In a healthy adult with confirmed COVID‑19 or influenza B and no evidence of bacterial co‑infection, are antibiotics indicated and what regimen should be used if a bacterial superinfection is suspected?

Antibiotic Treatment for COVID-19 and Influenza B

Antibiotics are NOT indicated for healthy adults with confirmed COVID-19 or influenza B who have no evidence of bacterial co-infection, as bacterial co-infection occurs in only 3.5% of COVID-19 cases at admission and similarly low rates in influenza B. 1

Core Principle: Restrictive Antibiotic Use

For uncomplicated viral respiratory infections (COVID-19 or influenza B), withhold antibiotics entirely unless specific clinical criteria for bacterial superinfection are met. 1, 2

• Bacterial co-infection at hospital admission occurs in only 3-8% of COVID-19 patients, making empiric antibiotics inappropriate for mild-to-moderate disease. 1, 2
• The rate of clinically relevant bacteremia in COVID-19 is only 1.0%, significantly lower than influenza A (4.0%) or influenza B (3.0%). 3
• Antibiotic overuse during COVID-19 was rampant (74.9% of patients received antibiotics) despite actual bacterial co-infection rates of only 3.5%. 4

When to START Antibiotics: Specific Clinical Triggers

Initiate empiric antibiotics ONLY when the following criteria are present:

Immediate Indications (Start Antibiotics Now)

• Severe illness requiring ICU admission - start empiric antibiotics immediately while awaiting cultures. 1, 2, 5
• Immunocompromised patients (chemotherapy, transplant recipients, HIV/AIDS, prolonged corticosteroids >20mg prednisone equivalent for >2 weeks). 1, 2
• Radiological consolidation PLUS elevated inflammatory markers (procalcitonin >0.5 ng/mL, markedly elevated CRP, elevated WBC with left shift). 1, 2, 5

Secondary Bacterial Infection (Hospital-Acquired)

• Clinical deterioration after initial improvement with new fever, increased oxygen requirements, or worsening infiltrates after day 5-7 of illness. 1
• Secondary infections occur in 15-20% of hospitalized COVID-19 patients overall, but concentrate in severely ill patients (up to 50% in non-survivors vs <1% in survivors). 2, 6

Essential Diagnostic Testing BEFORE Starting Antibiotics

Obtain the following tests before initiating empiric antibiotics whenever clinically feasible: 1

• Blood cultures (two sets from separate sites)
• Sputum culture (if patient can produce quality specimen)
• Pneumococcal urinary antigen test
• Legionella urinary antigen test (per local CAP guidelines)
• Procalcitonin level

Antibiotic Selection When Bacterial Infection is Suspected

For Mild-to-Moderate Community-Acquired Pneumonia Criteria

Amoxicillin 1g orally or IV every 8 hours is the preferred first-line agent. 1, 2

• Provides optimal coverage against Streptococcus pneumoniae and Haemophilus influenzae, the most common bacterial pathogens in COVID-19 co-infection. 2
• Do NOT routinely cover atypical pathogens (Mycoplasma, Chlamydia) in general ward patients with COVID-19. 1

For Severe CAP Requiring ICU Admission

Beta-lactam (ceftriaxone 2g IV daily OR cefotaxime 1-2g IV every 8 hours) PLUS azithromycin 500mg IV/PO daily. 2

For Suspected Hospital-Acquired/Secondary Infection

Cefepime 2g IV every 8 hours as single antipseudomonal agent for non-critically ill patients. 5

• For critically ill patients, consider double antipseudomonal coverage based on local resistance patterns. 5
• Common pathogens in secondary infections: Enterobacter cloacae, Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae. 1, 6

Antibiotic De-escalation and Duration

Stop antibiotics at 48 hours if cultures are negative and patient shows clinical improvement. 1, 2, 5

• If bacterial infection is confirmed, treat for 5 days total if patient demonstrates clinical improvement (resolution of fever, improved respiratory status, declining inflammatory markers). 1, 2, 5
• Maximum duration should be 5-7 days when bacterial infection is confirmed and clinical stability achieved. 5

Critical Pitfalls to Avoid

Do NOT Start Antibiotics Based on Imaging Alone

• 86% of COVID-19 patients have radiographic infiltrates representing viral pneumonitis, NOT bacterial infection. 2
• Viral pneumonia alone causes consolidation and ground-glass opacities that do not indicate bacterial co-infection. 5

Do NOT Rely on Biomarkers Alone in Non-Critically Ill Patients

• Elevated CRP and inflammatory markers occur with severe COVID-19 itself and should not be used alone to justify antibiotics. 1, 5
• Procalcitonin cannot be used as the sole criterion to start or withhold antibiotics in CAP. 1

Do NOT Underdose Amoxicillin

• Use high-dose regimens (1g every 8 hours in adults) to overcome intermediate resistance patterns in S. pneumoniae. 2

Do NOT Continue Antibiotics Beyond 48 Hours Without Evidence

• If cultures remain negative at 48 hours and patient is improving, discontinue antibiotics regardless of initial clinical suspicion. 1, 2, 5

Influenza B Considerations

• The same restrictive antibiotic principles apply to influenza B as to COVID-19. 7, 3
• Antibiotic prescriptions were less common during COVID-19 (9.6%) than during influenza seasons (20.7%), suggesting appropriate stewardship. 7