CEFOCEL 1000

Indications

• Severe infections caused by Gram-negative bacteria
• Pneumonia
• Urinary tract infections
• Intra-abdominal infections
• Skin and soft tissue infections
• Bacteremia and sepsis
• Infections in immunocompromised patients

Dosage

Children: Refer to the BNF for Children for specific dosing information based on the child's weight, age, and clinical condition.

Adults: Refer to the specific guidelines or consult the BNF for appropriate dosing based on the type and severity of the infection, renal function, and clinical response.

Mechanism of action

Cefoperazone works by inhibiting bacterial cell wall synthesis. It achieves this by binding to penicillin-binding proteins (PBPs) located inside the bacterial cell wall. This binding disrupts the transpeptidation process, which is essential for cell wall cross-linking, ultimately leading to cell lysis and death of the bacteria.

Pharmacodynamics

Cefoperazone exhibits time-dependent antibacterial activity, meaning that its efficacy is related to the time the drug concentration remains above the minimum inhibitory concentration (MIC) for the target organism. It has a broad spectrum of activity, particularly against Gram-negative bacteria, including Enterobacteriaceae and Pseudomonas species. The bactericidal effect of cefoperazone is a result of its ability to disrupt cell wall synthesis, leading to bacterial cell death.

Pharmacokinetics

Cefoperazone has a relatively good distribution throughout the body, including penetration into the central nervous system. After intravenous administration, peak plasma concentrations are achieved quickly. The drug is primarily excreted unchanged in the urine, with a half-life of approximately 2 to 3 hours in healthy adults. It is not extensively metabolized but can undergo some hydrolysis in the presence of beta-lactamase enzymes, which can affect its efficacy against resistant organisms.

Contra-indications

• Hypersensitivity to cefoperazone or any component of the formulation
• History of severe allergic reactions to beta-lactam antibiotics

Adverse effects

• Diarrhea
• Nausea
• Vomiting
• Rash
• Elevated liver enzymes
• Allergic reactions including anaphylaxis
• Thrombocytopenia
• Leukopenia

Interactions

• May enhance the anticoagulant effect of warfarin
• Probenecid may increase cefoperazone levels
• Other nephrotoxic agents may increase the risk of kidney damage

Precautions

• Use with caution in patients with renal impairment
• Monitor liver function during prolonged therapy
• Caution in patients with a history of gastrointestinal disease, particularly colitis

Pregnancy

Cefoperazone should be used during pregnancy only if clearly needed. Animal studies have not demonstrated teratogenic effects, but adequate and well-controlled studies in pregnant women are lacking.

Breast-feeding

Cefoperazone is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature away from light and moisture. Reconstituted solutions should be stored in the refrigerator and used within 24 hours.

Formulations

• Cefoperazone sodium for injection
• Cefoperazone in combination with sulbactam

Indications

• Complicated urinary tract infections
• Intra-abdominal infections
• Skin and soft tissue infections
• Pneumonia caused by susceptible strains
• Sepsis from beta-lactamase producing organisms

Dosage

Children: Refer to the BNF for Children for appropriate dosing based on age

Adults: Refer to specific guidelines for dosing based on the combination with the beta-lactam antibiotic being used. Dosing should consider the severity of the infection and renal function.

Mechanism of action

Salbactum works by irreversibly binding to and inhibiting the activity of beta-lactamase enzymes produced by certain bacteria. This inhibition prevents the hydrolysis of the beta-lactam ring of antibiotics, enabling these drugs to remain effective against bacteria that would otherwise be resistant due to the action of these enzymes. The presence of salbactum allows for sustained antimicrobial activity of the co-administered antibiotics, enhancing their therapeutic effectiveness.

Pharmacodynamics

Salbactum exhibits a synergistic effect when used in conjunction with beta-lactam antibiotics. It enhances the antibacterial spectrum of these antibiotics, particularly against penicillin-resistant strains. The combination therapy can lead to improved clinical outcomes and reduction in treatment failures associated with resistant infections. The pharmacodynamic profile is characterized by bactericidal activity, where the drug combination leads to the death of bacteria, particularly in rapidly dividing organisms.

Pharmacokinetics

The pharmacokinetics of salbactum, when administered with beta-lactam antibiotics, may vary based on the specific antibiotic used. Generally, salbactum is administered parenterally, with good tissue penetration observed. It is metabolized in the liver and excreted primarily through the kidneys. The half-life can range depending on the formulation and the concomitant antibiotics, necessitating careful consideration of dosing intervals to maintain effective plasma concentrations.

Adverse effects

• Hypersensitivity reactions
• Nausea
• Vomiting
• Diarrhea
• Rash
• Fever

Precautions

• Use with caution in patients with a history of allergies
• Monitor renal function in patients with renal impairment
• Consider potential interaction with other antibiotics

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised as it is not known if salbactum is excreted in human milk.

Storage

Store in a cool, dry place away from direct light. Keep out of reach of children.