Cefoperazone

MECHANISM OF ACTION

Cefoperazone, a third-generation cephalosporin antibiotic, works by inhibiting the final stage of bacterial cell wall synthesis. Like other beta-lactam antibiotics, it achieves this by binding to and inactivating penicillin-binding proteins (PBPs) inside the bacterial cell wall. 

PHARMACOKINETICS

Absorption

Cefoperazone is not absorbed orally and must be administered by injection, either intravenously (IV) or intramuscularly (IM). An intravenous injection provides immediate, complete (100%) bioavailability, quickly achieving peak serum concentrations. After an intramuscular injection, the drug is well absorbed, with maximum serum concentrations typically reached within one to two hours.

Distribution

The apparent volume of distribution for cefoperazone ranges from 9.9 to 16 liters.

Metabolism

Cefoperazone is minimally metabolized and primarily eliminated through the bile into the feces. A smaller amount is excreted by the kidneys. Its half-life is significantly prolonged in severe liver disease or biliary obstruction. Metabolism of a side chain releases N-methylthiotetrazole, which can cause bleeding risk by interfering with vitamin K and a reaction with alcohol.

Excretion

Cefotetan is approximately 88% bound to plasma proteins, and no significant metabolites have been detected in the urine. Cefoperazone is primarily eliminated through the bile. Its average serum half-life is about 2.0 hours, regardless of the route of administration.

PHARMACODYNAMICS

Cefoperazone is a third-generation cephalosporin antibiotic that primarily works by disrupting the synthesis of the bacterial cell wall. It is a time-dependent bactericidal drug, meaning its effectiveness depends on the duration of its concentration above the minimum inhibitory concentration (MIC), rather than the peak concentration. 

ADMINISTRATION

Cefoperazone is an injectable antibiotic administered either intravenously (IV) or intramuscularly (IM) by a qualified healthcare professional, typically in a hospital or clinic. It is most commonly available as a powder that must be reconstituted (dissolved) with a compatible solution before injection. 

DOSAGE AND STRENGTHS

The following strengths are commonly available in vials for reconstitution: 

Cefoperazone alone: 1 gram and 2 grams

Cefoperazone and sulbactam combination:

1 gram cefoperazone + 0.5 gram sulbactam

1 gram cefoperazone + 1 gram sulbactam

2 grams cefoperazone + 1 gram sulbactam 

DRUG INTERACTIONS

Cefoperazone has significant drug interactions, particularly with anticoagulants like warfarin, where it can increase bleeding risk due to its NMTT side chain inhibiting clotting factors. Alcohol consumption during treatment and for up to 72 hours after the last dose should be strictly avoided, as it can cause a severe disulfiram-like reaction. Co-administration with other medications also requires caution, including with aminoglycosides due to increased risk of kidney and ear toxicity, and with probenecid which elevates cefoperazone's serum concentration. Patients with liver or kidney impairment, vitamin K deficiency, or poor nutrition are at a higher risk for complications, necessitating close monitoring and potential dosage adjustment.

FOOD INTERACTIONS

Food interactions with cefoperazone are primarily related to alcohol consumption and the potential for stomach upset. There are no specific dietary restrictions for most foods while taking this antibiotic. 

CONTRAINDICATIONS

Cefoperazone is contraindicated in patients with a known allergy to penicillins, sulbactam, cefoperazone, or any cephalosporin antibiotics. Serious, and in some cases fatal, hypersensitivity (anaphylactic) reactions have been reported in individuals receiving beta-lactam or cephalosporin therapy.

SIDE EFFECTS

Common side effects:

• Diarrhea.

• Nausea and vomiting.

• Injection site reactions.

• Skin reactions.

Serious side effects:

• Severe diarrhea.

• Allergic reactions.

• Blood disorders.

• Liver and kidney issues.

• Neurological effects.

OVERDOSE

Neurological symptoms:

• Seizures

• Neuromuscular hypersensitivity

• Encephalopathy (altered brain function)

• Confusion

• Dizziness

Gastrointestinal symptoms:

• Severe nausea and vomiting

• Severe diarrhea

• Abdominal pain

Hematological (blood-related) symptoms:

• Hypoprothrombinemia (a blood-clotting disorder)

• Bleeding.

TOXICITY

Cefoperazone toxicity is primarily associated with its N-methylthiotetrazole (NMTT) side chain, which can cause bleeding problems and a reaction to alcohol. The drug can also lead to allergic reactions, gastrointestinal issues, and, in rare cases, nervous system toxicity.