IDSA News - June 2014
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SHEA, IDSA Release Updated Guidance on CLABSI Prevention
With an estimated 41,000 cases occurring in U.S. hospitals, central-line associated bloodstream infections (CLABSI) pose a dangerous threat to vulnerable patients, causing increased length of hospital stay and risk of mortality and contributing to an increase in healthcare costs of up to an additional $39,000 per episode. In a collaborative effort, led by the Society for Healthcare Epidemiology of America (SHEA), IDSA, the American Hospital Association, the Association for Professionals in Infection Control and Epidemiology, and The Joint Commission have released new practical recommendations to assist acute care hospitals in implementing and prioritizing efforts to prevent such infections.
The guidance, to be published in the July issue of Infection Control and Hospital Epidemiology (ICHE), includes a special section on implementation, emphasizing engagement with healthcare personnel and the sharing of data with employees on the frontlines to track prevention progress. Implementation recommendations include:
“There is no shortage of guidelines and recommendations to prevent CLABSI, including those from government, public health and professional organizations. But translating this evidence into practice, while challenging, is critically important,” said Leonard Mermel, DO, ScM, co-lead author of the guidelines with Jonas Marschall, MD. “We’ve included examples of successful implementation approaches and references to published examples that can be adapted and adopted by hospitals.”
- engaging both hospital frontline staff and senior leadership in the process of an outcome improvement plan,
- educating healthcare personnel involved in the insertion and care of central lines through multiple teaching strategies to best engage diverse learners,
- executing best practices by standardizing the care process to help increase staff compliance, and
- evaluating the impact of strategies with feedback provided to all personnel with the goals for improvement clearly and frequently articulated.
The new practice recommendations are part of Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2014 Updates. Guidance on surgical site infections, central-line associated urinary tract infections, Clostridium difficile, and methicillin-resistant Staphylococcus aureus (MRSA) infections have been published thus far in ICHE. A total of seven compendium articles will be published in the May through August issues including guidance on strategies to prevent, and ventilator-associated pneumonia, and an article focused on hand hygiene improvement strategies.
CDC Releases New Guidelines for HIV Testing
The U.S. Centers for Disease Control and Prevention (CDC) issued new guidelines for HIV testing on June 26 to yield more accurate, fewer indeterminate and faster results. The guidelines, “Laboratory testing for the Diagnosis of HIV Infection,” are available here and mark what the agency is calling “a new era in HIV testing.”
The new testing strategy no longer includes the Western blot, a first generation confirmatory test that, while long considered the gold standard for HIV diagnosis, has been surpassed by tests that can yield results as many as 25 days sooner, and accurately diagnose HIV-2 infection. While HIV-2 infection is uncommon in the United States, the CDC notes that its accurate diagnosis is essential for effective first-line treatment.
The CDC emphasizes that no test or testing strategy can be completely accurate in all cases of HIV infection and that inconsistent or conflicting test results should be investigated with follow-up testing on newly collected specimens.
For more information, read the CDC’s letter to providers.
CMS to Cover HCV Screening
The Centers for Medicare and Medicaid Services (CMS) has determined that screening for HCV is reasonable and necessary for the prevention or early detection of the illness and therefore will be covered under Medicare Part A or Part B under the following criteria:
Further details on the CMS coverage determination can be found here.
New Resource Helps ID Specialists Prove Their Value
Two new videos along with PowerPoint presentations have been added to the Value of the ID Specialists’ Toolkit to help IDSA members inform hospital administrators, payors, and others about the invaluable, cost-saving services ID clinicians provide. The videos provide an overview of the critical value of the infectious diseases specialist as reported in the IDSA-Avalere study published in Clinical Infectious Diseases and infectious disease strategies to limit hospitalization and reduce risk.
Please visit the Value of ID Specialists’ Toolkit (member login required) to see the multiple resources available to enhance the value of the ID specialist.
IDSA Continues Efforts to Advance AR Policy
There have been several developments over the past month relating to IDSA’s public policy agenda on antimicrobial resistance.
