IDSA News - April 2014
The Emerging Infections Network (EIN) is a forum for infectious diseases consultants and public health officials to report information on clinical phenomena and epidemiological issues with public health significance. Any diagnostic or therapeutic recommendations and all opinions presented are those of the individual contributor. They do not necessarily represent the views of EIN, IDSA (EIN’s sponsor), or the Centers for Disease Control and Prevention (CDC), which funds EIN. The reader assumes all risks in using this information.
The EIN goals include helping to connect members to the CDC and other public health investigators, and developing new methods for gathering epidemiological and clinical information, as in this recent case involving an investigator who is hoping to develop a better diagnostic test for Klebsiella pneumoniae (hvKp).
Recently an EIN member posted a case of hypervirulent (hypermucoviscous) hvKp in a patient without epidemiological links to Southeast Asia and asked how often others were seeing this entity in the U.S. Several respondents reported also seeing hvKp in patients without epidemiological links to Asia, and also that their clinical laboratories did not routinely assess for a hypermucoviscous phenotype without special requests from the clinicians involved or were not sure how to do this.
About six weeks later, the same member sent follow-up information to the EIN listserv, indicating that he had been contacted by a physician-scientist who investigates hvKp. This investigator is interested in developing diagnostic tests for the clinical microbiology lab to reliably identify hvKp. To accomplish this he would like to add more strains to his collection that have a clinical history consistent with hvKp infection.
The investigator, Dr. Thomas Russo of the University of Buffalo, characterized hvKp as an emerging variant (pathotype) of Klebsiella pneumoniae that was first recognized in Taiwan in 1986. hvKp infection initially was characterized and distinguished from traditional infections by (1) presentation as community-acquired pyogenic liver abscess, (2) occurrence in patients lacking a history of hepatobiliary disease, and (3) a propensity for metastatic spread to distant sites (e.g., eyes, central nervous system, lungs). More recently, this variant has been recognized to also cause a variety of serious, community-acquired non-hepatic abscesses/infections, including pneumonia, meningitis, endophthalmitis, splenic abscess, and necrotizing fasciitis. The affected individuals often have diabetes mellitus and are of Asian descent; however, non-diabetics and all ethnic groups can be affected.
There is currently no way to reliably identify hvKp. The “string test,” which tests for the hypermucovisvous phenotype, is not typically performed. Further, the string test has a subjective component, its sensitivity and specificity for hvKp strains has not been defined, and importantly classic K. pneumoniae strains may also be string test positive, which is particularly problematic in areas of low hvKp prevalence.
Dr. Russo believes that the development of a more objective diagnostic test will enhance researchers’ ability to perform more comprehensive epidemiologic studies. It will also enable the full spectrum of infectious syndromes and the incidence of infection to be defined, especially outside of the Asian Pacific Rim. He also notes that a better test will assist the clinician in disease management, as the knowledge that an hvKp strain is causing infection should prompt a search for concomitant or subsequent metastatic sites of infection (e.g. eye or CNS), which may require drainage or a site-driven modification of the antimicrobial regimen. Anecdotal data suggests that hvKp reinfection or relapse may develop months to years after treatment has been completed; thereby long-term follow-up may be necessary. A more objective diagnostic test will enable studies on whether the nature and duration of therapy for hvKp infection should be different, he says.
“Our laboratory is in the process of trying to develop an objective test(s) that could be used to distinguish classic from hvKp strains,” Dr. Russo says. “To achieve this goal we would like to increase our collection of hvKp isolates.” He is interested in hearing from clinicians who are aware of a potential case of hvKp infection and the isolate is available for further study. To contact Dr. Russo, email email@example.com or call (716) 829-2674.
Note: EIN does not collect either the samples or any patient identifiers, but rather serves as a “matchmaker” to connect the clinician with the investigator as it did in this case.
