Oseltamivir is the drug of choice for patients with pandemic influenza (H1N1 2009). However, sporadic cases of oseltamivir resistance have been described worldwide. Up to March 2010, a total of 11 strains (2.2% of tested isolates) of oseltamivir-resistant pandemic influenza (H1N1 2009) have been discovered in South Korea. We report a case of 46-year-old man with acute myeloid leukemia in whom an oseltamivir-resistant pandemic (H1N1) 2009 virus was isolated. Despite high dose oseltamivir therapy for 10 days he had persistent symptoms and showed positive results in repeated real-time RT-PCR for pandemic influenza (H1N1 2009) virus from nasopharyngeal specimen. The patient improved eventually after oseltamivir was replaced by zanamivir inhalation.
Humans ; Influenza, Human ; Inhalation ; Leukemia ; Leukemia, Myeloid, Acute ; Middle Aged ; Oseltamivir ; Pandemics ; Republic of Korea ; Viruses ; Zanamivir

In April 2009, the first swine origin pandemic influenza (H1N1 2009) infection was reported in Mexico and United states and has since spread rapidly worldwide. Finally on June 11, 2009, WHO officially declared the first pandemic of the 21st century. Until March 2010, more than 213 countries reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 16,931 deaths. The drug of choice for treatment and prophylaxis of pandemic (H1N1) 2009 influenza are the neuraminidase inhibitor (oseltamivir and Zanamivir). However, increased use of these drugs lead to the emergence of oseltamivir-resistant strains. We report a case of oseltamivir-resistant pandemic influenza (H1N1 2009) virus infection in a patient who were initially started with oseltamivir for laboratory-confirmed influenza. Patient's symptoms worsened despite the use of high-dose oral oseltamivir, and antiviral susceptibility test showed oseltamivir resistance (H275Y mutation). The patient resolved after treatment with zanamivir.
Humans ; Influenza, Human ; Mexico ; Neuraminidase ; Oseltamivir ; Pandemics ; Swine ; United States ; Viruses ; Zanamivir

To investigate the emergence and prevalence of antiviral resistance, we analyzed influenza A/H3N2 viruses isolated in Korea during 2002/03 to 2003/04 season by genetic and phenotypic assay. For the genetic analysis to the amantadine, an M2 protein inhibitor, the M gene was amplified by RT-PCR and regions corresponding to the amino acid at positions 27, 30, and 31 were amplified by nested PCR with size of 154 bp, 95 bp, and 153 bp fragments, respectively. A total of 3 of 31 (9.7%) viruses were found to be mutated by restriction fragment length polymorphism (RFLP) with Sca I and sequence analysis, showing the single amino acid change (Ser to Asn) at position 31. Also it was observed that their growths in Madin-Darby Canine Kidney (MDCK) cells were unaffected by amantadine (up to 1 microgram/ml) in both plaque assay and WST-1 assay, confirming that these viruses were resistant against amantadine. We also examined the resistant pattern against zanamivir, a neuraminidase inhibitor, for 15 Korean influenza A/H3N2 viruses isolated in 2002~2003 season. Sequence analysis showed that there were no genetic changes of NA genes including R292K, K274Y, R152K, and E119V which were related to resistance against the neuraminidase inhibitor. In the NA inhibition assay to zanamivir, Korean isolates were found to be sensitive, ranging from 0.17 nM to 1.77 nM in 50% inhibitory concentration (IC(50)). These results suggest that monitoring for the antiviral resistance should be intensified and maintained to provide guideline for prophylaxis and treatment of influenza in Korea.
Amantadine ; Influenza, Human ; Kidney ; Korea ; Neuraminidase ; Orthomyxoviridae ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Prevalence ; Seasons ; Sequence Analysis ; Zanamivir

OBJECTIVETo analyze the susceptibility of influenza A (H3N2) viruses to neuraminidase inhibitors during 2011-2012 in Mainland China.

METHODSAll the tested viruses were obtained from the Chinese National Influenza Surveillance Network, which covers 31 provinces in mainland China, including 408 network laboratories and 554 sentinel hospitals. In total 1 903 viruses were selected with isolation date from January 1, 2011 to December 31, 2012 in Mainland China, among these viruses, 721 were confirmed to be influenza A (H3N2) virus by Chinese National Influenza Center and tested for the susceptibility to oseltamivir and zanamivir using chemiluminescence-based assay. The neuraminidase inhibitor sensitive reference virus A/Washington/01/2007 (119E) and oseltamivir resistant virus A/Texas/12/2007 (E119V) were used as control in this study. The t -test was used to compare the difference of NAI susceptibility of viruses isolated from different years.