IDSA Sponsors Congressional Briefing
Danny Benjamin, MD, MPH, PhD, of IDSA’s Antimicrobial Resistance Committee presented at a congressional briefing on June 19 on behalf of the Society. The briefing, titled “Antimicrobial Marketplace Conference,” was co-sponsored by IDSA and the Antibiotic Innovation Alliance (AIA) and included speakers from medicine, industry, the Food and Drug Administration (FDA), and congressional Reps. Peter Roskam (R-IL), Danny Davis (D-IL), Phil Gingrey (R-GA) and Gene Green (D-TX). Reps Gingrey and Green are sponsors of the Antibiotic Development to Advance Patient Treatment (ADAPT) Act, which IDSA supports. Dr. Benjamin’s presentation offered the patient perspective and outlined IDSA’s priorities for combatting AR.
Two New Antibiotics Approved by FDA
FDA has approved tedizolid phosphate (Cubist’s Sivextro) to treat adults with acute bacterial skin and skin structure infections (ABSSSI) caused by certain susceptible bacteria, including Staphylococcus aureus (including methicillin-resistant strains (MRSA) and methicillin-susceptible strains), various Streptococcus species, and Enterococcus faecalis. The new drug is the second new antibacterial drug approved by the FDA in the past month to treat ABSSSI. The agency approved dalbavancin (Durata Therapeutics’ Dalvance) in late May, also to treat patients with ABSSSI caused by Staphylococcus aureus and various Streptococcus species. Both drugs count toward IDSA’s “10x’20” campaign for 10 new antibiotics by the year 2020. IDSA is pleased that these new drugs are available, and that pharmaceutical companies are active in the antibiotics market; however, there remains a tremendous unmet need for novel antibiotics that target Gram-negative bacteria.
AMA Approves IDSA Resolution on Antibiotic Use in Food Animals
IDSA submitted a resolution to the American Medical Association (AMA) House of Delegates (HOD) in support of banning the use of medically important antibiotics in food-producing animals for growth promotion, requiring veterinary oversight of antibiotic prescription and use, and improving surveillance and data collection of antibiotic use in agriculture. The resolution was approved as submitted at AMA’s meeting in Chicago on June 9. Michael Butera, MD, IDSA’s delegate to the HOD, led the effort with support from IDSA’s Public Health Committee and staff.
Also see “21st Century Cures Initiative” in this issue of IDSA News.
HIVMA Advocacy Day 2014
HIVMA Leaders Weigh in with Key Policy Makers
HIVMA Board Member, Melanie Thompson, MD, meets with Rep. John Lewis
HIVMA leaders met with White House officials, members of Congress, and key congressional staff this month to support funding for HIV care and prevention programs, as well as a robust budget for the National Institutes of Health (NIH) and global health programs.
While in Washington, DC for their Board meeting, the HIVMA leaders met with Sen. Cory Booker (D-NJ), and Reps. John Lewis (D-GA) and David Price (D-NC), as well as staffers from more than 30 congressional offices. In addition, they met with White House Office of Management and Budget examiners for NIH and HIV/AIDS accounts. In meetings such as these, HIVMA leaders have the opportunity to develop relationships with key staff as well as communicate the importance of HIV and ID issues.
With much at stake for key federally funded infectious diseases and other health programs in the FY2015 appropriations process and beyond, IDSA and HIVMA need members to join and support the Society’s advocacy efforts by weighing in with your legislators today.
You can also join the growing list of your colleagues who have signed up for the IDSA/HIVMA Membership Advocacy Program (MAP) (log in to My IDSA and click on the Advocacy tab). MAP members support the Society’s advocacy work by contacting members of Congress or talking to the media about ID priorities.
If you would like to meet with your congressional members when you are in Washington, IDSA and HIVMA staff are happy to assist. Please contact HIVMA Policy Officer Kim Miller at email@example.com or IDSA Director of Government Relations, Jonathan Nurse at firstname.lastname@example.org).
World Health Assembly Resolution on Hepatitis Calls for Syringe Exchange and Universal Access
Affordable treatment, syringe programs, and universal access to HIV prevention, treatment and care were among the recommendations in the World Health Assembly resolution on hepatitis. A post from Science Speaks, the blog of the Center on Global Health covered the resolution recommendations.
More from Science Speaks:
A president’s proposal to cut funding for global TB programs, and flat-line funding for international HIV responses overrode global health access advocates urgings to increase budgeting for the world’s two biggest infectious disease killers when the Senate State Foreign Operations Subcommittee produced its funding bill.