With repressive new laws threatening HIV responses in Uganda and Nigeria, a new U.S. Global AIDS Coordinator, new guidelines on hepatitis C from the World Health Organization, and a promising step in antiretroviral access, April was filled with global health news:
Police action in Uganda indicated the scope of threat to donor HIV responses:
A week after her swearing in as United States Global AIDS Coordinator, Ambassador Deborah Birx outlined her perspectives and priorities in her first official statement:
A deal promises wide access to an important new HIV medicine:
The World Health Organization issued its first guidelines for screening, treatment and prevention of hepatitis C:
Open Forum Infectious Diseases (OFID), the new, open access journal from IDSA and the HIV Medicine Association (HIVMA), has announced a team of associate editors who are working with Editor-in-Chief Paul Sax, MD, FIDSA, on the new journal:
Oxford University Press (OUP) is implementing an important initiative to gather feedback from its journal readers. Over time, the feedback will be used to help inform the information and services provided to readers and authors.
If you would like to support this initiative by offering feedback on any of the journals published by OUP, including The Journal of Infectious Diseases, Clinical Infectious Diseases and Open Forum Infectious Diseases, please click on the following link to begin: https://www.surveymonkey.com/s/journalreaders
IDSA is pleased to announce 26 recipients of this year’s Medical Scholars Program scholarships.
Supported by the IDSA Education and Research Foundation, the Medical Scholars Program was established in 2002 and has awarded scholarships to more than 450 medical students so they can pursue ID-related independent clinical or research activities outside their institutional programs. The Medical Scholars Program helps attract the best and brightest to the field by giving medical students a first-hand look at the challenges and opportunities of working in infectious disease.
Applications for next year will open early December 2014. For more information on the recipients’ research topics, please visit http://www.idsociety.org/Medical_Scholars_Program/.
Breona Barr, Wake Forest School of Medicine, Winston-Salem, NC
Nicholas Berlon, Duke University School of Medicine, Durham, NC
Tyler Burnett, University of Nebraska Medical Center, Omaha, NE
Sydni Coleman, University of Cincinnati College of Medicine, Cincinnati, OH
Jonathan Dyal, Johns Hopkins University School of Medicine, Baltimore, MD
Rebecca Edwards, Northwestern University Feinberg School of Medicine, Chicago, IL
Dora Friedman, University of California - San Francisco, San Francisco, CA
Matthew Givens, University of North Carolina, Chapel Hill, NC
Maurice Hajjar, The Warren Alpert Medical School of Brown University, Providence, RI
Rachel Hense, Emory University School of Medicine, Atlanta, GA
Christopher Hergott, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Daniel Huck, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH
Abby Johnson, University of Texas Southwestern Medical Center, Dallas, TX
Raaka Kumbhakar, Columbia University College of Physicians and Surgeons, New York, NY
Jacob Lemieux, Harvard Medical School, Boston, MA
Julia Liebner, Case Western Reserve University School of Medicine, Cleveland, OH
Kelsey Loeliger, Yale University School of Medicine and School of Public Health, New Haven, CT
Brandon Maust, University of Washington, Seattle, WA
Hong Loan Nguyen, The Pennsylvania State University College of Medicine, Hershey, PA
Aaron Richterman, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Patrick Sanger, University of Washington, Seattle, WA
Daniel Sedhom, Albany Medical College, Albany, NY
Caleb Seufert, University of Vermont College of Medicine, Burlington, VT
Daniel Silva, Boston University School of Medicine Boston, MA
Madeleine Sowash, Columbia University College of Physicians and Surgeons, New York, NY
Hansel Tookes, University of Miami Miller School of Medicine, Miami, FL
Rear Admiral Kenneth G. Castro, MD, currently acting director of the Division of HIV/AIDS Prevention for the National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention (NCHHSTP) at the Centers for Disease Control and Prevention, has announced his retirement. Dr. Castro served the last 20 years as director of the Division of Tuberculosis Elimination (DTBE). Joining CDC’s AIDS Program as an Epidemic Intelligence Service officer in 1983, he began his tenure as DTBE director 10 years later in 1993 and served in this position until June 2013. Under his leadership many remarkable events and advances occurred in U.S. tuberculosis control.
