Cefoperazone Sulbactam 

1. Drug Overview

Combination:

• Cefoperazone → 3rd generation cephalosporin
• Sulbactam → β-lactamase inhibitor (also intrinsic Acinetobacter activity)

Class: β-lactam + β-lactamase inhibitor (BL–BLI)

2. Mechanism of Action

 Cefoperazone

• Binds to PBPs
• Inhibits transpeptidation
• Bactericidal
• Time-dependent killing (T>MIC important)

 Sulbactam

• Irreversible β-lactamase inhibitor
• Inhibits Class A β-lactamases
• Intrinsic activity against Acinetobacter

 Does NOT inhibit:

• AmpC (reliably)
• ESBL (not sufficient alone)
• Carbapenemases

3. Spectrum of Activity

 Gram Negative Coverage

• Enterobacterales (E. coli, Klebsiella, Proteus)
• H. influenzae
• Neisseria
• Some Pseudomonas
• Acinetobacter (due to sulbactam)

 Weak/No Activity

• ESBL producers (in high inoculum)
• Carbapenem-resistant organisms
• MRSA
• Enterococcus
• Stenotrophomonas

4. Important Organisms in ICU

5. Pharmacokinetics 

Dose adjustment NOT required in renal failure
(Unlike most cephalosporins)

But:

• Dose adjust in hepatic failure
• Monitor in cholestasis

6. Unique Adverse Effects 

 Hypoprothrombinemia

• Inhibits vitamin K–dependent clotting factor synthesis
• Risk ↑ in:
• Malnutrition
• Prolonged ICU stay
• TPN patients
• Liver disease

Management:

• Vitamin K 10 mg IV weekly (prophylactic in ICU sometimes)

 Disulfiram-like Reaction

• Alcohol → flushing, hypotension

 Biliary sludge / cholestasis

7. Clinical Uses in ICU

1. HAP / VAP (non-ESBL setting)

Empirical option where carbapenem sparing strategy needed.

2. Intra-abdominal sepsis

Good biliary concentration.

3. Acinetobacter infection (if carbapenem-sensitive)

4. Biliary sepsis

Preferred due to biliary excretion.