When a diverse multi-lingual city where high-rise buildings surround a sprawling slum became an epicenter of drug-resistant tuberculosis, the health department couldn’t tackle it alone, Mumbai’s TB officer recounted.
IDSA to Launch New Mentorship Program at IDWeek 2014
IDSA is launching the IDWeek 2014 Mentorship Program to create an opportunity for medical students, residents, and fellows enrolled in U.S. programs to closely interact with leaders in their respective areas of investigation or career interest. The ultimate goal is to foster careers in ID. The program committee is seeking mentees and mentors to participate in this exciting new program.
Participants will attend a Mentorship Program lunch on October 8 at IDWeek, will attend at least one IDWeek session with their mentor or mentee, and will participate together in networking opportunities during the meeting. To learn more about the IDWeek Mentorship program and apply to become a mentor or a mentee, please visit the IDWeek site.
Adamkova, Vaclava, MD
Bachmann, Lawrence, MD
Beck, Anne, RN
Billauer, Barbara, DrPH
Cervantes, Anna, MD
Daley, Jessica, PharmD
Dias, Carolina, MD, MS
Foster, Dona, PhD
Higgins, Lynn, PA-C
Remtulla, Shahileen, PharmD
Rogge, Kathryn, MSN
Sasso, Michael, MD
Singhal, Tanu, MD
Torres, Sylvia, PharmD
Trivedi, Prashant, MD
Trivedi, Arti, MD
Whitney, Janet, DO
Wittke, Frederick, MD, PhD
Alhujailan, Ghanem, ChB, MBBS
Luke, David, PharmD
Sitnitskaya, Yekaterina, MD
Surana, Neeraj, MD, PhD
Sutton, Sarah, MD
Wolf, Lucas, MD
Al-Tarawneh, Mohammed, MD
Boswell, Erin, MD, MSc
Cheng, Lucy, MD
Chow, Jeremy, MD
DeMatteo, Christina, DO
Fenire, Mahmoud, MD
Gupta, Sakshee, PhD
Guzman, Luis, MD
Jain, Sachin, MD, MPH
Kodiyan Plakkal, Rosy, MD
Opardija, Almira, MD
Patterson, Benjamin, MD
Ramaiah, Arunachalam, PhD
Silwal, Adwait, MD
Veltman, Jennifer, MD
Walldorf, Jenny, MD
Shadchehr, Ali, DO
Terico, Adrienne, PharmD
Callahan, Patrick, MD
Furlong, Kayla, MS
Haas, Luke, DO
Members on the Move
HIVMA member Sally Hodder, MD, professor of medicine at Rutgers Medical School, has been named director and principal investigator of the West Virginia Clinical and Translational Science Institute. In addition, Dr. Hodder will be a professor in the West Virginia School of Medicine Section of Infectious Diseases.
Are you a member on the move? Do you know someone who is? Contact Jennifer Morales at email@example.com so we can announce it to our membership.
President's Message: ID Specialists Should Take a Stand
By Joel Gallant, MD, MPH, Chair, HIV Medicine Association
This month, IDSA President Barbara Murray, MD, FIDSA, invites a view from HIVMA Chair Joel Gallant, MD, MPH about recent legislative actions in Uganda to criminalize homosexuality and HIV transmission. He urges infectious diseases and HIV physicians to take a stand against these efforts and advocate for ethical and scientifically sound public health policy.
In the wake of President Yoweri Museveni’s signing of Uganda’s Anti-Homosexuality Act, which introduced a sentence of life in prison for “aggravated homosexuality” and criminalized support of gay individuals, including by health care providers, I worked with members of HIVMA to write President Obama requesting that he respond to the legislation with meaningful action. The letter was signed by nearly 1,000 HIV health care providers, and well received among infectious disease colleagues except for one. The exception was a physician member of both the IDSA and HIVMA who wrote to defend Museveni’s right to sign the legislation, considering it an appropriate response to Uganda’s HIV epidemic.
In fact, criminalization of homosexuality has been shown to be a barrier to effective HIV prevention for gay men. As infectious disease and HIV physicians, we have a responsibility to respond to measures that violate human rights and medical ethics and that endanger public health, and I submitted an editorial to Infectious Diseases News to share my views.
