2009-2010 H1N1: What's New This Week -- January 4, 2010

Commentary by John G. Bartlett, MD

H1N1 and Vaccine Update
Influenza-like illnesses (ILIs) accounted for 3.2% of outpatient visits during week 51 that ended December 26. This is an increase from 2.3% a week ago.
All influenza A isolates during the week of December 20-26 were 2009 influenza A (H1N1). Analysis of recent strains showed that 99.7% are related to the H1N1 vaccine strain.
Vaccine for 2009 influenza A is now readily available in most places in the United States. The total number of doses available as of December 30, 2009 was 118 million doses. About half of the states now offer this vaccine to people who are not in the high-risk groups, and many states are now using pharmacies to facilitate distribution.
Resistance tests completed on 2445 strains of 2009 influenza A (H1N1) found that 38 (1.6%) were resistant to oseltamivir; 34 of 36 patients with resistant strains were from patients with documented exposure to oseltamivir.
The total number of pediatric deaths attributed to 2009 influenza A (H1N1) since August 20, 2009 is 225. Reviews of 106 of these cases indicate bacterial superinfection in 35 (33%) patients, including Streptococcus pneumoniae in 10 patients and Staphylococcus aureus in 10 patients.

Commentary. What does this mean for practitioners?

The second wave of H1N1 is resolving, although the total ILI reports for week 51 were higher than for week 50: Nationally we are nearly back to baseline rates of ILI.
There is now plenty of 2009 influenza A vaccine: In fact, the US Centers for Disease Control and Prevention (CDC) has launched a big promotional campaign to encourage vaccination.
What will happen in January-March 2010 when seasonal flu usually hits? No one knows, but there are 3 possibilities: (1) seasonal flu will circulate as usual, with influenza A (H1N1 and H3N2) plus influenza B; (2) seasonal flu will occur with the pandemic 2009 influenza (H1N1) strain predominating; or (3) no flu will occur. Of note, seasonal flu strains are not evolving much in the world. Thomas Freiden, MD, MPH, Director of the CDC, asked 12 world influenza experts to predict what is going to happen with regard to influenza. Half of the experts said that there would be a third wave of pandemic (H1N1) flu, and half claimed that there would not be a third wave. In the southern hemisphere where the winter season ended in September, the 2009 influenza A (H1N1) strain "pushed out seasonal flu," and thus far Europe and the United States are almost exclusively finding the pandemic strain. In previous influenza pandemics (1918, 1957, and 1968) the pandemic strain also dominated in flu season. However, no one is confident enough to predict what will happen, in large part because the influenza virus continues to defy predictions.

Should your patients still get vaccinated? The CDC estimates that about one sixth (15%) of the population of the United States has had influenza, meaning that 85% have not contracted it yet. Their recommendation is for vaccination for both seasonal and pandemic flu—a single dose of each at separate injection sites for people older than 9 years of age and 2 doses separated by 4 weeks for children 6 months to 9 years of age. The original priority groups are still the highest priority for vaccination. The assumptions here are that there will be a flu season, but we cannot predict the strain(s) that will be responsible for it. Only time will tell whether this is sage advice. Of interest, President Barack Obama, First Lady Michelle Obama, and daughters Malia (11 years) and Sasha (8 years) have all received the H1N1 vaccine. The president said he knows that the vaccine is safe.[3]
2009 H1N1 Flu Virus Outbreaks in Animals[4]
Reports from the American Veterinary Medicine Association summarize the available data on 2009 influenza A (H1N1) in domestic animals and livestock:
Cats: 11 cases (Pennsylvania-1, Oregon-6, Colorado-2, Utah-1, Iowa-1) have been reported to have influenza; 8 were virologically confirmed; 4 deaths have occurred; and in 6 cases a human source was identified. One cat was stated to have chronic sinusitis and was treated with oseltamivir, but subsequently died.
Ferrets: 13 cases reported (Nebraska-4, Oregon-9); 1 death.
Dogs: 1 case reported (New York). This dog recovered after 2 days of hospitalization. The Chinese press has also reported 2009 H1N1 in dogs.
Turkeys: An outbreak occurred in a Virginia flock following contact with a human case. A second outbreak occurred later on the same Virginia farm, and positive tests have been reported in turkeys with surveillance cultures in Illinois, Canada, and Chile.
Cheetahs: 4 cheetahs in a cluster of respiratory illnesses occurred in a California zoo. The animals presented with harsh coughs, tachypnea, and rough haircoats. One case was virologically confirmed. All animals recovered in 5-16 days.
Pigs: 12 outbreaks have been reported in Indiana and Minnesota in the United States as well as in Germany, England, Indonesia, Taiwan, Canada, Argentina, Singapore, Ireland, Norway, and Japan. The US Department of Agriculture (USDA) Agricultural Research Service has confirmed that meat tissue from infected pigs does not contain the virus at 3, 5, or 7 days after exposure, and pork is not considered a foodborne threat. The USDA has a conditional license for a 2009 H1N1 influenza vaccine for pigs.

Commentary. Most cases in pets have been associated with human index cases, and none of these cases were known to represent human disease following animal exposure. The obvious exception is the index case of pig-to-human transmission that occurred at some unknown time and place. Veterinarians maintain that this is a veterinary health issue and not a human health issue. Most of the pets presented with fever, cough, and lethargy. People with flu who have dogs, cats, or ferrets are advised to wash their hands, sneeze into their sleeves, and practice "social distancing" to protect pets. A diagnostic test for the H1N1 virus in pets is available from Innovative Diagnostics and Technologies (IDEXX) laboratories.
Virus of the Year: The Novel H1N1 Influenza[5]
For years, scientists have warned about a pandemic of influenza that might be similar to the 1918 Spanish flu pandemic that is considered the worst epidemic in recorded medical history with 50-100 million deaths, but:
It was supposed to come from Asia: Instead, it came from North America;
It was supposed to be a new strain like avian flu (H5N1): It was simply another form of H1N1;
It was supposed to be severe with high lethality: It was severe in some unpredictable populations, such as children and pregnant women, but overall mortality was only about 0.2%-0.04%; and
It was supposed to cause catastrophe: Instead, it caused confusion.
A Cluster of Oseltamivir-Resistant H1N1 Influenza Cases[6]
This report concerns 10 students in Vietnam who shared a 42-hour train journey. These students did not know each other prior to the journey, and none had known contact with a person with influenza prior to the journey. None of the students were symptomatic during the journey, but 7 developed influenza symptoms within 48 hours after the journey. All 7 of these students had positive reverse-transcriptase polymerase chain reaction (RT-PCR) tests for influenza A (H1N1), and all 7 strains had the H275Y substitution that confers resistance to oseltamivir. None of the students had previously received oseltamivir. Six of the 7 students were hospitalized for isolation and 1 student was isolated at home. No additional cases were identified from this cluster.

