Treatment of an influenza A outbreak in a teaching nursing home. Effectiveness of a protocol for prevention and control

The safety and efficacy of current ACIP guidelines for the prevention and control of influenza in nursing home populations are uncertain. An outbreak of influenza A/Sichuan (H3N2) in a teaching nursing home during 1988 gave us the opportunity to evaluate the effectiveness of an influenza vaccination and amantadine prophylaxis protocol. Over 13 days, 12 of 60 residents developed influenza. Prior influenza vaccination had been given to 94% of the residents. Protection from infection occurred in those tested who had antibody levels greater than or equal to 1:16 to the A/Leningrad (H3N2) antigen contained in the standard 1987-88 trivalent vaccine. However, five of 17 vaccinated residents who were tested had antibody levels less than or equal to 1:16 at the start of the outbreak. Amantadine (less than or equal to 100 mg/day) was given to all but one resident starting on the third day of the outbreak, and to employees starting on the sixth day of the outbreaks. Seven residents developed illness after the start of amantadine, although amantadine appeared to ameliorate their symptoms. Although amantadine was generally well tolerated by residents, employees receiving amantadine identified a high incidence of side effects and only 44% of employees took at least 70% of the prescribed amantadine. In our opinion, early detection and protocol-directed intervention probably abated a more severe influenza outbreak. Therefore we support existing recommendations that formal nursing home policies be established to ensure that residents and employees receive annual influenza vaccine and that chemoprophylaxis be used when outbreaks of influenza A are suspected.     

Amantadine usage for influenza A during an influenza outbreak in a nursing home

An outbreak of an influenza like illness was found in a nursing home in Fukuoka in January, 1999. Results of hemagglutinin inhibition tests with paired sera of patients and rapid diagnosis kit for influenza A indicated that an influenza A (H3N2) outbreak had occurred. A total of 15 patients with influenza like illness from one residential area of the nursing home were administered amantadine, 100 mg per day for five days. Clinical records of 264 residents were surveyed retrospectively from the tenth to the thirty-first of January, 1999. Influenza like illness was found in 112 residents (42.4%). The incidence of influenza like illness differed by residential area, ranging from 27.6% to 54.0%. The mean duration of fever was 3.6 days among patients administered amantadine. The mean duration was 4.4 days for patients not administered amantadine. The incidence of influenza like illness decreased rapidly after amantadine administration in the residential area where amantadine administration was done. These results suggest that amantadine is effective in mitigating influenza symptoms in the elderly. Amantadine may be useful for diminishing the influence of influenza A outbreaks in nursing homes.     

Comparison of central nervous system adverse effects of amantadine and rimantadine used as sequential prophylaxis of influenza A in elderly nursing home patients

BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride are recommended by the Centers for Disease Control and Prevention for prophylaxis of influenza A. While data suggest that rimantadine is better tolerated, there are no data examining the rate of adverse reactions in elderly patients who receive amantadine vs rimantadine. Our objective was to assess the adverse reaction rate in elderly nursing home patients receiving sequential amantadine and rimantadine for influenza A prophylaxis. METHODS: Data were collected in 156 nursing home patients (70% women; mean+/-SD age, 83.7+/-10.1 years) in a single care setting who received sequential therapy with amantadine and rimantadine during the 1997-1998 influenza season. Patients were assessed for central nervous system adverse effects and therapy discontinuation occurring with each agent. RESULTS: Twenty-nine (18.6%) of the 156 patients experienced an adverse effect when receiving amantadine compared with 3 patients (1.9%) when rimantadine was given (P<.01). Drug use was discontinued due to adverse events in 17.3% (n = 27) of the amantadine courses and 1.9% (n=3) of the rimantadine courses (P<.001). Confusion was the most frequently observed adverse event (amantadine, 10.6%; rimantadine, 0.6%; P<.001). Multivariate logistic regression analysis showed that significant risk factors for central nervous system adverse events included male sex (odds ratio, 3.65), reduced calculated creatinine clearance (odds ratio, 1.78), and use of amantadine (odds ratio, 12.73). CONCLUSIONS: Amantadine use was associated with a significantly higher incidence of central nervous system adverse events than rimantadine use in this elderly population receiving influenza prophylaxis. In addition, the discontinuation rate of amantadine was significantly higher than that with rimantadine.     

