<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_384"
                     title="Few Surprises in Warning Signs for Infections in Kids (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/tb/18276?impressionId=1265796599229"
                     
      &lt;p&gt;Cyanosis, rapid breathing, poor peripheral perfusion, and petechial rash are red flags for serious childhood infection, a systematic review affirmed.&lt;/p&gt;
&lt;p&gt;Parental concern and physician instinct were also strong warning signs of serious illness in children in developed countries, but only in the primary care setting, Ann Van den Bruel, MD, of Katholieke Universiteit Leuven, Belgium, and colleagues reported online in &lt;em&gt;The Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The researchers also looked for &quot;rule-out&quot; signs, with a negative likelihood ratio of less than 0.2, but found none, highlighting the difficulties facing clinicians.&lt;/p&gt;
&lt;p&gt;Nor were any of the red flags consistent at presentation in serious cases, suggesting that effective safeguards are needed, they said.&lt;/p&gt;
&lt;p&gt;&quot;There should be more emphasis on parental concern in the diagnostic process,&quot; they wrote. &quot;However, we now need to identify the level of risk at which clinical action should be taken.&quot;&lt;/p&gt;
&lt;p&gt;While the warning signs will be no surprise to most physicians, the poor evidence base should be shocking, Martin Dawes, MBBS, MD, of McGill University in Montreal, wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;Only one of the 30 studies included in the review was conducted in a primary setting, but that&apos;s the most common environment in which sick children are seen, he said.&lt;/p&gt;
&lt;p&gt;&quot;What is clear is that in 2010 we do not know how to effectively recognize or rule out severe disease in ill children and, what is more, we do not even have a cohesive national or even global research strategy to address this problem,&quot; he wrote.&lt;/p&gt;
&lt;p&gt;The World Health Organization has sponsored large scale studies to address these issues in resource-poor countries, Van den Bruel&apos;s group noted, but the range of diseases is different in developed countries, so that evidence doesn&apos;t generalize.&lt;/p&gt;
&lt;p&gt;The investigators reviewed studies of diagnostic accuracy or prediction rules for serious infection (mostly sepsis, bacteremia, meningitis, pneumonia, or urinary tract infection) in otherwise healthy children ages 1 month to 18 years, using features assessable in an ambulatory care setting.&lt;/p&gt;
&lt;p&gt;The studies had generally modest quality and were predominantly conducted in emergency departments.&lt;/p&gt;
&lt;p&gt;Fever of 104&amp;#176;F or more increased the likelihood of serious infection from 0.8% to 5.0% in the lowest prevalence setting.&lt;/p&gt;
&lt;p&gt;In the one primary care study where there was a low prevalence of disease (under 5%), a parent&apos;s concern that her child&apos;s illness was different from prior illnesses had a positive likelihood ratio of 14.40 for serious infection, while the clinician&apos;s instinct that something is wrong had a 23.50 positive likelihood ratio.&lt;/p&gt;
&lt;p&gt;Other predictors of the presence of serious infection and their positive likelihood ratios were: &lt;ul&gt; &lt;li&gt;Turning blue (52.20)&lt;/li&gt; &lt;li&gt;Poor peripheral circulation (4.71 to 38.80 in the low-to-intermediate prevalence setting and 2.39 to 17.70 in the high-prevalence setting)&lt;/li&gt; &lt;li&gt;Rapid breathing (1.26 to 9.78)&lt;/li&gt; &lt;li&gt;Shortness of breath (1.11 to 9.30)&lt;/li&gt; &lt;li&gt;Meningeal irritation (2.57 to 275)&lt;/li&gt; &lt;li&gt;Petechial rash (6.18 to 83.70)&lt;/li&gt; &lt;li&gt;Unconsciousness (19.80 to 155)&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Changed crying pattern was a potential red flag in a low prevalence setting with a positive likelihood ratio of 10.50, but actually was associated with reduced probability of serious disease in a high prevalence setting (positive likelihood ratio 0.49 to 0.74).&lt;/p&gt;
&lt;p&gt;Sending all children with a probability of serious infection greater than 5% to the hospital would overwhelm services there, although parents would &quot;probably be unhappy to know that their child was not being referred despite a 1 in 20 risk of serious infection,&quot; the researchers observed.&lt;/p&gt;
&lt;p&gt;The most widely studied decision rule, the Yale Observation Scale, had disappointingly little value in confirming the possibility of serious infection, they noted (positive likelihood ratio range 1.10 to 6.70, negative likelihood ratio range 0.16 to 0.97).&lt;/p&gt;
