospitalization, prior antibiotic use, or other medical problems. An underappreciated and likely relevant part of the history for MDRO colonization is international travel.

Travel to Southeast Asia appears to be an emerging risk factor for acquisition of ESBL-producing Enterobacteriaceae with several prospective cohort studies identifying international travel as a risk factor for colonization and travel to India or the Indian subcontinent as the highest risk factor (1-5).
A prospective study of 100 Swedish adults travelling outside Northern Europe demonstrated 24 individuals with negative pre-travel stool samples were colonized with ESBL-producing Escherichia coli after return home. They found a statistically significant higher risk of acquisition of ESBL-producing Escherichia coli with travel to India and an association with gastroenteritis related to travel, which could be a surrogate parameter for exposure to fecally contaminated food or water (2).

Van der Bij provides a comprehensive list of studies which demonstrate the role international travelers play in the global spread of MDROs, some of whom did report contact with healthcare systems abroad (6). Several large clinical trials are currently looking at the acquisition of MDR Enterobacteriaceae including COMBAT: Carriage of Multidrug Resistant Bacteria After Travel (ClinicalTrials.gov Identifier: NCT01676974) and the VOYAG-R Study: Acquisition of Multidrug-resistant Bacteria After Travel in the Tropics: Prevalence, Determinants and Length of Carriage (ClinicalTrials.gov Identifier: NCT01526187). These studies are also evaluating duration of colonization and rate of secondary transmission within households. VOYAG-R reported on three healthy French travelers returning from India who reported no contact with any healthcare center while abroad who acquired carbapenemase-producing Enterobacteriaceae (CPE) (7).

A recent study utilized a metagenomic approach and investigated resistance genes in the human gut microbiota after international travel. They reported high rates of acquisition of the ESBL- encoding gene blaCTX-M and quinolone resistance encoding genes qnrB and qnrS related to international travel. The prevalence of the resistance genes increased from 9.0%, 6.6%, and 8.2% before travel to 33.6%, 36.9%, and 55.7% after travel, respectively (5).

These findings raise several questions and have implications for policies regarding infection control measures. Should we counsel patients about these risks during pre-travel consultation when there is no specific intervention or recommendation to be made? Should we screen and isolate patients after travel abroad if they are hospitalized? In France the Healthcare Safety Advisory Committee made national recommendations to screen and place any individual transferred from or hospitalized outside France on contact isolation (6). While at this time there is certainly not enough evidence to support screening and isolating every person who has recently travelled, the impact of international travel on the spread of MDROs is crucial to understand on the patient and public health level to determine optimal interventions and policies.

References:

  1. Kennedy K, Collignon P. Colonisation with Escherichia coli resistant to "critically important" antibiotics: a high risk for international travelers. Eur J Clin Microbiol Infect Dis. 2010;29:1501–6
     
  2. Tängdén T, Cars O, Melhus A, Lowdin E. Foreign travel is a major risk factor for colonization with Escherichia coli producing CTX-M–type extended-spectrum beta-lactamases: a prospective study with Swedish volunteers. Antimicrob Agents Chemother. 2010;54:3564–8
     
  3. Ostholm-Balkhed A, Tarnberg M, Nilsson M, Nilsson LE, Hanberger H, Hallgren A, et al. Travel-associated faecal colonization with ESBL-producing enterobacteriaceae: Incidence and risk factors. J Antimicrob Chemother. 2013;68:2144–53
     
  4. Paltansing S, Vlot JA, Kraakman MEM, Mesman R, Bruijning ML, Bernards AT, et al.Extended-spectrum β-lactamase–producing enterobacteriaceae among travelers from the Netherlands. Emerg Infect Dis. 2013;19:1206–13
     
  5. von Wintersdorff CJH, Penders J, Stobberingh EE, Oude Lashof AML, Hoebe CJPA, Savelkoul PHM et al. High acquisition rates of antimicrobial drug resistance genes after international travel, the Netherlands. Emerg Infect Dis. 2014
     
  6. van der Bij, AK, Pitout JDD. The role of international travel in the worldwide spread of multiresistant Enterobacteriaceae. J. Antimicrob. Chemother. (2012)67 (9): 2090-2100
     
  7. Ruppé E, Armand-Lefèvre L, Estellat C, El-Mniai A, Boussadia Y, Consigny PH, Girard PM, Vittecoq D, Bouchaud O, Pialoux G, Esposito-Farèse M, Coignard B, Lucet JC, Andremont A, Matheron S. Acquisition of carbapenemase-producing Enterobacteriaceae by healthy travellers to India, France, February 2012 to March 2013 . Euro Surveill. 2014;19 (14)

JPIDS Article Review: A National Study of the Impact of Rapid Influenza Testing on Clinical Care in the Emergency Department

Written by: Sunil K. Sood, MD

Read more: JPIDS Article Review: A National Study of the Impact of Rapid Influenza Testing on Clinical Care...

