IDSA News - February 1, 2008
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Meeting on Key Issues in TB Drug Development
Open Forum 3 is the third in a series of two-day Open Forum meetings aiming to discuss key issues in tuberculosis (TB) drug development, with a special focus on regulatory affairs. The Forum will include sessions on the current global TB drug development portfolio, key issues in the critical path to TB drug registration, designing pivotal trials, conducting registration trials in high burden countries, challenges in TB drug development for resistant disease, and developing regimens containing multiple novel agents. These meetings are designed to bring together regulators, TB drug developers and other interested stakeholders such as TB care providers, public health policy-makers, and community advocates from both major industrialized and high burden countries.
The meeting is being organized and sponsored by Global Alliance for TB Drug Development (TB Alliance), the Bill & Melinda Gates Foundation, The Stop TB Partnership Working Group on New Drugs, and Treatment Action Group.
The meeting is supported in part by unrestricted educational grants from AstraZeneca, Bayer, GlaxoSmithKline and Johnson & Johnson/Tibotec.
Pre-registration is required and registration is free. For more information about this event and to register, please go to: http://www.tballiance.org/events/openforum3.php.
For inquiries, please contact the Conference Secretariat at email@example.com.
CDC Survey Shows Less Effective Flu Medications Still Used
A recent survey conducted by the Centers for Disease Control and Prevention (CDC) suggests that many primary care physicians (PCPs) prescribed amantadine and rimantadine last influenza season despite a warning about viral resistance. PCPs are also using the rapid antigen test more than any other influenza testing method, which CDC cautioned has low sensitivity.
The survey was sent out to several academic institutions and state health departments in CDC’s Emerging Infections Program. The PCPs were asked which influenza medications they prescribed and which test they used, if any, when evaluating patients with influenza-like illness.
According to CDC, about 25 percent of the PCPs surveyed still prescribed the influenza medicines amantadine and rimantadine. CDC warned in January 2006 that widespread resistance to these drugs had emerged among influenza A strains.
Oseltamivir (Tamiflu) was the most prescribed medication for influenza (87 percent). Zanamivir (Relenza) was the least prescribed medication (5.3 percent).
When the PCPs saw the need for an influenza test, the most frequently used method was the rapid antigen test., The second-most common method was viral culture, followed by a serologic test. Due to low sensitivity of the rapid antigen test, which can miss up to 30 percent of cases, CDC urges physicians to use clinical judgment when testing for influenza.
The survey was published in the January 25, 2008 Morbidity and Mortality Weekly Report (57(03);61-65).
EIN: Decolonize MRSA Patients or Not?
An Emerging Infections Network (EIN) member in Saudi Arabia asked whether he should attempt to decolonize a 53-year-old male patient with psoriasis carrying methicillin-resistant Staphylococcus aureus (MRSA). MRSA had once before been eradicated from the patient. His wife and five children were screened and also found to be carrying MRSA in their noses, although none had invasive disease. “Should we attempt to eradicate MRSA in everyone in the family?” the EIN member asked.
In general, respondents agreed eradication should not be attempted in this situation. Additional comments from respondents included:
Florida: I would not eradicate the MRSA from the patient or the family unless they are having an invasive procedure that compromises skin integrity…. The patient with psoriasis will likely be colonized as long as his skin disease is active since the numerous skin squames allow for a great niche for MRSA or MSSA colonization.
Also, if there are no active infections then decolonization is unnecessary since 25 percent of the world at any one time has MSSA colonization and 1 percent may have MRSA colonization. Over 50 percent of patients with psoriasis and chronic skin diseases will be colonized with MSSA or MRSA.
Minnesota: I would not. MRSA is quickly becoming part of the human mucosal niche just like MSSA is now. If you screen the family and eradicate the bug from them, what about their neighbors? School mates? Co-workers? The cat is out of the bag.
Tennessee: Mupirocin resistance is [a more] likely outcome than eradication of MRSA…. Hand washing and standard hygienic precautions are the watch words.
Quebec: Decolonization should only be considered in circumstances of recurrent CA-MRSA skin infections defined as two or more in 6 months.
If you choose to decolonize them, go all the way, with two sensitive oral systemic agents, 4 percent chlorhexidine baths daily, and nasal mupirocin tid for 7 days. Remember that pets (dogs/cats) may also carry MRSA in their nares as well. In the community setting, nothing assures you that the initial carrier will not bring it back from school or work in the future.
In my opinion, I think we have arrived in an era when we all have to live with MRSA and not worry about it so much unless we start showing signs of infection. I think that you should reassure him and only try to decolonize him and his family if they start to have symptomatic disease. For now they should just be aware of their status and should inform physicians when they present for infections.