&lt;p&gt;The best performing clinical decision rule for excluding serious infection was a five-stage system with a negative likelihood ratio of 0.04.&lt;/p&gt;
&lt;p&gt;The researchers noted that these findings largely fit with those identified by WHO for developing countries, with the exception of difficulty feeding. The current review found that wasn&apos;t helpful in developed areas.&lt;/p&gt;
&lt;p&gt;They cautioned that their review was only as strong as the studies included and was particularly limited by the paucity of studies in the initial presentation primary care setting and difficulties of knowing how reproducible the findings were.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was funded by the Health Technology Assessment and National Institute for Health Research National School for Primary Care Research. The researchers reported no conflicts of interest.&lt;/p&gt;&lt;p&gt;Dawes reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_379"
                     title="Novel Compound Blocks Many Viruses (CME/CE)"
                     score="0.012"
                     href="http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/tb/18273?impressionId=1265796599229"
                     
      A search for a drug that would block one virus has yielded a compound that prevents infection by viral pathogens ranging from Ebola to HIV, researchers said.&lt;br&gt;
&lt;br&gt;The compound, dubbed LJ001, emerged when researchers were hunting for ways to block infection by Nipah virus, an emerging zoonosis identified only in 1999, according to Benhur Lee, MD, of the University of California Los Angeles, and colleagues.&lt;br&gt;
&lt;br&gt;Testing showed that it renders an entire class of viruses  --  those surrounded by a lipid envelope  --  unable to infect cells, they wrote online in &lt;em&gt;Proceedings of the National Academy of Sciences&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;In the lab, the compound blocked infection by more than 20 viruses, including Ebola, HIV, hepatitis C, influenza A, West Nile, Rift Valley fever, and yellow fever virus.&lt;/p&gt;
&lt;p&gt;That property raises the possibility that the compound  --  or others like it  --  can act as broad-spectrum antivirals, Lee and colleagues wrote.&lt;/p&gt;
&lt;p&gt;But clinical experts cautioned that the study is only a first step. &quot;There are a lot of ifs,&quot; said Aaron Glatt, MD, of New Island Hospital in Bethpage, N.Y., speaking for the Infectious Diseases Society of America.&lt;/p&gt;
&lt;p&gt;&quot;This is a very interesting  --  and very early  --  study,&quot; Glatt told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The study &quot;revved my motor, I liked reading it,&quot; said William Schaffner, MD, of Vanderbilt University in Nashville. But like Glatt, he told &lt;em&gt;MedPage Today&lt;/em&gt; he wants to see much more research.&lt;/p&gt;
&lt;p&gt;&quot;There are lots of starts and relatively few finishes&quot; in the hunt for new medications, Schaffner said. The next step, he said, is for the investigators to show the compound  --  or one of its chemical relatives  --  is safe and effective in animals.&lt;/p&gt;
&lt;p&gt;Lee and colleagues reported that the compound did not appear to have any overt toxicity in mice, other than a slight elevation in cholesterol levels.&lt;/p&gt;
&lt;p&gt;But a challenge test  --  in which mice were infected with Ebola after being treated once daily with the compound  --  did not show any benefit, they said.&lt;/p&gt;
&lt;p&gt;Analysis of the compound&apos;s behavior in serum showed that it did not reach a useful level for two hours after injection and that its half-life in the body was only about four hours.&lt;/p&gt;
&lt;p&gt;&quot;Clearly, once-daily dosing was not sufficient to maintain therapeutic steady-state plasma concentrations of LJ001,&quot; Lee and colleagues wrote.&lt;/p&gt;
&lt;p&gt;The compound appears to act by disrupting the lipid envelope of the virus, while leaving the viral particles themselves largely intact, the researchers said. The disruption prevents the virus from entering its target cells.&lt;/p&gt;
&lt;p&gt;Once the researchers realized LJ001 targeted enveloped viruses, &quot;we followed up and determined that it was somehow changing the lipid envelope to prevent the fusion of the virus particle with the host cell,&quot; according to Alexander Freiberg, PhD, director of the University of Texas Medical Branch at Galveston laboratory where much of the cell-culture work was done, as well as mouse studies with Ebola and Rift Valley fever viruses.&lt;/p&gt;