Preserving the Future of Pediatric Infectious Diseases

Written by: Matthew Kronman, MD, MSCE

In the last cycle of the match for fellowship positions in Pediatric Infectious Diseases, there were approximately 80% as many applicants (55 total) as there were available fellowship positions [1].

Read more: Preserving the Future of Pediatric Infectious Diseases

JPIDS Article Review: The Safety and Immunogenicity of Rotavirus Vaccination in Infants with Intestinal Failure

Written by: Rebecca Wallihan, MD 

Read more: JPIDS Article Review: The Safety and Immunogenicity of Rotavirus Vaccination in Infants with...

MERS Update: Key Points – Middle East Respiratory Syndrome Coronavirus (MERS-CoV)- 5/12/2014

CDC has provided updated key points regarding the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), dated 5/12/2014. Updates include information about the second imported case of MERS in the United States.

Read more: MERS Update: Key Points – Middle East Respiratory Syndrome Coronavirus (MERS-CoV)- 5/12/2014

CDC announces second imported case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in the United States

CDC and Florida Department of Health officials are investigating the second case of MERS-CoV infection in the United States. MERS-CoV, a virus relatively new to humans, was first reported in Saudi Arabia in 2012.  On May 2, 2014 CDC reported the first case of MERS in the United States.

WHO:

  • Tom Frieden, M.D., M.P.H., Director, U.S. Centers for Disease Control and Prevention
     
  • Anne Schuchat, M.D. (RADM, USPHS) Assistant Surgeon General, United States Public Health Service; Director, National Center for Immunization and Respiratory Diseases
     
  • John H. Armstrong, MD, FACS, FCCP Florida's State Surgeon General and Secretary of Health

WHEN: Monday, May 12, 2014 at 2:00 p.m. ET

DIAL-IN:
Listen-only: 877-546-1574
Passcode: CDC MEDIA

Transcript:
A transcript of this media availability will be available following the briefing at the CDC web site at www.cdc.gov/media.

U.S. Department of Health and Human Services
CDC works 24/7 saving lives, protecting people from health threats, and saving money through prevention. Whether these threats are global or domestic, chronic or acute, curable or preventable, natural disaster or deliberate attack, CDC is the nation's health protection agency.

April 2014: JPIDS Article Review & Commentary

Written by: Christina Gagliardo, MD

Sammons JS, Gerber JS, Tamma PD, Sandora PD, Sandora TJ, Beekmann SE, Polgreen PM, Hersh AL. Diagnosis and Management of Clostridium difficile Infection by Pediatric Infectious Disease Physicians. J Pediatric Infect Dis Soc 2014 Mar; 3(1):43-48.

Summary:

In the March 2014 issue of the Journal of the Pediatric Infectious Disease Society, Sammons and colleagues report on practices for the diagnosis and management of mild, severe, and recurrent Clostridium difficile infection (CDI) by pediatric infectious disease (ID) physicians. They performed a web-based survey via the Emerging Infections Network (EIN) whose membership includes nearly one-quarter of all pediatric ID physicians who received board-certification since 1994. The survey was adapted and modified from an EIN survey of adult physicians on treatment of CDI and use of fecal microbiota transplantation. The survey included questions regarding diagnostic techniques and treatment strategies employed for CDI in children with clinical vignettes aimed to determine how treatment would differ based on clinical presentation (recurrent, severe, etc.), underlying chronic conditions, and patient age. They defined severe CDI as presence of WBC count >15,000 cells/µL, serum creatinine ≥ 1.5 times patient’s baseline, hypotension or shock, ileus, perforation, or megacolon. Recurrent CDI was defined as an episode occurring 8 weeks or less after the onset of a previous episode, provided symptoms had resolved from the previous episode.

