Cefoperazone Spectrum of Activity
Cefoperazone is a third-generation cephalosporin with broad-spectrum bactericidal activity against most aerobic gram-positive bacteria (except enterococci), most aerobic gram-negative bacteria including Pseudomonas aeruginosa, and several pathogenic anaerobic bacteria. 1
Gram-Negative Coverage
Cefoperazone demonstrates robust activity against gram-negative organisms, which is its primary clinical strength:
- Enterobacteriaceae: Highly active against Escherichia coli, Klebsiella pneumoniae, and Proteus species 2, 1
- Pseudomonas aeruginosa: Remarkably superior activity compared to older cephalosporins like cefazolin and cefamandole, with over 200-fold greater potency 2
- Resistant gram-negative organisms: Demonstrates 50-90% clinical efficacy against organisms typically resistant to earlier cephalosporins, including Enterobacter species, Proteus vulgaris, Providencia species, Morganella morganii, and Serratia species 3
- Beta-lactamase stability: Relatively stable to hydrolysis by beta-lactamases produced by gram-negative bacteria, with hydrolysis rates ranging from 7.0 to 0.01 relative to cephaloridine 2
Gram-Positive Coverage
Cefoperazone maintains activity against common gram-positive pathogens:
- Staphylococci and streptococci: Activity comparable to cefazolin and cefamandole 2, 1
- Clinical efficacy: Over 90% satisfactory response rates in infections caused by susceptible staphylococci and streptococci 3
- Important limitation: Does NOT cover enterococci 4, 1
Anaerobic Coverage
Unlike most cephalosporins, cefoperazone has notable anaerobic activity:
- Bacteroides fragilis: Demonstrates activity against this important anaerobic pathogen 3, 1
- Other anaerobes: Effective against a number of pathogenic anaerobic bacteria 4, 1
Clinical Context and Limitations
Critical caveat: While cefoperazone has broad in vitro activity, it is NOT mentioned in current guidelines for empiric therapy of serious infections 5. Modern guidelines favor newer agents like ceftazidime, ceftolozane-tazobactam, and ceftazidime-avibactam for resistant gram-negative coverage 5.
- Inoculum effect: Like other beta-lactams, there is significant decrease in activity with increased inoculum size 2
- MIC-MBC spread: Only small differences between minimum inhibitory and bactericidal concentrations, indicating good bactericidal activity 2
- Serum effect: Activity not significantly altered by addition of human serum 2
Comparative Spectrum Position
Cefoperazone occupies a middle ground in the cephalosporin spectrum:
- Broader than: Cefazolin and cefamandole, particularly for gram-negative organisms 2, 1
- Narrower than: Modern fourth-generation cephalosporins (cefepime) and newer beta-lactam/beta-lactamase inhibitor combinations for resistant organisms 5, 6
- Unique feature: Dual excretion pathway (renal and biliary), unlike most cephalosporins 7, 4