Practice Guidelines

ACIP Updates Guidelines on Prevention and Control of Influenza

CARRIE A. MORANTZ

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) has released updated recommendations for the prevention and control of influenza. The guidelines are available online at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5408a1.htm.

The primary target groups recommended for annual vaccination include persons at increased risk for influenza-related complications (i.e., persons 65 years and older, children six to 23 months of age, pregnant women, and persons of any age with certain chronic medical conditions); persons 50 to 64 years of age; and persons who live with or care for persons at high risk (e.g., health care workers, household contacts who have frequent contact with persons at high risk). Vaccination is associated with reductions in influenza-related respiratory illness and physician visits in all age groups, hospitalization and death in persons at high risk, otitis media in children, and work absenteeism in adults.

The 2005 recommendations include the following principal updates:

• Persons with any condition (e.g., cognitive dysfunction, spinal cord injuries, seizure disorders, other neuromuscular disorders) that can compromise respiratory function or those who handle respiratory secretions should be vaccinated against influenza.

• All health care workers should be vaccinated against influenza annually, and facilities that employ health care workers are strongly encouraged to provide vaccine to workers by using approaches that maximize immunization rates.

• The use of both available vaccines (i.e., inactivated and live attenuated influenza vaccine [LAIV]) is encouraged in eligible persons every influenza season, especially persons in recommended target groups. During periods when inactivated vaccine is in short supply, the use of LAIV especially is encouraged for eligible persons.

• The 2005-2006 trivalent vaccine virus strains are A/California/7/2004 (H3N2)-like; A/New Caledonia/20/99 (H1N1)-like; and B/Shanghai/361/2002-like antigens. For the A/California/7/2004 (H3N2)-like antigen, manufacturers may use the antigenically equivalent A/New York/55/2004 (H3N2) virus, and for the B/Shanghai/361/2002-like antigen, manufacturers may use the antigenically equivalent B/Jilin/20/2003 virus or B/Jiangsu/10/2003 virus.

TABLE 1 Recommended Daily Dosage of Antiviral Agents for Treatment and Prophylaxis of Influenza
Antiviral agent	Age group (years)
	1 to 6	7 to 9	10 to 12	13 to 64	65 and older
Amantadine (Symmetrel)*
Treatment of influenza A	5 mg per kg per day, up to 150 mg per day in 2 divided doses†	5 mg per kg per day, up to 150 mg per day in 2 divided doses†	100 mg twice daily‡	100 mg twice daily‡	<= 100 mg daily
Prophylaxis of influenza A	5 mg per kg per day, up to 150 mg per day in 2 divided doses†	5 mg per kg per day, up to 150 mg per day in 2 divided doses†	100 mg twice daily‡	100 mg twice daily‡	<= 100 mg daily
Rimantadine (Flumadine)§
Treatment of influenza A	-	-	-	100 mg twice daily‡||	100 mg daily
Prophylaxis of influenza A	5 mg per kg per day, up to 150 mg per day in 2 divided doses†	5 mg per kg per day, up to 150 mg per day in 2 divided doses†	100 mg twice daily‡	100 mg twice daily‡	100 mg daily¶
Zanamivir (Relenza)**
Treatment of influenza A and B	-	10 mg twice daily	10 mg twice daily	10 mg twice daily	10 mg twice daily
Oseltamivir (Tamiflu)
Treatment of influenza A and B††	Dosage varies by child's weight‡‡	Dosage varies by child's weight‡‡	Dosage varies by child's weight‡‡	75 mg twice daily	75 mg twice daily
Prophylaxis of influenza A and B	-	-	-	75 mg daily	75 mg daily
*-See drug package insert for dosage recommendations in patients with creatinine clearance <= 50 mL per minute per 1.73 m2. †-5 mg per kg dose of amantadine or rimantadine syrup = 1 tsp per 2.2 lb (1 kg). ‡-Children 10 years and older who weigh less than 88 lb (40 kg) should be given amantadine or rimantadine at a dosage of 5 mg per kg per day. §-A reduction in dosage of rimantadine to 100 mg daily is recommended in patients who have severe hepatic dysfunction and in those with creatinine clearance of 10 mL per minute or less. Patients with less severe hepatic or renal dysfunction taking 100 mg of rimantadine daily should be observed closely, and the dosage should be reduced or the drug discontinued if necessary. ||-Rimantadine is approved for treatment of influenza A in adults. However, some subspecialists consider rimantadine appropriate for treatment of influenza A in children. Studies evaluating the effectiveness of amantadine and rimantadine in children are limited but indicate that treatment with either agent diminishes the severity of infection when administered within 48 hours of illness onset. ¶-Older nursing home residents should be given 100 mg of rimantadine daily, and a reduction in dosage to 100 mg daily should be considered in all patients 65 years and older if they experience side effects when taking 200 mg daily. **-Zanamivir is administered through inhalation using a plastic device included in the medication package. Patients will benefit from instruction and demonstration of the correct use of the device. ††-A reduction in the dosage of oseltamivir is recommended in patients with creatinine clearance of less than 30 mL per minute. ‡‡-The dosage recommendation for children who weigh 33 lb (15 kg) or less is 30 mg twice daily. For children who weigh 15 kg to 50.6 lb (23 kg), the dosage is 45 mg twice daily. For children who weigh 23 kg to 88 lb, the dosage is 60 mg twice daily. For children who weigh more than 88 lb, the dosage is 75 mg twice daily. Adapted from Centers for Disease Control and Prevention. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2005;54(RR08):1-40. Accessed online August 18, 2005, at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5408a1.htm.

