Influenza - Guidelines for Clinical Management of Adult Patients with

Publication: 24/12/2010

Next review: 09/11/2025

Clinical Guideline

CURRENT

ID: 2356

Approved By: Trust Clinical Guidelines Group

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guidelines for the Clinical Management of Adults with Influenza
For further detail, please refer to the national guidance

Background
Clinical Presentation
Diagnostics
Management
Definitions

Background

Influenza is an acute respiratory illness caused by RNA viruses of the family Orthomyxoviridae (influenza viruses). There are two types of influenza virus of clinical concern:

Influenza A: occurs more frequently and is more virulent. It is responsible for local outbreaks, larger epidemics or pandemics.
Influenza B: often co-circulates with influenza A during the yearly outbreaks, typically in early spring. Generally, influenza B causes less severe clinical illness, although it can still be responsible for outbreaks.

Clinical Presentation

Symptoms of influenza typically appear abruptly, around 2 days after exposure.

The incubation period prior to the onset of symptoms is 1 – 4 days.

The period of infectivity is from a day before symptom onset to:

7 days after symptom onset or 5 days after start of antivirals in immunocompetent adults
7 days after symptom onset or until no symptoms (whichever is longer) in immunocompromised patients.

Symptoms of influenza:

fever (38°C or above) or history of fever with
Two or more of the following symptoms: cough, sore throat, headache, rhinorrhoea, myalgia, coryza, diarrhoea or vomiting (counts as one symptom)

Influenza related pneumonia

The incidence of pneumonia (defined as a combination of respiratory symptoms and signs supported by CXR changes consistent with infection) complicating influenza varies from 2% to 38% and is dependent on viral and host factors. Two main types of influenza-related pneumonia are recognised; the uncommon but severe primary viral pneumonia and the more common secondary bacterial pneumonia (see Appendix i)

Patients at risk of complications should be considered for antibiotics in the presence of lower respiratory features (see Figure 2). These include patients who are within the group currently recommended for influenza vaccination.

Diagnostics

For patients with a suspected diagnosis of influenza and/or concurrent community acquired pneumonia the following diagnostic tests should be performed:

All patients with suspected influenza	Rapid / Point of care test (POCT) where available Throat swab in virus transport medium for respiratory virus PCR (regardless of POCT result) Basic observations
Selected patients suspected to have concurrent pneumonia	Sputum M, C & S Blood culture (preferably before antibiotic treatment is commenced) Full blood count, Urea and electrolytes, Liver function tests, CRP Chest x-ray ECG (Patients with cardiac and respiratory complications or co-morbid illnesses)
Severely immunosuppressed patients	Contact Virology (ext. 23962 option 2) to request typing if patient tests positive for influenza A.

Management

All patients with influenza A or B should be immediately assessed for treatment. Choice of treatment can be determined using the below definitions and Figure 1
- All patients hospitalised with influenza should receive antiviral treatment as soon as possible, regardless of symptom onset date.
- All patients with influenza who are not being admitted to hospital need assessing for their requirement of antiviral treatment. Severely immunosuppressed and at-risk patients should receive antivirals, regardless of whether they are admitted or not.
- Antiviral treatment should ideally be started within 48 hours of symptom onset, however, there is evidence that treatment may reduce the risk of mortality even if started up to 5 days after symptom onset. Starting antiviral treatment more than 48 hours after symptom onset is an off-label use but is supported in the national guidance according to clinical discretion.
People with influenza should drink adequate fluids, take paracetamol or ibuprofen to relieve symptoms, rest, and stay off work or school until symptoms have resolved.
A minority of patients with influenza require treatment with antibiotics for secondary infection (see Figure 2).

Contacts of influenza in hospital require assessment for antiviral prophylaxis – see separate IPC guidance

Definitions

See Appendix ii

Figure 1 Treatment for influenza A and B

As of 22/12/22, the influenza A strains circulating are mixed (both H3N2 and H1N1) and the predominant strain is unclear. Therefore zanamivir diskhaler should be used as empiric first line treatment for severely immunocompromised patients with influenza A where typing is not immediately available.

