Tamiflu
Identification of a human influenza type B strain with reduced sensitivity to neuraminidase inhibitor drugs.

Hurt AC, McKimm-Breschkin JL, McDonald M, Barr IG, Komadina N, Hampson AW.

WHO Collaborating Centre for Reference and Research on Influenza, 45 Poplar Road, Melbourne, Vic. 3052, Australia. aeron_hurt csl.com.au

A total of 126 influenza B isolates isolated between 1998 and 2002 from Australasia and the Asia-Pacific region were tested for their sensitivity to the neuraminidase (NA) inhibitor drugs zanamivir and oseltamivir carboxylate using a fluorescence-based enzyme assay. The mean (+/-1 S.D.) 50% inhibitory concentration (IC50) of the influenza B viruses tested was 1.41+/-0.53 nM against zanamivir and 14.91+/-14.31 nM with oseltamivir carboxylate. However, a single type B isolate (B/Perth/211/2001) from an infant who had not been treated with either of the NA inhibitor drugs, showed a nine-fold lower sensitivity to zanamivir and a 14-fold lower sensitivity to oseltamivir carboxylate compared with the mean IC50 of influenza B strains. A decrease in sensitivity to oseltamivir carboxylate and RWJ-270201 was also seen in both: a chemiluminescent assay and a second different fluorescent assay. Sequence analysis of the haemagglutinin HA1 region and the neuraminidase gene of B/Perth/211/2001 revealed no amino acid changes in sites that have previously been reported to confer resistance to either of the NAI drugs. Further investigations are in progress to identify the basis for this reduced sensitivity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15163511&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Effect of antiviral treatment on the outcome of secondary bacterial pneumonia after influenza.

McCullers JA.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA. jon.mccullers stjude.org

Secondary bacterial pneumonia is an important cause of influenza-associated death. Although antibacterial therapy is standard, antiviral therapy has been ignored because viral infections usually resolve by the time bacterial pneumonia presents. In the present study, antiviral compounds were tested in a mouse model of secondary pneumococcal pneumonia after influenza. Treatment with oseltamivir improved survival in mice from 0% to 75%, even when therapy was delayed for up to 5 days after infection with influenza virus. In mice, treatment with rimantadine had no effect on survival. Treatment with ampicillin cleared infection but, in the absence of treatment with oseltamivir, did not improve survival. Pneumonia developed in only 7 of the 22 mice receiving oseltamivir, and subsequent treatment with ampicillin resulted in cure (100% survival). Treatment of the predisposing influenza-virus infection with inhibitors specific for the viral neuraminidase may improve the efficacy of antibiotics and increase survival in persons who are at high risk for complications and mortality during influenza.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15243927&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Health outcomes among patients receiving oseltamivir.

Enger C, Nordstrom BL, Thakrar B, Sacks S, Rothman KJ.

Ingenix Epidemiology, Auburndale, MA 02466, USA.

PURPOSE: Oseltamivir was approved by the FDA for the treatment of influenza in 1999. The primary objective was to compare health outcomes among influenza patients who were treated with oseltamivir and those who were not. METHODS: The patient population included UnitedHealthcare members who received an influenza diagnosis during the 1999-2000 influenza season, divided into those who were dispensed oseltamivir on the same day (N = 3211) and those who were not dispensed oseltamivir (N = 19,985). Cardiovascular, neuropsychiatric and respiratory outcomes were assessed from medical claims for a 30-day period. RESULTS: The adjusted incidence rate ratio for major cardiac outcome was 0.56 (95%CI: 0.34-0.93) in those without a positive history of major cardiac disease, indicating that those in the oseltamivir group tended to be at lower risk of cardiac outcomes than those without oseltamivir. The adjusted incidence rate ratio for major neuropsychiatric outcome was 0.72 (95%CI: 0.53-0.97) in the negative history of neuropsychiatric disease stratum. The incidence rate ratios for respiratory events were more variable. CONCLUSIONS: There appears to be no increased risk of cardiac or neuropsychiatric outcomes among subjects with influenza who were treated with oseltamivir in comparison with those who were not.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15255089&dopt=Abstract oseltamivir Tamiflu



Tamiflu
[A multicenter randomized controlled study of the efficacy and safety of oseltamivir in the treatment of influenza in a high risk population]

[Article in Chinese]

Lin JT, Yu XZ, Cui DJ, Chen XY, Zhu JH, Wang YZ, Wu XD, Gao H, Huo ZL, Zhu SH, Hu SL, Wang AX.