Serum concentration of amantadine in the treatment of children with influenza type A infection

Fifteen children with influenza type A (H3N2) virus infection (mean age, 38 months) were treated with amantadine. Amantadine was prescribed as 5 mg/kg/day and the serum concentration was measured in 5-7 days. As a result, the mean serum concentration of amantadine was 164.6 +/- 92.5 ng/ml (range, 67.4-446.9 ng/ml). Adverse reactions were not associated to them. Amantadine therapy against influenza type A infection is probably safe in children because of the low serum concentration shown in this study.     

Emergence and transmission of amantadine-resistant influenza A in a nursing home

OBJECTIVES: To prospectively detect amantadine-resistant influenza when amantadine was used for influenza A outbreak control. DESIGN: Prospective clinical surveillance and viral culture of all new respiratory illnesses during the course of amantadine prophylaxis. SETTING: A 721-bed, 14-ward nursing home for veterans and spouses during an influenza A outbreak (1993-94). PARTICIPANTS: Residents of a veterans hospital and their spouses. MEASUREMENTS: Nasopharyngeal and throat viral culture. All residents with positive cultures who developed new respiratory symptoms while receiving or residing on a unit receiving amantadine prophylaxis had antiviral-resistance testing and polymerase chain reaction restriction analyses performed. RESULTS: Amantadine prophylaxis was administered sequentially on nine of 14 wards to all well residents for 14 to 31 days/ward to control influenza outbreaks between December 9, 1993, and January 28, 1994. Amantadine treatment was simultaneously provided to 29 ill residents. Between December 3, 1993, and January 22, 1994, 68 culture-positive cases of influenza A were detected. Twenty subjects were receiving or residing on units receiving amantadine prophylaxis. Amantadine sensitivity testing could be performed on 16 residents; 12 residents had amantadine resistant strains. Four of the 12 had not received any antiviral treatment. Illness onset ranged from 1 to 22 days after amantadine prophylaxis was begun on the individual's unit. Two ribonucleic acid (RNA) mutations in the gene coding the M2 protein transmembrane region were observed that were clustered in time and space. Isolates from two roommates, one receiving amantadine for 18 days and one on no antiviral, had identical RNA sequences. CONCLUSION: Antiviral resistance may be responsible for failure of prophylaxis in nursing home outbreaks. Strategies that use different classes of antivirals for prophylaxis and treatment may limit emergence and transmission of resistant virus.     

The roles of vaccination and amantadine prophylaxis in controlling an outbreak of influenza A (H3N2) in a nursing home

An outbreak caused by influenza A/Philippines/2/82 (H3N2)-like viruses occurred in a partially vaccinated nursing home population in January 1985. During the first six days of the outbreak, 14 (25%) of 55 residents developed influenzalike illness. The risk of illness was most strongly associated with undetectable levels of antibody against the epidemic strain, with unvaccinated case-patients having more severe illnesses and a higher rate of hospitalization than vaccinated case-patients (5/8 vs 0/6). During the period of amantadine hydrochloride prophylaxis (100 mg/d) from days 7 to 35, only two (5%) of the remaining 41 residents became ill, even though 11 (27%) had no detectable antibody. Serum amantadine levels obtained on day 35 ranged from 117 to 737 ng/mL (mean 309 ng/mL), similar to therapeutic levels documented in younger adults who have taken the standard regimen of 200 mg/d; there were few clinically significant side effects. These findings illustrate the benefits of influenza vaccination and support the use of amantadine hydrochloride at a dosage of 100 mg daily for outbreak control among elderly persons.     

