Outbreak of Antiviral Drug�CResistant Influenza A in Long-Term Care Facility, Illinois, USA, 2008

An outbreak of oseltamivir-resistant influenza A (H1N1) occurred in a long-term care facility. Eight (47%) of 17 and 1 (6%) of 16 residents in 2 wards had oseltamivir-resistant influenza A virus (H1N1) infections. Initial outbreak response included treatment and prophylaxis with oseltamivir. The outbreak abated, likely because of infection control measures.     

磷酸奥司米韦的合成研究

目的 研究磷酸奥司米韦的合成方法。方法 以莽草酸为起始原料,通过酯化、缩酮保护、甲磺酰化、缩酮交换、还原,闭环反应得关键中间体(3R,4S,5S)-4,5-环氧基-3-(1-乙基丙氧基)-1-环己烯甲酸乙酯(2);化合物2在氯化镁催化下和叔丁胺反应,经甲磺酰化、闭环得氮丙啶中间体,再经开环、乙酰化、脱叔丁基、脱烯丙基后成磷酸盐共13步反应得抗病毒药磷酸奥司米韦。结果与结论 合成的磷酸奥司米韦经1H-NMR和MS谱确证结构,总收率为29.5 %。     

Economic evaluation of oseltamivir phosphate for postexposure prophylaxis of influenza in long-term care facilities

OBJECTIVES: To compare the cost-effectiveness of oseltamivir postexposure prophylaxis during influenza A outbreaks with that of amantadine postexposure prophylaxis or no postexposure prophylaxis in long-term care facilities (LTCFs). DESIGN: Cost-effectiveness analysis based on decision analytic model from a government-payer perspective. SETTING: A Canadian LTCF, with high staff vaccination, at the beginning of influenza season. PARTICIPANTS: Elderly, influenza-vaccinated patients living in a Canadian LTCF. MEASUREMENTS: Incremental costs (or savings) per influenza-like illness case avoided compared with usual care. RESULTS: From a government-payer perspective, this analysis showed that oseltamivir was a dominant strategy because it was associated with the fewest influenza-like illness cases, with cost savings of $1,249 per 100 patients in 2001 Canadian dollars compared with amantadine and $3,357 per 100 patients compared with no prophylaxis. Costs for amantadine dose calculation and hospitalization for adverse events contributed to amantadine being a more-expensive prophylaxis strategy than oseltamivir. Both prophylaxis strategies were more cost-effective than no prophylaxis. CONCLUSION: Despite high influenza vaccination rates, influenza outbreaks continue to emerge in LTCFs, necessitating cost-effective measures to further limit the spread of influenza and related complications. Although amantadine has a lower acquisition cost than oseltamivir, it is associated with more adverse events, lower efficacy, and individualized dosing requirements, leading to higher overall costs and more influenza-like illness cases than oseltamivir. Therefore the use of oseltamivir postexposure prophylaxis is more cost-effective than the current standard of care with amantadine prophylaxis or no prophylaxis.     

Use of oseltamivir during influenza outbreaks in Ontario nursing homes, 1999-2000

OBJECTIVES: To describe the experience of Ontario long-term care facilities that used oseltamivir during influenza outbreaks in 1999/2000. DESIGN: Case series. SETTING: Ten Ontario long-term care facilities for older people and their residents. PARTICIPANTS: Older residents of long-term care facilities. INTERVENTION: Oseltamivir for treatment or prophylaxis during 11 influenza outbreaks in 1999/2000. MEASUREMENTS: Control of outbreaks; pneumonia, hospitalization, and death complicating acute influenza. RESULTS: All outbreaks were due to influenza A//H3N2/Sydney/05/97. One facility elected to use oseltamivir for treatment and amantadine for prophylaxis. The remaining nine facilities (10 outbreaks) recommended oseltamivir for treatment and prophylaxis (after amantadine failure in five and as primary prophylaxis in five). Use of oseltamivir was associated with termination of the outbreak in all eight evaluable outbreaks. Overall, 178/185 (96%) case-residents met the case definition of influenza and had complete data for evaluation. Of these, 63 (35%) were treated with antibiotics, 37 (21%) were diagnosed with pneumonia, 19 (11%) were hospitalized, and 16 (9%) died. Compared with residents receiving no therapy or who became ill while taking amantadine, residents who received oseltamivir within 48 hours of the onset of symptoms were less likely to be prescribed antibiotics, to be hospitalized, or to die (P <.05 for each outcome). These differences persisted and remained statistically significant when corrected for influenza immunization status. A total of 730 residents received oseltamivir prophylaxis for a median of 9 days (range 5-12). Of these, side effects were identified in 30 (4.1%), the most common being diarrhea (12 residents, 1.6%), cough (5, 0.7%), confusion (4, 0.5%) and nausea (4, 0.5%). CONCLUSIONS: Oseltamivir is safe and appears to be effective when used as treatment or prophylaxis to control outbreaks of influenza in older nursing home residents.     