&lt;p&gt;&quot;It was, of course, very exciting,&quot; he told &lt;em&gt;MedPage Today&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The researchers showed that viruses  --  once treated with the compound  --  could not infect cells. The concentration needed to yield the effect was roughly similar for all of the tested viruses, they found.&lt;/p&gt;
&lt;p&gt;In a parallel experiment, the researchers treated viral particles of Rift Valley fever virus or a mouse version of Ebola-Zaire virus with LJ001 and then administered them to mice.&lt;/p&gt;
&lt;p&gt;Viral particles treated with inert compounds led to death from the viruses with a few days, the researchers said, but 100% of animals given the treated Rift Valley virus survived the challenge as did 80% of those given the LJ001-treated Ebola.&lt;/p&gt;
&lt;p&gt;Although the compound appears to perturb the viral membrane, it had no effect on cell-cell fusion, perhaps because mammalian cells can repair lesions to their membranes while viruses cannot, the researchers said.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the NIH, the UCLA Center for Aids Research, the Burroughs Wellcome Fund, the March of Dimes, the California NanoSystems Institute (R.D.), a UCLA Microbial Pathogenesis Training Grant, a Warsaw Fellowship Endowment, and a Rheumatology Training Grant.&lt;/p&gt;&lt;p&gt;The authors said they had no disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_310"
                     title="Rotavirus Vaccine Effective in Third World Nations (CME/CE)"
                     score="0.006"
                     href="http://www.medpagetoday.com/Pediatrics/Vaccines/tb/18174?impressionId=1265796599229"
                     
      &lt;p&gt;Vaccination against rotavirus appears to be highly effective in reducing death and serious gastrointestinal disease among young children in developing countries, according to two&lt;strong&gt; &lt;/strong&gt;publications in the Jan. 28 &lt;em&gt;New England Journal of Medicine.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;In Malawi and South Africa, a vaccination program significantly reduced infantile gastroenteritis associated with the pathogen, researchers said.&lt;/p&gt;
&lt;p&gt;In a companion paper, investigators reported that a rotavirus vaccination program in Mexico appears to have been the cause of a marked reduction in deaths from diarrhea among young children.&lt;/p&gt;
&lt;p&gt;Taken together, the two studies suggest that physicians have &quot;another powerful weapon&quot; to help prevent death from diarrhea among young children, according to Mathuram Santosham, MD, of the Johns Hopkins Bloomberg School of Public Health, who was not involved in the research.&lt;/p&gt;
&lt;p&gt;&quot;It is time to act to combat the 1.8 million unnecessary deaths from diarrhea that continue to occur each year,&quot; Santosham wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;Two oral, live attenuated vaccines against rotavirus have been shown to prevent the associated gastroenteritis  --  GlaxoSmithKline&apos;s Rotarix and Merck&apos;s RotaTeq, according to Nigel Cunliffe, MBChB, PhD, of the University of Liverpool in England, and colleagues.&lt;/p&gt;
&lt;p&gt;But trials of those drugs mainly occurred in more developed countries, the researchers noted, so the World Health Organization  --  fearing they might not work as well among the very poor  --  suggested additional trials in the Third World.&lt;/p&gt;
&lt;p&gt;To fill the knowledge gap, Cunliffe and colleagues conducted a randomized, placebo-controlled trial in Malawi and South Africa, enrolling 4,939 healthy infants.&lt;/p&gt;
&lt;p&gt;They were assigned to get either three doses of placebo (at six, 10, and 14 weeks of age), two doses of the Rotarix vaccine and one of placebo to maintain blinding, or three doses of the vaccine.&lt;/p&gt;
&lt;p&gt;The researchers found: &lt;ul&gt; &lt;li&gt;Severe gastroenteritis caused by rotavirus occurred in 4.9% of the placebo group and in 1.9% of the pooled vaccine group, yielding a vaccine efficacy of 61.2%, which was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001. &lt;/li&gt; &lt;li&gt;Vaccine efficacy was lower in Malawi than in South Africa  --  49.4% versus 76.9%. But the vaccine prevented more cases of severe rotavirus gastroenteritis in Malawi  --  6.7 cases prevented per 100 infants vaccinated yearly versus 4.2.&lt;/li&gt; &lt;li&gt;Efficacy against all-cause severe gastroenteritis was 30.2%.&lt;/li&gt; &lt;li&gt;At least one serious adverse event was reported in 9.7% of the vaccinated infants and 11.5% of the placebo group, but only three were judged to be related to the vaccine.&lt;/li&gt; &lt;li&gt;There was a single case of intussusception -- a 6-month-old child in the three-dose vaccine group, who recovered after bowel resection.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The findings have led WHO to recommend that rotavirus vaccination be included in all national immunization programs, Cunliffe and colleagues noted.&lt;/p&gt;