Adverse reactions to amantadine prophylaxis of influenza in a retirement home

OBJECTIVE: Controversy exists about the safety of following the recommendation of the Immunization Practice Committee of the Centers for Disease Control that nursing home residents be given amantadine prophylaxis during influenza outbreaks. This study was undertaken to define the incidence of adverse reactions to amantadine in the elderly and to identify risk factors for side effects. DESIGN: A retrospective cohort study. SETTING: A retirement home which offered amantadine prophylaxis to its residents during a presumed influenza outbreak. PARTICIPANTS: Of the 96 elderly residents, 79 accepted the offer of amantadine prophylaxis. MAIN OUTCOME MEASURES: Attributable adverse health outcomes as assessed by chart review. RESULTS: 41% of the people receiving amantadine had attributable adverse reactions, of which 22% were classified as severe. Severe adverse reactions were associated with residence in the assisted living section of the facility (P = 0.002), a greater number of underlying diagnoses (P = 0.009), congestive heart failure (P = 0.02), and high serum creatinine (P = 0.02). A person with none of these risk factors had a 7% chance of having a severe adverse outcome compared to a 70% chance for someone with all four risk factors. CONCLUSION: The findings raise concern that the prophylactic administration of amantadine to all elderly residents of nursing and retirement homes may be associated with a high incidence of unacceptable reactions, particularly among less healthy residents.     

Amantadine prophylaxis during an institutional outbreak of type A (H1N1) influenza

In January 1984, an outbreak of influenza caused by A/Victoria/7/83-like virus, a new H1N1 variant, occurred in an institution for mentally handicapped children and adults. During the first 18 days of the outbreak, 35 (81%) of 43 residents in two housing modules became ill, nearly all of whom had received influenza vaccine the previous autumn. Amantadine hydrochloride prophylaxis was initiated in two other housing modules and was continued for 28 days. While factors influencing the risk of introduction and secondary spread of influenza virus were comparable in all four modules, only ten (16%) of 63 residents who received amantadine were infected, only one of whom became symptomatic. Most side effects associated with amantadine were mild, but residents with active, preexisting major-motor seizure disorders demonstrated an increase in seizure activity compared with the previous eight-month period; those who took the maximum daily dose of amantadine hydrochloride (200 mg) and those who were also taking anticonvulsants other than phenobarbital were at highest risk.     

Amantadine therapy for chronic hepatitis C: a dose escalation study

OBJECTIVES: Amantadine reduces liver transaminase levels in some patients with chronic hepatitis C at doses of 200 mg daily and may improve the sustained virological response (SVR) when given with interferon and ribavirin. The primary purpose of the present investigation was to study the safety and toxicity of higher doses of amantadine in subjects who previously failed or were intolerant to interferon. The secondary aim was to test the efficacy of higher dose of amantadine against hepatitis C. METHODS: An open-labeled prospective study was conducted starting with amantadine 200 mg daily and increasing to 500 mg daily while monitoring for safety, toxicity, and efficacy. An amantadine blood level exceeding 1,600 ng/ml was considered toxic requiring dose reduction. The patient's symptoms, laboratory tests, and quality of life were monitored. RESULTS: One hundred patients enrolled in the study. Normalization of alanine aminotransferase (ALT) for each dose was as follows: 200 mg (35%), 300 mg (49%), 400 mg (53%), and 500 mg (56%). The incidence of toxic amantadine plasma levels increased with dose, i.e., 200 mg (0%), 300 mg (6%), 400 mg (27%), and 500 mg (49%). The frequency and severity of arthralgias and fatigue improved at all dosages administered. No changes in the occurrence or severity of headache, insomnia, or depression were reported. Serious adverse events included myocardial infarction and suicide attempt. Other side effects included impotence, confusion, alopecia, and hoarseness. CONCLUSIONS: Amantadine given at a dose of 300 mg daily is safe, and significantly lowers ALT blood levels more than 200 mg daily. The enzyme response rate does not significantly improve above 300 mg, but toxicity increases.     

Amantadine for prophylaxis against influenza A

Amantadine, 200 mg daily, for 5 days was used in an attempt to restrict the spread of influenza A in a hospital ward. After index cases of influenza A amantadine was given to 2 patients with clinical symptoms and to 8/10 patients who were not yet ill. No further case of clinical influenza was seen among the patients, but 3 of those receiving amantadine developed subclinical infection. No side effects of amantadine were noted. Amantadine was not given to any of the 23 hospital staff on duty. In this group 8 cases of influenza A appeared, 3 of them during the week after the introduction of amantadine to patients.     