Are you a member on the move? Do you know someone who is? Contact Jennifer Morales at firstname.lastname@example.org so we can announce it to our membership.
Charles Farthing, MD (1953-2014)
Atillasoy, Ercem, MD
Devine, Ben, PharmD
Evans, Derek, PharmD
Fares, Elias, MD
Fliethman, Rochelle, PharmD
Jacques, Kimberly, PharmD
Johnson, Kevin, PharmD, RPh
Kagan, Ron, PharmD
Kent, Dan, PharmD
Malik, Shalabh, MD
Matsuo, Ken, MD
Orear, Shon, MBA
Pallin, Daniel, MD, MPH
Patwari, Priti, MD
Price, Justin, MD
Raddatz, Janet, PharmD
Thorpe, Cheleste, MD
Tuite, Helen, MB
Venes, Donald, MD
White, Janet, NP
Williams, Krista, MS
Brown, Ashley, PhD
Guilfoose, John, MD
Haseeb, Faiuna, MD
Ivezic-Schoenfeld, Zrinka, PhD
Khan, Sarah, MD
Leung, Daniel, MD, MSc
Pablani, Lata, MD
Pols, Joanna, PhD
Renzi, Michael, PhD
To, Kelvin, MBBS, MRCP
Udani, Paras, DO
Zuzak, Kimberly, MD
MEMBERS IN TRAINING
Alsultan, Arwa, MD
Andersen, Heidi, MD
Herce, Michael, MD, MPH
Jahromi, Maryam, MD
Khullar, Neha, DO
Marr, Ian, MBBS
Morjaria, Sejal, MD
Parveen, Azra, MBBS
Ryan, Katie, MD
Sampath, Rahul, MD
Singh, Samsher, MSc
Vincent, Jean, MD
Kaveski, Lauren, PharmD
Malik, Nilma, MD
Serota, David, MD
Warner, Nathaniel, MD
Burnett, Tyler, MD
Connally III, Robert
Kumbhakar, Raaka, MD
Loeliger, Kelsey, MD, PhD
Myers, Kevin, BSN
Silvera, Richard, MPH
Hardly any other field is as intellectually stimulating and rewarding as ID. Yet the number of IM residents applying to ID training programs is down. It is our job, as individuals and as a Society, to understand and address the barriers that keep young doctors from choosing to specialize in infectious disease.
If you are like me, you cannot imagine working in any area of medicine
other than ID. True, our reimbursement is less than some other
subspecialties. But what other field is as intellectually stimulating
and personally rewarding?
Who, but the ID specialist, solves complex medical mysteries that perplex everyone else? Who explores the fascinating place where the microbial world and the human world interconnect? Who helps relieve human suffering, from the individual patient to the population as whole?
So why don’t more young doctors see it this way? The recent data from the National Resident Match Program are discouraging—in the 2014 appointment year, the number of internal medicine residents applying to Infectious Disease was down from previous years, leaving 41 percent of ID fellowship programs unfilled. Yet the need for ID specialists is strong. Think antimicrobial resistance, ongoing outbreaks of vaccine-preventable diseases, emerging and re-emerging infections, exciting breakthroughs in HIV and hepatitis C, and the emphasis on infection control and quality improvement under health reform.
At the IDSA Board of Directors meeting in March, we discussed at length the future of the ID profession. Several members of the Board shared their inspiration for becoming an ID specialist. Some recalled a specific mentor, while others spoke of a particular case that motivated them because of the intellectual challenge it presented. It is our responsibility, as individuals and as a Society, to understand and address the barriers to choosing ID as a subspecialty. There are several initiatives in which IDSA is engaged to do that.
A research project is underway under the leadership of Wendy Armstrong, MD, of Emory University and Erin Bonura, MD, of Oregon Health and Science University to examine the factors influencing residents’ decisions about applying to fellowship training programs. Researchers will conduct in-depth telephone interviews followed by a national survey of internal medicine residents. The data gathered from this study will then be used to lay the groundwork for national initiatives to address the decline in ID applications.