The Uganda parliament has since passed the even more objectionable HIV and AIDS Prevention and Control Act, which is awaiting president Museveni’s signature. This bill would criminalize HIV transmission and attempted transmission and would mandate HIV testing and treatment in pregnant women, at the risk imprisonment. While the Anti-Homosexuality law has already impeded the access of gay and lesbian Ugandans to critical health care services, the signing of the HIV criminalization bill by the President would even further impair efforts to address Uganda’s growing HIV epidemic. Many countries already have anti-gay or anti-HIV laws, and other sub-Saharan countries are now attempting to follow Uganda’s lead. In Nigeria, a similar law is already affecting health care access, and other African leaders are lining up to enact similar legislation.
Sadly, the U.S. is not a role model for Uganda or other counties. We also criminalize risk behavior at the expense of public health and the rights of U.S. citizens. Thirty-two states have HIV criminalization laws, and people with HIV are serving time in U.S. prisons for the crime of consensual sex with disclosure of HIV status in which no transmission occurred.
It is our duty to advocate ethical and scientifically sound public health policy here at home and abroad. HIVMA and IDSA’s Center for Global Health Policy recently wrote to President Obama expressing our concern regarding the law, and Ken Mayer, MD, FIDSA, co-chair of the Center, published an editorial in The Hill supporting the International Human Rights Defense Act of 2014 that was recently introduced by Sen. Edward Markey (D-MA) to combat homophobia globally.
Please urge your senator to support the bill by becoming a co-sponsor and look for other opportunities from HIVMA and IDSA to take a stand against these laws that undercut basic human rights and threaten our ability to turn the tide on the global HIV pandemic.
New IDSA Guideline Covers Skin and Soft Tissue Infections
An updated guideline for the diagnosis and management of skin and soft tissue infections (SSTI) provides guidance to help physicians make the correct diagnosis, establish the source and cause, and determine the severity of the infection.
IDSA has released an updated guideline for the diagnosis and management of skin and soft tissue infections (SSTI), which provides guidance to help physicians make the correct diagnosis, establish the source and cause, and determine the severity of the infection. While antibiotics are life-saving drugs for many types of SSTIs, they should only be given when needed and the updated guidelines will help physicians know when they are appropriate to use.
The number of skin and soft tissue infections has skyrocketed due to the spread of methicillin-resistant Staphylococcus aureus (MRSA), but many are minor and either heal on their own or are treated easily with antibiotics. The guidelines will assist in making treatment determinations.
“SSTI is a very broad category and its diagnosis and treatment can be extremely complicated depending on many factors, from the symptoms, to the patient’s health, to the type of bacteria causing it,” said Dennis L. Stevens, MD, PhD, FIDSA, lead author of the guidelines and chief of the Infectious Diseases Section of the Veterans Affairs Medical Center, Boise, Id.
The guidelines contain a chart to help physicians quickly diagnose and treat the SSTI, determine whether the infection is mild, moderate or severe, and recommend appropriate treatment. In addition, these guidelines are the only source for extensive recommendations for treating SSTIs in immunocompromised patients, including those with HIV/AIDS or who have had an organ transplant.
A 10-member guidelines panel comprised of SSTI experts from around the country reviewed hundreds of scientific studies, papers and presentations. In addition to Dr. Stevens, the panel included: Alan L. Bisno, MD, FIDSA; Henry F. Chambers, MD, FIDSA; E. Patchen Dellinger, MD, FIDSA; Ellie J.C. Goldstein, MD, FIDSA; Sherwood L. Gorbach, MD, FIDSA; Jan V. Hirschmann, MD; Sheldon Kaplan, MD, FIDSA; Jose G. Montoya, MD, FIDSA; and James C. Wade, MD, FIDSA.
21st Century Cures Initiative
Congressional Effort Aims to Foster Development of New Drugs and Diagnostics
A recently announced Congressional initiative focuses on accelerating the discovery, development, and delivery of promising new treatments to patients. IDSA is working with the lawmakers to bring the infectious disease perspective to the table, emphasizing strategies for spurring the development of new antibiotics and rapid diagnostic tools.