Effect of post-exposure prophylaxis with oseltamivir for those in contacts with influenza patients in pediatric wards

During the influenza season, outbreaks of influenza may occur in the pediatric wards due to spread from the patients hospitalized with influenza, or from those hospitalized during the latency period and develop influenza afterwards. Post-exposure prophylaxis with neuraminidase inhibitors has been reported to be effective in preventing outbreaks among household members and nursing home residents. However, for nosocomial spread, its effectiveness and possible adverse effects are to be determined. During the 2002/2003 influenza season, we experienced a total of 3 nosocomial outbreaks of influenza in the pediatric wards in two hospitals in the Kanto district, Japan. Since the number of contacts who developed influenza had been increasing despite the isolation precaution implemented, post-exposure prophylaxis with oseltamivir (2 mg/kg/dose, maximum 75 mg/dose, once a day for 7-10 days) was implemented with a permission from the parents to terminate the outbreaks. In the outbreaks (one with influenza A, two with influenza B), a total of 29 inpatients had contact with influenza patients: among those 29, 13 were given post-exposure prophylaxis, 16 were not. Out of 16 patients who did not receive post-exposure prophylaxis, 11 (69%) developed influenza: out of 13 with post-exposure prophylaxis, none developed influenza. Those patients who developed influenza were given oseltamivir (2 mg/kg/dose, maximum 75 mg/dose, twice a day for 5 days) and accommodated in a private room or a room with other patients with influenza of the same type. No significant adverse effects due to oseltamivir were observed among those who were enrolled in this study.     

Mild vitamin D deficiency and secondary hyperparathyroidism in nursing home patients receiving adequate dietary vitamin D.

OBJECTIVE: To compare the vitamin D metabolite and nutritional status of institutionalized elderly males with a noninstitutionalized control group. DESIGN: Case-control study. SETTING: Veterans Administration Medical Center Nursing Home (NH) in Richmond, Virginia. PATIENTS: Fifty-seven consecutive nursing home subjects were screened. After excluding blacks, those receiving anticonvulsants, glucocorticoids, or vitamin supplements, and those with liver or renal failure (creatinine greater than 1.5 mg/dL), 35 subjects were enrolled, and 22 completed the study. The noninstitutionalized control group (n = 18) consisted of consecutive volunteers, meeting the above criteria, from either a senior citizen group or a geriatric clinic. MEASUREMENTS AND MAIN RESULTS: The serum 25-hydroxy-vitamin D level in the NH residents was significantly lower than in community dwellers (17.4 +/- 5.2 ng/mL vs 31.2 pg/mL +/- 8.0 ng/mL, P less than 0.0001). No significant difference was demonstrated in 1,25-dihydroxyvitamin D levels (36.5 pg/mL +/- 10.5 in NH residents vs 42.0 pg/mL +/- 11.1 in controls). In the NH group PTH levels were inversely correlated with 25 OHD levels (P less than 0.008) and positively correlated with length of stay in the NH (P less than 0.016). There was no significant seasonal variation in vitamin D metabolite levels in the NH group. In the NH patients, the mean dietary intake of vitamin D was 232 +/- 378 mg/day and of calories was 1811 +/- 447 kcal/day. CONCLUSION: Despite apparently adequate calories, calcium, and vitamin D intake, hypovitaminosis D with compensatory PTH elevations occurs, regardless of season, in the nursing home population.     

Amantadine's Viral Kinetics in Chronic Hepatitis C Infection

Treatment for hepatitis C virus infection is limited in patients not responding to traditional therapy. Amantadine is effective for influenza infections and has been studied in patients with hepatitis C. Our aim was to determine the efficacy and safety of amantadine and to study the viral kinetics following amantadine therapy. Twelve patients with detectable HCV antibodies received amantadine 100 mg, orally twice daily. Serial HCV RNA and ALT blood samples were drawn and adverse effects were evaluated. Mean HCV RNA levels did not decrease in the first 24 hr of amantadine therapy but did decline significantly by day 3, only to rebound by day 7. All HCV RNA levels remained detectable throughout therapy and were not different from baseline values. Thirty-three percent of the patients obtained normal ALT levels after the first 24 hr of treatment and levels remained within normal range throughout the study period. More than a third of the patients discontinued therapy due to severe adverse effects occurring within one to three months after initiating treatment. In conclusion, although amantadine therapy alone was not effective, it should be considered as an adjunctive form of therapy along with interferon and ribavirin.     

