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    Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza (beta)

    Based on guidelines from the Infectious Diseases Society of America.

    Strength
    Grade A
    Grade B
    Grade C
    N/A
    Refer to recommendation
    Evidence
    Level I
    Level II
    Level III
    N/A
    Refer to recommendation

    Diagnosis

    Outpatients (Including Emergency Department Patients)
    1. During influenza activity (defined as the circulation of seasonal influenza A and B viruses among persons in the local community), clinicians should test for influenza in high-risk patients, including immunocompromised persons who present with influenza-like illness, pneumonia, or nonspecific respiratory illness (e.g. cough without fever) if the testing result will influence clinical management.
    2. During influenza activity (defined as the circulation of seasonal influenza A and B viruses among persons in the local community), clinicians should test for influenza in patients who present with acute onset of respiratory symptoms with or without fever, and either exacerbation of chronic medical conditions (e.g. asthma, COPD, heart failure) or known complications of influenza (e.g. pneumonia) if the testing result will influence clinical management.
    3. During influenza activity (defined as the circulation of seasonal influenza A and B viruses among persons in the local community), clinicians can consider influenza testing for patients not at high risk for influenza complications who present with influenza-like illness, pneumonia, or nonspecific respiratory illness (e.g. cough without fever) and who are likely to be discharged home if the results might influence antiviral treatment decisions or reduce use of unnecessary antibiotics, further diagnostic testing, and time in the emergency department, or if the results might influence antiviral treatment or chemoprophylaxis decisions for high-risk household contacts.
    4. During low influenza activity without any link to an influenza outbreak, clinicians can consider influenza testing in patients with acute onset of respiratory symptoms with or without fever, especially for immunocompromised and high-risk patients.
    Hospitalized Patients
    1. During influenza activity, clinicians should test for influenza on admission in all patients requiring hospitalization with acute respiratory illness, including pneumonia, with or without fever.
    2. During influenza activity, clinicians should test for influenza on admission in all patients with acute worsening of chronic cardiopulmonary disease (e.g. COPD, asthma, coronary artery disease, or heart failure), as influenza can be associated with exacerbation of underlying conditions.
    3. During influenza activity, clinicians should test for influenza on admission in all patients who are immunocompromised or at high risk of complications and present with acute onset of respiratory symptoms with or without fever, as the manifestations of influenza in such patients are frequently less characteristic than in immunocompetent individuals.
    4. During influenza activity, clinicians should test for influenza in all patients who, while hospitalized, develop acute onset of respiratory symptoms, with or without fever, or respiratory distress, without a clear alternative diagnosis.
    5. During periods of low influenza activity, clinicians should test for influenza on admission in all patients requiring hospitalization with acute respiratory illness, with or without fever, who have an epidemiological link to a person diagnosed with influenza, an influenza outbreak or outbreak of acute febrile respiratory illness of uncertain cause, or who recently traveled from an area with known influenza activity.
    6. During periods of low influenza activity, clinicians can consider testing for influenza in patients with acute, febrile respiratory tract illness, especially children and adults who are immunocompromised or at high risk of complications, or if the results might influence antiviral treatment or chemoprophylaxis decisions for high-risk household contacts.
    Specimen Collection
    1. Clinicians should collect upper respiratory tract specimens from outpatients for influenza testing as soon after illness onset as possible, preferably within 4 days of symptom onset.
    2. Nasopharyngeal specimens should be collected over other upper respiratory tract specimens to increase detection of influenza viruses.
    3. If nasopharyngeal specimens are not available, nasal and throat swab specimens should be collected and combined together for influenza testing over single specimens from either site (particularly over throat swabs) to increase detection of influenza viruses.
    4. Mid-turbinate nasal swab specimens should be collected over throat swab specimens to increase detection of influenza viruses.
    5. Flocked swab specimens should be collected over nonflocked swab specimens to improve detection of influenza viruses.
    6. Clinicians should collect nasopharyngeal (optimally, as for outpatients), mid-turbinate nasal, or combined nasal–throat specimens from hospitalized patients without severe lower respiratory tract disease for influenza testing as soon as possible.
    7. Clinicians should collect endotracheal aspirate or bronchoalveolar lavage fluid specimens from hospitalized patients with respiratory failure receiving mechanical ventilation, including patients with negative influenza testing results on upper respiratory tract specimens, for influenza testing as soon as possible.
    8. Clinicians should not collect or routinely test specimens for influenza from nonrespiratory sites such as blood, plasma, serum, cerebrospinal fluid, urine, and stool.
    9. Clinicians should not collect serum specimens, including single or paired sera, for serological diagnosis of seasonal influenza virus infection for clinical management purposes.
    Testing
    1. Clinicians should use rapid molecular assays (i.e., nucleic acid amplification tests) over rapid influenza diagnostic tests in outpatients to improve detection of influenza virus infection.
    2. Clinicians should use reverse-transcription polymerase chain reaction or other molecular assays over other influenza tests in hospitalized patients to improve detection of influenza virus infection.
    3. Clinicians should use multiplex reverse-transcription polymerase chain reaction assays targeting a panel of respiratory pathogens, including influenza viruses, in hospitalized immunocompromised patients.
    4. Clinicians can consider using multiplex reverse-transcription polymerase chain reaction assays targeting a panel of respiratory pathogens, including influenza viruses, in hospitalized patients who are not immunocompromised if it might influence care (e.g. aid in cohorting decisions, reduce testing, or decrease antibiotic use).
    5. Clinicians should not use immunofluorescence assays for influenza virus antigen detection in hospitalized patients except when more sensitive molecular assays are not available.
    6. Follow-up testing with reverse-transcription polymerase chain reaction or other molecular assays should be performed to confirm negative immunofluorescence test results.
    7. Clinicians should not use rapid influenza diagnostic tests in hospitalized patients except when more sensitive molecular assays are not available.
    8. Follow-up testing with reverse-transcription polymerase chain reaction or other molecular assays should be performed to confirm negative rapid influenza diagnostic test results.
    9. Clinicians should not use viral culture for initial or primary diagnosis of influenza because results will not be available in a timely manner to inform clinical management.
    10. However, viral culture can be considered to confirm negative test results from rapid influenza diagnostic tests and immunofluorescence assays, such as during an institutional outbreak, and to provide isolates for further characterization.
    11. Clinicians should not use serologic testing for diagnosis of influenza because results from a single serum specimen cannot be reliably interpreted, and collection of paired (acute/convalescent) sera 2–3 weeks apart are needed for serological testing.