Of 285 physicians surveyed, 145 (51%) responded and were included for analysis (twenty-two other respondents were excluded because they reported they had not managed patients with CDI in the past year). To diagnose CDI, 97 (67%) respondents used nucleic acid amplification assays alone or in combination with other laboratory methods, while 32 (22%) respondents used toxin enzyme immunoassay (EIA), and of these, over one-third used EIA alone. Forty respondents reported infant testing was restricted or required approval, with the majority reporting restrictions for below 12 months of age. Mild CDI in an immunocompetent host was managed with oral metronidazole in 100% of respondents, however oral metronidazole use varied and was less frequently preferred for patients with underlying comorbidities such as Crohn’s disease, renal transplant, and neutropenic AML patients. Oral vancomycin alone or in combination with at least one other agent was the preferred treatment for severe CDI by 65% of respondents. Oral vancomycin alone or in combination with another agent was used for treatment of a second recurrence by 131 (92%) respondents, with 16 of these respondents indicating they would initiate a vancomycin taper. For a third CDI recurrence and beyond, management varied greatly and included use of combination therapy or single agents including metronidazole, vancomycin, nitazoxanide, rifaximin, fidaxomicin, intravenous immunoglobulin, and fecal microbiota transplantation. Fecal microbiota transplantation was recommended most commonly for treatment of a third or later recurrence.

Commentary:

This study highlights the variability in practice among pediatric ID physicians in the diagnosis and management of recurrent and severe CDI. With regards to diagnosis, nearly 10% of respondents rely on toxin EIA only which has been shown to have poor sensitivity. Testing of infants < 12 months of age was not restricted at most institutions and some physicians felt CDI was a viable diagnosis in certain infants. The AAP 2013 Policy Statement [1] recommends that testing in infants < 12 months of age be limited to those with gastrointestinal motility disorders and outbreaks, and alternative diagnoses to be sought even in the event of a positive C. difficile test due to the high rate of colonization in infants [1]. The AAP also acknowledges the difficulty in test interpretation in the two and three year old age group. Wendt and colleagues recently reported results from a large community based epidemiologic surveillance study that young children from 1 to 3 years of age actually represent the highest CDI infection incidence and felt this young age group reflected true disease and not colonization [2]. This emphasizes the need for further study of CDI in this younger age group.

For treatment of mild CDI in immunocompetent children, oral metronidazole was unanimously the treatment of choice. For mild CDI in children with underlying chronic conditions, for severe CDI, and for recurrent CDI, treatment varied significantly. Although the AAP recommends oral vancomycin for severe CDI [1], this was not uniformly used by the respondents for severe disease. One recent study  identified predictors of vancomycin use for CDI in children and identified significantly more vancomycin use in patients who were older, white, had private insurance, who had testing within 48 hours of admission, who were on antibiotic at the time of testing, or who had a gastrointestinal comorbidity [3]. Many respondents reported use of alternative agents such as fidaxomicin, which is not FDA approved in children, and use of fecal microbiota transplantation which demonstrated efficacy in a randomized controlled trial of adults [4]; pediatric data for both treatments are lacking.

Limitations of the study included use of EIN membership, which may not be generalizable to all pediatric ID physicians, clinical vignettes which may not reflect actual practice, and recall bias. The study highlights the important issue of variability in approach to management of severe and recurrent CDI, CDI in certain subpopulations of children, and the lack of comparative effectiveness studies for the optimal treatment of CDI in children. Finally, antibiotic overuse plays an important role in CDI and emphasizes the role for antimicrobial stewardship in the outpatient and inpatient settings. In short, less antibiotic use and more studies are needed for CDI in children.

References:

  1. Schutze GE, Willoughby RE; Committee on Infectious Disease; American Academy of Pediatrics. Clostridium difficile infection in infants and children. Pediatrics 2013; 131(1):196-200.
     
  2. Wendt JM, Cohen KA, Mu Y, et al. Clostridium difficile Infection Among Children Across Diverse US Geographic Locations. Pediatrics 2014; 133(4):651-8.
     