IDSA will also launch a Mentorship Pilot Program during IDWeek 2014. The goal of this program is to create an opportunity for medical students, residents and fellows to closely interact with leaders in their respective areas of investigation and career interest, in an effort to attract more people into the field.
IDWeek 2014 will offer several other opportunities to nurture and celebrate the next generation. The popular “Posters in the Park” reception will be another great opportunity for selected students, residents and fellows to have their work highlighted, while providing a networking forum for all. In addition, the meeting will also feature a “Careers in ID” session highlighting the diverse options available to people in our field.
The IDSA Education and Research Foundation also continues to support the Medical Scholars program and the HIVMA Minority Clinical Fellowship program, both of which provide mentorship and funding to those starting out in the field. Recognizing the great attraction of careers in global health, we continue to provide information for medical fellows interested in participating in observerships overseas.
Through each of these initiatives, IDSA hopes to understand the choices made by young doctors and share with them our passion for the field. I encourage you to work with the Society and within your own community to help us in these efforts. So many of us consider a career in infectious diseases to be a calling. We must invest in the future of the field that means so much to each of us.
Haemophilus influenzae Infection During Pregnancy and Adverse Fetal Outcomes; Hospital Readmissions for OPAT: Can We Predict Who Will Be Readmitted?; Is HPV More Commonly Transmitted from Women to Men? Implications for Prevention; Stem Cell Transplants and RSV: Factors Behind Progression to Lower Respiratory Tract Infection
In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.
Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases.
Researchers used public health surveillance in England and Wales to investigate cases of invasive Haemophilus influenzae and pregnancy outcomes, in an article published in the March 19 issue of The Journal of the American Medical Association.
Clinicians were surveyed three months after laboratory-confirmed cases in women aged 15 to 44. Between 2009 and 2012, 171 cases of invasive infection with serotyped isolates were identified. Of these, 144 cases were from unencapsulated H. influenzae. Thirty-eight percent of the women had an underlying condition. The most common presentations were bacteremia followed by pneumonia.
In this study, 75 women were pregnant at the time of infection and 72 had unencapsulated H. influenzae. Pregnant women were more likely to be younger and healthier; all of the pregnant women survived. The overall incidence of infection was higher in pregnant women (3.01 per 100,000 woman-years, compared to 0.22 in non-pregnant women). In infections with unencapsulated H. influenzae that occurred up to week 24 of pregnancy, 44 of 47 cases ended in miscarriage, and three infants were born prematurely. In the 28 infections that occurred after week 24, two infants were stillborn, and eight were born prematurely. Eighty percent of the infants had respiratory distress and/or sepsis at birth. The case fatality rate for neonates and infants was 62 percent. Of all live born infants, one died.
This study demonstrates that invasive H. influenzae infection is uncommon, but the incidence of infection, especially with unencapsulated H. influenzae, which is not prevented by the current vaccine, is increased in pregnancy and associated with a high rate of pregnancy loss. H. influenzae is known to colonize the genital tract and may be an under-recognized cause of pregnancy loss especially in early pregnancy. It is a fastidious organism, so specific culture techniques are needed to confirm the infection. This study also highlights the role of a robust public health surveillance system in identifying rare but potentially preventable or treatable causes of pregnancy loss and neonatal illness.
Outpatient parenteral antibiotic therapy (OPAT) is an effective, cost-saving, and convenient way for patients to receive intravenous antibiotics at home. However, OPAT can be associated with complications such as adverse drug effects, line infections, and hospital readmissions. With OPAT use on the rise, there is a growing need to determine which patients are at risk for complications.
In the March 15, 2014, issue of Clinical Infectious Diseases, researchers described the results of their retrospective review of 782 adult patients who received OPAT between 2009 and 2011. They sought to identify factors that predicted hospital readmission following discharge with OPAT.