Inactivated Influenza Vaccine Recommendations

Inactivated influenza vaccine should not be administered to persons known to have anaphylactic hypersensitivity to eggs or to other components of the influenza vaccine without first consulting a physician. Prophylactic use of antiviral agents is an option for preventing influenza in such persons (Table 1). However, persons who have a history of anaphylactic hypersensitivity to vaccine components but who also are at high risk for complications from influenza can benefit from vaccination after appropriate allergy evaluation and desensitization. Persons with acute febrile illness usually should not be vaccinated until their symptoms have abated. However, minor illnesses with or without fever do not contraindicate use of influenza vaccine, particularly in children with mild upper respiratory tract infection or allergic rhinitis. Dosages for inactivated vaccine are given in Table 2.

TABLE 2 Inactivated Influenza Vaccine* Dosage, 2005-2006 Season
Age group†	Dose	Number of doses	Route of administration‡
6 to 35 months	0.25 mL	1 or 2§	Intramuscular
3 to 8 years	0.5 mL	1 or 2§	Intramuscular
9 years and older	0.5 mL	1	Intramuscular
*-A 0.5-mL dose contains 15 mg each of A/California/7/2004 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Shanghai/361/2002-like antigens. For the A/California/7/2004 (H3N2)-like antigen, manufacturers may use the antigenically equivalent A/New York/55/2004 virus. For the B/Shanghai/361/2002-like antigen, manufacturers may use the antigenically equivalent B/Jilin/20/2003 virus or B/Jiangsu/10/2003 virus. Manufacturers include Sanofi Pasteur, Inc., (FluZone split virus) and Chiron (Fluvirin purified surface antigen vaccine). FluZone is approved for use in persons 6 months and older, and Fluvirin is approved for use in persons 4 years and older. †-Because of the decreased potential for causing febrile reactions, only split-virus vaccines should be used in children younger than 13 years. Whole-virus vaccine is not available in the United States. Split-virus vaccine may be labeled as "split," "subvirion," or "purified surface antigen" vaccine. Immunogenicity and side effects of split- and whole-virus vaccines are similar in adults when vaccines are administered at the recommended dosage. ‡-The recommended site of vaccination in adults and older children is the deltoid muscle. The preferred site in infants and young children is the anterolateral aspect of the thigh. §-Two doses administered at least one month apart are recommended in children younger than 9 years who are receiving influenza vaccine for the first time. Adapted from Centers for Disease Control and Prevention. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2005;54(RR08):1-40. Accessed online August 18, 2005, at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5408a1.htm.