  3. Schwenk HT, Graham DA, Sharma TS, et al. Vancomycin Use for Pediatric Clostridium difficile infection Is increasing and Associated with Specific Patient Characteristics. AAC 2013, 57(9):4307-13
  4. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. NEJM 2013; 386(5): 407-15

A Call to Medical Billing Coding Greatness

Written by: Pui-Ying Iroh Tam, MD

 Previous PIDS newsletters have included worthy and weighty communications on issues of profound importance, from vaccinations to antimicrobial stewardship. Certainly, part of the mission of PIDS is to 'care for children worldwide, through clinical care, education, research and advocacy,' and those are compelling problems that we hope to address and overcome in this generation. However, what has occupied my thoughts more recently have been more banal thoughts of billing codes.

Now, to be clear, I have never before had any interest in billing. I never received any orientation nor training on this as a medical student, resident, or fellow. To me this was the antithesis of why I went into medicine, something I regarded as another bureaucratic hurdle in order to complete my documentation.

However, I have developed a keen interest in the International Classification of Diseases, 10th Edition (ICD-10), which was scheduled to go into effect on 1st October, 2014, but has now been pushed back to 2015. With these codes, which include codes for new procedures and diagnoses that improve the information available for payment purposes, the healthcare delivery system will be transformed. As the secretary of the Department of Health and Human Services, Kathleen Sebelius, wrote, "ICD-10 is foundational for building a modernized health care system that will facilitate broader access to high quality care."

What has fascinated me most has been the new, expanded medical billing codes designed to provide greater detail in describing illnesses, injuries, and treatments. The 10th Edition was evaluated by a technical advisory panel in consultation with physician groups and clinical coders, and overseen by the World Health Organization. The main intent behind ICD-10 is to serve as a tool in classifying morbidity data for medical care review, indexing health records, and for basic health statistics; however, in the United States the codes are also used for billing purposes.

The uniqueness of some of the billing codes has captivated me. I have been enthralled by how one could have envisioned a use for a medical billing code for burn due to water skis on fire (V91.07XD) to being bitten by an Orca whale (W56.21XS – being struck by an Orca whale is a different code W56.22XS). What about a code for problems in relationship with spouse or partner (Z63.0)? Can I use it to bill myself when I've had a fight? It seems it would be difficult to outdo one of the earlier ICD classifications of 'visitation from God' as a cause for death; however, the ICD-10 code of 'asphyxiation as a result of encasement in a discarded refrigerator' (T71.231D) may have done just that.

Humor aside, these billing codes lead me to reflect on how the field of pediatric infectious diseases is recognized and remunerated. With the newest edition, 18,000 ICD codes have now expanded to around 140,000 codes, and one gets a sense from perusing this how much more weight is placed on surgical services. For balloon accidents and spacecraft injuries, there are 14 results each. There are 27 ICD-10 codes for various injuries to the nose, from abrasion to blister to contusion to puncture wound to laceration to nonvenomous insect bite. Conversely, when I typed in 'infection,' there were only 103 results. And not anything as exciting as involving chicken coops (Y92.72) or opera houses (Y92.253) or bunjee jumping (Y93.34). About half were infection billing codes associated with orthopedic procedures.

Therein lies the limitation of billing codes and the problematic orientation of insurance companies to our specialty as a whole. Why is there no billing code for severe infection caused by an esoteric organism that was identified by an astute physician? What about a billing code for quality of life improved and illness prevented due to immunization? Instead, we have a code for infection following immunization (T88.0XXS).

Given our specialty's relative adeptness at extracting details in the history, perhaps the ICD-10 codes are beckoning us to coding greatness. Whom else would be better able to identify whether an event occurred on the interstate highway (Y92.411), parkway (Y92.412), state road (Y92.413), sidewalk (Y92.480), parking lot (Y92.481), bike path (Y92.482) railroad track (Y92.85) or exit ramp (Y92.415)? Curiously, ICD-10 has 13 codes for immunization that were not administered because of various reasons, including due to patient refusal (Z28.21) and caregiver refusal (Z28.82). Billing for something that was not done? Perhaps that is progress.

References

Anna Wilde Mathews, Wall Street Journal, "Walked Into a Lamppost? Hurt While Crocheting? Help Is on the Way." 13th September, 2011.

US Department of Health and Human Services, News release. 24th August, 2012.

Erin McCann, Health IT news, "8 zaniest ICD-10 codes." 25th July, 2013.

Andrew Pollack, New York Times, "Roughed Up by an Orca? There's a Code for That." 29th December, 2013.