Previous creatinine levels safely predict amantadine dose for influenza A outbreak control

BACKGROUND:

Amantadine, an antiviral agent, is the only drug currently approved in Canada for prophylaxis of influenza A virus infection. To minimize side effects, the amantadine dose is adjusted for age and estimated creatinine clearance (CrCl) based on plasma creatinine (Cr) levels. As amantadine is used more frequently for influenza A outbreak control in care facilities for elderly people, physicians are increasingly called on to prescribe it for residents and to consider the necessity of requesting plasma Cr levels.

OBJECTIVE:

To determine whether previous Cr levels are predictive in estimating current CrCl and safe amantadine dose determination.

DESIGN AND SETTING:

Residents'' charts were reviewed in two facilities in Vancouver, British Columbia. CrCl estimated using previous or current Cr results, current weight and age, as well as recommended amantadine doses based on Canadian National Advisory Committee on Immunization guidelines, were studied.

RESULTS:

165 charts with Cr results in March 1998 were included; 122 had results before March 1998, and 103 had Cr results after March 1998. Pearson''s correlation coefficient for CrCl estimated from current and previous Cr values was 0.929 for results less than six months previously, 0.974 for six to 12 months previously and 0.952 for 12 to 18 months previously. The same or a more conservative dose of amantadine was predicted in 92% of cases when using a Cr result taken within the previous year and in 76% of cases when using a Cr result taken 12 to 18 months previously.

CONCLUSION:

In long term care facilities, Cr levels measured up to 12 months previously can usually safely be used to estimate CrCl. Using previous Cr results permits advance preparation of doctor''s orders for amantadine prophylaxis and avoids repeating Cr testing on every resident when an outbreak occurs, reducing related staff time and cost.Key Words: Amantadine hydrochloride, Care facilities, Creatinine clearance, Influenza, Plasma creatinine, ProphylaxisInfluenza is a major infectious cause of death in the elderly, with institutionalized seniors particularly at high risk. Amantadine hydrochloride is the only drug approved in Canada for prophylaxis of influenza A virus infection. Because amantadine is used more frequently for influenza A outbreak control in long term care facilities (LTCFs), physicians are increasingly called on to prescribe it for residents and to consider the necessity of requesting plasma creatinine (Cr) levels to determine the appropriate amantadine dose.Amantadine is 70% to 90% effective in preventing illness caused by influenza A viruses (1), and reduces the severity and duration of influenza A illness if administered within 48 h of onset. About 5% to 10% of healthy young adults taking amantadine for prophylaxis report difficulty concentrating, insomnia, light-headedness and irritability. These side effects are usually mild and cease shortly after the prophylaxis is stopped but may be more frequent in the older population unless a reduced dosage is used. Serious side effects (eg, marked behavioural changes, delerium, hallucinations, agitation and seizures) have been associated with high plasma drug concentrations. Amantadine is excreted by the kidney unmetabolized. To avoid toxic levels, persons with impaired renal function should receive a lower dose. Creatinine clearance (CrCl) is used to reflect renal function and is estimated from Cr levels using the following formulas (2):Male CrCl (mL/min) = [(140 - age) x weight (kg)] / [serum creatinine (µmol/L) x 0.81]Female CrCl (mL/min) = 0.85 x male CrCl

Rimantadine hydrochloride and amantadine hydrochloride use in influenza A virus infections

Amantadine and rimantadine are oral antiviral drugs useful in the prophylaxis and treatment of influenza A virus infections. This article reviews the pharmacology, antiviral activity and mechanism of action, pharmacokinetics, toxicities, efficacy, and clinical applications of these agents. When administered in equivalent dosages (200 mg per day), rimantadine has prophylactic efficacy comparable to amantadine but lower potential for causing adverse effects. Despite structural similarities, these drugs differ significantly in their pharmacokinetics, and these differences may account for rimantadine's more favorable toxicity profile. Both drugs provide therapeutic benefit if administered early in uncomplicated influenza, and studies are currently in progress to determine the effectiveness of oral rimantadine in preventing or treating the serious complications of influenza A virus infections.     

An outbreak of influenza A (H3N2) in a well immunized nursing home population.