LAIV Recommendations

LAIV is an option for vaccinating healthy persons five to 49 years of age, including health care workers and other persons in close contact with high-risk groups. During periods when inactivated vaccine is in short supply, the use of LAIV is encouraged when feasible for eligible persons (including health care workers) because the use of LAIV by these persons may increase the availability of inactivated vaccine for persons in high-risk groups. Possible advantages of LAIV include its potential to induce a broad mucosal and systemic immune response, its ease of administration, and the acceptability of an intranasal rather than intramuscular route of administration.

The following populations should not be vaccinated with LAIV: persons younger than five years and persons 50 years and older; persons with asthma, reactive airways disease, or other chronic disorders of the pulmonary or cardiovascular systems; persons with other underlying medical conditions, including diabetes, renal dysfunction, and hemoglobinopathies; persons with known or suspected immunodeficiency diseases or who are receiving
immunosuppressive therapies; children or adolescents taking aspirin or other salicylates; persons with a history of Guillain-Barré syndrome; pregnant women; and persons with a history of hypersensitivity reactions to any of the components of LAIV or to eggs.

LAIV should be administered annually according to the following schedule:

• Children five to eight years of age who were previously unvaccinated with LAIV or inactivated influenza vaccine should receive two doses of LAIV six to 10 weeks apart.

• Children five to eight years of age who were previously vaccinated at any time with LAIV or inactivated influenza vaccine should receive only one dose of LAIV.

• Persons nine to 49 years of age should receive one dose of LAIV.

LAIV may be administered to persons with minor acute illnesses (e.g., diarrhea, mild upper respiratory tract infection with or without fever). However, in the presence of nasal congestion that might impede delivery of the vaccine to the nasopharyngeal mucosa, deferral of administration should be considered until resolution of the illness.

The effect on safety and effectiveness of LAIV coadministration with influenza antiviral medications has not been studied. However, because influenza antiviral agents reduce replication of influenza viruses, LAIV should not be administered until 48 hours after cessation of influenza antiviral therapy, and influenza antiviral medications should not be administered for two weeks after administration of LAIV.

Timing of Influenza Vaccination

To allow vaccine providers to plan for the upcoming vaccination season, taking into account the yearly possibility of vaccine delays or shortages and the need to ensure vaccination of persons at high risk and their contacts, ACIP recommends that inactivated influenza vaccine campaigns conducted in October focus primarily on persons at increased risk for influenza complications and their contacts, including health care workers. Campaigns conducted in November and later should continue to vaccinate high-risk persons and their contacts, but also should vaccinate other persons who wish to decrease their risk for influenza infection. Vaccination for all groups should continue into December and beyond. Because LAIV is approved for use in healthy persons five to 49 years of age, its use has not been subject to tiered timing.

Vaccine Shortages

The United States has experienced disruptions in the manufacture or distribution of inactivated influenza vaccine during three of the past five influenza seasons. Delays in delivery of influenza vaccine or vaccine shortages remain possible because of inherent time constraints in manufacturing the vaccine. Although total vaccine supply for the 2005-2006 influenza season is not yet known, the minimum anticipated supply is approximately 58 to 60 million doses of inactivated vaccine and 3 million doses of LAIV. This estimated supply is similar to that available during the 2004-2005 season and would be adequate to satisfy historic demand for influenza vaccine in persons at high risk for serious complications, health care workers, and household contacts of children younger than six months. Additional doses of inactivated influenza vaccine may be available for the U.S. market in 2005-2006, but this cannot be confirmed yet. Availability of additional vaccine would allow for expansion of the priority groups and, preferably, vaccination of all persons who desire it.