Key members of Congress are focusing their attention on policy proposals to speed patient access to new therapies. U.S. Reps. Fred Upton (R-MI) and Diana DeGette (D-CO) recently announced their 21st Century Cures Initiative aimed at accelerating the discovery, development, and delivery of promising new treatments to patients. IDSA is working with the lawmakers to bring the infectious disease perspective to the table, emphasizing strategies for spurring the development of new antibiotics and rapid diagnostic tools.
IDSA responded to the Initiative’s first white paper with details on the economic and regulatory obstacles to research and development (R&D) of new antibiotics and rapid infectious disease diagnostics. The Society supports several policy proposals including:
IDSA also promoted policies recommended in its 2013 “Better Tests, Better Care” paper, including establishing a biorepository to help foster diagnostic development, and funding outcomes research to demonstrate the impact of diagnostics on patient care and encourage the appropriate use of antibiotics.
- The Antibiotic Development to Advance Patient Treatment (ADAPT) Act, which would create a new approval pathway at the Food and Drug Administration in which companies could use smaller clinical trials to study new antibacterial or antifungal drugs that treat serious or life-threatening infections for which there is an unmet medical need. Companies would receive approval for the limited population in most need of these therapies,
The Developing Innovative Strategies for Antimicrobial Resistance Microorganisms (DISARM) Act, which addresses prevention, surveillance, and R&D,
Tax credits for antibiotics and rapid diagnostics proposals,
Public and private partnerships, and
- Increased funding for research through the National Institute for Allergy and Infectious Diseases (NIAID), Biomedical Advanced Research and Development Authority (BARDA) and other federal agencies.
The second white paper sought input on recommendations made in the 2012 President’s Council of Advisors on Science and Technology (PCAST) Report on drug development. IDSA responded, again using this opportunity to highlight its antimicrobial drug incentives proposals.
Lastly, the third white paper sought input from a patient perspective regarding what treatments are most urgently needed and how the federal government can help spur their development. Because there are no large, highly organized patient organizations representing individuals with multidrug-resistant organisms, IDSA responded on behalf of the many patients its members treat. This response highlighted patient stories and again made the compelling case for urgently needed new antimicrobial drugs.
Countdown to IDWeek 2014
Program Has Much to Offer From Bench to Bedside
IDWeek 2014 will feature comprehensive, cutting-edge and scientifically rigorous content from bench to bedside, with lots of networking and career development opportunities. Don’t miss the July 25 deadline for early registration discounts.
IDWeek 2014 is only four months away! The Program Committee has been working hard to create the most comprehensive, cutting-edge and scientifically rigorous content on everything from bench to bedside regarding infectious diseases. From the Opening Plenary, “Resource-Limited Health Care Issues” featuring global health leaders Jeremy Farrar, MD, PhD from Wellcome Trust and Linda-Gail Bekker, MBChB, DTMH, DCH, FCP(SA), PhD, from the Desmond Tutu HIV Centre to the cutting-edge Closing Plenary, “Frontiers in Infectious Disease Diagnostics” that will include presentations on molecular diagnostics–state of the science, whole genome sequencing and a wrap up of how next generation diagnostics can be used to improve the public’s health--there will be something for everyone at IDWeek 2014.
Over the week-long program, there are over 100 sessions from antimicrobial stewardship to zoonosis. Perennial favorites will return again including: “Clinical Controversies,” “What’s Hot in HIV and ID,” and “Challenging Cases in Pediatric ID, HIV, Tropical Medicine and Clinical ID.” There are over 25 early morning meet-the-professor sessions, 27 oral abstract sessions, 11 interactive sessions and over 1,000 posters will be on display. Back again this year, “Posters in the Park” will be held on Friday evening along with the four societies’ business meetings. Enjoy selected posters in a relaxed reception atmosphere with young investigators presenting their novel research.
There is also plenty that is new this year including timely sessions on obesity and infectious disease, infectious disease in natural disasters, immunization in pregnancy, and uncommon presentations of common syndromes. A “Careers in ID” session will focus on what lies ahead for the medical student, fellow or resident planning to specialize in infectious disease. Also, IDWeek will be launching a pilot mentorship program. Fellows, residents and students enrolled in U.S. programs will be paired with experienced ID leaders in their respective areas of investigation or career interest to attend sessions together and facilitate networking opportunities.