OBJECTIVE: To describe the epidemiologic features of an outbreak of influenza A that occurred in a skilled nursing home although over 90 percent of the resident population had previously received influenza vaccine. DESIGN: Retrospective cohort study. SETTING: Skilled nursing home facility in western New York State. PATIENTS: Nursing home residents and patient-care staff. MAIN OUTCOME MEASURE: Incidence of influenza-like illness among vaccinated versus unvaccinated nursing home residents and staff. RESULTS: Thirty-seven of 124 residents (attack rate = 30%) and 18 of 146 staff (attack rate = 12%) had an influenza-like illness. Staff illness began 16 days prior to onset among residents. Six cases of pneumonia and three influenza-related deaths occurred, all among the vaccinated residents. Ninety percent of the nursing home residents and 10% of the staff received the influenza vaccine prior to the outbreak. The calculated vaccine efficacies were minus 21% and plus 45% for residents and staff, respectively. CONCLUSION: While antigenic drift of the circulating influenza virus was the major factor in the apparent vaccine failure, the observed poor staff immunization rate (10%) and absence of surveillance which precluded the use of amantadine chemoprophylaxis suggest that the use of these strategies may be of importance in controlling influenza outbreaks in nursing homes.     

Experience with oseltamivir in the control of nursing home influenza A outbreak

OBJECTIVE: Influenza outbreaks have revealed that elderly persons are a great risk of death and serious complications after infection. The administration of oseltamivir, a neuramidase inhibitor, is effective for prophylaxis of influenza and to reduce disease duration and severity in healthy adults with naturally acquired febrile influenza. To clarify the usefulness of oseltamivir in the elderly we administered oseltamivir to all residents when an influenza A outbreak occurred in a nursing home. PATIENTS: Sixty-eight residents in the nursing home were investigated in which the influenza A outbreak occurred; 32 residents had fever and 28 residents were positive for influenza A with direct enzyme immunoassay. METHODS: Oseltamivir was administered at 75 mg twice daily for 5 days to all residents. RESULTS: Oseltamivir almost inhibited symptom onset in the influenza A-positive afebrile group. Initiation at 0 hour (22 cases), 1-12 hours (4 cases), 13-24 hours (5 cases) or 72 hours (1 case) from onset of symptoms was associated with mean fever durations of 26+/-18 hours, 38+/-21 hours, 54+/-12 hours and 120 hours, respectively, indicating that earlier initiation of therapy was associated with faster resolution of fever in elderly patients. Oseltamivir may be effective for household prophylaxis in the elderly persons. Oseltamivir administration was well tolerated in elderly persons. CONCLUSION: Oseltamivir is effective for the reduction or prophylaxis of influenza A infection in elderly persons.     

Pharmacokinetics and pharmacodynamic action of budesonide in early- and late-stage primary biliary cirrhosis

Budesonide has been discussed as a potential treatment option in primary biliary cirrhosis (PBC). Therefore, we studied the pharmacokinetics and pharmacodynamics of budesonide in patients with PBC stage I/II and stage IV. Twelve patients with early PBC stage I/II and 7 patients with PBC stage IV under continuous treatment with ursodeoxycholic acid (UDCA) were enrolled in an exploratory trial. Each patient received oral budesonide for 3 weeks at weekly increasing dosages of 3 mg once to thrice per day. Budesonide and cortisol plasma levels, urinary cortisol excretion, serum liver tests, and immunoglobulins were determined on days 1, 7, and 21 of the study. Patients with PBC stage IV showed significantly higher peak plasma concentrations (4.9 +/- 3.5 vs. 1.5 +/- 0.4 ng/mL; P <.05) and areas under the plasma concentration-time curves (AUC) (23.2 +/- 16.8 vs. 5.1 +/- 1.4 hours. ng/mL, P <.01, total AUC extrapolated to infinity [AUC(0- infinity )]) after a single dose of 3 mg budesonide when compared with patients with PBC stage I/II. Equally, AUC of budesonide were significantly increased under a multiple dose regimen on day 21 (14.0 +/- 11.6 vs. 5.0 +/- 1.9 hours. ng/mL, P <.01, AUC at steady state from dosing time to 8 hours [AUC(ss,0-8 h)]). Higher levels of budesonide were related to a significant decrease in plasma cortisol and reduction of urinary cortisol excretion in patients with stage IV disease. Two patients with stage IV disease developed portal vein thrombosis (PVT). In conclusion, administration of budesonide leads to markedly elevated plasma levels in cirrhotic patients with PBC associated with serious adverse drug reactions. Thus, further evaluation of combined treatment with UDCA may be considered in early-stage PBC but not in cirrhotic patients with PBC.     