RESULTSThe half maximal inhibitory concentration (IC₅₀) of A/Washington/01/2007 for oseltamivir and zanamivir was (0.10 ± 0.02) and (0.30 ± 0.05) nmol/L, respectively. The IC₅₀ of A/Texas/12/2007 for oseltamivir and zanamivir was (4.27 ± 1.60) and (0.20 ± 0.03) nmol/L, respectively. Among the 721 influenza A (H3N2) viruses, 132 influenza A (H3N2) viruses were isolated in 2011 and 589 influenza A (H3N2) viruses were isolated in 2012. The IC50 for oseltamivir ranged from 0.04 to 0.62 nmol/L for viruses isolated in 2011 and ranged from 0.02 to 0.95 nmol/L for viruses in 2012, and the IC₅₀ of all the viruses tested was within 10-fold IC₅₀ (1.0 nmol/L) of the neuraminidase inhibitor sensitive reference virus A/Washington/01/2007. The IC50 of zanamivir ranged from 0.12 to 0.80 nmol/L for viruses in 2011 and ranged from 0.04 to 0.72 nmol/L for viruses in 2012, and was within 10-fold IC₅₀ (3.0 nmol/L) of the neuraminidase inhibitor sensitive reference virus A/Washington/01/2007.

CONCLUSIONThe influenza A(H3N2) viruses isolated during 2011-2012 in Mainland China were tested to be sensitive to oseltamivir and zanamivir.

Antiviral Agents ; China ; Drug Resistance, Viral ; Enzyme Inhibitors ; Epidemiological Monitoring ; Humans ; Influenza A Virus, H3N2 Subtype ; Influenza, Human ; Neuraminidase ; Oseltamivir ; Zanamivir

More than 60 antiviral agents for various infectious diseases such as herpes, hepatitis, influenza, and AIDS are currently prescribed worldwide. Among the viral infections, hepatitis B and influenza are those frequently seen in primary care situations in Korea. This review discusses the anti-hepatitis B (HBV) drugs entecavir and adefovir, and the anti-influenza drugs oseltamivir and zanamivir. In addition, the pharmacology and therapeutic guidance suggested by the Korean Association for the Study of the Liver were reviewed for entecavir and adepovir, the most frequently prescribed anti-HBV drugs. For influenza, oseltamivir is commonly used despite debates on neuropsychiatric safety issues and zanamivir may be used when an inhalation form is necessary. Although currently used drugs show considerable clinical efficacy, efforts to optimize their use and further research to find new molecules that may overcome their limitations are necessary.
Adenine ; Antiviral Agents ; Communicable Diseases ; Guanine ; Hepatitis ; Hepatitis B ; Influenza, Human ; Inhalation ; Korea ; Liver ; Organophosphonates ; Oseltamivir ; Primary Health Care ; Zanamivir

Influenza causes variable epidemics annually and imposes public health problems and socioeconomic burden. They cause epidemic acute respiratory disease, characterized by fever, cough and systemic symptoms. The annual epidemics of seasonal influenza can affect any age group and result in serious illness or death, particularly in high risk populations such as adults > 65 years old, children < 2 years old and those with chronic medical condition at any age. Three types (A, B, and C) are recognized as well as many subtypes within the type A. New influenza A virus subtypes sporadically emerge in humans to cause widespread disease or pandemics. Antiviral therapy with oseltamivir or zanamivir is available and shorten the duration of illness and reduce the rate of complications. Influenza vaccines are effective in the prevention of influenza illness, although improved vaccines are needed.
Adult ; Child ; Cough ; Fever ; Humans ; Influenza A virus ; Influenza Vaccines ; Influenza, Human* ; Oseltamivir ; Pandemics ; Public Health ; Seasons ; Vaccines ; Zanamivir