ICD-10 codes, http://www.cdc.gov/nchs/data/icd/Detailed%20List%20of%20Codes%20Exempt%20from%20POA.pdf accessed 4th February, 2014

Chris Dimick, Journal of AHIMA, "Senate passes ICD-10 delay bill." 31st March, 2014.

 

 

 

March 2014: JPIDS Article Review & Commentary

Written by: Matthew Kronman, MD, MSCE 

Simon TD, Mayer-Hamblett N, Whitlock KB, Langley M, Kestle JRW, Riva-Cambrin J, Rosenfeld M, Thorell EA. Few Patient, Treatment, and Diagnostic or Microbiological Factors, Except Complications and Intermittent Negative Cerebrospinal Fluid (CSF) Cultures During First CSF Shunt Infection, Are Associated with Reinfection. J Pediatric Infect Dis Soc. 2014 Mar;3(1):15-22.

Summary

In the March 2014 issue of the Journal of the Pediatric Infectious Diseases Society, Simon and colleagues report the findings of their retrospective cohort study of children at Primary Children’s Medical Center with first ventricular shunt infection. The authors compiled an extensive dataset through meticulous chart review, gathering records on 118 children who had a first shunt placed between January 1, 1997 and October 12, 2006, and who developed a first shunt infection prior to December 31, 2006. The authors then collected patient, treatment, and surgical factors to evaluate which factors were associated with developing a second shunt infection prior to June 28, 2010. The overall median follow-up time was 5.7 years, and 31 (26%) subjects developed a shunt re-infection.

The authors evaluated numerous factors, but found only three factors associated with risk of re-infection in their adjusted multivariate model: use of ventriculoatrial shunts (adjusted hazard ratio [aHR] 4.0, 95% confidence interval [CI] 1.3-10.0) or complicated shunts, defined as shunts involving multiple reservoirs or connections (aHR 7.7, 95% CI 1.2-28.1); complications – including shunt malfunction, hemorrhage, and abdominal abscess – after first infection (aHR 3.1, 95% CI 1.2-7.0); and what the authors termed "intermittently negative CSF cultures" – i.e., having positive CSF cultures, followed by negative cultures, and then having further subsequent positive cultures (aHR 3.2, 95% CI 1.3-7.0). In a sensitivity analysis, higher white blood cell count in the CSF at first infection was also associated with re-infection. None of the many other variables that were evaluated - including pathogen isolated at first infection, duration of first infection treatment, concordance of antibiotics with pathogen identified, use of intrathecal antibiotics, or surgical approach - were associated with the risk of developing re-infection.

Commentary

Ventricular shunt infections are a common reason for inpatient Infectious Disease consultation. It can be difficult to know how intensively to evaluate for a shunt infection in patients with ventricular shunts who have only non-specific symptoms such as fever. Once identified, ventricular shunt infections often lead to substantial morbidity, including invasive surgery and prolonged hospitalization. While the 2004 IDSA meningitis guidelines mention ventricular shunt infections, there is little current guidance for Infectious Disease physicians to assist in treating these infections in children and preventing recurrences [Tice et al.].

This study builds upon our existing knowledge of factors associated with re-infection after a first ventricular shunt infection. Prior pediatric multicenter work has demonstrated a similar 26% rate of re-infection, and suggested that duration of antibiotic treatment is not associated with risk of ventricular shunt infections recurrence [Kestle et al.]. The rate of infection relapse or re-infection in children appears to be higher than that in adults [Conen et al.]. Retrospective studies to determine whether use of antibiotic-impregnated catheters can reduce the risk of subsequent shunt infection have had mixed results, with some studies demonstrating no benefit [Kan et al.], and others demonstrating a reduction in shunt infections [Parker et al.].

In the Simon et al. study, duration of antimicrobial therapy was not associated with re-infection risk, and the median duration was nearly identical between the groups that did (15 days) or did not (13 days) develop re-infection. Likewise, rates of intrathecal antibiotic and rifampin use were similar between the two groups but very low in both groups, limiting the ability to evaluate the impact of these factors. Future studies may elucidate whether there are patients who could safely receive a shorter duration of antibiotics without increasing the risk of re-infection, and whether intrathecal antibiotics or adjuvant rifampin decrease the risk of re-infection.

