What are the guidelines for managing patients with flu-like symptoms, particularly those at high risk due to age or underlying health conditions?

Management of Influenza-Like Illness: Evidence-Based Guidelines

Immediate Risk Stratification

All patients presenting with flu-like symptoms require immediate assessment for high-risk features, with antiviral therapy (oseltamivir 75mg twice daily for 5 days) initiated within 48 hours for high-risk patients, and hospitalization considered for those with severe illness markers regardless of symptom duration. 1

High-Risk Patient Identification

Patients at elevated risk for complications and mortality include: 1

• Age-related risk:

  • Adults ≥65 years (account for >90% of influenza deaths) 1
  • Children <5 years, particularly infants <6 months (hospitalization rate ~1,040/100,000) 1
  • Children 0-1 years have hospitalization rates comparable to elderly patients 1

• Underlying medical conditions:

  • Chronic respiratory disease (COPD, asthma requiring continuous steroids, cystic fibrosis, bronchiectasis) 1
  • Chronic heart disease (congenital heart disease, heart failure, ischemic heart disease requiring medication) 1
  • Chronic renal disease (nephrotic syndrome, renal failure, transplantation) 1
  • Diabetes mellitus requiring insulin or oral hypoglycemics 1
  • Immunosuppression (HIV, malignancy, chemotherapy, systemic steroids ≥20mg prednisolone daily for >1 month) 1
  • Chronic liver disease (cirrhosis, inflammatory bowel disease) 1
  • Neurological disease with muscle weakness or cerebral palsy 1
  • Pregnancy and postpartum period 2
  • Long-stay residential care home residents 1

Antiviral Treatment Algorithm

Standard Treatment Window (≤48 Hours)

Initiate oseltamivir 75mg orally twice daily for 5 days if ALL of the following are present: 1, 3

• Acute influenza-like illness (fever, myalgia, headache, malaise, cough, sore throat, rhinitis) 1
• Fever >38°C 1
• Symptoms present for ≤2 days 1

Dosing adjustments: 2, 3

• Renal impairment (CrCl <30 mL/min): reduce to 75mg once daily 2, 3
• Take with food to reduce nausea (occurs in 10-15% of patients) 2, 3

Critical Exceptions: Treatment Beyond 48 Hours

Do NOT withhold antiviral therapy beyond 48 hours in the following situations: 2, 3

1. Hospitalized patients with severe illness (regardless of illness duration) 2
2. Progressive or worsening illness at any point in disease course 2
3. High-risk patients (as defined above) even if presenting late 2
4. Immunocompromised patients who may require extended treatment courses 2, 3
5. Elderly patients without documented fever (may not mount adequate febrile response) 2

The evidence base for treatment beyond 48 hours is limited as most trials enrolled patients within 36-48 hours, but pathophysiology and viral replication patterns support potential benefit in severely ill patients. 2

Pediatric Dosing

Oseltamivir dosing by weight: 1

• <15 kg (<3 years): 30mg every 12 hours
• 15-23 kg (<7 years): 45mg every 12 hours

• 24 kg (>7 years): 75mg every 12 hours

• FDA approved for children as young as 2 weeks of age 1

Zanamivir alternative: 10mg (2 inhalations) twice daily for 5 days, approved for children >7 years 1, 2, 3

Critical caveat: Avoid zanamivir in patients with asthma or COPD due to bronchospasm risk 2, 3

Hospital Admission Criteria

Adults: CURB-65 Score Assessment

Calculate CURB-65 score (1 point each): 1, 3

• Confusion (new onset)
• Urea >7 mmol/L
• Respiratory rate ≥30/min
• Blood pressure (SBP <90 or DBP ≤60 mmHg)
• Age ≥65 years

Management based on score: 1, 3

• CURB-65 = 0-1: Consider home treatment
• CURB-65 = 2: Consider short inpatient stay or hospital-supervised outpatient management
• CURB-65 = 3-5: Urgent hospital admission for severe pneumonia
• Bilateral chest X-ray changes: Hospital referral regardless of CURB-65 score (suggests primary viral pneumonia with rapid, fulminant course) 1, 3

Additional Admission Indicators

Consider hospitalization if ≥2 of the following: 3

• Temperature >37.8°C
• Heart rate >100/min
• Respiratory rate >24/min
• Systolic blood pressure <90 mmHg
• Oxygen saturation <90%
• Inability to maintain oral intake
• Abnormal mental status

Pediatric Admission Criteria

Transfer to hospital if any of the following: 1, 3

• Signs of respiratory distress or cyanosis
• Severe dehydration
• Altered conscious level
• Complicated or prolonged seizure
• Shock
• Recurrent apnea or slow irregular breathing
• Evidence of encephalopathy

ICU/HDU transfer criteria: 1

• Failing to maintain SaO2 >92% in FiO2 >0.6
• Severe respiratory distress with PaCO2 >6.5 kPa
• Rising respiratory and pulse rates with severe distress