Commentary. During the 2008-2009 influenza season, a sudden development of oseltamivir resistance occurred in the seasonal influenza A (H1N1) strains, increasing resistance from <> 98% in most areas of the world, including the United States. This change in resistance pattern was unrelated to oseltamivir use. So far, > 98% of pandemic 2009 influenza A (H1N1) strains have been sensitive to oseltamivir, and nearly all resistant strains have been associated with prior oseltamivir use. This cluster of cases in Vietnam demonstrates how a dramatic change in oseltamivir sensitivity without oseltamivir use is possible, which explains the reason for close watching of the new pandemic strain.

Diagnostic Testing for 2009 Influenza A (H1N1) Virus in Hospitalized Patients[7]
RT-PCR is the most sensitive test;
The problem with rapid diagnostic tests and immunofluorescence assays is false-negative results;
The best specimens are nasopharyngeal swabs, aspirates or washes, or nasal and throat swabs tested as early in the infection as possible; and
Some patients with negative RT-PCR tests from nasopharyngeal specimens have had positive RT-PCR tests from endotracheal aspirates or bronchoalveolar lavage specimens.

Commentary. The last bulleted point above is relatively new and important information for clinicians. The pandemic strain of influenza binds to the lower airway cells, and this apparently accounts for positive endotracheal aspirates after the upper nasopharyngeal infection has cleared.
Clinical Features of the Initial Cases of 2009 Pandemic Influenza A (H1N1) Virus in China[8]
The study concerned 426 travelers with confirmed influenza who were quarantined in 61 hospitals in China. Cases were detected by thermal screening at airports and by contact tracing. The mean patient age was 24 years: Five percent were white; 43% had recently traveled to the United States; and 41% had airplane exposure. Results of interest include the following:
Of 56 million travelers screened
17,909 had fever and a respiratory illness
757 (14 per million) had influenza with the 2009 influenza A (H1N1) strain
Lab tests showed
C-reactive protein > 10 mg/L (31%)
Median CD4 count, 576 cells/µL
White blood cell (WBC) count > 10,000/mm3 (3%)
Mean WBC count, 3440/mm3
Total lymphocyte count, < 15,000/mm3 (68%)
Abnormal chest x-ray (5%) with "patchy infiltrates" in 12 of 14
Abnormal chest computed tomographic (CT) scan (7%)
Symptoms included
Fever (67%)
Cough (70%)
Sputum production (25%)
Sore throat (37%)
Diarrhea (3%)
Nausea (2%)
Viral shedding
Mean of 6 days by RT-PCR
Mean of 3 days after becoming afebrile
Longer with age < 14 years (odds ratio [OR] 1.94)
Longer with delayed oseltamivir treatment (> 48 hours after onset of symptoms [OR 4.5]).

Commentary. Extensive data of this type that are systematically collected in patients who are not very sick are difficult to find. Of note:
Viral shedding persisted an average of 3 days after the patients became afebrile;
Oseltamivir appeared to substantially reduce viral shedding if given within that 48-hour window after the onset of symptoms;
5% had patchy infiltrates on x-ray and 7% had abnormal chest CT scans;
Gastrointestinal symptoms were less common than reported in the US literature; and
Airport screening detected influenza in about 1 of 100,000 travelers.
Pediatric Hospitalizations Associated With 2009 Pandemic Influenza A (H1N1) in Argentina[9]
These investigators retrospectively reviewed the experience with 2009 H1N1 infections in 251 children from 6 pediatric hospitals in Buenos Aires. Highlights include the following:
42 of 251 children (17%) had respiratory syncytial virus coinfection;
Median patient age was 10 months, and 75% were ≤ 2 years of age and 60% were ≤ 1 year of age;
Oseltamivir was given within 48 hours of the onset of symptoms in only 11 of 251 (4%);
Suspected bacterial superinfection was present in 25 of 251 children (10%);
Intensive care unit admission was required in 41 (16%), mechanical ventilation in 42 (17%), and 13 died (5%);
Overall death rates in children were 10 times the rates in 2007: 2009, 1.1 of 100,000 children; 2008, 0 of 100,000 children; 2007, 0.1 of 100,000 children;
Death rate for infants < 1 year of age was 7.6 of 100,000; and
9 of 13 children (69%) who died had preexisting illnesses, especially asthma, chronic lung disease, or neurologic disease.
The investigators emphasized that this influenza was associated with an exceptionally high rate of respiratory failure and hypoxemic deaths in children, especially those < 1 year of age.

Commentary. Data from the United States showed that 2009 influenza A (H1N1) was responsible for an estimated 1090 deaths in children, far more than in in any of the 3 previous influenza seasons. This report from Argentina documents the same phenomenon—a 10-fold increase in mortality in children. The mortality rate in children <> 6 months of age, the need for vaccination among care providers of infants < 6 months of age, the importance of vaccine in pregnant women to protect both newborn and mother, and the importance of the new recommendations for oseltamivir in children.
H1N1 Influenza May Increase Maternal Deaths: Importance to Clinicians
A report of a study conducted in California[10] verified the high risk for severe disease among pregnant women and women who have just given birth who are infected with H1N1 influenza virus. Pregnant women accounted for nearly 10% of patients who have died or were hospitalized with H1N1 influenza.