Footnotes for Figure 1

¹The manufacturer recommends a longer treatment course of 10 days for immunosuppressed or critically ill patients.

²If there is a poor clinical response to first line treatment switch to inhaled zanamivir. If there is evidence of gastrointestinal dysfunction which could cause decreased absorption of enterically-administered medications, use inhaled zanamivir.

³If zanamivir is indicated but patients cannot use a zanamivir (Relenza) Diskhaler® or have severe complicated illness such as multi-organ failure, IV zanamivir should be considered.

⁴Patients who have suspected or confirmed oseltamivir resistant infection and cannot use a zanamivir (Relenza) Diskhaler® should be considered for IV zanamivir; note, this would be outside the marketing authorisation. IV zanamivir should be commenced as soon as possible and usually within 6 days of the onset of symptoms of influenza. IV zanamivir is renally excreted and requires dose modification for patients with renal dysfunction including those on renal replacement therapy

Dosing and Administration of Antvirals for Influenza

See Appendix iii

Provenance

Record:	2356
Objective:
Clinical condition:	Influenza
Target patient group:	Adults
Target professional group(s):	Pharmacists Secondary Care Doctors Secondary Care Nurses
Adapted from:

Evidence base

UK Health Security Agency: Guidance on use of antiviral agents for the treatment and prophylaxis of seasonal influenza: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1058443/ukhsa-guidance-antivirals-influenza-11v4.pdf
Oseltamivir or zanamivir – can they be used in breastfeeding mothers for the treatment or prophylaxis of influenza?: https://www.sps.nhs.uk/wp-content/uploads/2018/02/UKMI_QA_Oseltamivir-and-Zanamavir-in-breastfeeding_July2020_Final.pdf

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.1

Related information

Appendix i - viral and bacteaial pneumonia

Primary viral pneumonia

Patients with primary viral pneumonia typically become breathless within the first 48 hours of onset of fever. An initially dry cough may become productive of blood-stained sputum. Cyanosis, tachypnoea, bilateral crepitations and wheeze on chest examination and leucocytosis are usual. The commonest chest radiographic abnormality is of bilateral interstitial infiltrates predominantly in the mid-zones, although focal consolidation is also seen. Rapid clinical deterioration with respiratory failure may ensue. The mortality in hospitalised patients is high (>40%) despite maximum supportive treatment. In the majority of fatal cases, death occurs within 7 days of hospital admission. Patients with bilateral lung infiltrates on CXR consistent with primary viral pneumonia should be managed as having severe pneumonia regardless of CURB-65 score.

Secondary bacterial pneumonia

Secondary bacterial pneumonia is more common than primary viral pneumonia. Typically, symptoms and signs of pneumonia develop during the early convalescent period (4 – 5 days from onset of initial symptoms). Chest radiography usually demonstrates a lobar pattern of consolidation. Mortality rate ranges from 7 - 24%. The spectrum of pathogens implicated in secondary bacterial pneumonia includes Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Groups A, C and G beta-haemolytic streptococci.

Bronchial complications without influenza-related pneumonia

Previously well adults with acute bronchitis complicating influenza, in the absence of pneumonia, do not routinely require antibiotics. Antibiotics should be considered in those previously well adults who develop worsening symptoms. Procalcitonin (PCT) can be used in patients without sepsis or proven secondary bacterial infection to reduce the use of unnecessary antibiotics.

Appendix ii - Definitions

Uncomplicated influenza	Influenza presenting with fever, coryza, generalised symptoms (headache, malaise, myalgia, arthralgia) and sometimes gastrointestinal symptoms, but without any features of complicated influenza.
Complicated influenza:	Influenza requiring hospital admission and/or with symptoms and signs of lower respiratory tract infection (hypoxaemia, dyspnoea, lung infiltrate), central nervous system involvement and/or a significant exacerbation of an underlying medical condition.
At risk group (At risk of complicated influenza)	neurological, hepatic, renal, pulmonary and chronic cardiac disease diabetes mellitus severe immunosuppression age over 65 years pregnancy (including up to 2 weeks post-partum) morbid obesity (BMI ≥40)
Examples of severe immunosuppression:	severe primary immunodeficiency current or recent (within 6 months) chemotherapy or radiotherapy for malignancy solid organ transplant recipients on immunosuppressive therapy bone marrow transplant recipients currently receiving immunosuppressive treatment, or within 12 months of receiving immunosuppression patients with current graft-versus-host disease patients currently receiving high dose systemic corticosteroids (equivalent to ≥40 mg prednisolone per day for >1 week in an adult) and for at least 3 months after treatment has stopped HIV infected patients with severe immunosuppression (CD4<200/μl or <15% of total lymphocytes in an adult) patients currently or recently (within 6 months) on other types of highly immunosuppressive therapy or where the patient’s specialist regards them as severely immunosuppressed.

