What bacteria are covered by cefepime and doxycycline (Doxycycline)?

Antimicrobial Coverage of Cefepime and Doxycycline

Cefepime and doxycycline together provide broad coverage against gram-positive, gram-negative, and atypical pathogens, making this combination particularly effective for mixed infections and severe community-acquired pneumonia.

Cefepime Coverage

Gram-Positive Bacteria

• Streptococcus pneumoniae - Excellent activity, including against many penicillin-resistant strains 1, 2
• Methicillin-susceptible Staphylococcus aureus (MSSA) - Good activity 2
• Streptococcus pyogenes (Group A) - Excellent activity 2
• Streptococcus agalactiae (Group B) - Excellent activity 2

Gram-Negative Bacteria

• Escherichia coli - Excellent activity, including against many ESBL-producing strains 3, 2
• Klebsiella pneumoniae - Excellent activity 1, 2
• Haemophilus influenzae - Excellent activity 1, 4, 2
• Pseudomonas aeruginosa - Good activity, superior to many third-generation cephalosporins 1, 2
• Enterobacter species - Good activity, including against many resistant strains 1
• Acinetobacter species - Moderate activity 2

Limited or No Activity Against

• Methicillin-resistant Staphylococcus aureus (MRSA) - Poor activity 2
• Enterococcus species - Limited activity (only about 44% of isolates inhibited) 2
• Anaerobes - Limited activity
• Atypical pathogens (Mycoplasma, Chlamydia, Legionella) - Poor activity

Doxycycline Coverage

Gram-Positive Bacteria

• Streptococcus pneumoniae - Moderate activity (resistance increasing) 3
• Group A Streptococcus - Moderate activity

Gram-Negative Bacteria

• Haemophilus influenzae - Moderate activity (25-85% coverage) 3
• Moraxella catarrhalis - Good activity (78-96%) 3
• Vibrio species (including V. vulnificus and V. cholerae) - Excellent activity 5
• Aeromonas hydrophila - Good activity 5

Atypical Pathogens

• Mycoplasma pneumoniae - Excellent activity 3
• Chlamydia pneumoniae - Excellent activity 3
• Legionella species - Good activity 3

Other Organisms

• Rickettsia - Excellent activity
• Spirochetes - Good activity
• Some protozoa (including malaria)

Combined Coverage Benefits

The combination of cefepime and doxycycline provides complementary coverage:

1. Enhanced respiratory pathogen coverage - Particularly effective for community-acquired pneumonia where both typical and atypical pathogens may be present 3

2. Coverage for mixed infections - The combination addresses the gaps in each individual agent's spectrum:

   • Doxycycline covers atypical pathogens that cefepime misses
   • Cefepime provides reliable coverage against resistant gram-negatives that doxycycline may not adequately treat

3. Specific synergistic combinations for certain infections:

   • Vibrio infections - Doxycycline plus a cephalosporin is recommended as first-line therapy for severe Vibrio vulnificus infections 5
   • Aeromonas hydrophila infections - Doxycycline plus either a cephalosporin or fluoroquinolone is recommended 5

Clinical Applications

• Community-acquired pneumonia - Particularly useful for hospitalized patients with risk factors for both typical and atypical pathogens 3, 6
• Mixed respiratory infections - When both gram-negative and atypical pathogens are suspected 3
• Severe skin and soft tissue infections - Especially those involving Vibrio or Aeromonas species 5
• Empiric therapy for neutropenic fever - Cefepime is a recommended agent, though doxycycline is not typically part of this regimen 3

Important Limitations and Considerations

• MRSA coverage - Neither agent provides reliable coverage against MRSA
• Anaerobic coverage - Limited coverage against anaerobes
• Enterococcus coverage - Limited activity against enterococci
• Resistance concerns - Increasing resistance to both agents in certain pathogens:
  • Tetracycline resistance in S. pneumoniae may limit doxycycline utility 3
  • ESBL-producing organisms may have variable susceptibility to cefepime 3, 7

When considering this combination, clinicians should evaluate local resistance patterns and consider supplementing with additional agents if MRSA, enterococci, or resistant gram-negative coverage is needed.