Department of Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100029, China.

OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of influenza in a high risk population. METHODS: A randomized, open, control trial was conducted from Nov. 2002 to Feb. 2003. Patients with chronic respiratory disease, such as chronic bronchitis, obstructive emphysema, bronchial asthma, bronchiectasis or chronic cardiac disease, and with symptoms of influenza were enrolled. They should satisfy the following criteria: Fever > or = 37.8 degrees C plus at least two of the following influenza symptoms: coryza/nasal congestion, sore throat, cough, myalgia/muscle aches and pain, fatigue, headache and chills/sweats. Within 48 h after the onset of the symptoms, the patients were randomly assigned to oseltamivir group (oseltamivir 75 mg, twice daily for 5 days) or control group (symptom relief medicine only). RESULTS: Fifty-six of the 108 recruited patients were identified as influenza-infected through laboratory test. They were defined as intent-to-treat infected population (ITTI) (27 oseltamivir, 29 control). The duration of influenza symptom was 64 h shorter (36.7%) and AUC score of the influenza symptom was decreased by 618 (43.1%) in the oseltamivir group as compared with those in the control group. The fever duration was 46.8 h (45.0%) less in the oseltamivir group than that in the control group. It took 6 d for the oseltamivir group and 11 days for the control group to recover to the basic health status. Secondary complications such as bronchitis, sinusitis and pneumonia occurred 11% (3/27) in the oseltamivir group and 45% (13/29) in the control group. The treatment expense for influenza and its complication was 587.4 RMB in the oseltamivir group and 786.5 RMB in the control group, which showed no significant difference (P = 0.246). CONCLUSIONS: It is suggested that oseltamivir is effective and well tolerated in patients with chronic respiratory or cardiac diseases. It can reduce the fever duration and severity of influenza symptom, and decrease the incidence of secondary complications and antibiotic use, while does not increase the total medical cost.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15312558&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Resistant influenza A viruses in children treated with oseltamivir: descriptive study.

Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, Hayden FG, Sugaya N, Kawaoka Y.

Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

BACKGROUND: Oseltamivir is an effective inhibitor of influenza virus neuraminidase. Although viruses resistant to oseltamivir emerge less frequently than those resistant to amantadine or rimantadine, information on oseltamivir-resistant viruses arising during clinical use of the drug in children is limited. Our aim was to investigate oseltamivir resistance in a group of children treated for influenza. METHODS: We analysed influenza A viruses (H3N2) collected from 50 children before and during treatment with oseltamivir. We sequenced the genes for neuraminidase and haemagglutinin and studied the mutant neuraminidases for their sensitivity to oseltamivir carboxylate. FINDINGS: We found neuraminidase mutations in viruses from nine patients (18%), six of whom had mutations at position 292 (Arg292Lys) and two at position 119 (Glu119Val), which are known to confer resistance to neuraminidase inhibitors. We also identified another mutation (Asn294Ser) in one patient. Sensitivity testing to oseltamivir carboxylate revealed that the neuraminidases of viruses that have an Arg292Lys, Glu119Val, or Asn294Ser mutation were about 10(4)-10(5)-fold, 500-fold, or 300-fold more resistant than their pretreatment neuraminidases, respectively. Oseltamivir-resistant viruses were first detected at day 4 of treatment and on each successive day of the study. More than 10(3) infectious units per mL of virus were detected in some of the patients who did not shed drug-resistant viruses, even after 5 days of treatment. INTERPRETATION: Oseltamivir-resistant mutants in children being treated for influenza with oseltamivir arise more frequently than previously reported. Furthermore, children can be a source of viral transmission, even after 5 days of treatment with oseltamivir.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15337401&dopt=Abstract oseltamivir Tamiflu