    Treatment

    Antivirals
    1. Clinicians should start antiviral treatment as soon as possible for adults and children with documented or suspected influenza, irrespective of influenza vaccination history, who meet the following criteria: (a) persons of any age who are hospitalized with influenza, regardless of illness duration prior to hospitalization (Grade A, Level II); (b) outpatients of any age with severe or progressive illness, regardless of illness duration (Grade A, Level III); (c) outpatients who are at high risk of complications from influenza, including those with chronic medical conditions and immunocompromised patients (Grade A, Level II); (d) children younger than 2 years and adults ≥65 years (Grade A, Level III); (e) pregnant women and those within 2 weeks postpartum (Grade A, Level III).
    2. Clinicians can consider antiviral treatment for adults and children who are not at high risk of influenza complications, with documented or suspected influenza, irrespective of influenza vaccination history, who are either: (a) outpatients with illness onset ≤2 days before presentation (Grade C, Level I); (b) symptomatic outpatients who are household contacts of persons who are at high risk of developing complications from influenza, particularly those who are severely immunocompromised (Grade C, Level III); (c) symptomatic healthcare providers who care for patients who are at high risk of developing complications from influenza, particularly those who are severely immunocompromised (Grade C, Level III).
    3. Clinicians should start antiviral treatment as soon as possible with a single neuraminidase inhibitor (either oral oseltamivir, inhaled zanamivir, or intravenous peramivir) and not use a combination of neuraminidase inhibitors.
    4. Clinicians should not routinely use higher doses of U.S. Food and Drug Administration–approved neuraminidase inhibitor drugs for the treatment of seasonal influenza.
    5. Clinicians should treat uncomplicated influenza in otherwise healthy ambulatory patients for 5 days with oral oseltamivir or inhaled zanamivir, or a single dose of intravenous peramivir.
    6. Clinicians can consider longer duration of antiviral treatment for patients with a documented or suspected immunocompromising condition or patients requiring hospitalization for severe lower respiratory tract disease (especially pneumonia or acute respiratory distress syndrome), as influenza viral replication is often protracted.
    Bacterial Coinfection
    1. Clinicians should investigate and empirically treat bacterial coinfection in patients with suspected or laboratory-confirmed influenza who present initially with severe disease (extensive pneumonia, respiratory failure, hypotension, and fever), in addition to antiviral treatment for influenza.
    2. Clinicians should investigate and empirically treat bacterial coinfection in patients who deteriorate after initial improvement, particularly in those treated with antivirals.
    3. Clinicians can consider investigating bacterial coinfection in patients who fail to improve after 3–5 days of antiviral treatment.
    Lack of Clinical Improvement or Deterioration with Antiviral Treatment
    1. Clinicians should investigate other causes besides influenza virus infection in influenza patients who fail to improve or deteriorate despite antiviral treatment.
    Antiviral-resistant Influenza Virus
    1. Influenza neuraminidase inhibitor resistance testing can be considered for: (a) patients who develop laboratory-confirmed influenza while on or immediately after neuraminidase inhibitor chemoprophylaxis (Grade C, Level III); (b) patients with an immunocompromising condition and evidence of persistent influenza viral replication (e.g. after 7–10 days, demonstrated by persistently positive reverse-transcription polymerase chain reaction or viral culture results) and remain ill during or after neuraminidase inhibitor treatment (Grade B, Level III); (c) patients with laboratory-confirmed influenza who inadvertently received subtherapeutic neuraminidase inhibitor dosing (Grade C, Level III); (d) patients with severe influenza who do not improve with neuraminidase inhibitor treatment and have evidence of persistent influenza viral replication (e.g. after 7–10 days) (Grade C, Level II).
    2. Clinicians should remain informed on current CDC and World Health Organization surveillance data on the frequency and geographic distribution of neuraminidase inhibitor-resistant influenza viruses during influenza season, and with the latest CDC antiviral treatment recommendations.
    Adjunctive Therapy
    1. Clinicians should not administer corticosteroid adjunctive therapy for the treatment of adults or children with suspected or confirmed seasonal influenza, influenza-associated pneumonia, respiratory failure, or acute respiratory distress syndrome, unless clinically indicated for other reasons.
    2. Clinicians should not routinely administer immunomodulation using immunoglobulin preparations such as intravenous immunoglobulin for treatment of adults or children with suspected or confirmed seasonal influenza.