&lt;p&gt;Mexico phased in rotavirus vaccination over slightly more than a year, from February 2006 through May 2007, according to Manish Patel, MD, of the CDC, and colleagues.&lt;/p&gt;
&lt;p&gt;To estimate the effect of the program, Patel and colleagues compared annual deaths from diarrhea before and after the immunization program began.&lt;/p&gt;
&lt;p&gt;Over the four years before the program started, the median annual number of diarrhea-related deaths among children younger than five was 1,793, the researchers found, for a mortality rate of 18.1 deaths per 100,000.&lt;/p&gt;
&lt;p&gt;In 2008, by contrast, there were 1,118 deaths, a reduction of 765, which yielded a mortality rate of 11.8 per 100,000 children, they reported in the journal.&lt;/p&gt;
&lt;p&gt;The rate reduction of 35% was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001, Patel and colleagues said.&lt;/p&gt;
&lt;p&gt;The findings come with some caveats, the researchers said. Among them: &lt;ul&gt; &lt;li&gt;It was not possible to pin down the reduction in deaths attributable to vaccination because precise vaccine coverage information is lacking. &lt;/li&gt; &lt;li&gt;Other changes, such as hygiene improvements, might also have affected the trend.&lt;/li&gt; &lt;li&gt;Because of difficulty obtaining fecal specimens, it wasn&apos;t possible to study trends in rotavirus deaths specifically.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;While the studies suggests that rotavirus vaccination would prevent much disease and many deaths, there are obstacles to introducing the vaccine to poorer countries, Santosham noted in the editorial.&lt;/p&gt;
&lt;p&gt;A key obstacle, he said, is that the vaccine requires more refrigeration  --  so-called &quot;cold-chain&quot; storage  --  than typical childhood vaccines.&lt;/p&gt;
&lt;p&gt;Also problematic, he said, is the current recommendation that the vaccines be given early in life to avoid age-dependent occurrence of intussusception, which led to an earlier vaccine being taken off the market.&lt;/p&gt;
&lt;p&gt;In many of the poorest countries, on-time vaccination is rare, which may impede the use of a rotavirus vaccine unless the time window for administration can be opened wider, he said.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The African study was supported by GlaxoSmithKline and the PATH Rotavirus Vaccine Program, a collaboration with the World Health Organization and the CDC with support from the Global Alliance for Vaccines and Immunization (GAVI). Cunliffe reported financial links with Sanofi Pasteur and GlaxoSmithKline.&lt;/p&gt;&lt;p&gt;For the Mexican study, the researchers did not report any external support or any conflicts.&lt;/p&gt;&lt;p&gt;Santosham reported financial links with GlaxoSmithKline and Merck, both of which make rotavirus vaccines.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_277"
                     title="Liver Cell Culture System Might Test New HCV Drugs (CME/CE)"
                     score="0.004"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/18133?impressionId=1265796599229"
                     
      &lt;p&gt;Researchers say they can now grow liver cells that maintain their functions long enough to test potential treatments for hepatitis C.&lt;/p&gt;
&lt;p&gt;The method uses so-called &quot;micropatterned co-cultures&quot; of primary human hepatocytes and supportive stroma, according to Sangeeta N. Bhatia, MD, PhD, of MIT, and colleagues.&lt;/p&gt;
&lt;p&gt;The co-cultures were able to support the entire life cycle of hepatitis C, including infection and replication, Bhatia and colleagues reported online in the &lt;em&gt;Proceedings of the National Academy of Sciences&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Coupled with reporter systems, the co-cultures have &quot;potential as a high-throughput platform for simultaneous assessment of in vitro efficacy and toxicity&quot; of antiviral drugs, the researchers said.&lt;/p&gt;
&lt;p&gt;The lack of such a system has been a roadblock to testing potential treatments for the virus, which affects 130 million people around the world, the researchers noted in the journal.&lt;/p&gt;
&lt;p&gt;Recently, they added, researchers have been able to propagate the virus in human hepatoma cells, but those cells, among other issues, proliferate abnormally and have disturbed gene expression.&lt;/p&gt;