Commentary. The major issues for clinical management of pregnant women with potential influenza are listed below:
Avoid delays in starting oseltamivir. Starting antiviral therapy more than 2 days after the onset of symptoms resulted in a 4.3-fold increase in mortality. In the women who died, the median length of time before oseltamivir was started was 6.5 days after the onset of symptoms.
Rapid tests for influenza are often falsely negative (38% false-negative rate), so antivirals need to be started on the basis of clinical features without reliance on the rapid test results.
Pregnancy is an acknowledged risk for bad outcome with influenza, but the 2009 influenza A (H1N1) has been unusually severe.
Pregnant women are a very high priority for vaccination and should be assured that this vaccine appears to be just as safe in pregnant women as in women who are not pregnant. The added benefit of vaccinating the mother is protection for her newborn infant in the 6 months between delivery and the time when the baby can be vaccinated.
Single Dose of H1N1 Vaccine Needed for Adults, 2 for Children
Randomized clinical trials of the safety and immunogenicity of pandemic H1N1 vaccines were recently conducted in the United States,[11] China,[12] and Hungary.[13] The new research confirms that a single dose of H1N1 vaccine is sufficient for adults, but not for many children.

Commentary. The new data have significance for practitioners. Influenza vaccine potency is determined by the serologic response rate that is conventionally defined as a hemagglutination titer of ≥ 1:40 at 21 days after vaccination. Response rates vary according to the antigen used, the dose, presence or absence of adjuvant (to boost the antigenic response), and the age of the recipient. These 3 trials support current US policy with regard to the following:
Response rates are good after single vaccine doses in persons > 9 years of age.
Children < 9 years of age require 2 doses, presumably because of lack of antigenic experience with flu and/or previous vaccine to this new strain.
The current policy was based on data in regard to the immunogenic response rates to vaccines without adjuvant. The decision was made for products in the United States to be unadjuvanted due to consumer concerns about the safety of adjuvants.
The bottom line is that the current policy is appropriate—a single dose for people > 9 years and 2 doses for children ≤ 9 years. The data are limited for seroresponse rates in high-priority groups in some studies, but most are not characterized by immunodeficiency so there is less concern that most of these groups would respond differently.
Sanofi Pasteur Recalls 800,000 Doses of Pediatric H1N1 Vaccine Due to Deficient Antigen Levels
Sanofi Pasteur recalled approximately 800,000 doses of its pediatric influenza A (H1N1) monovalent vaccine (single-dose, prefilled syringes) because antigen content was lower than required levels. The doses were part of 4 lots shipped in November and intended for children aged 6-35 months.

Commentary. Practitioners should be aware that:
The reduction in antigen in the recalled vaccine lots was modest, so children who received the vaccine probably had an antigenic response;
Revaccination of children vaccinated with recalled vaccine is not necessary; and
There are no safety issues with the recalled lots.
One 15-µg Dose of H1N1 Vaccine May Suffice in Infants and Children
In a study published in JAMA,[14] a single 15-µg dose of vaccine against the 2009 influenza A (H1N1) virus was safe and immunogenic in infants and children 6 months of age and older. The randomized, observer-blind, age-stratified, parallel-group study was conducted in Australia.

Commentary. The reported study has limitations, and the data may not be applicable to all vaccine products. The current US policy of giving 2 doses of vaccine to children 6 months to 9 years of age should continue.
H1N1 Vaccine to Be Distributed Soon to Countries That Need It
In early 2010, Azerbaijan, Afghanistan, and Mongolia will be the first 3 countries to receive H1N1 influenza vaccine from donations made by manufacturers to the World Health Organization (WHO). In response to requests by WHO to donate vaccine supplies, 6 manufacturers in 12 countries agreed to provide a total of 180 million vaccine doses. These will be distributed to 95 countries that need vaccines. Countries in the northern hemisphere are the first targets for vaccine distribution because H1N1 activity remains high in those areas.

Commentary. The primary responsibility of most governments is to protect its citizens. Thus, the countries that can afford to make or buy vaccine will use most of it for its own population. The policy of the United States has been to allocate10% of its vaccine supply to resource-limited countries. WHO plans to give each country enough vaccine to protect 10% of its population, with the first 2% targeted to healthcare workers. To put these figures into perspective, the current US vaccine supply is about 110 million doses, enough to vaccinate about 35% of the population. Total use to date is estimated at 60 million doses or about 20% of the US population.

Decolonizing Nasal Carriers May Reduce Surgical-Site Staphylococcus aureus Infections