Notably, none of the factors associated with re-infection in this study were ones that Infectious Disease physicians might typically influence. The association of complex and ventriculoatrial shunts with re-infection seems logical, given the difficulty and likely increased operative time for these procedures; Infectious Disease physicians may be able to discuss these data with their neurosurgeon colleagues to help them determine what replacement shunt position is best after a first infection. It is not clear, however, why intermittent negative CSF cultures predict shunt re-infection. These intermittent negative cultures may simply suggest factors associated with a more difficult infection to clear, such as a larger burden of organism, more loculated and therefore intermittently draining collections, subtherapeutic antibiotic penetration and levels, or organisms that produce biofilms.

While more work needs to be done to illuminate the optimal treatment of ventricular shunt infections in children, a history of uncommon shunt types and prior complications or intermittently negative cultures with a prior infection should all increase the suspicion for shunt re-infection. After an infection of a ventriculoatrial shunt, it may also be worth placing the new shunt in a non-atrial position, if feasible.

References:

  1. Simon TD, Mayer-Hamblett N, Whitlock KB, Langley M, Kestle JRW, Riva-Cambrin J, Rosenfeld M, Thorell EA. Few Patient, Treatment, and Diagnostic or Microbiological Factors, Except Complications and Intermittent Negative Cerebrospinal Fluid (CSF) Cultures During First CSF Shunt Infection, Are Associated with Reinfection. J Pediatric Infect Dis Soc. 2014 Mar;3(1):15-22.
  2. Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for outpatient parenteral antimicrobial therapy. IDSA guidelines. Clin Infect Dis 2004 Jun 15;38(12):1651-72.
  3. Kestle JR, Garton HJ, Whitehead WE, et al. Management of shunt infections: a multicenter pilot study. J Neurosurg 2006 Sep;105(3 Suppl):177-81.
  4. Conen A, Walti LN, Merlo A, Fluckiger U, Battegay M, Trampuz A. Characteristics and treatment outcome of cerebrospinal fluid shunt-associated infections in adults: a retrospective analysis over an 11-year period. Clin Infect Dis 2008 Jul 1;47(1):73-82.
  5. Kan P, Kestle J. Lack of efficacy of antibiotic-impregnated shunt systems in preventing shunt infections in children. Childs Nerv Syst 2007 Jul;23(7):773-7.
  6. Parker SL, Attenello FJ, Sciubba DM, et al. Comparison of shunt infection incidence in high-risk subgroups receiving antibiotic-impregnated versus standard shunts. Childs Nerv Syst 2009 Jan;25(1):77-83.

 

 

Antibiotic Resistance, PIDS and You

By: Saul R. Hymes, MD

On September 16, 2013, the CDC issued a report on the extent of harm caused by antibiotic-resistant infections. While those of us in the infectious disease field have been aware of this growing problem, its extent was striking: 2,000,000 people sick every year with an antibiotic-resistant infection and 23,000 dead yearly from the same. The problem of antibiotic resistance, they said, "is one of our most serious health threats." Aside from the existing (and growing) number of infections and deaths, the CDC predicted "the loss of effective antibiotics will undermine our ability to fight infectious diseases and manage the infectious complications common in vulnerable patients." Complex infections would no longer be treatable due to complete antibiotic resistance, and thus procedures with known infectious complications like organ transplantation or cancer chemotherapy could become riskier or possibly abandoned altogether. Journalists envisioned this post-antibiotic era; the PBS series Frontline spent an hour of primetime TV on the subject; and in these reports and others, we doctors were labeled as part of the problem.

On March 4 of this year, the CDC released a report on the problem of antibiotic overuse in hospitalized patients. The report looks primarily at adult data, and found that 55.7% of patients discharged from 323 hospitals in 2010 received antibiotics while hospitalized; in more than a third of those patients, the antibiotic use was inappropriate and could have been improved upon. On the pediatrics side, we see similar findings: a recent study published in Infection Control and Hospital Epidemiology by Gerber et al (Gerber and 4 of his 6 coauthors are PIDS members) found that a majority of pediatric patients are similarly prescribed antibiotics while hospitalized. They found that just 4 conditions, representing only 1% of the diagnoses, contained 10% of the antibiotic use—and that use was highly inconsistent and often inappropriate. Our poor antibiotic prescribing practices in the past have now caught up to us—with a vengeance.

However, clichéd as it may be, we are not only part of the problem, but have been and can continue to be part of the solution. First and foremost, through the creation of inpatient antimicrobial stewardship programs (ASP’s), both adult and pediatric hospitals can gain control of their antibiotic use, standardize and minimize prescribing, and improve care as well as cut costs. PIDS and PIDS members have a number of ongoing efforts aimed at promoting ASP growth and research.