Kentucky: I am using a skin survey after daily bathing on the patient and any household member with [skin and soft tissue infection (SSTI)] history. To any new "lesion" of any kind, topical triple antibiotic cream or ointment [over-the-counter] Neosporin in the US) is applied BID for three days or until all signs are resolved. The trick is getting them to bathe daily and take the time to comply with the survey and topical application, so I [give them] a diagram of the human [body] and ask them to mark the place(s) [with a lesion] on the diagram, put it up in the bathroom, and make a check by it each time they apply the topical. Only two have recurrent lesions and they admit to non-compliance with the survey until the lesions are quite painful. The series is not large enough for statistical significance yet, so please know it is more anecdotal experience currently; however, it has made my call backs from this population much better!
Health Alerts, Drug Approvals, Recalls, Adverse Events
IDSA offers two members-only e-mail services to inform subscribers about important infectious diseases information of immediate concern. The CDC HAN forwarding service relays Health Alert Network (HAN) messages from the Centers for Disease Control and Prevention (CDC) and is intended for members who do not receive these messages from other sources. The FDA Alert forwarding service e-mails ID-related messages from the Food and Drug Administration on label changes, adverse events, newly approved drugs, and other information on FDA-approved drugs and biologics. Recent alerts included:
CDC HAN Alert:
IDSA members may sign up for this service online.
In the IDSA Journals
PVL Not Necessary for Severe MRSA Infection
In the latest study on the clinical role of Panton-Valentine leukocidin (PVL) genes in methicillin-resistant Staphylococcus aureus (MRSA) infections, researchers in Canada studied isolates from 42 patients hospitalized with community-acquired USA400 MRSA. These patients were found to be infected with one of two subclones that were identical except for the presence or absence of PVL genes. Both were capable of causing severe illness. This evidence suggests PVL genes are not required for epidemic community transmission or severe infection. (Zhang et al., J Infect Dis. 2008;197:195–204. Also see editorial commentary by Gorwitz, J Infect Dis. 2008;197:179–182.)
CCR5 Deficiency Increases Human Susceptibility to Severe West Nile Virus and Tickborne Encephalitis Virus Infections
Two studies suggest those individuals with deletions in the CCR5 gene are at higher risk of symptomatic West Nile virus (WNV) infection (Lim et al., J Infect Dis. 2008;197:262-265) and tickborne encephalitis (Kindberg et al., J Infect Dis. 2008;197:266-269) than individuals who do not have these deletions. On the other hand, CCR5 deletions have been shown to reduce the risk of HIV infection. The new HIV entry inhibitor maraviroc works by blocking CCR5. Lim et al. hypothesize that CCR5 inhibitor therapy could increase rates of symptomatic (WNV) infection, though this has not been observed in patients to date. (Also see editorial commentary by Klein, J Infect Dis. 2008;197:183-186.)
Influenza Death Risk is Genetic
Death from influenza is a heritable risk, according to researchers studying a genealogic database of Utah residents dating back 100 years. Up to third-degree relatives of those who died from influenza were found to have an increased risk of dying from influenza as well. As a control, the researchers looked at relatives of the spouses of those who died from influenza, who would have experienced a similar environment. They found that relatives of spouses did not have as high a risk of death. (Albright et al., J Infect Dis. 2008;197:18–24. Also see editorial commentary by Mubareka and Palese, J Infect Dis. 2008;197:1–3.)
Utility of Guidelines in Preventing TB among Foreign-born Persons
In 2000, guidelines for targeted testing and treatment of latent tuberculosis (TB) infection in foreign-born persons residing in the United States were issued and were aggressively followed in San Francisco, California, but there was no subsequent decrease in the incidence of TB. A review of cases among foreign-born persons with TB in San Francisco during the period from 2002 to 2003 showed that only 38 percent of these cases were preventable if they adhered to the guidelines. Following the guidelines, though, will likely not significantly reduce the rate of TB among foreign-born persons residing in the United States. (Walter et al., Clin Infect Dis. 2008;46:103-106. Also see editorial commentary by Cain and MacKenzie, Clin Infect Dis. 2008;46:107-109.)
Influenza Vaccinations for Health Care Workers
Last year, several committees issued recommendations about the vaccination of health care workers to prevent transmission of influenza within health care facilities and to help prevent absenteeism among the workers. According to a survey of more than 400 members of the Infectious Diseases Society of America’s Emerging Infections Network, the rates of immunization at various institutions were 41 percent to 60 percent and were higher at institutions that required signed declination statements. Other effective elements of a successful vaccination campaign included making the vaccine free of charge, devoting adequate resources to vaccination efforts, and educating targeted groups of health care workers. (Polgreen et al., Clin Infect Dis. 2008;46:14-19.)