During periods of inactivated influenza vaccine shortfall, vaccination is prioritized on the basis of risk for serious influenza-associated complications (Table 3). The CDC and ACIP recommend the use of vaccination priority groups only in the event of vaccine supply disruptions. Three tiers of priority groups are ranked on the basis of influenza-associated mortality and hospitalization rates. In the event of an influenza vaccine shortfall, persons in tier 1 should be vaccinated preferentially, followed by persons in tier 2, then persons in tier 3. On rare occasions when local vaccine supply is extremely limited, state and local health officials and vaccine providers should prioritize persons in group 1A before all other groups. However, in all other vaccine shortfall situations, persons in groups 1A, 1B, and 1C should be considered equivalent and should be vaccinated simultaneously. Eligible persons in group 1C and tiers 2 and 3 should be encouraged to receive LAIV during periods of inactivated influenza vaccine shortfall.

TABLE 3 Priority Groups for Vaccination with Inactivated Influenza Vaccine
Tier	Priority group
1A	Persons 65 years and older with comorbid conditions
	Residents of long-term care facilities
1B	Persons 2 to 64 years of age with comorbid conditions
	Persons 65 years and older without comorbid conditions
	Children 6 to 23 months of age
	Pregnant women
1C	Health care workers
	Household contacts and out-of-home caregivers of children younger than 6 months
2	Household contacts of children and adults at increased risk for influenza-related complications
	Healthy persons 50 to 64 years of age
3	Persons 2 to 49 years of age without high-risk conditions
note: Some persons may be included in more than one group. Adapted from Centers for Disease Control and Prevention. Tiered use of inactivated influenza vaccine in the event of a vaccine shortage. MMWR Wkly Rep 2005;54:749-50. Accessed online August 18, 2005, at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5430a4.htm.

Laboratory Diagnosis

Appropriate treatment of patients with respiratory illness depends on accurate and timely diagnosis. Early diagnosis of influenza can reduce the inappropriate use of antibiotics and provide the option of using antiviral therapy. However, because certain bacterial infections can produce symptoms similar to influenza, bacterial infections should be considered and appropriately treated, if suspected. In addition, bacterial infections can occur as a complication of influenza.

Diagnostic tests available for influenza include viral culture, serology, rapid antigen testing, polymerase chain reaction, and immunofluorescence assays. Sensitivity and specificity of any test for influenza may vary by the laboratory that performs the test, the type of test used, and the type of specimen tested. Among respiratory specimens for viral isolation or rapid detection, nasopharyngeal specimens are typically more effective than throat swab specimens. As with any diagnostic test, results should be evaluated in the context of available clinical and epidemiologic information.

Commercial rapid diagnostic tests are available that can detect influenza viruses within 30 minutes. Some tests are approved for use in any outpatient setting, whereas others must be used in a moderately complex clinical laboratory. These rapid tests differ in the types of influenza viruses they can detect and whether they can distinguish between influenza types. None of the tests provides any information about influenza A subtypes. The types of specimens acceptable for use (i.e., throat, nasopharyngeal, or nasal aspirates, swabs, or washes) also vary by test.

Because of the lower sensitivity of rapid tests, physicians should consider confirming negative test results with viral culture or other means because of the possibility of false-negative rapid test results, especially during periods of peak community influenza activity. In contrast, false-positive rapid test results are less likely but can occur during periods of low influenza activity. Therefore, when interpreting results of a rapid influenza test, physicians should consider the positive and negative predictive values of the test in the context of the level of influenza activity in their community.

Despite the availability of rapid diagnostic tests, collecting clinical specimens for viral culture is critical, because only culture isolates can provide specific information regarding circulating strains and subtypes of influenza viruses. This information is needed to compare current circulating influenza strains with vaccine strains, to guide decisions about influenza treatment and chemoprophylaxis, and to formulate vaccine for the coming year. Virus isolates also are needed to monitor the emergence of antiviral resistance and the emergence of novel influenza A subtypes that might pose a pandemic threat.