Every year for the past 4 years, PIDS has sponsored a conference on antimicrobial stewardship. Cosponsored by Children’s Mercy Hospital & Clinics, and led by Jason Newland, MD, MEd, the Director of Antimicrobial Stewardship there, the 5th annual conference will be occurring June 5–6, 2014, and offers the opportunity for PIDS members and nonmembers to learn more about starting an ASP, share their research and outcomes data, and learn from the work and research of others. Dr. Newland has also been instrumental in another broader effort around ASP research—the formation of the SHARPS group. A group made up of 7 children’s hospitals and their ASP’s, SHARPS was organized with the aim of conducting multi-center research on the benefits of pediatric ASP’s and where and how to implement strategies for improvement. To say the eventual results of their research are eagerly-awaited would be an understatement.

But most antibiotic prescribing goes on in the outpatient setting, far from the watchful eye of a traditional hospital-based ASP. Critical research by Theo Zaoutis, MD, MSCE, and others, has illustrated how we can perform outpatient stewardship to better ensure adherence to prescribing guidelines and use of narrower-spectrum antibiotics in the outpatient setting. This is an area many children’s hospitals, pediatric residencies, and infectious disease specialists have only begun to venture into and is one where we can make significant progress. Educational interventions through Grand Rounds and targeted lectures at practice sites, increased use of outpatient pediatric infectious disease care and phone consults to generalists, and, where feasible, active surveillance via prospective audit and feedback all have the potential to help improve antibiotic practices in this setting and are all areas where we as pediatric infectious disease practitioners can get involved.

The problem of antibiotic resistant infections is a daunting one, but it is one that PIDS members, pediatric infectious disease practitioners, and indeed all pediatricians and physicians can help combat. Think before you write a vancomycin order for one of your hospitalized patients. Do you really need to use that cephalosporin for ambulatory treatment of pneumonia, otitis or a UTI? On an individual level, every little bit helps, and on a larger scale, every institution and multi-institution group that can work on antimicrobial stewardship can make a real difference. Will we reach a post-antibiotic era? Some practitioners, for some patients and some infections, are already effectively working within it, though I certainly hope to never see its full arrival. Through improving our antimicrobial stewardship—in all settings—we have the best chance of delaying it as long as possible.

Among U.S. Children, More Infections Caused by Drug-Resistant Bacteria

Infections caused by a concerning type of antibiotic-resistant bacteria are on the rise in U.S. children, according to a new study published in the Journal of the Pediatric Infectious Diseases Society and available online. Although still uncommon, the bacteria are increasingly found in children of all ages, especially those 1-5 years old, raising concerns about dwindling treatment options.

Researchers led by Latania K. Logan, MD, of Rush University Medical Center in Chicago, analyzed resistance patterns in approximately 370,000 clinical isolates from pediatric patients, collected nationwide between 1999 and 2011. Specifically, they determined the prevalence of a resistant type of Gram-negative bacteria, Enterobacteriaceae, that produces a key enzyme, extended-spectrum beta-lactamase (ESBL). The enzyme thwarts many strong antibiotics. Another indicator of ESBL prevalence, susceptibility to third-generation cephalosporins—an important class of antibiotics used to treat many infections—was also measured.

The prevalence of ESBL-producing bacteria increased from 0.28 percent to 0.92 percent from 1999 to 2011; resistance to third-generation cephalosporins increased from 1.4 percent to 3.0 percent. ESBLs were found in children across the country of all ages, but slightly more than half of the isolates with this resistance were from those 1-5 years old. Nearly three-quarters (74.4 percent) of these bacteria were resistant to multiple classes of antibiotics.

"These antibiotic-resistant bacteria have traditionally been found in health care settings but are increasingly being found in the community, in people who have not had a significant history of health care exposure," Dr. Logan said. "In our study, though previous medical histories of the subjects were unknown, 51.3 percent of the children presented in the outpatient or ambulatory setting."

While the overall rate of these infections in children is still low, ESBL-producing bacteria can spread rapidly and have been linked to longer hospital stays, higher health care costs, and increased mortality, the study authors noted. In a 2013 report, the Centers for Disease Control and Prevention called ESBLs a "serious concern" and a significant threat to public health.