Laurie Barclay, MD

January 6, 2010 — Rapid screening and decolonizing of Staphylococcus aureus nasal carriers on admission reduces hospital-acquired, surgical-site S. aureus infections, according to the results of a double-blind, placebo-controlled, multicenter trial reported in the January 7 issue of the New England Journal of Medicine.
"Nasal carriers of Staphylococcus aureus are at increased risk for health care–associated infections with this organism," write Lonneke G.M. Bode, MD, from Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues. "Decolonization of nasal and extranasal sites on hospital admission may reduce this risk."
The goal of the study was to determine whether using a real-time polymerase-chain-reaction (PCR) assay to rapidly identify S. aureus nasal carriers, followed by treatment with mupirocin nasal ointment and chlorhexidine soap, would lower the risk for hospital-associated S. aureus infection.
From October 2005 through June 2007, the investigators screened 6771 patients on admission and identified 1270 nasal swabs from 1251 patients that were positive for S. aureus. Of 917 of these patients enrolled in the intent-to-treat analysis, 808 (88.1%) underwent a surgical procedure.
All of the S. aureus strains identified with PCR assay were susceptible to methicillin and mupirocin. In the mupirocin-chlorhexidine group, 17 (3.4%) of 504 patients developed S. aureus infections vs 32 (7.7%) of 413 patients in the placebo group. Therefore, relative risk for infection was 0.42 (95% confidence interval [CI], 0.23 - 0.75).
For deep surgical-site infections, mupirocin-chlorhexidine treatment had an even greater effect (relative risk, 0.21; 95% CI, 0.07 - 0.62). All-cause in-hospital mortality rate did not differ significantly between groups. Compared with the mupirocin-chlorhexidine group, the placebo group had shorter time to onset of nosocomial infection (P = .005).
"The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission," the study authors write. "This intervention also significantly reduced the mean hospital stay by almost 2 days."
Limitations of this study include needed modification in the study design because of a perceived change in the overall cumulative incidence of S. aureus infections and difficulty making inferences about nonsurgical patients.
"Mupirocin and chlorhexidine are considered to be relatively safe," the study authors conclude. "However, since S. aureus strains can become resistant to mupirocin, we recommend restricting the use of this agent to known carriers who are at risk for infection."
In an accompanying editorial, Richard P. Wenzel, MD, from Virginia Commonwealth University in Richmond, discusses minimizing surgical-site infections, based on this study and a second study evaluating preoperative surgical scrubs.
"The weight of evidence suggests that chlorhexidine–alcohol should replace povidone–iodine as the standard for preoperative surgical scrubs," Dr. Wenzel writes. "The use of intranasal mupirocin and chlorhexidine baths for carriers of S. aureus who have been identified preoperatively by means of a real-time [PCR] assay could be reserved primarily for patients who are undergoing cardiac surgery, all patients receiving an implant, and all immunosuppressed surgical candidates. Currently, the incremental value of preoperative baths with chlorhexidine alone for all surgical patients is unclear, but this relatively straightforward procedure could be examined critically in future studies."

Grants from ZonMw, Mölnlycke Health Care (formerly Regent Medical), GlaxoSmithKline, Roche, bioMérieux, and 3M supported this study. Some of the study authors have disclosed various financial relationships with 3M, Wyeth, Destiny Pharma, Becton Dickinson, bioMérieux, Pfizer, Cardinal Health, JohnsonDiversey, Merck Sharp & Dohme, and/or Cepheid. Dr. Wenzel has received speaking fees from 3M and research funding and consultation fees from Pfizer.
N Engl J Med. 2010;362:9-17, 75-77.

Two Novel Cleaning Methods Remove Most Bacteria from Hospital Rooms

From Medscape Medical News

Barbara Boughton

September 23, 2009 (San Francisco, California) — Two novel methods for cleaning hospital rooms are not only easy to use, they are more effective than standard disinfection for removing hardy bacteria, researchers announced here at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
Results of 2 studies on new cleaning methods show that they can reduce bacteria, including hard-to-remove Clostridium difficile spores, by almost 90%, according to researchers. One method uses an automated ultraviolet (UV) radiation device, and the other uses ultramicrofiber cloths and mops containing a copper-based biocide. The cleaning system with ultramicrofiber cloths, mops, and copper biocide also has a preventive residual effect, protecting surfaces from bacteria for hours after cleaning, researchers said.
In the Mayday Hospital Cleaning study, British investigators from London compared standard cleaning with mops, chlorine, and water, and cleaning with ultramicrofiber mops and cloths with water or with a copper biocide. Sampling for bacteria was performed 1 hour before and 1 hour after cleaning at 10 different sites on 4 hospital wards. Each site was cleaned using each of the 3 different methods. The study took place over 12 weeks.
Results revealed that cleaning with the ultramicrofiber mops and cloths plus copper biocide removed 80% to 85% of bacteria, and the analysis indicated that both the ultramicrofiber material and biocide contributed to these results. The antibacterial effect of the copper biocide persisted for 23 hours after cleaning. The study confirms the ability of ultramicrofiber to more effectively remove dirt, but the copper biocide was needed for bacterial control, the authors said in their poster at ICAAC.
"Other studies have found that microfiber mops are better than cotton ones," said John Boyce, MD, chief of the Infectious Diseases Section at the Hospital of Saint Raphael and clinical professor of medicine at Yale University School of Medicine in New Haven, Connecticut. Dr. Boyce was not involved with the study.
"The authors are to be commended for documenting the effects of a new kind of disinfectant or biocide that can be used in healthcare settings that also has a residual antibacterial effect," he said. Dr. Boyce noted that other novel compounds with antibacterial effects are being investigated by different teams of researchers, including those that contain copper and silver.
In another study presented at ICAAC, researchers used an automated UV radiation device to decontaminate hospital rooms at the Cleveland Veterans Affairs (VA) Medical Center in Ohio, and analyzed its ability to remove troublesome bacteria, including C. difficile spores. The Tru-D device, manufactured by Lumalier in Memphis, Tennessee, uses UVC radiation for decontamination.
Tru-D reduced methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus bacteria by 89% and C. difficile spores by 83% in hospital rooms.
The Tru-D device was able to decontaminate all surfaces in 40 hospital rooms, including hard-to-clean surfaces such as the undersides of tables, said lead researcher Curtis Donskey, MD, chair of the Infection Control Committee at the Cleveland VA Medical Center. After testing, the researchers found that Tru-D cleaning removed all MRSA on the undersides of bedside tables, whereas 18% of sites tested after standard hospital cleaning remained contaminated with the bacteria.
C. difficile spores are especially challenging for hospital staff, since they can only be removed by soaking surfaces in bleach for 8 to 10 minutes, Dr. Donskey said in an interview with Medscape Infectious Diseases. The UV radiation device is computerized, and once placed in a room and turned on, can assess how much power is needed for decontamination by measuring the reflected UV radiation from surfaces in the room, Dr. Donskey said. It requires no special training to use. However, because the UV radiation produced can be dangerous to people, the device is placed in a closed, empty room, and operated with a remote control by housekeeping staff located outside the room. A sensor at the door turns the machine off if anyone enters the room.
Although the cost is steep, running from $75,000 to $100,000 per unit, it's inexpensive to operate; it requires no cleaning supplies and uses a small amount of electricity. Dr. Donskey has already put in a request for several units to the administration of the Cleveland VA Medical Center. The next step in his research is to incorporate the Tru-D into the standard cleaning routine of the housekeeping staff at the Center, and to assess how easy it is for "real world" housekeepers to use it as part of their daily routine.
UVC radiation is an exciting new technology for disinfecting patient rooms and contaminated surfaces in healthcare, said Luke Chen, MBBS, FRACP, assistant professor of medicine in the Division of Infectious Diseases at Duke University Medical Center in Durham, North Carolina. UVC technology has been used to disinfect water, to reduce food-borne microorganisms, and to purify air, he said, and is now being tested by the healthcare industry.
"UVC technology represents a major step forward for disinfection in hospitals and patient care areas," Dr. Chen explained. "The Tru-D device demonstrated consistency and rapidity in killing microorganisms." The safety profile in the study appeared to be good, but further research is needed to validate this finding, Dr. Chen said.
"There is potential to use this technology to rapidly clean and turn around patient rooms, clinic space, or waiting rooms," he added. "The technology could also be adapted for disinfection of surfaces of healthcare equipment, for example, monitoring devices, wheelchairs, and ventilators. Overall, I think technologies like this are versatile and are likely to be widely used."
Dr. Boyce noted that the advantages of the Tru-D device are that it is easy to employ and that it can reduce the number of positive bacterial cultures substantially. "It would be interesting to compare this device with other new methods for decontaminating hospital rooms," Dr. Boyce said.
In 2008, Dr. Boyce published a study on a disinfection system using vaporized hydrogen peroxide (Infect Control Hosp Epidemiol. 2008;29:723-729). "Our data so far indicate that it reduces contamination to virtually 0," he said. However, unlike the UV radiation device, the vaporized hydrogen peroxide system requires 4 to 6 hours to clean a room and operators with special training to manage it, Dr. Donskey said.
"The UV radiation device has the potential to be effective, faster, and less expensive to operate — a good supplement to bleach or more effective than bleach," he said.