Appendix iii

Please refer to the summary of product characteristics (SPC) for each antiviral product.

Duration: Prescribers are reminded that use of oseltamivir as treatment for longer than 5 days is an off-label use (except for oseltamivir use in immunosuppressed persons, as per Figure 1 above). Prolonged treatment can be associated with the development of antiviral resistance and antiviral resistance monitoring is recommended.

Administration: Zanamivir powder for inhalation should NOT be nebulised by dissolving the capsules in water.

Weight: No dose adjustment is needed in obese patients for Oseltamivir/inhaler Zanamivir/IV Zanamivir

Renal impairment: No dose adjustments needed for Zanamivir INH. Refer to the SPC for Oseltamivir PO or Zanamivir IV, dose adjustments are needed.

Oseltamivir: dosing in renal impairment
CrCL (mL/min)	Dosing
>60mL/min	75mg 12 hourly
31-60mL/min	30mg 12 hourly
11-30mL/min	30mg 24 hourly
≤ 10mL/min	30mg ONCE
Haemodialysis	30mg ONCE and then 30mg after every haemodialysis session
Continuous Ambulatory Peritoneal Dialysis	30mg ONCE
Haemo-diafiltration	30mg 12 hourly

Note: It is acknowledged that some of the advice for dosing in renal impairment may differ to the renal drug handbook. However, the dosage information presented above is consistent with the summary of product characteristics provided by the manufacturer at the time of writing.

Zanamivir inhaler: no renal adjustments needed.

Intravenous Zanamivir: dosing in renal impairment
CrCL (mL/min)	Dosing	Administration timings
50 to < 80mL/min	600mg stat 400mg 12 hourly	Begin maintenance dosing 12 hours after the initial dose
30 to < 50mL/min	600mg stat, 250mg 12 hourly	Begin maintenance dosing 12 hours after the initial dose.
15 to < 30mL/min	600mg stat, 150mg 12hourly	Begin maintenance dosing 24 hours after the initial dose
< 15mL/min	600mg stat, 60mg 12 hourly	Begin maintenance dosing 48 hours after the initial dose
Peritoneal Dialysis	600mg stat, 60mg 12 hourly	Begin maintenance dosing 48 hours after the initial dose
Continuous Renal Replacement Therapy (CRRT)	600mg stat, 250mg 12 hourly	Begin maintenance dosing 12 hours after the initial dose.

Note: If the patient has a morning dialysis session: administer the morning dose after their dialysis and their afternoon dose 12 hours after their morning dose.

If the patient has an afternoon dialysis session: administer the morning dose at 8am and the afternoon dose after their dialysis session, 12 hours after the morning dose.

Hepatic impairment: No dose adjustments are needed.

Pregnancy: Recent studies suggest there is no evidence of harm in pregnant women treated with oral oseltamivir or inhaled zanamivir. However, published data is limited. The use of oseltamivir may be considered during pregnancy if necessary and after considering the available safety and benefit information.

Breastfeeding: Both oseltamivir and zanamivir are considered acceptable for use in breastfeeding mothers. The benefits of breastfeeding are considered to outweigh any, albeit unidentified, risks. Use of either drug is not a reason to discontinue, or put limitations on breastfeeding.

Equity and Diversity

The Leeds Teaching Hospitals NHS Trust is committed to ensuring that the way that we provide services and the way we recruit and treat staff reflects individual needs, promotes equality and does not discriminate unfairly against any particular individual or group.