Adverse effects of amantadine and oseltamivir used during respiratory outbreaks in a center for developmentally disabled adults.

BACKGROUND AND OBJECTIVES: Antiviral prophylaxis is recommended for the control of institutional influenza A outbreaks. In long-term-care institutions other than nursing homes, neither the seriousness of influenza nor the risks and benefits of antiviral prophylaxis is clearly understood. We studied the severity of illness due to influenza among adults residing in a center for the developmentally disabled and assessed adverse reactions to amantadine and oseltamivir prophylaxis. METHODS: Data were collected from the charts of consenting residents. Complications of upper respiratory tract illness were recorded. Potential adverse events were documented during amantadine and oseltamivir therapy, and during a baseline period with neither medication. RESULTS: The median age of the 287 participants was 46.4 years. Only 15 (5%) were older than 65 years, and 69 (24%) had chronic underlying medical illness placing them at high risk for influenza. Of the 122 residents with an upper respiratory tract infection, 16 (13%) developed pneumonia, 12 (9.8%) were hospitalized, and 5 (4%) died. Twenty-eight (25%) of 112 residents had an adverse neurologic event while receiving amantadine prophylaxis, compared with 3 (2.7%) receiving no antiviral medication and 5 (4.5%) receiving oseltamivir (P < .001). Sixteen percent of the residents discontinued amantadine due to adverse events; in contrast, adverse events were identified in 2.9% of the residents prescribed oseltamivir, and none discontinued therapy. CONCLUSIONS: Viral respiratory tract infections are associated with a high risk of complications in this population. The rate of adverse neurologic events associated with amantadine was significantly higher than that associated with oseltamivir.

Influenza infections after hematopoietic stem cell transplantation: risk factors, mortality, and the effect of antiviral therapy.

BACKGROUND: Community-acquired respiratory viruses, such as influenza virus, are thought to be major causes of morbidity and mortality in patients who had undergone hematopoietic stem cell transplantation (HSCT). Risk factors for acquisition, progression to pneumonia, and the effect of antiviral therapy are unknown. METHODS: We reviewed records from patients with documented influenza over 12 consecutive respiratory-virus infection seasons at a single transplantation center. RESULTS: From 1 September 1989 through 31 March 2002, influenza virus was isolated from 62 of 4797 persons undergoing HSCT (1.3%); 44 patients had upper respiratory tract infections (URIs) alone, and 18 developed pneumonia. Among patients with influenza virus infection, pneumonia developed more commonly among those infected earlier after transplantation (median, 36 vs. 61 days, P=.04) and those with concurrent lymphopenia. Of the 51 cases that were initially diagnosed as URIs, 17 were treated with antivirals, and 34 were not treated. Six untreated patients (18%) developed pneumonia, whereas 1 (13%) of 8 patients treated with rimantadine and 0 of 9 treated with oseltamivir developed pneumonia. The duration of influenza virus shedding was longer in patients treated with steroid doses of >1 mg/kg than among those treated with doses of <1 mg/kg (mean, 15 vs. 9 days); there was a trend towards decreased shedding with oseltamivir therapy (but not rimantadine therapy) after controlling for steroid use (P<.08). The 30-day mortality rate was highest among patients who had progression to pneumonia (5 [28%] of 18 patients); pulmonary copathogens (such as Aspergillus fumigatus) were commonly isolated. CONCLUSIONS: Influenza virus infection is an important cause of mortality early after HSCT. Our nonrandomized data suggest that early antiviral therapy with neuraminidase inhibitors may prevent progression to pneumonia and decrease viral shedding, which may prevent both influenza-related death in index patients and nosocomial transmission to others.

In vivo influenza virus-inhibitory effects of the cyclopentane neuraminidase inhibitor RJW-270201.

The cyclopentane influenza virus neuraminidase inhibitor RWJ-270201 was evaluated against influenza A/NWS/33 (H1N1), A/Shangdong/09/93 (H3N2), A/Victoria/3/75 (H3N2), and B/Hong Kong/05/72 virus infections in mice. Treatment was by oral gavage twice daily for 5 days beginning 4 h pre-virus exposure. The influenza virus inhibitor oseltamivir was run in parallel, and ribavirin was included in studies with the A/Shangdong and B/Hong Kong viruses. RWJ-270201 was inhibitory to all infections using doses as low as 1 mg/kg/day. Oseltamivir was generally up to 10-fold less effective than RWJ-270201. Ribavirin was also inhibitory but was less tolerated by the mice at the 75-mg/kg/day dose used. Disease-inhibitory effects included prevention of death, lessening of decline of arterial oxygen saturation, inhibition of lung consolidation, and reduction in lung virus titers. RWJ-270201 and oseltamivir, at doses of 10 and 1 mg/kg/day each, were compared with regard to their effects on daily lung parameters in influenza A/Shangdong/09/93 virus-infected mice. Maximum virus titer inhibition was seen on day 1, with RWJ-270201 exhibiting the greater inhibitory effect, a titer reduction of >10(4) cell culture 50% infective doses (CCID(50))/g. By day 8, the lung virus titers in mice treated with RWJ-270201 had declined to 10(1.2) CCID(50)/g, whereas titers from oseltamivir-treated animals were >10(3) CCID(50)/g. Mean lung consolidation was also higher in the oseltamivir-treated animals on day 8. Both neuraminidase inhibitors were well tolerated by the mice. RWJ-270201 was nontoxic at doses as high as 1,000 mg/kg/day. These data indicate potential for the oral use of RWJ-270201 in the treatment of influenza virus infections in humans.

Effectiveness of oseltamivir on influenza and influencing factors: age of patients, type of influenza virus and timing of initial administration

A multi-center open study using the internet was performed during the influenza season of 2001-2002 to evaluate the effectiveness of the anti-influenza agent, oseltamivir, on influenza in relation to: (1) age of patients; (2) type of influenza virus; and (3) timing of initial administration after the onset of the first symptoms of influenza. The study comprised of 779 cases of influenza confirmed by rapid detection tests from 44 clinics in Japan. Patients consisted of 4 age groups, 0-6, 7-15, 16-64 and 65-85 years. All patients were administered oseltamivir within 24 hours, at 25-48 or after 48 hours from the onset of the first symptoms of influenza. Data collected from each age group were the highest body temperature and duration of fever (> or = 37.5 degrees C). The percentage of afebrile patients was calculated at 24, 48 and 72 hours after the initial administration; data were also evaluated by the type of influenza virus A and B. The highest body temperature was higher with statistical significance as patients' age decreased. The duration of febrile period (days) was significantly longer in 0-6 years (2.57 +/- 0.95) than in 65-85 years (2.18 +/- 0.93). Evaluation of the percentage of afebrile patients revealed: the percentage at 24 hours was significantly lower in 0-6 years (28.4%) than in 16-64 years (44.0%); the percentage at 48 and 72 hours showed similar results in each age group; the percentage at 48 and 72 hours was significantly higher when administered initially within 24 hours than over 48 hours after the onset of the first symptoms of influenza; the percentage at 24 and 48 hours was significantly higher when administered within 24 hours than at 25-48 hours; and the type of influenza virus did not affect the percentage. In conclusion, effectiveness of oseltamivir seemed to be affected to an extent by the patients' age and little by the type of influenza virus. Oseltamivir was more effective when administered as early as possible after the onset of the symptoms of influenza.