GENCEF PLUS

Indications

• Bacterial infections
• Susceptible infections due to sensitive Gram-positive and Gram-negative bacteria
• Community-acquired pneumonia
• Hospital-acquired pneumonia
• Intra-abdominal infections
• Complicated urinary tract infections
• Severe diabetic foot infections
• Prophylaxis of infection from human and animal bites

Dosage

Adults: 1–2 g once daily, or 2 g every 8 hours for severe infections or hospital-acquired pneumonia.

Mechanism of action

Ceftriaxone works by inhibiting mucopeptide synthesis in the bacterial cell wall. Its beta-lactam structure binds to carboxypeptidases, endopeptidases, and transpeptidases located in the bacterial cytoplasmic membrane, which are crucial for cell wall synthesis and division. This binding leads to enzyme inactivity, resulting in the formation of defective cell walls and ultimately bacterial cell death.

Pharmacodynamics

Ceftriaxone is a beta-lactam antibiotic with bactericidal properties, primarily affecting the synthesis of bacterial cell walls. It exhibits activity against a variety of Gram-positive and Gram-negative organisms. The drug is stable against hydrolysis by many beta-lactamases, which enhances its effectiveness against resistant bacterial strains. However, it can still be subject to resistance mechanisms such as beta-lactamase production and alterations in penicillin-binding proteins.

Pharmacokinetics

Ceftriaxone has a long half-life, allowing for once-daily dosing in many cases. It is widely distributed in body tissues and fluids, including the central nervous system, making it effective for treating infections such as meningitis. The drug is primarily eliminated via the kidneys, with a portion excreted in the bile. Dose adjustments may be necessary in patients with renal impairment.

Contra-indications

• Hypersensitivity to ceftriaxone or any of its ingredients
• History of severe allergic reactions to penicillins or other beta-lactam antibiotics
• Newborns with hyperbilirubinemia
• Concurrent use with calcium-containing solutions in neonates

Adverse effects

• Diarrhea
• Nausea
• Vomiting
• Rash
• Thrombocytosis
• Thrombophlebitis at the injection site
• Antibiotic-associated colitis
• Acute kidney injury
• Jaundice
• Biliary sludge
• Neurotoxicity (rare, may include seizures)

Interactions

• Calcium-containing solutions (risk of precipitation)
• Probenecid (may increase plasma concentrations of ceftriaxone)
• Anticoagulants (may enhance anticoagulant effect)
• Other nephrotoxic agents (increased risk of renal impairment)

Precautions

• Use with caution in patients with renal impairment
• Caution in patients with hepatic impairment
• Monitor for signs of antibiotic-associated colitis
• Use with caution in patients with a history of gastrointestinal disease

Pregnancy

Not known to be harmful, but should be used only if clearly needed.

Breast-feeding

Present in milk in low concentrations, but generally considered appropriate to use.

Storage

Store in a cool, dry place away from light. Reconstituted solutions should be used immediately or stored at 2-8 degrees Celsius and used within 24 hours.

Formulations

• Powder for solution for injection: 500 mg, 1 g, 2 g vials

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.

Mechanism of action

Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. Binding of ceftriaxone to these enzymes causes the enzyme to lose activity; therefore, the bacteria produce defective cell walls, causing cell death.

Pharmacodynamics

Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. Ceftriaxone has <i>in vitro</i> activity against gram-positive aerobic, gram-negative aerobic, and anaerobic bacteria. The bactericidal activity of ceftriaxone results from the inhibition of cell wall synthesis and is mediated through ceftriaxone binding to penicillin-binding proteins (PBPs). Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended-spectrum beta-lactamases. However, resistance to ceftriaxone usually occurs through beta-lactamase hydrolysis, altered PBPs, or reduced bacterial cell permeability. Ceftriaxone should not be mixed with or giving in the same IV line as diluents/products containing calcium as they may cause ceftriaxone to precipitate. Ceftriaxone use may also cause biliary sludge or gallbladder pseudolithiasis.