What are effective antibiotics for patients with COVID-19 and suspected bacterial co-infections?

Antibiotic Use in COVID-19 Patients

Antibiotics should generally NOT be routinely prescribed for COVID-19 patients, as bacterial co-infections are rare (occurring in less than 8% of cases at admission), and restrictive antibiotic use is strongly recommended for mild-to-moderately ill patients to prevent antimicrobial resistance. 1

When Antibiotics ARE Indicated

Antibiotics should be considered in specific high-risk scenarios:

High-Risk Patient Groups Requiring Antibiotics

• Critically ill patients requiring ICU admission or mechanical ventilation have higher bacterial co-infection risk and may require empirical antibiotics 1
• Immunocompromised patients (those on chemotherapy, transplant recipients, poorly controlled HIV/AIDS, or prolonged corticosteroid use) 1
• Patients with radiological findings and/or inflammatory markers compatible with bacterial co-infection 1

Laboratory Indicators Suggesting Bacterial Co-infection

• Elevated white blood cell count 1, 2
• Elevated C-reactive protein (CRP) 1, 2
• Procalcitonin (PCT) level >0.5 ng/mL 1, 2

Important caveat: Serum biomarkers alone should NOT determine when to start antibiotics, especially in non-critically ill patients, as these markers can be elevated from COVID-19 itself 1, 2

Pre-Treatment Diagnostic Testing (MANDATORY)

Before starting any empirical antibiotics, obtain: 1

• Sputum culture (if patient can produce sputum)
• Blood cultures (two sets)
• Pneumococcal urinary antigen test
• Legionella urinary antigen test (per local CAP guidelines)

This testing is critical for de-escalation and stopping antibiotics if cultures remain negative at 48 hours 1

Recommended Antibiotic Regimens

For Non-ICU/Non-Critically Ill Patients with Suspected Bacterial Co-infection

Follow standard community-acquired pneumonia (CAP) guidelines: 1, 2

First-line options:

• Beta-lactam (amoxicillin-clavulanate, ceftriaxone, or cefotaxime) PLUS either:
  • Doxycycline (preferred over macrolides due to cardiac safety concerns) 1, 2
  • OR a macrolide (azithromycin or clarithromycin) if no QT-prolonging medications are being used 1
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin or moxifloxacin) 1

Do NOT routinely cover atypical pathogens (Mycoplasma, Chlamydia) in general ward patients, as evidence shows minimal benefit 1

For ICU/Critically Ill Patients with Suspected Bacterial Co-infection

Enhanced coverage regimen: 1, 2

• Beta-lactam PLUS macrolide
• OR beta-lactam PLUS respiratory fluoroquinolone
• Add empirical anti-MRSA coverage (vancomycin or linezolid) in selected critically ill patients 1, 2

For Secondary Bacterial Infections (Hospital-Acquired)

Non-critically ill patients: 1

• Single anti-pseudomonal antibiotic (piperacillin-tazobactam, cefepime, or meropenem)

Critically ill/ICU patients: 1

• Consider double anti-pseudomonal coverage AND/OR anti-MRSA antibiotics based on local epidemiology and resistance patterns

Antibiotic Duration and De-escalation

Critical de-escalation strategy to prevent resistance:

• Stop antibiotics at 48 hours if sputum/blood cultures and urinary antigen tests are negative and patient is improving 1, 3
• For confirmed bacterial infections: 5-7 days total duration if patient shows clinical improvement with resolution of fever for 48 hours 1, 2
• Use procalcitonin levels to guide early discontinuation, particularly in patients with low PCT (<0.25 ng/mL) 2, 3

Common Bacterial Pathogens in COVID-19

When bacterial co-infection does occur, expect typical CAP pathogens: 1, 2

• Streptococcus pneumoniae
• Haemophilus influenzae
• Staphylococcus aureus (including MRSA in ICU patients)
• Mycoplasma pneumoniae (most common atypical pathogen)

Critical Pitfalls to Avoid

Major antimicrobial stewardship concerns:

1. Overuse of azithromycin: Despite widespread early pandemic use, azithromycin has no direct antiviral effect against SARS-CoV-2 and should only be used for documented bacterial infection 4, 5, 6

2. Empirical antibiotics in mild-moderate COVID-19: The vast majority of non-critically ill COVID-19 patients do NOT have bacterial co-infection (>92% have no bacterial pathogen) 1, 7

3. Radiographic findings alone: COVID-19 itself causes extensive radiographic abnormalities that do not indicate bacterial co-infection 2

4. Routine antibiotics with immunomodulatory therapy: Do NOT routinely prescribe antibiotics for patients receiving corticosteroids or IL-6 inhibitors, as evidence for increased bacterial infection risk is weak 1

5. Antimicrobial resistance: Inappropriate antibiotic use during COVID-19 significantly contributes to AMR, which was already a critical global health problem before the pandemic 6

The evidence strongly supports restrictive antibiotic use in COVID-19, with the 2023 Taiwan guidelines and 2021 European guidelines providing the most comprehensive, evidence-based approach to this clinical question. 1