Experience with oseltamivir in the control of a nursing home influenza B outbreak.

Oseltamivir prophylaxis was very effective in protecting nursing home residents from ILI and in halting this outbreak of influenza B. A portion of the total ILI cases may have been due to influenza A, as this strain was isolated in one resident. The 10% attack rate in this facility, controlled with oseltamivir, compares favourably with another influenza B outbreak in a similar facility in the same region, over the same time frame (ILI onset 27 December to 17 January). Oseltamivir prophylaxis was not used to manage this second outbreak of laboratory-confirmed influenza B. Of the 236 residents, 45 developed ILI for an overall attack rate of 19%, nearly double the rate in the oseltamivir-controlled setting (10%). While oseltamivir was effective in controlling influenza B in this outbreak, further experience and evaluation is required before it can be routinely recommended for prophylaxis of influenza in nursing home outbreaks. Although earlier attempts by others using oseltamivir in the control of influenza A outbreaks have also met with success, it is not yet licensed for this purpose. Compared to amantadine, oseltamivir has a relatively high cost for the control of influenza A outbreaks and this may continue to limit its wider acceptance. The cost-effectiveness of oseltamivir in the control of influenza B outbreaks needs to be specifically addressed given the typically milder nature of influenza B strains. However, such a distinction is not clinically reliable and elderly residents of long-term care facilities remain vulnerable to serious complications associated with influenza infection in general. An alternate agent for influenza chemoprophylaxis that is effective against both influenza A and B, is easily administered and has few side effects, could greatly enhance current prevention and control measures and warrants serious assessment. The spread of this outbreak from the geographically separate ward to other areas of the facility in which residents had not received prophylaxis, underscores the likely role of staff as a vehicle for transmission during facility outbreaks. While accurate staff ILI rates could not be determined, their immunization rates were low, and many staff were ill during the outbreak. Isolation of residents with ILI and prophylaxis of non-ill residents on the initial outbreak wards was insufficient to prevent the spread of the outbreak, although it was subsequently halted once prophylaxis was extended to all residents. In view of the uncertainty over this medication's widespread use, in the absence of licensure or previous studies demonstrating its effectiveness in the prophylaxis and control of influenza B outbreaks, initiation of oseltamivir prophylaxis was staggered by ward. In a declared influenza A outbreak, the protocol in a long term care facility is to initiate amantadine prophylaxis on all residents, rather than ward-by-ward. While anti-viral prophylaxis may be an effective secondary control measure in the management of influenza outbreaks, optimal primary prevention would be more effective. This would require increased vaccine coverage of residents and particularly of staff, who play an important role in the importation and transmission of influenza within these facilities.     

An investigation of the steady-state pharmacokinetics of oral valacyclovir in immunocompromised children

Valacyclovir was administered to 28 immunocompromised children (ages 5-12 years) to obtain preliminary pharmacokinetic and safety information. Patients were randomized to valacyclovir regimens of 250 mg (9.4-13.3 mg/kg) or 500 mg (13.9-27.0 mg/kg) twice daily or 500 mg (13.2-21.7 mg/kg) 3 times a day. Acyclovir pharmacokinetics were evaluated at steady state. Valacyclovir was rapidly absorbed and converted to acyclovir. Mean (+/-SD) acyclovir peak concentrations from 250 mg and 500 mg valacyclovir were 4.11+/-1.41 and 5.19+/-1.96 microg/mL, respectively. Corresponding single dose area-under-curve values were 12.14+/-6.60 and 14.49+/-4.69h microg/mL. By using historical data for intravenous acyclovir as reference, the overall estimate of acyclovir bioavailability from valacyclovir was 48%, 2- to 4-fold greater than for oral acyclovir. In general, adverse events were not attributable to valacyclovir and were consistent with disease-related expectations and concomitant therapies. Dosage options for using valacyclovir in children are discussed.