There will also be several pre-meeting workshops to consider attending. These include: the “Andriole ID Board Review Course,” “HCV Treatment Options,” “Antimicrobial Stewardship,” “TB Workshop,” two “Fellows Day Workshops”--one pediatric and one general adult ID--and two “Maintenance of Certification Workshops.” Sign up early for the workshops as space is limited!
This is just a small sampling of what IDWeek 2014 has to offer. See more of the programming through the interactive program accessible on line at www.idweek.org. There you can search for sessions by topic, day, track and faculty. Map out your schedule in advance to ensure you don’t miss sessions important to you. If you haven’t registered yet, now is the time. Discounted early registration ends July 25.
New for IDWeek 2014 is a Career Networking Event
Thursday, October 9, 5:30 p.m. – 7:30p.m.
Don’t miss out on this opportunity to meet and speak with hiring representatives from dozens of companies across the country. Participating companies will be representing a variety of practice types and career opportunities, with positions ranging from novice to experienced clinicians, all looking to hire infectious diseases specialists. Save time and register in advance so you can directly enter the career fair upon your arrival by clicking here.
Abstracts to be Published in OFID
IDWeek 2014 abstracts will be published as an online supplement to Open Forum Infectious Diseases (OFID), the new open access journal from IDSA. They will be permanently archived as part of the journal and will be accessible to all journal readers, not only meeting attendees or Society members. Abstracts will also be available in the IDWeek Interactive Program, and in the official IDWeek app for iPhone and Android.
We look forward to an exceptional program this year and hope you will join us in Philadelphia!
The program committee congratulates IDSA and PIDS member, David J. Witt, MD, winner of the free IDWeek Registration for completing the Needs Assessment Survey.
Rotavirus Vaccine in the NICU: Is it Safe?; Infection with Phenotypically Drug-Susceptible and MDR TB Increases the Risk for Poor Clinical Outcomes; Once-Weekly Dalbavancin Versus Daily Conventional Therapy for Skin Infections; PK/PD of β-lactams in ICU Patients: Are Standard Dosing Regimens Adequate?; Cytomegalovirus Antiviral Drug Resistance: Is Viral Load Predictive?
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, FIDSA, in each issue of Clinical Infectious Diseases.
Rotavirus Vaccine in the NICU: Is it Safe?In 2009, the Advisory Committee on Immunization Practices (ACIP) updated its recommendations regarding administration of rotavirus vaccine. In that update, the maximum age for the first dose of the vaccine was raised to 14 weeks and six days. Given the risk of viral shedding and potential horizontal transmission to other inpatients, the ACIP maintained its recommendation for preterm infants that rotavirus vaccine be given at the time of discharge from the neonatal intensive care unit (NICU).
Reviewed by Terri Stillwell, MD
In the case of extremely premature infants and those with complex congenital medical conditions, hospitalization can be prolonged, with nearly one-fourth of patients remaining hospitalized at 14 weeks and six days of life, thus making them ineligible for rotavirus vaccine under current recommendations. A recent article in Pediatrics addresses the safety of rotavirus vaccine administration in the NICU setting. The institution in the study routinely administered rotavirus vaccine if an infant was receiving other scheduled two-month vaccinations and was tolerating enteral feeds.
During the study time period, 96 patients received rotavirus vaccine while still in the NICU. A majority of those patients (76 percent) were either asymptomatic or symptomatic but unchanged from baseline after receiving the vaccine. Twenty-four percent had changes in their clinical baseline post-vaccination, none of which were attributed to rotavirus vaccine.
As a comparator, 801 unvaccinated patients, hospitalized in the same geographic location as the vaccinated patients, were monitored for clinical changes. Only 10 patients (1 percent) exhibited gastrointestinal symptoms within 15 days of their neighbor receiving the vaccine. Upon further review, it was determined that all 10 patients had other medical reasons for their clinical change.
Despite the limitation that rotavirus testing was not routinely performed in these patients, the study suggests that the risk of post-vaccine shedding may not be as great as previously thought. Further studies are needed to address this issue and the potential use of rotavirus vaccine in infants in this setting.
(Monk et al. Pediatrics. 2014;133(6): e1555 -e1560.)