&lt;p&gt;To overcome those obstacles, the researchers turned to primary hepatocytes, which would make a better test system, except that they are notoriously hard to maintain in culture.&lt;/p&gt;
&lt;p&gt;To form the co-cultures, Bhatia and colleagues seeded multi-well plates with human hepatocytes, followed several hours later by murine fibroblasts.&lt;/p&gt;
&lt;p&gt;&quot;If you just put cells on a surface in an unorganized way, they lose their function very quickly,&quot; Bhatia said in a statement. &quot;If you specify which cells sit next to each other, you can extend the lifetime of the cells and help them maintain their function.&quot;&lt;/p&gt;
&lt;p&gt;In a series of experiments, Bhatia and colleagues found:&lt;ul&gt; &lt;li&gt;Pseudoparticles bearing the hepatitis C glycoproteins E1 and E2 were able to infect between 1% and 3% of the hepatocytes, but did not infect the fibroblasts.&lt;/li&gt; &lt;li&gt;A hepatitis C virus modified to express a fluorescent protein persistently replicated over a two-week period.&lt;/li&gt; &lt;li&gt;Infectious virus was found in the co-culture supernatant from four through 12 days after initial infection.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The researchers also tested some possible therapeutics, including antibodies against viral entry factors and viral protease inhibitors, and were able to show effects on replication of hepatitis C.&lt;/p&gt;
&lt;p&gt;They were also able to test two or more drugs simultaneously to show the feasibility of combination drug studies using the system.&lt;/p&gt;
&lt;p&gt;Although the system is &quot;an important step forward,&quot; Bhatia and colleagues said, the co-cultures have some limitations, including the relatively inefficient uptake of virus.&lt;/p&gt;
&lt;p&gt;But they concluded that the co-cultures have the potential to be a &quot;highly valuable system for studies of (hepatitis C) biology.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;This study had support from the Greenberg Medical Research Institute, the Ellison Medical Foundation, the Starr Foundation, the Ronald A. Shellow Memorial Fund, the Richard Salomon Family Foundation, and the NIH. The researchers said they had no conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_216"
                     title="Novel Treatment Cuts Recurrence of &lt;em&gt;C. difficile&lt;/em&gt; (CME/CE)"
                     score="-0.001"
                     href="http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/tb/18067?impressionId=1265796599229"
                     
      &lt;p&gt;Adding two investigational monoclonal antibodies to standard antibiotics reduced the rate of recurrent &lt;em&gt;Clostridium difficile &lt;/em&gt;infection, a phase II randomized controlled trial showed.&lt;/p&gt;
&lt;p&gt;Patients who received a single infusion with the two monoclonal antibodies were significantly less likely to have a recurrence through 84 days of follow-up than those who received placebo (7% versus 25%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001), according to Israel Lowy, MD, PhD, of Medarex in Princeton, N.J., and colleagues.&lt;/p&gt;
&lt;p&gt;Adverse events occurred at similar rates in the two groups, the researchers reported in the Jan. 21 &lt;em&gt;New England Journal of Medicine.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;Medarex is a subsidiary of Bristol-Myers Squibb focused on developing fully human antibody-based therapies.&lt;/p&gt;
&lt;p&gt;&quot;The trial results are impressive,&quot; Lorraine Kyne, MD, MPH, of University College Dublin, wrote in an accompanying editorial.&lt;/p&gt;
&lt;p&gt;Although monoclonal antibodies probably would not be used as first-line treatment, she said, &quot;this novel nonantibiotic approach to secondary prevention is likely to offer hope to physicians and patients battling &lt;em&gt;C. difficile&lt;/em&gt; infection.&quot;&lt;/p&gt;
&lt;p&gt;Agreeing was Neil Fishman, MD, of the University of Pennsylvania, who called the findings &quot;very encouraging and very exciting&quot; in an interview.&lt;/p&gt;
&lt;p&gt;However, he noted that the safety of the treatment would have to be established in a much higher number of patients.&lt;/p&gt;
&lt;p&gt;The proper place for the antibody therapy in the management of &lt;em&gt;C. difficile&lt;/em&gt; needs to be established in future studies as well, said Fishman, who is also chair of the antimicrobial resistance work group for the Infectious Diseases Society of America.&lt;/p&gt;
