Is cefixime (third-generation cephalosporin) a broad-spectrum antibiotic effective against both Gram-positive and Gram-negative bacteria, including resistant organisms like Pseudomonas aeruginosa, in a patient with a persistent elevated Total Leukocyte Count (TLC) despite azithromycin treatment?

Cefixime Spectrum of Coverage

Cefixime is a broad-spectrum third-generation cephalosporin with excellent activity against many Gram-negative bacteria and some Gram-positive organisms, but it has critical gaps in coverage—it lacks activity against Pseudomonas aeruginosa, has poor staphylococcal coverage, and has no anaerobic activity. 1, 2, 3, 4

Spectrum Breakdown

Strong Gram-Negative Coverage

• Cefixime demonstrates potent activity against Haemophilus influenzae (including beta-lactamase-producing strains), Neisseria gonorrhoeae, and most Enterobacteriaceae. 1, 3, 4
• The drug is highly resistant to beta-lactamase degradation, making it effective against many resistant Gram-negative organisms. 2, 4

Limited Gram-Positive Coverage

• Cefixime has limited activity against Streptococcus pneumoniae (penicillin-susceptible strains only) and Streptococcus pyogenes. 1, 4
• It has no clinically significant activity against drug-resistant S. pneumoniae (DRSP) and no activity against staphylococci, including Staphylococcus aureus. 1, 3
• Cefixime is inappropriate for staphylococcal infections such as skin/soft tissue infections or bacteremia. 1

Critical Coverage Gaps

Pseudomonas aeruginosa:

• Cefixime has little to no activity against Pseudomonas aeruginosa and should never be used for suspected or confirmed pseudomonal infections. 3, 4
• For anti-pseudomonal coverage, other third-generation cephalosporins like ceftazidime or fourth-generation agents like cefepime are required. 5

Anaerobic Coverage:

• Cefixime has no clinically significant activity against anaerobes, including Bacteroides fragilis. 1
• It is inappropriate for anaerobic infections and should not be used for intra-abdominal or mixed aerobic-anaerobic infections without additional anaerobic coverage. 1

Enterococcal Coverage:

• Cefixime is inactive against enterococci. 1

Clinical Context for Your Patient

For a patient with persistent elevated TLC despite azithromycin treatment:

• Cefixime would provide coverage for common Gram-negative respiratory pathogens like H. influenzae and some Enterobacteriaceae. 3, 4
• However, if there is concern for Pseudomonas aeruginosa (common in healthcare-associated infections, immunocompromised patients, or structural lung disease), cefixime is completely inadequate. 3, 4
• If staphylococcal infection (including S. aureus) is suspected, cefixime will not provide coverage. 1, 3

Practical Algorithm for Antibiotic Selection

Choose cefixime when:

• H. influenzae is confirmed or strongly suspected (respiratory tract infections, otitis media). 1, 4
• Gram-negative urinary tract infection without concern for Pseudomonas. 4
• Uncomplicated gonorrhea. 4

Do NOT choose cefixime when:

• Pseudomonas aeruginosa is a concern—use ceftazidime, cefepime, or piperacillin/tazobactam instead. 5, 6
• Staphylococcal infection is suspected—requires anti-staphylococcal coverage. 1, 3
• Anaerobic coverage is needed—add metronidazole or use piperacillin/tazobactam. 6, 1
• Drug-resistant S. pneumoniae is suspected—cefixime has inadequate coverage. 1

Common Pitfalls

• Assuming "third-generation cephalosporin" means anti-pseudomonal activity: Only certain third-generation agents (ceftazidime, cefoperazone) have meaningful Pseudomonas coverage; cefixime does not. 5, 3, 4
• Using cefixime for empiric community-acquired pneumonia: Inadequate coverage for S. pneumoniae, especially DRSP, makes this inappropriate. 1
• Substituting cefixime for first-generation cephalosporins in skin infections: Cefixime lacks staphylococcal activity and would be ineffective. 1, 3