    Antiviral Chemoprophylaxis in Community Settings

    Preexposure Chemoprophylaxis
    1. Antiviral drugs should not be used for routine or widespread chemoprophylaxis outside of institutional outbreaks.
    2. Clinicians can consider antiviral chemoprophylaxis for the duration of the influenza season for adults and children aged ≥3 months who are at very high risk of developing complications from influenza and for whom influenza vaccination is contraindicated, unavailable, or expected to have low effectiveness (e.g. persons who are severely immunocompromised).
    3. Clinicians can consider antiviral chemoprophylaxis for the duration of the influenza season for adults and children aged ≥3 months who have the highest risk of influenza-associated complications, such as recipients of hematopoietic stem cell transplant in the first 6-12 months posttransplant and lung transplant recipients.
    4. Clinicians can consider short-term antiviral chemoprophylaxis in conjunction with prompt administration of inactivated influenza vaccine for unvaccinated adults and children aged ≥3 months who are at high risk of developing complications from influenza in whom influenza vaccination is expected to be effective (but not yet administered) when influenza activity has been detected in the community.
    5. Clinicians can consider short-term antiviral chemoprophylaxis for unvaccinated adults, including healthcare personnel, and for children aged ≥3 months who are in close contact with persons at high risk of developing influenza complications during periods of influenza activity when influenza vaccination is contraindicated or unavailable and these high-risk persons are unable to take antiviral chemoprophylaxis.
    6. Clinicians can consider educating patients and parents of patients to arrange for early empiric initiation of antiviral treatment as an alternative to antiviral chemoprophylaxis.
    7. Clinicians should use an neuraminidase inhibitor (oral oseltamivir or inhaled zanamivir) if preexposure chemoprophylaxis for influenza is administered rather than an adamantane antiviral.
    8. Clinicians should administer preexposure antiviral chemoprophylaxis for adults and children aged ≥3 months who are at very high risk of developing complications from influenza (e.g. severely immunocompromised persons such as hematopoietic stem cell transplant recipients) for whom influenza vaccination is contraindicated, unavailable, or expected to have low effectiveness, as soon as influenza activity is detected in the community and continued for the duration of community influenza activity.
    9. Clinicians should test for influenza and switch to antiviral treatment dosing in persons receiving preexposure antiviral chemoprophylaxis who become symptomatic, preferably with an antiviral drug with a different resistance profile if not contraindicated.
    Postexposure Chemoprophylaxis
    1. Clinicians can consider postexposure antiviral chemoprophylaxis for asymptomatic adults and children aged ≥3 months who are at very high risk of developing complications from influenza (e.g. severely immunocompromised persons) and for whom influenza vaccination is contraindicated, unavailable, or expected to have low effectiveness, after household exposure to influenza.
    2. Clinicians can consider postexposure antiviral chemoprophylaxis (in conjunction with influenza vaccination) for adults and children aged ≥3 months who are unvaccinated and are household contacts of a person at very high risk of complications from influenza (e.g. severely immunocompromised persons), after exposure to influenza.
    3. Clinicians can consider educating patients and arranging for early empiric initiation of antiviral treatment as an alternative to postexposure antiviral chemoprophylaxis.
    4. If chemoprophylaxis is given, clinicians should administer postexposure antiviral chemoprophylaxis as soon as possible after exposure, ideally no later than 48 hours after exposure.
    5. Clinicians should not administer once-daily postexposure antiviral chemoprophylaxis if >48 hours has elapsed since exposure. Full-dose empiric antiviral treatment should be initiated as soon as symptoms occur, if treatment is indicated.
    6. Clinicians should administer postexposure antiviral chemoprophylaxis in a nonoutbreak setting for 7 days after the most recent exposure to a close contact with influenza.
    7. Clinicians should test for influenza and switch to antiviral treatment dosing in persons receiving postexposure antiviral chemoprophylaxis who become symptomatic, preferably with an antiviral drug with a different resistance profile if not contraindicated.
    8. Clinicians should administer an neuraminidase inhibitor (inhaled zanamivir or oral oseltamivir) if postexposure chemoprophylaxis for influenza is given, rather than an adamantane antiviral.