Antiviral Agents

Antiviral drugs for influenza are an adjunct to influenza vaccine for controlling and preventing influenza. However, these agents are not a substitute for vaccination. Four licensed influenza antiviral agents are available in the United States: amantadine (Symmetrel), rimantadine (Flumadine), zanamivir (Relenza), and oseltamivir (Tamiflu). An overview of the indications for use and administration of these medications is presented in Table 1.

When administered within two days of illness onset to otherwise healthy adults, amantadine and rimantadine can reduce the duration of uncomplicated influenza A illness and zanamivir and oseltamivir can reduce the duration of uncomplicated influenza A and B illness by approximately one day compared with placebo. More clinical data are available concerning the efficacy of zanamivir and oseltamivir for treatment of influenza A
infection than for treatment of influenza B infection. Zanamivir and oseltamivir have activity against influenza B viruses.

Data are limited regarding the effectiveness of the four antiviral agents in preventing serious influenza-related complications (e.g., bacterial or viral pneumonia, exacerbation of chronic diseases). Evidence for the effectiveness of these four antiviral drugs is based principally on studies of patients with uncomplicated influenza. Data are limited and inconclusive concerning the effectiveness of amantadine, rimantadine, zanamivir, and oseltamivir for treatment of influenza among persons at high risk for serious complications of influenza. Inadequate data exist regarding the safety and effectiveness of any of the influenza antiviral drugs for use among children younger than one year.

To reduce the emergence of antiviral drug-resistant viruses, amantadine or rimantadine therapy for persons with influenza A illness should be discontinued as soon as clinically warranted, typically after three to five days of treatment or within 24 to 48 hours after the disappearance of signs and symptoms. The recommended duration of treatment with zanamivir or oseltamivir is five days.

chemoprophylaxis

Chemoprophylactic drugs are not a substitute for vaccination, although they are critical adjuncts in preventing and controlling influenza. Amantadine and rimantadine are indicated for chemoprophylaxis of influenza A infection, but not influenza B. Both drugs are approximately 60 to 90 percent effective in preventing illness from influenza A infection. When used as prophylaxis, these antiviral agents can prevent illness while permitting subclinical infection and development of protective antibody against circulating influenza viruses. Therefore, some persons who take these drugs will develop protective immune responses to circulating influenza viruses. Amantadine and rimantadine do not interfere with the antibody response to the vaccine.

Among the neuraminidase inhibitor antivirals zanamivir and oseltamivir, only oseltamivir has been approved for prophylaxis, but community studies of healthy adults indicate that both drugs are similarly effective in preventing febrile, laboratory-confirmed influenza illness (84 percent effectiveness for zanamivir versus 82 percent for oseltamivir). Both agents have been reported to prevent influenza illness among persons administered chemoprophylaxis after a household member was diagnosed with influenza.

Data are not available regarding the effectiveness of any of the four antiviral agents in preventing influenza among severely immunocompromised persons.

When determining the timing and duration for administering influenza antiviral medications for prophylaxis, factors related to cost, compliance, and potential side effects should be considered. To be maximally effective as prophylaxis, the drug must be taken each day for the duration of influenza activity in the community. However, to be most cost-effective, one study of amantadine or rimantadine prophylaxis reported that the drugs should be taken only during the period of peak influenza activity in a community.

Practice Guideline Briefs

AMBER HUNTZINGER

LAURA COUGHLIN

AHA Scientific Statement on Diagnosis and Management of Infective Endocarditis

The American Heart Association (AHA) has released evidence-based guidelines for the diagnosis, treatment, and follow-up care of patients with endocarditis. The updated recommendations, which were published in the June 14, 2005, issue of Circulation, reflect the evolving nature of the condition and new issues that physicians face when treating patients with infective endocarditis.

Diagnosis

Early diagnosis of endocarditis is important to initiate therapy and identify patients at high risk for complications. Although case definitions should not replace clinical judgment, physicians commonly use newly updated Duke criteria to diagnose suspected endocarditis.