Influenza is an acute respiratory disease caused by the influenza virus. Each year, it causes a significant disease burden, especially in older adults. Furthermore, influenza pandemics occasionally occur because of antigenic change. Common signs and symptoms of influenza include fever, cough, sore throat, headache, myalgia, and runny nose. Severe cases may progress to pneumonia, which causes shortness of breath, tachycardia, hypotension, and the need for supportive respiratory interventions. Mild cases are self-limited and supportive care is sufficient. Antiviral treatment shortens the clinical course if it is administered within 48 hours from the onset of disease. Neuraminidase inhibitors, such as oseltamivir, zanamivir, and peramivir, are widely used. Although annual vaccination is the best means of prevention, its effectiveness can vary from year to year and among different age and risk groups.
Adult ; Cough ; Dyspnea ; Fever ; Headache ; Humans ; Hypotension ; Influenza, Human ; Myalgia ; Neuraminidase ; Nose ; Orthomyxoviridae ; Oseltamivir ; Pandemics ; Pharyngitis ; Pneumonia ; Tachycardia ; Vaccination ; Zanamivir

BACKGROUND AND OBJECTIVES: This study aimed to investigate the differences in the morphologic changes of the nasal mucosa with influenza virus infection between zanamivir treated groups and non-treated group. MATERIALS AND METHOD: Zanamivir was administrated to the 15 rabbits before or after inoculation of the influenza viruses with time difference and 5 rabbits were inoculated the influenza viruses but not treated with zanamivir. The nasoturbinal mucosa was harvested and examined with the light microscope and electron microscope at 7th day after virus inoculation. RESULTS: The light microscopy results revealed that the total inflammatory scores were decreased in the zanamivir treated group. The electron microscopy results showed that the degree of ciliary loss, vacuolar degeneration of mitochondria and endoplasmic reticulum and rupture of cell membrane in the zanamivir treated group was less than those in the untreated group. The effects of inoculated zanamivir was related to the time of administration and best timing was immediate after inoculation of the influenza A virus. CONCLUSION: The use of zanamivir in the treatment of influenza A virus infection during the epidemic period is effective in controlling the inflammatory change.
Cell Membrane ; Endoplasmic Reticulum ; Influenza A virus* ; Influenza, Human* ; Microscopy ; Microscopy, Electron ; Mitochondria ; Mucous Membrane ; Nasal Mucosa* ; Orthomyxoviridae ; Rabbits ; Rupture ; Zanamivir*

BACKGROUNDIt is the first multicenter clinical study in China to investigate zanamivir use among Chinese adolescents and adults with influenza-like illness (ILI) since 2009, when inhaled zanamivir (RELENZA(®)) was marketed in China.

METHODSAn uncontrolled open-label, multicentre study to evaluate the antiviral activity, and safety of inhaled zanamivir (as Rotadisk via Diskhaler device); 10 mg administered twice daily for 5 days in subjects ≥ 12 years old with ILI. Patients were enrolled within 48 hours of onset and followed for eight days. Patients were defined as being influenza-positive if the real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) test had positive results.

RESULTSA total of 400 patients ≥ 12 years old were screened from 11 centers in seven provinces from March 2010 to January 2011. Three hundred and ninety-two patients who took at least one dose of zanamivir were entered into the safety analysis. The mean age was 33.8 years and 50% were male. Cardiovascular diseases and diabetes were the most common comorbidities. All the reported adverse events, such as rash, nasal ache, muscle ache, nausea, diarrhea, headache, occurred in less than 1% of subjects. Mild sinus bradycadia or arrhythmia occurred in four subjects (1%). Most of the adverse events were mild and did not require any change of treatment. No severe adverse events (SAE) or fatal cases were reported. Bronchospasm was found in a 38 years old woman whose symptoms disappeared after stopping zanamivir and without additional treatment. All the 61 influenza virus isolates (43 before enrollment, 18 during treatment) proved to be sensitive to zanamivir.

CONCLUSIONSZanamivir is well tolerated by Chinese adolescents and adults with ILIs. There is no evidence for the emergence of drug-resistant isolates during treatment with zanamivir.

Adolescent ; Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Humans ; Influenza, Human ; drug therapy ; Male ; Middle Aged ; Treatment Outcome ; Zanamivir ; administration & dosage ; adverse effects ; therapeutic use

Adamantane ; therapeutic use ; Amantadine ; therapeutic use ; Antiviral Agents ; therapeutic use ; Child ; Guanidines ; Humans ; Influenza, Human ; drug therapy ; prevention & control ; Pyrans ; Rimantadine ; therapeutic use ; Sialic Acids ; therapeutic use ; Zanamivir