Of the 782 subjects, 207 (26 percent) met the primary outcome measure of an unplanned hospital readmission within 30 days of being discharged with OPAT. The main indications for readmission were non-infection related (30 percent), worsening infection (29 percent), new infection (19 percent), and adverse drug reaction (14 percent). In the final regression analysis, age (odds ratio [OR], 1.09 per decade; 95 percent confidence interval [CI], .99-1.21), aminoglycoside use (OR, 2.33; 95 percent CI, 1.17-4.57), a history of previously isolated drug-resistant organisms (OR, 1.57; 95 percent CI, 1.03-2.36), and the number of prior hospital discharges without intravenous antibiotics in the preceding year (OR, 1.20 per prior admission; 95 percent CI, 1.09-1.32) were found to be associated with a higher rate of readmission.
Within the overall cohort, 25 percent (199/782) were treated with cephalosporins and 19 percent (149/782) with carbapenems. Only 5 percent (41/782) received daptomycin and none received intravenous vancomycin.* Thus, the study results may not represent practices in which daptomycin or intravenous vancomycin OPAT use is more common. Other limitations of the study include its retrospective and single-academic center design. Nonetheless, these findings may help clinicians identify OPAT patients with a higher risk for hospital readmission.
*Clarification (5/12/14): Some patients in the study did receive vancomycin (290/782), according to a recently published erratum for the CID article. This use was not significantly associated with readmissions.
While risk factors for human papillomavirus (HPV) transmission have been studied, differences in rates of transmission from women to men versus men to women have not been well-characterized. To help fill this knowledge gap, investigators studied a subset of participants from the prospective HPV in Men (HIM) study. Their findings appear in the April 1 issue of The Journal of Infectious Diseases.
Male study participants from the Tampa, Fla., area with steady female partners were recruited, and 99 couples were analyzed. HPV infection was diagnosed by PCR testing of genital swabs plus swabs of warts or lesions. Results of serologic testing were not reported. Self-reported monogamy was not required.
Of the 99 couples, 65 were HPV-discordant at baseline, such that one partner was infected with at least one HPV genotype not found on his or her partner. Among such couples, incident rates of infection with one of these discordant HPV genotypes were insignificantly higher among men (12.3 infections per 1,000 person-months) than women (7.3 infections per 1,000 person-months). When all 99 couples were studied, incident rates of genital infection were essentially equivalent among men and women (23.9 vs. 22.9 infections per 1,000 person-months, respectively). Couples of ≤2 years’ duration were more likely to acquire infection with any HPV genotype than were couples of >2 years’ duration, with men more likely than women to be infected regardless of relationship duration.
Like several smaller, earlier studies, this study shows that HPV might be more commonly transmitted from women to men than men to women. These findings highlight the importance of HPV vaccination for boys and girls aged 11-12 years, as per the Advisory Committee on Immunization Practices’ current Recommended Immunization Schedules. Catch-up vaccination is recommended for women through age 26 and men through age 21 (with consideration of vaccinating men through age 26).
Respiratory syncytial virus (RSV) presents major challenges for patients undergoing hematopoietic stem cell transplantation (HSCT): RSV infection of the upper airway causes sniffles and congestion, but it may descend to cause lower respiratory tract infection (LRTI), which is profoundly dangerous and difficult to treat. Fundamental questions remain unanswered about this common infection, including: What host and viral factors are associated with progression to lower-tract infection?
An article in the April 15 edition of The Journal of Infectious Diseases provides some important answers. The investigators retrospectively reviewed the medical records of 181 HSCT recipients with proven RSV upper respiratory tract infection (URI). In their multivariable analysis, several factors predicted progression from URI to LRTI:
On the other hand, progression was not different between the following groups:
Significant questions remain regarding RSV in this vulnerable patient population: Is inhaled or systemic ribavirin best for treatment of active disease, and is immune globulin (polyclonal or monoclonal) effective enough to use in spite of its cost and toxicity? Until an effective RSV vaccine is at hand, these questions will be important to answer. In the meantime, based on this study, we at least have more data on which to base a prognosis for those with RSV URI.