&lt;p&gt;Whether it should be administered during a first episode or at first recurrence is an open question, he said, and the answer will depend both on phase III results and cost, which tends to be high for monoclonal antibody therapies.&lt;/p&gt;
&lt;p&gt;Still, he said, &quot;All disclaimers aside, I think this is a very significant, important study and an important new development in the management of &lt;em&gt;C. difficile&lt;/em&gt;.&quot;&lt;/p&gt;
&lt;p&gt;Lowy&apos;s group wrote in the journal that new therapies are needed to manage &lt;em&gt;C. difficile&lt;/em&gt;, which is increasing in prevalence and severity.&lt;/p&gt;
&lt;p&gt;Some 15% to 30% of patients will have a recurrence despite antibiotic treatment, which itself puts patients at risk for &lt;em&gt;C. difficile&lt;/em&gt; diarrhea or colitis. Broad-spectrum antibiotics knock the infection down but do not allow for the re-establishment of normal bowel flora.&lt;/p&gt;
&lt;p&gt;In addition, a hypervirulent strain  --  called BI/NAP1/027 --  has emerged in several large, deadly outbreaks in the U.S., Canada, and Europe. (See &lt;a href=&quot;http://www.medpagetoday.com/InfectiousDisease/PublicHealth/2254&quot; mce_href=&quot;http://www.medpagetoday.com/InfectiousDisease/PublicHealth/2254&quot; target=&quot;_blank&quot;&gt;Virulent Strain of &lt;em&gt;C. Difficile&lt;/em&gt; Called Cause of Diarrhea Outbreaks&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;The two fully human, monoclonal antibodies evaluated by Lowy&apos;s group  --  one each against &lt;em&gt;C. difficile&lt;/em&gt; toxins A (CDA1) and B (CDB1)  --  showed efficacy in a hamster model and safety in healthy people.&lt;/p&gt;
&lt;p&gt;To further establish safety and efficacy, the researchers enrolled 200 patients with &lt;em&gt;C. difficile&lt;/em&gt; infection at 30 sites in the U.S. and Canada and randomized half to receive the antibodies and half to placebo.&lt;/p&gt;
&lt;p&gt;The antibodies were given together in a single infusion, both at a dose of 10 mg/kg.&lt;/p&gt;
&lt;p&gt;All patients were also receiving either metronidazole or vancomycin.&lt;/p&gt;
&lt;p&gt;In the antibody group, all cases of recurrence within 84 days of infusion occurred in patients who had been hospitalized during their initial episode.&lt;/p&gt;
&lt;p&gt;Echoing the primary finding, the rate of recurrence was significantly lower following the antibody infusion among the subgroup of patients who had had more than one previous episode of &lt;em&gt;C. difficile&lt;/em&gt; infection (7% versus 38%, &lt;em&gt;P&lt;/em&gt;=0.006).&lt;/p&gt;
&lt;p&gt;The recurrence rate also tended to be lower in the antibody group among patients who had the epidemic BI/NAP1/027 strain (8% versus 32%), although the difference did not reach statistical significance (&lt;em&gt;P&lt;/em&gt;=0.06).&lt;/p&gt;
&lt;p&gt;During the initial episode, the antibody treatment did not shorten the length of hospitalization or the time to resolution or severity of diarrhea compared with placebo.&lt;/p&gt;
&lt;p&gt;The antibodies were not immunogenic.&lt;/p&gt;
&lt;p&gt;Safety from the monoclonal antibody infusion was not a concern. Adverse events during infusion or within the next two hours occurred in 15 patients in the antibody group and 10 in the placebo group. All were mild to moderate, with headache the most common.&lt;/p&gt;
&lt;p&gt;During follow-up, at least one serious adverse event was reported by 18 patients in the antibody group and 28 in the placebo group, a difference that was not statistically significant (&lt;em&gt;P&lt;/em&gt;=0.09).&lt;/p&gt;
&lt;p&gt;There were 15 deaths during the study  --  seven in the antibody group and eight in the placebo group. None was attributed to the study drug.&lt;/p&gt;
&lt;p&gt;Lowy stressed that larger studies are needed to confirm the findings.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by MassBiologics and Medarex, which employs two of the study authors.&lt;/p&gt;&lt;p&gt;Lowy and one of his co-authors reported being employees of Medarex and having an equity interest in the company. Lowy reported being named as a co-inventor on relevant patents with all rights or royalties assigned to Medarex and having an equity interest in Merck. His co-authors reported being named as co-inventors on relevant patents and sharing a partial interest in them, and having relationships with MassBiologics, Medarex, Robert Michael Associates, ViroPharma, GOJO Industries, Salix, Schering-Plough, Cepheid, Merck, TheraDoc, Optimer, and Genzyme.&lt;/p&gt;&lt;p&gt;Kyne reported receiving salary support from a Clinician Scientist Award from the Health Research Board, Ireland.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
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