Pneumococcal Disease in the Era of PCV7
This study found that rates of invasive pneumococcal disease among Spanish children increased substantially after the 2002 introduction of 7-valent pneumococcal conjugate vaccine (PCV7), compared with rates during the period before the availability of the vaccine. The increased rates after 2002 were largely caused by non‐PCV7 serotypes. One might conclude that nature deeply resents vacuums. (Muñoz-Amagro et al., Clin Infect Dis. 2008;46:174–182. Also see editorial commentary by Moore and Whitney, Clin Infect Dis. 2008;46:183–185.)
More from the literature…
See the “In This Issue” section of the January 1 and January 15 issues of Clinical Infectious Diseases for summaries of other key articles.
For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, M.D., in each issue of Clinical Infectious Diseases.
- Antibiotic Lock Therapy
- Antibiotic Therapy in the Intensive Care Unit (ICU): A Life Sentence?
- Toxoplasmosis in the United States: A Bear Market
- Methicillin‐Resistant Staphylococcus aureus (MRSA): Quantifying the Problem
- A Primary Immunodeficiency in a Toll-Like Receptor (TLR) Predisposing to Herpes Simplex Virus (HSV) Encephalitis
- The Increased Virulence of West Nile Virus (WNV): Problem Solved?
Multidrug-resistant Staph Reported among MSM
The Annals of Internal Medicine last month reported an outbreak of a multi-drug resistant strain of virulent Staphylococcus aureus among men who have sex with men (MSM) in San Francisco and Boston. This USA300 strain is resistant to β-lactams, fluoroquinolones, tetracycline, macrolide,clindamycin, and mupirocin. The authors suggest the infection might have been transmitted sexually among MSM because it often was located on the buttocks, genitals, or perineum.
The authors acknowledge, however, they did not document specific sexual behaviors associated with the infection and note that MRSA infections in these regions also have been reported among heterosexuals. The key point regarding sexual transmission, said study co-author Kenneth Mayer, MD, FIDSA, is that this strain of multidrug-resistant USA300 “is being spread within a subgroup of the population who are likely to have the type of contact with each other that could disseminate it.” Isolated cases of this multidrug-resistant strain have been reported among heterosexuals, but the potential to spread more widely beyond MSM is currently unknown, he said. “The challenge is to get better data to give people a realistic sense of what are the necessary and sufficient conditions to amplify and spread the infection,” he added.
Regarding treatment, an editorial accompanying the article by authors at the Centers for Disease Control and Prevention, notes clinicians may opt for antibiotics based on a patient’s age, immunosuppression, severity of symptoms, or presence of fever, but “most uncomplicated MRSA skin infections respond well to drainage alone. It has not been established through controlled studies whether certain patients benefit from ancillary antimicrobial therapy.” The authors advise clinicians who opt for antimicrobials that this strain usually responds to trimethoprim-sulfamethoxazole; and even tetracycline-resistant strains usually respond to minocycline and doxycycline. However, clinicians should be aware of resistance to these and other agents since the strain contains a plasmid that can acquire additional resistance traits easily.
For clinicians, what’s important is “having the index of suspicion,” said Dr. Mayer. “Since not everyone volunteers their sexual history, and this infection is not limited to MSM, it’s important to remember there is more nasty staph out in the community. That means that if you start a more conventional antibiotic, just be sure to instruct the patient that if it’s not getting better between 24 and 48 hours to come back sooner rather than later.”
CMS Requires NPI on Claims Starting March 1
Beginning March 1, physicians submitting claims to the Centers for Medicare and Medicaid Services (CMS) must use their National Provider Identifier (NPI) numbers or their claims will be rejected.
CMS has been accepting legacy identification numbers, such as Unique Physician Identification Numbers (UPIN), or others during the transition to NPI, but as of March 1 claims must include NPIs in order to be processed.
Private plans are not required to switch until May 23, but William Rogers, MD, director of the CMS Physicians Regulatory Issues Team, told Part B News, “That date really means nothing to practices.” Even many private plans already are rejecting claims without NPIs.
More information on the NPI and how to get one is available on the billing and coding section of our website.
Europe Reports High Percentage of Oseltamivir-resistant Influenza Virus
European health officials have reported finding oseltamivir resistance in a surprisingly high percentage of H1N1 influenza virus isolates tested so far this season. The highest percentage came from a country where oseltamivir usage is low, suggesting the emergence of fit and transmissible oseltamivir-resistant viruses.