It’s not a permanent fix, but the Patient Access to Medicare Acttemporarily adjusts the SGR and extends the 0.5 percent update. It also seeks to improve reimbursement for diagnostics as advocated for by IDSA.
The Patient Access to Medicare Act was signed into law by President Obama on
April 1. The law, which is the most recent in a series known as the “Doc Fix,” temporarily adjusts the Medicare Sustainable Growth Rate (SGR) formula to prevent a 24 percent reduction in reimbursements to physicians. The law extends the 0.5 percent update, previously provided for Medicare services for the first quarter of 2014 through the remainder of the year.
During the last few months, health groups – including IDSA – coalesced around a policy proposal to permanently repeal the SGR and consolidate three existing federal programs to promote quality care. However, leaders in Congress proved unable to agree on funding reductions to offset the $138 billion proposal.
While the inability of Congress to pass a permanent repeal of the SGR is a disappointment, the new law was a step forward for diagnostics—a key IDSA priority area. The law seeks to improve reimbursement for diagnostics as advocated for by IDSA. The outcome demonstrates the importance of advocacy efforts like IDSA’s action alerts to the ID community and ultimately to patients.
IDSA continues to make progress advocating for new drugs and diagnostics to address drug-resistant infections, with promising signals coming from Congress, FDA, and the White House. Meanwhile, two new drugs could soon get FDA approval—potentially counting toward IDSA’s 10x'20 goal.
IDSA continues to make progress advocating for new drugs and diagnostics to address drug-resistant infections, with promising signals coming from Congress, the Food and Drug Administration (FDA), and the White House. Meanwhile, two new drugs could soon get FDA approval—potentially counting toward IDSA’s 10x'20 goal.
At the White House, the President’s Council of Advisors on Science and Technology (PCAST) is expected to issue a report on antimicrobial resistance and recommendations to President Obama in May. Topics under consideration include: federal coordination of stakeholders, antibiotic stewardship in human healthcare and agricultural settings, economic incentives for antibiotic development, collection of data on antibiotic use (including dosage and duration of therapy), better clinical trial designs, limited population antibiotic development, and the need for new rapid diagnostics. IDSA’s Vice President for Public Policy & Government Relations, Amanda Jezek, delivered brief oral remarks at an April 4 meeting of PCAST, and the Society also submitted comments.
In Congress, U.S. Reps. Phil Gingrey (R-GA) and Gene Green (D-TX) have lined up several new cosponsors for the Antibiotic Development to Advance Treatment (ADAPT) Act (PDF), which IDSA supports. The bipartisan group includes Reps. Bill Cassidy (R-LA), John Barrow (D-GA), John Dingell (D-MI), Renee Ellmers (R-NC), Leonard Lance (R-NJ), Bob Latta (R-OH), Jim Matheson (D-UT), Doris Matsui (D-CA), Pete Olson (R-TX), Mike Pompeo (R-KS), Paul Tonko (D-NY), and John Yarmuth (D-KY). IDSA continues to work closely with Gingrey and Green to strengthen the bill’s provision regarding antibacterial drug labeling and to push for a committee hearing on the bill. IDSA members can use the web action alert to ask their House members to support the ADAPT Act.
At FDA, IDSA presented testimony and provided comments to the Anti-Infective Advisory Committee (AIDAC), which was reviewing tedizolid and dalbavancin. Although IDSA does not take a position on specific drugs or companies, the Society was able to weigh in on the need for new antibiotics. The Committee voted to recommend approval tedizolid (14-0) and dalbavancin (12-0, 2 abstentions) for acute bacterial skin and skin structure infections.
IDSA also submitted comments to the FDA on the agency’s recent guidance for industry on community-acquired-bacterial pneumonia clinical trials. The Society applauded the agency’s efforts to make clinical trials more feasible and offered recommendations to improve the guidance.