Dr. Boyce reports being a consultant to Bioquell, 3M, Clorox, Advanced Sterilization Products, and Cardinal Health. Dr. Donskey and Dr. Chen have disclosed no relevant financial relationships.

49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstracts K-2107a and K-2107b. Presented September 15, 2009.

Authors and Disclosures
Journalist
Barbara Boughton
Barbara Boughton is a freelance writer for Medscape.

Las Creencias Religiosas se Debilitan por el Avance Científico

Yaiza Martínez

Si el conflicto entre conocimiento científico y creencias religiosas no ha sido tan importante en sí mismo, al menos hay cuatro fuentes de tensión entre ciencia y religión que sí que han sido relevantes.
Steven Weinberg, físico estadounidense ganador del Premio Nobel de física en 1979 por combinar el electromagnetismo y la fuerza nuclear débil en el Modelo electrodébil, escribe en un reciente artículo publicado por The New York Review of Books acerca del conflicto derivado de la expansión de la ciencia y el debilitamiento paralelo de las creencias religiosas.
Según Weinberg, la idea del conflicto entre ciencia y religión es antigua. Edward Gibbon, historiador británico del siglo XVIII, ya señaló que “el estudio de la naturaleza es el síntoma más seguro de una mente incrédula”.
Weinberg, por su parte, afirma que aunque la ciencia y la religión no sean del todo incompatibles –tal y como lo señalan científicos muy creyentes como Charles Townes o Francis Collins-, la confluencia de ambas ha ido debilitando gradualmente las creencias religiosas, especialmente en Occidente, donde la ciencia está más avanzada.
Cuatro fuentes de tensión
¿Cuáles son las causas de esta tensión? Para Weinberg, el hecho de que existan contradicciones entre los descubrimientos científicos y las doctrinas religiosas específicas no sería una de las causas. Estas contradicciones se han dado muchas veces a lo largo de las historia, y generalmente el conocimiento científico ha terminado siendo adoptado por las personas con mayor visión entre los grupos religiosos.
Pero si el conflicto entre conocimiento científico y creencias religiosas no ha sido tan importante en sí mismo, al menos hay cuatro fuentes de tensión entre ciencia y religión que sí que han sido relevantes.
La primera de ellas es el hecho de que la religión haya tomado gran parte de su fuerza de la observación de fenómenos misteriosos como los terremotos, las enfermedades, los truenos, etc, que parecerían requerir para su existencia de la intervención de algún ser divino.
A medida que el tiempo ha ido pasando, esos misterios se han ido explicando desde una perspectiva cada vez más naturalista. Evidentemente, la ciencia no ha podido explicar todo ni podrá hacerlo nunca pero, lo más importante es que, según Weinberg, no ha constatado nunca nada que requiera de una intervención sobrenatural para su explicación.
Transformación del auto-concepto humano
Una segunda fuente de tensión entre religión y ciencia se deriva del hecho de que las explicaciones científicas hayan aumentado las dudas del rol especial del ser humano en el mundo.
El ser humano ha pasado de considerarse un actor creado por Dios para desempeñar su papel en un gran drama cósmico de pecado y salvación a tener que aceptar que nuestro hogar, la Tierra, es tan sólo otro planeta más que gira alrededor del sol; que nuestro sol es tan sólo una estrella entre cientos de miles de millones de estrellas de una galaxia que, además, está entre miles de millones de galaxias visibles.
Otro descubrimiento importante, y que también cambiaría el concepto que teníamos de nosotros mismos, fue el realizado por Charles Darwin, que señaló que el ser humano es un producto de la evolución a partir de animales que nos precedieron. Es decir, que no existe un plan divino que explique la existencia de la humanidad.
En ciencia no hay profetas infalibles
La cuarta fuente de tensión entre ciencia y religión es la siguiente: las religiones tradicionales se basan en la autoridad, representada por un líder infalible (un profeta, un Papa, un Imán) o por un texto sagrado, como la Biblia o el Corán.
Los científicos se apoyan también en autoridades, pero de otra índole. Si quiero comprender la teoría de la relatividad, buscaré información escrita por un experto. Pero siempre sé que dicho experto podría estar equivocado. Para los científicos, ni siquiera los héroes de la ciencia, como Einstein, son considerados como profetas infalibles.
Weinberg señala que su propósito no es argumentar que el declive de las creencias religiosas sea algo bueno (aunque el físico piensa que sí lo es), sino más bien explicar las razones que han llevado a la pérdida de la fe en los últimos tiempos. Señala asimismo que hay que tener mucho cuidado con los sustitutos de la fe: regímenes que rechazaban la religión cometieron grandes atrocidades con la población, como la Alemania nazi o la Rusia de Stalin.
Finalmente, Weinberg apunta que no diría que es fácil vivir sin Dios y que la ciencia es lo único que se necesita. Porque, por más que se avance en el estudio de la naturaleza, los científicos son conscientes de que nunca podrán alcanzar el fondo final de las cosas. Para ayudar a aceptar este hecho, el físico propone la ayuda del humor, de los placeres sencillos de la vida y del placer del arte.
Según Weinberg, “podríamos estar tristes porque no se escriba más poesía religiosa en el futuro… pero, por supuesto, se podrá también escribir buena poesía en adelante sin la religión”. En definitiva, señala el físico, no debemos preocuparnos con que la superación de la religión conduzca a una decadencia moral porque muchas personas no religiosas han vivido vidas moralmente ejemplares.
Publicado originalmente en Bolsón Web (Argentina)