Echocardiography should be performed immediately when endocarditis is suspected. Transesophageal echocardiography is preferred, but if clinical suspicion is low, or if transesophageal echocardiography is unavailable or shows abnormalities, transthoracic echocardiography is acceptable. If transthoracic echocardiography is positive or if worrisome clinical signs persist after a negative transthoracic echocardiography, physicians should follow-up with transesophageal echocardiography.

Treatment

Physicians should consider surgical therapy for patients with infective endocarditis and congestive heart failure. Other presentations that may require surgical intervention include fungal infective endocarditis, antibiotic-resistant infection, left-sided infective endocarditis caused by gram-negative bacteria, persistent infection after one week of antibiotic therapy, one or more embolic events in first two weeks of antimicrobial therapy, and certain echocardiographic findings. The decision to perform surgery should be based on the individual case, but surgery is most effective in the early phase of infective endocarditis.

Outpatient parenteral antibiotic therapy is safe, effective, and less expensive than inpatient therapy. Therefore, physicians should treat patients with intravenous antibiotics on an outpatient basis for at least two weeks if surgery is not indicated. Oral antibiotics are unreliable and not recommended for management of endocarditis. Outpatient therapy should be initiated only after the patient is evaluated and stabilized in the hospital. Rarely, low-risk patients may be treated entirely as outpatients. Effective outpatient care is dependent on a reliable in-home patient support system, easy access to the hospital, regular home nurse visits, and regular visits with a physician.

Follow-up

In most cases, infective endocarditis is resolved with appropriate treatment, but follow-up efforts are necessary.

Short-term follow-up should include:

Long-term follow-up should include:

IDSA Guidelines for Diagnosis and Treatment of Asymptomatic Bacteriuria

The Infectious Diseases Society of America (IDSA) has released evidence-based recommendations for the diagnosis and treatment of asymptomatic bacteriuria in adults. The IDSA guidelines, which appear in the March 1, 2005, issue of Clinical Infectious Diseases and are available online at http://www.sochinf.cl/documentos/bacteriuria.pdf, are as follows:

• Diagnosis of asymptomatic bacteriuria should be based on the results of a urine culture collected in a way that prevents contamination. Diagnosis of bacteriuria in asymptomatic women is defined as two consecutive voided urine specimens in which the same strain of bacteria is isolated in quantitative counts of at least 105 cfu per mL. In men, diagnosis of bacteriuria is defined as one bacterial species isolated in a quantitative count of at least 105 cfu per mL in a clean-catch voided urine sample. In women and men, bacteriuria is diagnosed when, in a single catheterized urine sample, one bacterial species is isolated in a quantitative count of at least 102 cfu per mL.

• Antimicrobial treatment is not indicated when pyuria accompanies asymptomatic bacteriuria.

• Pregnant women should be screened for bacteriuria during early pregnancy and given antimicrobial therapy for three to seven days if the results are positive. Women with a positive screen should be monitored for recurrence of bacteriuria after treatment.

• Shortly before transurethral resectioning of the prostate, patients should be screened and treated for bacteriuria, but treatment should not be continued after the procedure unless a catheter remains in place.

• Screening and treatment are recommended before any urologic procedure in which mucosal bleeding is expected.

• Screening and treatment are not recommended for premenopausal women who are not pregnant, women with diabetes, older persons living in the community or institutions, patients with spinal cord injury, or catheterized patients while the catheter is in situ.

• Physicians should consider antimicrobial treatment of asymptomatic women with catheter-acquired bacteriuria if it persists for 48 hours after catheter removal.

• The IDSA does not recommend for or against screening or treatment of patients with renal or other solid-organ transplants. n

Answers to This Issue's Clinical Quiz Q1. B Q2. D Q3. A Q4. A Q5. D Q6. C, D Q7. B, C Q8. A, B, C, D Q9. A, B, D

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