Antibiotic Management

When Antibiotics Are NOT Indicated

Do NOT prescribe antibiotics for: 3

• Previously healthy adults with uncomplicated influenza 3
• Acute bronchitis complicating influenza without pneumonia 3
• Absence of clinical evidence of bacterial co-infection 3

When Antibiotics ARE Indicated

Prescribe antibiotics empirically for: 2, 3

1. Patients with COPD or severe pre-existing illness 2, 3
2. Previously well patients with worsening symptoms after initial presentation, particularly:
   • Recrudescent fever 2, 3
   • Increasing breathlessness 2, 3
3. Clinical evidence of bacterial pneumonia on examination 2, 3
4. High-risk patients with lower respiratory features 3

First-line antibiotic choices: 2

• Doxycycline
• Co-amoxiclav
• Clarithromycin (preferred over azithromycin for better H. influenzae activity) 2

Pediatric antibiotic dosing (co-amoxiclav): 1

• <1 year: 2.5 mL/kg of 125/31 suspension three times daily
• 1-6 years: 5 mL of 125/31 suspension three times daily

• 6 years: 5 mL of 250/62 suspension three times daily

Supportive Care

Oxygen Therapy

Maintain oxygen targets: 1, 3

• PaO2 >8 kPa
• SaO2 ≥92%

Non-invasive ventilation considerations: 3

• May be helpful in COPD patients with ventilatory failure
• Should be used in respiratory/critical care units experienced in infection control measures

Monitoring Requirements

Vital signs monitoring: 3

• At least twice daily for all hospitalized patients
• More frequently in severe cases
• Consider Early Warning Score system for convenient tracking

Prior to discharge, ensure: 3

• Clinical stability achieved
• Follow-up arranged for patients with significant complications or worsening underlying disease

Clinical Presentation and Natural History

Typical Symptoms

Uncomplicated influenza characterized by abrupt onset of: 1

• Fever (typically present, but may be absent in elderly) 1
• Myalgia 1
• Headache 1
• Severe malaise 1
• Nonproductive cough 1
• Sore throat 1
• Rhinitis 1

Transmission and Infectivity

Key epidemiologic features: 1

• Incubation period: 1-4 days (average 2 days) 1
• Infectious period: day before symptoms through ~5 days after illness onset 1
• Children can be infectious for longer periods 1
• Very young children can shed virus for <6 days before illness onset 1
• Severely immunocompromised persons can shed virus for weeks 1

Disease Course

Expected resolution: 1

• Illness typically resolves after several days for most persons 1
• Cough and malaise can persist for >2 weeks 1

Potential complications: 1

• Exacerbation of underlying conditions (pulmonary or cardiac disease) 1
• Secondary bacterial pneumonia 1
• Primary influenza viral pneumonia 1
• Co-infection with other viral or bacterial pathogens 1
• Encephalopathy 1
• Transverse myelitis 1
• Reye syndrome (particularly in children on long-term aspirin) 1
• Myositis, myocarditis, pericarditis 1

Diagnostic Testing Considerations

Clinical diagnosis limitations: 1

• Respiratory illness caused by influenza is difficult to distinguish from other respiratory pathogens based on symptoms alone 1
• Reported sensitivity of clinical definitions (fever + cough): 63-78% 1
• Reported specificity: 55-71% compared with viral culture 1
• Sensitivity and predictive value vary depending on co-circulation of other pathogens and influenza activity level 1

Treatment decisions should not be delayed for laboratory confirmation in high-risk patients. 1, 2, 3

Common Pitfalls to Avoid

1. Do not withhold oseltamivir beyond 48 hours in severely ill, hospitalized, or high-risk patients 2
2. Do not use double-dose oseltamivir (150mg twice daily) - no additional benefit demonstrated 2
3. Do not prescribe zanamivir to patients with asthma or COPD due to bronchospasm risk 2, 3
4. Do not routinely prescribe antibiotics for uncomplicated influenza without evidence of bacterial co-infection 3
5. Do not rely on absence of fever to exclude influenza in elderly or immunocompromised patients 2
6. Do not use negative rapid antigen tests to rule out influenza or make treatment decisions (suboptimal sensitivity) 1

Expected Treatment Benefits

Oseltamivir reduces: 2, 3

• Illness duration by 24-36 hours 2, 3
• Risk of complications in high-risk patients 2
• Hospitalization rates when given early 4

In hospitalized children, early antiviral treatment (≤2 days after illness onset) was associated with: 4

• 37% increase in daily discharge probability for children with medical conditions 4
• 46% increase in daily discharge probability for ICU patients 4
• Median length of stay reduced from 3 days to 2 days 4

Current evidence does not definitively demonstrate mortality reduction with oseltamivir, though it does not rule it out. 2