Do I need to add other antibiotics to cefepime (a fourth-generation cephalosporin) for treating pneumonia or urinary tract infections?

Cefepime Monotherapy is Sufficient for Most Pneumonia and UTI Cases

For most cases of pneumonia and urinary tract infections (UTIs), cefepime monotherapy is sufficient and additional antibiotics are not needed, unless dealing with specific resistant organisms.

Cefepime as Monotherapy for Standard Infections

• Cefepime is a fourth-generation cephalosporin with broad-spectrum activity against many organisms that cause pneumonia and UTIs 1
• Cefepime has excellent activity against both Gram-positive organisms (including Staphylococcus aureus and Streptococcus pneumoniae) and Gram-negative organisms (including Pseudomonas aeruginosa) 1
• Clinical trials have demonstrated that cefepime monotherapy (1-2g IV twice daily) is as effective as other standard antibiotic regimens for treating moderate to severe community-acquired and nosocomial pneumonia 1, 2
• For UTIs, cefepime monotherapy has shown high clinical success rates (90%) compared to broad-spectrum combination therapy (83%) 2

When Additional Antibiotics May Be Needed

For Carbapenem-Resistant Pseudomonas aeruginosa (CRPA)

• If dealing with difficult-to-treat CRPA, guidelines recommend:
  • Ceftolozane-tazobactam if active in vitro 3
  • For DTR-PA (difficult-to-treat P. aeruginosa), options include colistin monotherapy or combination therapy, ceftolozane/tazobactam, or ceftazidime/avibactam 3

For Carbapenem-Resistant Enterobacterales (CRE)

• For severe infections due to CRE:
  • Meropenem-vaborbactam or ceftazidime-avibactam is recommended if active in vitro 3
  • For CRE carrying metallo-β-lactamases resistant to other options, cefiderocol is recommended 3
  • For CRE susceptible only to polymyxins, aminoglycosides, tigecycline, or fosfomycin, combination therapy with more than one active drug is suggested 3

For UTIs Due to CRE

• For complicated UTIs caused by CRE:
  • Ceftazidime-avibactam 2.5g IV q8h 3
  • Meropenem-vaborbactam 4g IV q8h or imipenem-cilastatin-relebactam 1.25g IV q6h 3
  • Plazomicin 15 mg/kg IV q12h 3
  • Single-dose aminoglycoside for simple cystitis due to CRE 3

Important Considerations

• Susceptibility testing is crucial: Treatment should be guided by antimicrobial susceptibility testing or genotypic characterization of resistance 3
• Risk of neurotoxicity: Cefepime has been associated with neurotoxicity, particularly in patients with renal impairment, presenting as confusion, myoclonus, or expressive aphasia 4
• Stewardship considerations: For non-severe infections or low-risk infections, consider using older antibiotics that show in vitro activity to preserve newer agents 3
• Combination therapy caution: For patients with CRE infections susceptible to and treated with newer agents (ceftazidime-avibactam, meropenem-vaborbactam, cefiderocol), combination therapy is not recommended 3

Algorithm for Decision-Making

1. Identify the pathogen and obtain susceptibility testing
2. For standard susceptible organisms:
   • Use cefepime monotherapy at appropriate dosing (2g IV q8-12h) 3
3. For resistant organisms:
   • If CRPA: Consider ceftolozane-tazobactam or other targeted therapy based on susceptibility 3
   • If CRE: Use newer agents like ceftazidime-avibactam or meropenem-vaborbactam 3
4. For critically ill patients with suspected resistant organisms:
   • Consider empiric combination therapy until susceptibility results are available
   • De-escalate to monotherapy once susceptibility is confirmed 3

Conclusion

Cefepime monotherapy is generally sufficient for most pneumonia and UTI cases when the causative organisms are susceptible. Additional antibiotics should be reserved for specific scenarios involving resistant organisms, particularly CRE and CRPA, based on susceptibility testing and the severity of infection.