Is cefpodoxime effective against Proteus mirabilis and other Gram-negative rods?

Cefpodoxime Efficacy Against Proteus mirabilis and Gram-Negative Rods

Cefpodoxime is effective against Proteus mirabilis but not against all gram-negative rods, with notable exceptions including Pseudomonas aeruginosa which is resistant to cefpodoxime. 1

Spectrum of Activity

• Cefpodoxime is active against Proteus mirabilis as confirmed by the FDA drug label, which specifically lists P. mirabilis among the susceptible organisms 1

• For gram-negative bacteria, cefpodoxime demonstrates good activity against:

  • Escherichia coli 1
  • Klebsiella pneumoniae 1
  • Proteus mirabilis 1
  • Haemophilus influenzae (including beta-lactamase producing strains) 1
  • Moraxella catarrhalis 1
  • Neisseria gonorrhoeae (including penicillinase-producing isolates) 1

• Additional gram-negative bacteria with documented in vitro susceptibility include:

  • Citrobacter diversus 1
  • Klebsiella oxytoca 1
  • Proteus vulgaris 1
  • Providencia rettgeri 1
  • Haemophilus parainfluenzae 1

Important Limitations

• Cefpodoxime lacks activity against Pseudomonas aeruginosa 2
• Unlike tigecycline, which has poor activity against both P. aeruginosa and P. mirabilis, cefpodoxime is effective against P. mirabilis but not P. aeruginosa 2
• For intra-abdominal infections involving Pseudomonas, alternative agents such as carbapenems, aminoglycosides, or newer combinations like ceftolozane/tazobactam would be more appropriate 2

Mechanism and Pharmacology

• Cefpodoxime is a third-generation oral cephalosporin that acts by inhibiting bacterial cell wall synthesis 1
• It maintains activity in the presence of many beta-lactamases, both penicillinases and cephalosporinases 1, 3
• The drug achieves good tissue penetration, particularly in lung tissue where concentrations exceed the MIC90 for susceptible organisms for at least 12 hours after dosing 1
• Cefpodoxime proxetil is an orally administered prodrug that is absorbed and de-esterified by the intestinal mucosa to release the active cefpodoxime 3

Clinical Applications

• Cefpodoxime is FDA-approved for uncomplicated urinary tract infections caused by E. coli, K. pneumoniae, P. mirabilis, or S. saprophyticus 1
• It is also indicated for skin and soft tissue infections, respiratory tract infections, and gonorrhea 1
• In comparative studies, cefpodoxime has shown efficacy similar to other beta-lactams for respiratory, urinary tract, and skin/soft tissue infections 3

Resistance Considerations

• In settings with high incidence of ESBL-producing Enterobacteriaceae, extended use of cephalosporins including cefpodoxime should be discouraged due to selection pressure 2
• For intra-abdominal infections with suspected resistant pathogens, newer agents like ceftolozane/tazobactam or ceftazidime/avibactam (combined with metronidazole) may be more appropriate 2
• Always obtain cultures and antimicrobial susceptibility testing when treating serious infections to guide therapy 2

Clinical Decision Making

• For empiric treatment of infections potentially involving P. mirabilis and other susceptible gram-negative rods, cefpodoxime is an appropriate option 1
• For suspected or confirmed Pseudomonas infections, alternative agents must be selected 2
• For serious infections, consider obtaining cultures before initiating therapy to guide appropriate antibiotic selection 2
• In patients with renal impairment, dosage adjustment may be necessary as cefpodoxime elimination is reduced 1

In summary, cefpodoxime is effective against Proteus mirabilis and several other gram-negative rods, but has important gaps in its coverage, particularly against Pseudomonas aeruginosa. When treating infections potentially involving gram-negative pathogens, understanding these limitations is essential for appropriate antibiotic selection.