Physicians should obtain cultures for suspected bacterial infections to help determine which antibiotics are best, Dr. Logan said. "Some infections in children that have typically been treated with oral antibiotics in the past may now require hospitalization, treatment with intravenous drugs, or both, as there may not be an oral option available."

More research is needed to define risk factors for these infections in children, their prevalence in different settings, and their molecular epidemiology, Dr. Logan said. A companion study by several of the same researchers, also now available online in the Journal of the Pediatric Infectious Diseases Society, suggests that children with neurologic conditions are at higher risk for infections caused by ESBL-producing bacteria.

Additional drug development, keeping younger patients in mind, is also needed. "The overwhelming majority of current research for new pharmaceuticals against antibiotic-resistant organisms are in adults," Dr. Logan said. "New drug options will need to be available for young children."

###

Published quarterly, the Journal of the Pediatric Infectious Diseases Society represents the spectrum of peer-reviewed, scientific and clinical information on perinatal, childhood, and adolescent infectious diseases. The journal is a publication of the Pediatric Infectious Diseases Society (PIDS), the world's largest professional organization of experts in the care and prevention of infectious diseases in children.

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

 

 

President's Corner

As we embark on a new year, PIDS activities continue to build on the goals and objectives identified in the Strategic Planning meeting that the PIDS Council (now Board of Directors) undertook last May.  Over the next several months, we will focus on membership development, education, and training.  The Communications Committee has revamped the Society’s newsletter to include news and important updates related to pediatric infectious diseases and patient care, as well as promote articles published in JPIDS and other mainstream media.  The Membership Committee assisted in the development of the Fellow of the Pediatric Infectious Diseases Society (FPIDS) membership category and brochure.  We are now seeking applications for 2014 candidates (click here to view the criteria and deadline to submit an application).  The newly formed Pediatric Transplant ID Working Group developed the first Pediatric Transplant ID Course.  This course will be held in front of the St. Jude/PIDS Pediatric Infectious Diseases Research Conference and will provide trainees and junior faculty an overview of the state of the art in Transplant ID including research gaps and new research areas.  The St. Jude/PIDS Pediatric Infectious Diseases Conference features a "Frontiers in Infectious Diseases" symposium, with presentations from leading investigators in infectious diseases and microbiology and a series of career development workshops that will focus on writing and ethical issues in research and academia.  Thank you goes to the Research Affairs Committee for developing another superb program.  The Program and Meetings Committee has developed more outstanding programs for the Pediatric Academic Societies’ Meeting, May 3-6, in Vancouver, British Columbia, Canada and the 30th Annual Meeting of the European Society for Paediatric Infectious Diseases, May 6-10, in Dublin, Ireland.  Planning also is underway for the Pediatric Antimicrobial Stewardship Conference, to be held June 5-6 in Kansas City, Missouri, with joint sponsorship with Children’s Mercy Hospitals and Clinics.  I encourage members to attend, if possible, at least one of these conferences.  More information can be found on the PIDS website (www.pids.org).  

The 2014 Spring Election will be held in March.  PIDS is now accepting nominations for Board Members to serve a four-year term.  If you are interested in nominating yourself or a colleague to serve as a Board Member, please click here to view the nomination form and instructions for submission.  In addition, PIDS staff recently sent out the second dues reminder to all PIDS members.  Your membership and active participation in the Society is what makes PIDS strong and vibrant.  If you have not received your 2014 PIDS dues invoice, please contact the PIDS Headquarters at This email address is being protected from spambots. You need JavaScript enabled to view it..  Along with dues, we are asking members to consider making a contribution to the PIDS Education and Research Foundation to ensure continuation of the PIDS Fellowship and Research Awards and educational programs.  As a reminder, the deadline for applications for the PIDS awards, including the PIDS and PIDS-St. Jude Fellowship Awards, the Young Investigator Award, and the Distinguished Physician Award is fast approaching.  Links to award applications and submission deadlines can be found in this newsletter.  Or, you may visit the PIDS website at www.pids.org.  I encourage you to nominate a colleague or trainee for an award. Your questions, concerns, and suggestions are always welcomed.  Please contact the PIDS Headquarters office at (703) 299-6764 and speak with Christy or Faith.

Here’s to another productive year!

Website developed by Katalyst Solutions, LLC