New Highly Virulent Strain of Vancomycin-Resistant MRSA Carries High Mortality Rate

November 5, 2009 (Philadelphia, Pennsylvania) — The USA 600 strain of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is potentially lethal and is associated with vancomycin resistance, according to a study from the Henry Ford Health System in Detroit, Michigan, reported here at the Infectious Diseases Society of America 47th Annual Meeting. This is bad news, experts warned, because vancomycin is the drug most often used to treat MRSA.
"USA600 was associated with a worse outcome compared with other strains of MRSA. Our study did not explore why patients with USA600 do so poorly. It could be patient characteristics, strain characteristics, or resistance. We need to find out what is going on in other big healthcare systems. If USA600 turns out to be present in systems other than Henry Ford Hospital, we will need studies to identify effective drugs, to monitor the incidence, and to make sure this strain is not spreading," said Carol Moore, PharmD, who presented results.
USA600 occurs mainly in older, sicker patients with more comorbidities. In the current study, 38% of those with the strain were from nursing homes. The study was prompted by the observation that patients with USA600 did worse than patients with other strains of MRSA. It has been reported that this strain has been in Germany and the Netherlands for the past 10 years, but outcome studies in this patient group are lacking.
Dr. Moore and colleagues looked at MRSA blood stream infections at Henry Ford Hospital from 2005 to 2008. Of 420 blood stream infections, 16 were USA600-positive. "USA600 accounted for a small percentage of blood stream infections, under 5%," she said. No increase in the proportion of USA600 strains was seen over the 3-year period, suggesting that the strain is stable, at least in blood stream infections.
"We haven't studied this in skin or respiratory infections. We plan to do that," Dr. Moore announced.
Of the 16 patients with USA600, 80% failed (death within 30 days, positive blood cultures after 10 days, or new MRSA blood stream infection within 30 days of treatment) and 20% got better. Mortality in patients with the USA600 strain was 50% (8 deaths), compared with 11% in those with non-USA600 MRSA. The non-USA600 MRSA group was comprised mostly of USA300 and USA100 strains, and was evenly distributed between these 2 strains. Mortality in USA100 patients was 18% and in USA300 patients was 7%. All deaths occurred within the first 15 days of infection, she said.
Analysis of USA600 isolates in the microbiological research lab at Henry Ford Hospital showed that 50% were vancomycin heteroresistant, meaning that in the presence of vancomycin, resistant subcolonies of the strain emerged. Other lab tests of USA600 showed resistance to vancomycin, clindamycin, trimethoprim, and sulfamethoxazole, Dr. Moore said.
"At this point in time, although it would make sense to switch a patient with MRSA USA600 to a different antibiotic [than vancomycin], there are no data to guide clinicians," she said.
Vancomycin Resistance
"This is one of the first reports on this emerging strain of MRSA. USA600 is particularly resistant to vancomycin, which is worrisome because it is the drug we depend on. Vancomycin has had perhaps the slowest rate of development of resistance among antibiotics. This study suggests we are seeing the loss of good traction with this drug in the USA600 strain," said Paul G. Auwaerter, MD, MD, IDSA program chair and clinical director of the Division of Infectious Diseases at Johns Hopkins University School of Medicine in Baltimore, Maryland.
Dr. Moore reports financial ties with Cubist. Dr. Auwaerter has disclosed no relevant financial relationships.
Infectious Diseases Society of America (IDSA) 47th Annual Meeting: Late-Breaking Abstract 40. Presented October 31, 2009.

Tigeciclina – un nuevo antibiótico para administración parenteral

La tigeciclina es el primer antibiótico disponible del grupo de las glicilciclinas. Se trata de derivados de la tetraciclina modificados químicamente de tal forma que también son eficaces contra cepas resistentes a las tetraciclinas.
El efecto contra bacterias resistentes es independiente del hecho de si los gérmenes han adquirido su resistencia a través de alteraciones en el ribosoma [Tet(M)] o de mecanismos de eflujo [Tet(A-E)]. La fórmula química de la tigeciclina posee una gran similitud con la de la minociclina. No obstante, existen diferencias considerables en cuanto al espectro antimicrobiano y a las propiedades terapéuticas.1