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Infection with Phenotypically Drug-Susceptible and MDR TB Increases the Risk for Poor Clinical Outcomes
Reviewed by Michael T. Melia, MD
A minority of patients with tuberculosis are concurrently infected with drug-susceptible and drug-resistant strains of the organism. Much about such individuals remains unknown, including the pathogenesis of infection with organisms of different drug susceptibilities, optimal therapeutic regimens, and whether there are differences in clinical outcomes. To help address this last point, investigators conducted a retrospective cohort study of 475 patients with multidrug-resistant (MDR) tuberculosis in Botswana; their findings appear in a recent issue of The Journal of Infectious Diseases.
Phenotypic heterogeneity in drug-susceptibility test (DST) results was defined as the recovery of isoniazid- and rifampicin-susceptible M. tuberculosis within three months of treatment initiation for MDR tuberculosis. Outcomes were classified as “good” (cure or treatment completion) or “poor” (treatment failure, treatment default, or death). Time to culture-conversion was also studied. There were no baseline between-group differences in bacillary burden, prevalence of extrapulmonary tuberculosis, number of effective drugs in the treatment regimen, or HIV infection status.Thirty-three (7 percent) of the patients had heterogeneity in phenotypic DST results. Nineteen of these 33 (58 percent) had poor outcomes, as compared with 106 of 442 (24 percent) patients without such heterogeneity (P <0.001). This difference was driven by (and only significant among) HIV-infected patients (unadjusted HR 3.4; 95 percent CI, 1.8-6.4). HIV-infected patients also had significantly longer times to culture-conversion, and nearly half of HIV-infected patients with phenotypic DST heterogeneity did not achieve culture-conversion, as compared with 15 percent of patients without phenotypic DST heterogeneity.
These intriguing results beg a number of questions, including ones about surveillance for phenotypic DST heterogeneity, particularly among HIV-infected persons, and ones about optimal treatment, such as the inclusion of isoniazid and/or rifampicin in the medication combination for such patients. Implications include not only individual patient health but, given the longer times to culture conversion among HIV-infected patients with phenotypic DST heterogeneity, public health as well.
(Zetola et al. J Infect Dis. 2014;209(11):1754-63.)
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Once-Weekly Dalbavancin Versus Daily Conventional Therapy for Skin Infections
Reviewed by George R. Thompson III, MD
Bacterial skin and skin-structure infections are among the most common reasons for adult hospitalizations in the United States. These infections are primarily caused by Staphylococcus aureus and streptococcal spp. The emergence of methicillin-resistant S. aureus is problematic due to the toxicity of currently available agents, development of antibiotic resistance, or the need for daily intravenous treatment.
In the June 5 issue of The New England Journal of Medicine, researchers report the results of a double-blind, double-dummy, multicenter randomized trial comparing intravenous dalbavancin (a lipoglycopeptide with a long plasma half-life and activity against Gram-positive pathogens) on days one and eight to vancomycin intravenously for at least three days followed by linezolid in the treatment of acute bacterial skin and skin-structure infections. The primary outcome of interest, an early clinical response at 48-72 hours, was no different between treatment groups, with a response observed in the dalbavancin group (79.7 percent) no different than that of the vancomycin/linezolid group (79.8 percent). The secondary end-point of response at the end of therapy was also no different between groups: dalbavancin (90.7 percent) vs. vancomycin/linezolid (92.1 percent).
Adverse events were more common in the vancomycin/linezolid group, although these were primarily limited to nausea, diarrhea, and pruritus.
Dalbavancin may be a welcome addition to the fight against Gram-positive infections, and the possibility of once-weekly dosing offers a considerable advantage over currently available agents. However, pricing has not yet been released, and the potential for the development of resistance with continued exposure to subtherapeutic levels has not yet been assessed.
(Boucher et al. New Engl J Med. 2014;370(23):2169-2179.)
Back to topPK/PD of β-lactams in ICU Patients: Are Standard Dosing Regimens Adequate?
Reviewed by Christopher J. Bruno, MD
In a multicenter, prospective study of ICU patients published in the April 15 issue of Clinical Infectious Diseases, researchers sought to examine the pharmacokinetics (PK) and pharmacodynamics (PD) of β-lactam antibiotics in critically ill patients and correlate established PK/PD determinants of efficacy with clinical outcomes.