    Institutional Outbreak Control

    Implementation of Control Measures
    1. Active surveillance for additional cases should be implemented as soon as possible when one healthcare-associated laboratory-confirmed influenza case is identified in a hospital or one case of laboratory-confirmed influenza is identified in a long-term care facility.
    2. Outbreak control measures should be implemented as soon as possible, including antiviral chemoprophylaxis of residents/patients, and active surveillance for new cases, when 2 cases of healthcare-associated laboratory-confirmed influenza are identified within 72 hours of each other in residents or patients of the same ward or unit.
    3. Implementation of outbreak control measures can be considered as soon as possible if one or more residents or patients has suspected healthcare-associated influenza and results of influenza molecular testing are not available on the day of specimen collection.
    Antivirals
    1. When an influenza outbreak has been identified in a long-term care facility or hospital, influenza testing should be done for any resident/patient with one or more acute respiratory symptoms, with or without fever, or any of the following without respiratory symptoms: temperature elevation or reduction, or behavioral change.
    2. Empiric antiviral treatment should be administered as soon as possible to any resident or patient with suspected influenza during an influenza outbreak without waiting for the results of influenza diagnostic testing.
    Antiviral Chemoprophylaxis
    1. Antiviral chemoprophylaxis should be administered as soon as possible to all exposed residents or patients who do not have suspected or laboratory-confirmed influenza regardless of influenza vaccination history, in addition to implementation of all other recommended influenza outbreak control measures, when an influenza outbreak has been identified in a long-term care facility or hospital.
    2. Antiviral chemoprophylaxis should be administered to residents on outbreak-affected units, in addition to implementing active daily surveillance for new influenza cases throughout the facility.
    3. Clinicians can consider antiviral chemoprophylaxis for unvaccinated staff, including those for whom chemoprophylaxis may be indicated based upon underlying conditions of the staff or their household members for the duration of the outbreak.
    4. Clinicians can consider antiviral chemoprophylaxis for staff who receive inactivated influenza vaccine during an institutional influenza outbreak for 14 days postvaccination.
    5. Clinicians can consider antiviral chemoprophylaxis for staff regardless of influenza vaccination status to reduce the risk of short staffing in facilities and wards where clinical staff are limited and to reduce staff reluctance to care for patients with suspected influenza.
    6. Clinicians should administer antiviral chemoprophylaxis for 14 days and continue for at least 7 days after the onset of symptoms in the last case identified during an institutional influenza outbreak.
    What do the icons mean?  
    Research PaperUyeki TM, Bernstein HH, Bradley JS, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Infect Dis. 2019;68(6):e1-e47.