Propiedades antibacterianas

De forma similar a las tetraciclinas, la tigeciclina también inhibe la biosíntesis proteica de las bacterias por depósito en la subunidad 30S de los ribosomas. De esta forma, se bloquea la acumulación de las moléculas aminoacil-ARN-t en los ribosomas y se impide la prolongación de la creciente cadena proteica. Sin embargo, las glicilciclinas se unen con una afinidad cinco veces superior a la de las tetraciclinas, por lo que también pueden actuar contra bacterias resistentes a las tetraciclinas.
Tigeciclina es eficaz frente a un amplio espectro de gérmenes grampositivos y gramnegativos. El principal efecto es bacteriostático, aunque en algunos gérmenes, como por ejemplo S. pneumoniae y H. influenzae, también se observan efectos bactericidas. Se ha podido demostrar un efecto postantibiótico de alrededor de 3 horas. En el espectro hay estafilococos resistentes a la oxacilina o a la meticilina (SAMR). La concentración inhibitoria mínima frente a estos gérmenes fue de 0,25 a 0,5 mg/l (valor CMI90). También se observa una elevada actividad frente a cepas de E. faecalis resistentes a la vancomicina (ERV).1,2
También se han determinado valores CMI de 0,5 mg/l o inferiores en cepas de E. coli. Se registraron independientemente de si los gérmenes formaban ß-lactamasas (los denominados ESBL, extended spectrum ß-lactamases) o no las formaban. El antibiótico también es activo frente a especies de Acinetobacter (CMI90: 2 mg/l), pero menos contra Proteus. En general, no presenta una actividad suficiente contra Pseudomonas aeruginosa. Las bacterias gramnegativas que sobreexpresan sistemas de eflujo (Mex-XY, AcrAB) presentan una sensibilidad reducida o son resistentes.
La actividad contra anaerobios importantes, como especies de clostridios y bacteroides, es suficiente. Las concentraciones necesarias para inhibir Bacteroides fragilis son variables (valores CMI90 entre 0,25 y 16 mg/l).1

Propiedades farmacocinéticas

La tigeciclina se administra como infusión. La dosis recomendada es de 50 mg/ cada 12 horas, pudiéndose administrar una única dosis inicial doble. En estas condiciones se alcanza el "estado estable" al cabo de tres o cuatro días. Las concentraciones plasmáticas máximas son de 0,6 mg/l. En diferentes estudios se calcularon valores ABC de alrededor de 3 mg/l x h ó 4,7 mg/l x h.2 La biodisponibilidad tisular del antibiótico es buena, el volumen de distribución aparente es de 600 litros, y alrededor del 70 al 90% del principio activo está unido in vitro a proteínas plasmáticas, en función de la concentración. La tigeciclina se acumula en los granulocitos neutrófilos y las concentraciones intracelulares son de 20 a 30 veces superiores a las registradas en el líquido extracelular.3
La eliminación se produce de forma inalterada mayoritariamente en heces. En orina, se ha determinado un 32%. Una pequeña parte de la dosis se transforma en glucurónido y en otros metabolitos. La semivida de eliminación es de 42 horas. En pacientes con insuficiencia renal significativa o pacientes en hemodiálisis no se apreciaron alteraciones significativas de la eliminación. Por el contrario, la alteración de la función hepática provoca un retraso en la eliminación de la tigeciclina. La semivida se vio prolongada en un 23% (Child Pugh B) o en un 43% (Child Pugh C).4

Eficacia terapéutica

En dos grandes estudios de Fase III a doble ciego, publicados, se examinaron la eficacia y la tolerancia de la tigeciclina en infecciones cutáneas complicadas e infecciones intraabdominales, respectivamente. En cada una de las dos indicaciones se evaluaron conjuntamente y forma adicional los datos publicados en otros dos trabajos.5,6 En las infecciones cutáneas complicadas (por ejemplo, celulitis, abscesos, etc.) se administró una combinación de vancomicina (1,0 g i.v.) y aztreonam a una dosis de 2,0 g i.v. en el grupo control. Los gérmenes más frecuentes fueron estafilococos sensibles y resistentes a la meticilinas, así como E. coli. Pudieron evaluarse clínicamente los datos de más de 800 pacientes. Según los criterios clínicos y microbiológicos no se observaron diferencias significativas entre los dos grupos. Se obtuvo un éxito terapéutico en el 86,5% (tigeciclina) y en el 88,6% (grupo control) de los pacientes. No hubo diferencias significativas en la erradicación de gérmenes entre los grupos de tratamiento.5
En pacientes con infecciones intraabdominales complicadas, el tratamiento comparador fue imipenem.6 Los diagnósticos más frecuentes en un total de 1.642 pacientes fueron apendicitis complicada, colecistitis o abscesos intraabdominales; los gérmenes más frecuentemente aislados fueron E. coli y Klebsiella. En estas indicaciones tampoco se observaron diferencias entre ambos grupos de tratamiento. Se obtuvo éxito en el 80,2% (tigeciclina) y el 81,5% (imipenem); en el 86% de los pacientes evaluables de los dos grupos se erradicaron los gérmenes.

Efectos adversos, interacciones

La frecuencia de interrupción del tratamiento por intolerancia fue casi idéntica en todos los grupos. La tigeciclina provocó efectos secundarios gastrointestinales con mayor frecuencia que los antibióticos con los que se comparó. Los pacientes con infecciones abdominales, presentaron náuseas con una frecuencia significativamente superior a la registrada en el grupo control (24,4% frente al 19,0%), siendo la diferencia incluso más evidente en pacientes con infecciones cutáneas. En los estudios de Fase III, se produjeron vómitos en el 19% de los pacientes con tigeciclina, en el 14% con imipenem y en el 3,6% con vancomicina / aztreonam. En cambio, con vancomicina / aztreonam fue más frecuente el incremento de las transaminasas; también las reacciones cutáneas fueron significativamente más frecuentes que con tigeciclina (19,3% frente al 10,6%).
Las investigaciones in vitro con microsomas hepáticos humanos indican que no cabe esperar interacciones con otros medicamentos que se metabolizan a través de las monooxigenasas dependientes del citocromo P450. Con la administración simultánea de tigeciclina y warfarina aumentaron las concentraciones plasmáticas de warfarina R y S (valores ABC) en un 68% y 29%, respectivamente. Si bien no se ha podido observar un efecto directo en la coagulación de la sangre, se recomienda controlar INR durante la administración simultánea.4