Respiratory illnesses in Canadian health care workers: a pilot study of influenza vaccine and oseltamivir prophylaxis during the 2007/2008 influenza season

Please cite this paper as: Coleman et al. (2011) Respiratory illnesses in Canadian health care workers: a pilot study of influenza vaccine and oseltamivir prophylaxis during the 2007/2008 influenza season. Influenza and Other Respiratory Viruses 5(6), 404–408. Background Data regarding both rates of acute respiratory illness in health care workers and experience with long‐term antiviral prophylaxis are sparse. Objective To determine the efficacy and tolerability of oseltamivir prophylaxis versus seasonal influenza vaccine for the prevention of influenza among health care workers. Methods We conducted a pilot, randomized control study during the 2007/2008 influenza season in a tertiary care setting. Adult health care workers 18–69 years of age were recruited and randomly assigned in a 4:1 ratio to receive either oseltamivir (Tamiflu^®; Roche) 75 mg once daily prophylaxis or seasonal influenza (Fluviral^®) vaccine. Results Of 56 adults enrolled, 12 received vaccine and 44 received prophylaxis. Incidence of symptomatic laboratory‐confirmed influenza was similar for participants in the vaccine and prophylaxis arms (17% and 24%, respectively; P = 0·71). Participants who developed an acute respiratory illness during the study period reported working 85% of scheduled work days, and 29% stated that they worked despite feeling miserable because they were too busy to stay home. Of 42 participants who initiated oseltamivir prophylaxis, four discontinued it owing to side effects. Median duration of oseltamivir prophylaxis was 121 days, with 34 (81%) continuing ≥12 weeks. Conclusions During an extended season of suboptimal vaccine match, 22% of health care workers receiving antiviral prophylaxis or seasonal influenza vaccine developed symptomatic laboratory‐confirmed influenza. Long‐term antiviral prophylaxis against influenza was generally well tolerated with good compliance.     

Comparisons of oseltamivir‐resistant (H275Y) and concurrent oseltamivir‐susceptible seasonal influenza A(H1N1) virus infections in hospitalized adults, 2008–2009

In an observational cohort study, we found that adults hospitalized for oseltamivir‐resistant (H275Y) seasonal H1N1 influenza (n = 46) were older than those infected with oseltamivir‐susceptible strains (n = 31) [74(IQR 59–83) versus 64(IQR 48–76) years; P = 0·045], and most had major comorbidities (78% versus 65%). Disease severity and clinical outcomes were comparable between the two groups: radiographic pneumonia 40–42%, supplemental oxygen use 47–48%, critical illness 11–13%, median duration of hospitalization 5–6 days, death rate 6–9%. Failure to receive effective antiviral therapy was associated with progression to critical illness (23% versus 0%, P = 0·016) and death (20% versus 0%, P = 0·033) in hospitalized patients with seasonal H1N1 influenza.     

2009 pandemic Influenza A (H1N1): clinical and laboratory characteristics in pediatric and adult patients and in patients with pulmonary involvement

Please cite this paper as: Lee and Liu et al. (2012) 2009 pandemic Influenza A (H1N1): clinical and laboratory characteristics in pediatric and adult patients and in patients with pulmonary involvement. Influenza and Other Respiratory Viruses 6(601), e152–e161. Background To better understand clinical and laboratory characteristics in children, adults, and patients with lung involvement suffering 2009 pandemic influenza A (H1N1). Methods A total of 442 patients with 2009 pandemic influenza A (H1N1) were retrospectively analyzed. Results Comparing to their adult counterpart (n = 55), pediatric patients (n = 387) had significantly higher frequencies of fever, rhinorrhea, cough, sore throat, nausea/vomiting, and longer length of fever; lower frequencies of chest pain and dyspnea; higher incidence of lymphopenia; and lower incidence of elevated serum C‐reactive protein. Among the 227 patients with radiographs available, lung involvement was found in 19 (8·4%) (52·6% consolidation and 47·4% interstitial infiltrations), including 18 children and one adult. One child with lung consolidation died of multiorgan failure. Significant findings in patients with lung involvement included predominant young age (≤10 years), prolonged fever, and delayed oseltamivir therapy (≥48 hours after onset of illness); higher frequencies of dyspnea, nausea/vomiting, and altered consciousness; and higher incidences of leukopenia, elevated serum creative kinase, and lactic dehydrogenase. Conclusions Among patients with 2009 pandemic influenza A (H1N1), we found significant difference in clinical manifestations between children and adults, and significant differences in clinical and laboratory manifestations between patients with lung involvement and those without. On the basis of data from this study and the existing literature, early treatment with oseltamivir is recommended for patients with 2009 pandemic influenza A (H1N1), regardless of age.     

Clinical and virologic outcomes in patients with oseltamivir-resistant seasonal influenza A (H1N1) infections: results from a clinical trial

Nineteen patients with oseltamivir-resistant seasonal influenza A (H1N1) infections were randomized to receive oseltamivir or placebo. Nasopharyngeal swabs were obtained, and clinical and virologic outcomes were compared, stratified by early or late treatment. Neuraminidase inhibition assay and pyrosequencing for H275Y confirmed resistance. Twelve (63%) patients received oseltamivir; 8 (67%) received late treatment. Seven (37%) patients received placebo; 6 (86%) presented >48 hours after onset. Time to 50% decrease in symptom severity, complete symptom resolution, and first negative culture were shortest among the early treatment group. While sample size prohibits a strong conclusion, future studies should evaluate for similar trends.     

Mutations I117V and I117M and oseltamivir sensitivity of pandemic (H1N1) 2009 viruses

Analysis of mutations I117V and I117M in the neuraminidase of influenza A pandemic (H1N1) 2009 viruses showed that I117V confers a mild reduction in oseltamivir sensitivity and has a synergistic effect of further increasing resistance when combined with H275Y. Contrary to recent reports, the I117M mutation does not alter oseltamivir sensitivity.