As of Feb. 14, 20 percent of H1N1 isolates (202 out of 987) had a mutation -- H274Y -- that confers resistance to oseltamivir. Norway reported the highest percentage of resistant H1N1 isolates -- 66 percent -- despite the fact that oseltamivir is infrequently used in Norway. France had the second-highest percentage, with 40 percent.
Last season, oseltamivir resistance was not detected in Europe; nor was it found in Japan, where the neuraminidase inhibitor is used more frequently. One percent of isolates tested in the United States last season were resistant.
“These viruses appear to have arisen without drug pressure,” said Arnold S. Monto, MD, FIDSA, founding director of the University of Michigan Bioterrorism Preparedness Initiative and a member of the IDSA Pandemic Influenza Task Force. “It is a surpriseand it is something that needs to be watched.”
Neuraminidase inhibitors, such as oseltamivir and zanamivir, have become the primary influenza antivirals as resistance to adamantane inhibitors has grown in recent years. Dr. Monto said experts were aware that adamantane-inhibitor resistance could develop relatively easily. “But we didn’t know that about the neuraminidase-inhibitor resistant strains. As a matter of fact, we thought that these resistant strains had some competitive disadvantage. One of the things that need to be done with these new resistant viruses is see how they have changed and whether this will persist,” said Dr. Monto. He also noted the oseltamivir-resistant strains are sensitive to zanamivir.
Dr. Monto observed the overall number of samples tested so far is small and the rates of resistance varied widely from country to country. These geographic variations may be real, he said, or, “It also may mean that we don’t have enough specimens that have been examined. We need more data.”
Resistance has not appeared in H3N2 or B strains of virus circulating this year, Dr. Monto said. And although H1N1 and the highly pathogenic H5N1 share the neuraminidase gene where the resistance-conferring H274Y mutation is located, there is no evidence that similar resistant, transmissible strains of H5N1 strains have emerged.
IDSA and other organizations have been recommending stockpiling of oseltamivir to prepare for an influenza pandemic. No changes in treatment recommendations have been made and Dr. Monto said it’s too soon to say whether any will be necessary. “It’s early days,” he said. “We need to better understand what’s going on here.” The U.S. national stockpile includes zanamivir as well.
His advice for now: stay tuned.
The latest information on H1N1 oseltamivir resistance is available online from WHO.
IDSA Policy & Advocacy Update
IDSA Opposes Anti-Thimerosal Legislation
IDSA continues to advocate at the state level against legislation banning the use of thimerosal in vaccines due to unfounded concerns about its link to autism. IDSA maintains there is no scientific evidence that thimerosal causes autism, and banning its use in vaccines would be exceptionally expensive and could result in limited vaccine quantities. The Society sent letters to legislators in New Hampshire, Oklahoma, Maryland, South Dakota, and Washington urging them to oppose anti-thimerosal legislation. All three letters are located on the IDSA website under “Legislative Letters” on the “State and Regional Societies Advocacy Efforts” page.
In a related story, IDSA expressed its disapproval of a new ABC drama portraying a link between vaccines and autism in a letter to Disney-ABC Television Group President Anne Sweeney.
Other recent policy & advocacy items include:
- IDSA issued a statement saying President Bush’s fiscal year 2009 budget proposal would leave infectious diseases programs “in shock.”
- IDSA joined the American Medical Association (AMA) and more than a dozen other specialty societies in proclaiming strong support for the Medicare Improvement Act of 2007 (H.R. 4992). If enacted, it would improve seniors' access to vaccines by shifting all preventive vaccines from Medicare Part D to Part B.
Welcome, New IDSA Members!
Bhardwaj, Nina, MD, PhD
Collins, Adriane, MD
Hennessy, Thomas, MD
Kircher, Lorence, MD
Nowbahar, Vahid, MD
Parta, Mark, MD
Perlroth, Joshua, MD
Teixeira Johnson, Lucileia, MD
Yuan, Wen, PhD
Vasquez, Emily, PA-C
Weiksner, Lizanne, PA-C
Akinyemi, Emmanuel, MD
Al Raiy, Basel, MD
Alkhatib, Mohammad, MD
Carpenter, Robert, DO
Desai, Shalini, MD
Kessler, Jason, MD
Khan, Shameen, DO
Naidu, Latasha, MD
Onunkwo, Charles, MD
Park, Sun, MD
Pereira, Marcus, MD
Rusieki, Ronald, MD
Salvani, Jerome Keith, MD
Sen, Ajanta, MD
Sharma, Rohini, MD
Sydnor, Emily, MD
Tran, Maryann, MD
Uhlemann, Anne-Catrin, MD, PhD