Resumen

Tigeciclina es un nuevo antibiótico para el tratamiento parenteral antibacteriano. Se trata del primer representante de las glicilciclinas cuya estructura y mecanismo de acción presenta similitudes con las tetraciclinas. La tigeciclina actúa frente a gérmenes grampositivos y gramnegativos, inclusive aquellas cepas resistentes a tetraciclinas u otros antibióticos (SAMR, EVR y bacterias productoras de ESBL, entre otros). Se administra como infusión breve y se elimina principalmente en forma inalterada con las heces. La biodisponibilidad tisular es buena y el volumen de distribución elevado. La semivida es de alrededor de 40 horas. La dosis habitual es de 50 mg / dos veces al día, tras una dosis inicial única de 100 mg. En amplios estudios a doble ciego, la tigeciclina ha demostrado ser igual de eficaz, en infecciones dérmicas complicadas y en infecciones intraabdominales, que los otros antibióticos utilizados. En infecciones dérmicas, se trataba de una combinación de vancomicina y aztreonam; en los pacientes con infecciones intraabdominales, se utilizó imipenem como comparador. Los efectos secundarios gastrointestinales fueron significativamente más frecuentes con tigeciclina que con los otros antibióticos, mientras que las reacciones cutáneas fueron menos frecuentes que en los grupos control. El principio activo constituye una ampliación esencial de las opciones terapéuticas, especialmente de las infecciones de heridas tras intervenciones intraabdominales en las que cabe esperar cepas SAMR (S. aureus meticilina resistente), así como enterobacterias. También puede considerarse como alternativa útil en infecciones cutáneas bacterianas complicadas, sobre todo cuando existe una alergia frente a otros antibióticos.

NOTA
Este artículo, junto con más de 130 descripciones detalladas de medicamentos, se encuentran en nuestra página web www.zct-berlin.de, en el apartado "Neueinfuehrungen / Kurzbeschreibungen" (Nuevos fármacos / Descripciones breves). En esta página también se mencionan los trabajos citados en el artículo y se facilitan los links directos de los resúmenes de los trabajos originales.


Agradecemos la colaboración de los Profesores H. Lode y R. Stahlmann, editor y coeditor de la Revista Zeitschrift für Chemotherapie. Steinplatz 1. D-10623 Berlin. http://www.zct-berlin.de/

Antes que 'Lucy,' estuvo 'Ardi': descubren los huesos de nuestro antepasado más antiguo

1 de octubre de 2009, 01:00 PM
(www.neomundo.com.ar / saludyciencias.com.ar)

Un equipo internacional de científicos por primera vez ha descrito minuciosamente a Ardipithecus ramidus, una especie de homínido que vivió hace 4.4 millones de años en lo que hoy es Etiopía. Esta investigación se publica en la revista científica Science.
Se cree que el ultimo antepasado común compartido por humanos y chimpancés vivió hace seis o más millones de años. Aunque este Ardipithecus no es el último antepasado común, probablemente compartió varias de las características de este antecesor.
Como comparación, Ardipithecus es más de un millón de años más antiguo que "Lucy", el esqueleto parcial femenino de Australopithecus afarensis.
Hasta el descubrimiento de los nuevos restos de Ardipithecus, el registro de fósiles contenía escasa evidencia de otros homínidos más antiguos que Australopithecus. Y se estableció que "Ardi" era una hembra, que pesaba alrededor de 50 kilogramos y medía unos 120 centímetros de altura.
El análisis
A través de un análisis del cráneo, dientes, pelvis, manos, pies y otros huesos, los investigadores han determinado que Ardipithecus tenía una mezcla de rasgos "primitivos" compartidos con sus predecesores, los primates del Mioceno, y rasgos "derivados", que comparte exclusivamente con homínidos posteriores.
Dada su antigüedad, Ardipithecus nos acerca más al aún elusivo último ancestro común. Sin embargo, varios de sus rasgos no aparecen en los simios africanos de la época moderna.
Por consiguiente, una conclusión sorprendente es que es probable que los simios africanos hayan evolucionado ampliamente desde que compartimos ese último ancestro común, lo que convierte así a chimpancés y gorilas vivos en pobres modelos para el último antepasado común y para entender nuestra propia evolución desde ésa época.
"En Ardipithecus tenemos una forma no especializada que no ha evolucionado mucho en la dirección de Australopithecus. Por lo que cuando vas de la cabeza a los dedos del pie, lo que ves es una criatura mosaico, que no es ni chimpancé, ni es humano. Es Ardipithecus", dijo Tim White de la Universidad de California Berkeley, uno de los principales autores de la investigación.
"Estos artículos de Science contienen una enorme cantidad de datos recolectados y analizados a través de un importante esfuerzo internacional de investigación. Ellos abren una ventana a un periodo de la evolución humana de la que hemos sabido poco, cuando los homínidos primitivos estaban estableciéndose en África, poco después de separarse del último antepasado que compartieron con los simios africanos", dijo Brooks Hanson.
Nuevos conocimientos
Hasta ahora, los investigadores habían asumido generalmente que los chimpancés, gorilas y otros simios africanos modernos han conservado varios de los rasgos del último antepasado que compartieron con los humanos. En otras palabras, se pensaba que este presunto ancestro era más tipo chimpancé que tipo humano.
Por ejemplo, se habría adaptado para balancearse y colgarse de las ramas de los árboles, y quizá anduvo sobre sus nudillos mientras estaba en el suelo.
Sin embargo, Ardipithecus cuestiona esos supuestos. Estos homínidos parecen haber vivido en un entorno boscoso, en donde treparon en cuatro patas a lo largo de las ramas de los árboles como lo hicieron algunos de los primates del Mioceno y caminaron, erguidos, en dos patas, cuando en el suelo.
No parecen haber sido andadores sobre nudillos, o haber pasado mucho tiempo columpiándose y colgándose de las ramas de los árboles, especialmente como lo hacen los chimpancés. En general, los hallazgos sugieren que los homínidos y los simios africanos han seguido, cada uno, diferentes senderos evolutivos, y que ya no podemos considerar a los chimpancés como "reemplazos" de nuestro último antepasado común.