September 5, 2008 (CIDRAP News) - In the middle of growing concern about resistance (Tamiflu) in influenza A/H1N1 oseltamivir, the Dutch team this week reported the death of leukemia patient who was infected with H1N1 virus that is resistant to anti-viral medicines.
In a letter this week's New England Journal of Medicine (NEJM), the Dutch authors said the case shows that oseltamivir-resistant H1N1 viruses to cause disease, although studies in animals have shown that resistance mutations allow the virus less dangerous. The letter stated that the man was a virus resistant to amantadine, an older antiviral drugs.
20 August, the World Health Organization (WHO) states that 31% of influenza A/H1N1 isolates from 16 countries conducted last test H274Y mutation, which confers resistance to oseltamivir. Resistance levels range from 100% (10 of 10 isolates), Australia 13% (4 of 32 isolates) in Chile.
The emergence of oseltamivir-resistant H1N1 virus was first observed in Norway in January and since then researchers have found that the virus in 35 countries, including the United States and Canada.
Dissemination of oseltamivir-resistant H1N1 virus was puzzled experts because it is not clearly linked to treatment with drugs.
In the case report, the authors of the Erasmus University Medical Center in Rotterdam said that 67-year-old man who was on chemotherapy at 3-year battle with chronic lymphocytic leukemia were included shortness of breath, dry cough and fever. On his second day in hospital, experienced acute respiratory failure, and his doctors placed him on the ventilator and started empirical antibiotic treatment.
Computer tomography (CT) showed that the patient patchy pulmonary infiltrates, and tests on samples from the respiratory tract, showed him influenza A/H1N1.
Sixth day in hospital Man oseltamivir, but 13 days doctors stopped the drug because sequence analysis of the virus and the H274Y mutation showed that no decrease in viral load.
The authors state that the mutation was found in samples obtained before the patient started oseltamivir therapy. Family of man and the hospital records showed that he had no contact with patients with oseltamivir.
15th day in male hospital doctors prescribed amantadine, and after several days of neutrophils increased, signs of recovery of bone marrow, the group reported.
The day 20 doctors patient from the ventilator and set zanamivir treatment. However, 2 days later of respiratory failure a man again, and his medical team to fan it back and ended zanamivir therapy. (As osteltamivir, zanamivir is neuramnidase inhibitor, but no increase in zanamivir resistance has recently been announced.)
26 days from the identification of doctors is not influenza virus, but note that sequence analysis showed amantadine-resistance mutations in the virus M2 protein (L26F). She said that the recovery of the immune system is probably responsible for the clearance of virus, since only the patient received three doses of zanamivir.
CT repeat the procedure on the day showed that 28 infiltrates progressed. Due to forecast bad man, was removed on day 34 fan, and he died 3 days later.
The authors cited studies in animals indicate that oseltamivir resistance leaves H1N1 virus "seriously compromised. Despite these reports wrote, "we describe the case suggests that oseltamivir-resistant virus can be pathogenic, at least in immunocompromised patients."
In Eurosurveillance editorial published in January announced resistant viruses with mutations H274Y were observed in previous flu seasons, but were rare and not easily spread. But more recent H1N1 isolates with the mutation were "plumber" and spread in society, she wrote.
In a letter this week's New England Journal of Medicine (NEJM), the Dutch authors said the case shows that oseltamivir-resistant H1N1 viruses to cause disease, although studies in animals have shown that resistance mutations allow the virus less dangerous. The letter stated that the man was a virus resistant to amantadine, an older antiviral drugs.
20 August, the World Health Organization (WHO) states that 31% of influenza A/H1N1 isolates from 16 countries conducted last test H274Y mutation, which confers resistance to oseltamivir. Resistance levels range from 100% (10 of 10 isolates), Australia 13% (4 of 32 isolates) in Chile.
The emergence of oseltamivir-resistant H1N1 virus was first observed in Norway in January and since then researchers have found that the virus in 35 countries, including the United States and Canada.
Dissemination of oseltamivir-resistant H1N1 virus was puzzled experts because it is not clearly linked to treatment with drugs.
In the case report, the authors of the Erasmus University Medical Center in Rotterdam said that 67-year-old man who was on chemotherapy at 3-year battle with chronic lymphocytic leukemia were included shortness of breath, dry cough and fever. On his second day in hospital, experienced acute respiratory failure, and his doctors placed him on the ventilator and started empirical antibiotic treatment.
Computer tomography (CT) showed that the patient patchy pulmonary infiltrates, and tests on samples from the respiratory tract, showed him influenza A/H1N1.
Sixth day in hospital Man oseltamivir, but 13 days doctors stopped the drug because sequence analysis of the virus and the H274Y mutation showed that no decrease in viral load.
The authors state that the mutation was found in samples obtained before the patient started oseltamivir therapy. Family of man and the hospital records showed that he had no contact with patients with oseltamivir.
15th day in male hospital doctors prescribed amantadine, and after several days of neutrophils increased, signs of recovery of bone marrow, the group reported.
The day 20 doctors patient from the ventilator and set zanamivir treatment. However, 2 days later of respiratory failure a man again, and his medical team to fan it back and ended zanamivir therapy. (As osteltamivir, zanamivir is neuramnidase inhibitor, but no increase in zanamivir resistance has recently been announced.)
26 days from the identification of doctors is not influenza virus, but note that sequence analysis showed amantadine-resistance mutations in the virus M2 protein (L26F). She said that the recovery of the immune system is probably responsible for the clearance of virus, since only the patient received three doses of zanamivir.
CT repeat the procedure on the day showed that 28 infiltrates progressed. Due to forecast bad man, was removed on day 34 fan, and he died 3 days later.
The authors cited studies in animals indicate that oseltamivir resistance leaves H1N1 virus "seriously compromised. Despite these reports wrote, "we describe the case suggests that oseltamivir-resistant virus can be pathogenic, at least in immunocompromised patients."
In Eurosurveillance editorial published in January announced resistant viruses with mutations H274Y were observed in previous flu seasons, but were rare and not easily spread. But more recent H1N1 isolates with the mutation were "plumber" and spread in society, she wrote.
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