Patients treated with β-lactams had blood antibiotic levels measured half way through—and at the end of—a dosing interval. The percent of patients in which free drug levels were maintained above the minimum inhibitory concentration (MIC) of the infecting organism for 50 percent and 100 percent of the dosing interval (50 percent T>MIC, 100 percent T>MIC) were calculated. These parameters were then correlated with a positive clinical outcome, defined as completion of the treatment course without change or addition of antibiotic therapy for 48 hours after completion.
Of 248 patients treated, 16 percent did not achieve 50 percent T>MIC. These patients were 32 percent less likely to have a positive clinical outcome (OR, 0.68 [95 percent CI, 0.52-0.91]; P=0.009). Not surprisingly, patients treated with intermittent bolus dosing (67 percent) were less likely than those receiving prolonged infusion dosing to achieve 50 percent T>MIC (80 percent vs. 93 percent). In a multivariate regression analysis, 50 percent T>MIC and 100 percent T>MIC were significantly associated with clinical outcome (P<.05). Additional significant factors were disease severity.
Significant limitations were noted in an accompanying editorial. Most prominently, MIC data was not available for a significant number of patients, as only 73 percent had an organism recovered, of which only a third had MIC determined. For these patients, the “worst case scenario” was used: The highest European Committee on Antimicrobial Susceptibility Testing (EUCAST) MIC for all organisms for which that drug was active was used. This may have caused an overestimation of patients failing to achieve 50 percent T>MIC. Additionally, 62 percent of patients received combination antibiotic therapy, which may have influenced clinical outcome; results were not stratified on this basis.
Despite these limitations, this study raises questions about standard dosing regimens and adds interesting data on the PK/PD of β-lactams in critically ill patients, a topic that warrants further study.
(Roberts et al. Clin Infect Dis. 2014;58(8):1072-1083.)
Back to topCytomegalovirus Antiviral Drug Resistance: Is Viral Load Predictive?
Reviewed by Jennifer Brown, MD
Cytomegalovirus (CMV) disease causes significant morbidity and mortality in immunocompromised patients. Especially challenging is the management of patients who develop antiviral drug-resistant CMV. Nucleic acid amplification testing has improved CMV diagnosis and treatment; however, the characterization of drug-resistant CMV continues to evolve.
In a report recently published online in Transplant Infectious Diseases, researchers describe their genomic analysis of 570 CMV-positive plasma specimens. In this study, specimens submitted by physicians to a commercial reference laboratory for resistance testing were evaluated by nucleic acid sequence analysis. Overall, 28 UL97 and 43 UL54 mutations (all previously confirmed to confer antiviral drug resistance by marker transfer experiments) were included in the analysis. Associations between CMV viral loads and the presence of resistance mutations were examined.
Antiviral drug resistance mutations were detected in 176 of 570 specimens (30.9 percent). Within the 570 specimens, 17 and 29 different mutations were identified out of a total of 173 UL97 mutations and 69 UL54 mutations, respectively. The mean viral load for specimens without antiviral resistance was 3.92 log10 copies/mL (range, 1.72-6.99 log10 copies/mL) while that for specimens with any resistance mutation was 3.93 log10 copies/mL (range, 2.03-7.15 log10 copies/mL).
Statistically significant differences were not observed when viral loads were compared between groups without and with resistance mutations, including those with UL97 or UL54 mutations only or mutations in both. Likewise, there was no association between CMV viral load and the presence or absence of resistance mutations when paired specimens from a subset of patients (n=85) with multiple specimens (mean, 2.36 samples) were analyzed.
The study is limited by pre-selection bias and the lack of clinical data. However, this work does augment the current understanding of drug-resistant CMV and demonstrates that CMV viral load alone is not predictive of drug-resistant CMV.
(Kleiboeker et al. Transpl Infect Dis. 2014; published online June 5, 2014. doi: 10.1111/tid.12241.)
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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:
- Cefepime-Associated Neurotoxicity
- Travel as a Risk Factor for Antibiotic Resistance
- Orally Administered Trimethoprim-Sulfamethoxazole for Deep Staphylococcal Infections
- mec-Free MRSA