Neomicef-S 1.5G

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

• Intra-abdominal infections
• Skin and soft tissue infections
• Respiratory tract infections
• Urinary tract infections
• Gynecological infections

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing guidance, as it varies based on the child's age, weight, and specific condition being treated.

Adults: Refer to the BNF for specific dosing recommendations, which vary based on the infection being treated and the antibiotic used in combination with sulbactam.

Mechanism of action

Sulbactam works by irreversibly binding to the active site of beta-lactamase enzymes, thereby inhibiting their ability to hydrolyze and deactivate beta-lactam antibiotics. This action results in increased levels of these antibiotics in the presence of resistant bacteria, allowing them to maintain their antibacterial activity.

Pharmacodynamics

Sulbactam has no intrinsic antibacterial activity on its own but enhances the activity of beta-lactam antibiotics. Its action allows for higher concentrations of antibiotics like ampicillin or amoxicillin to remain effective against resistant strains of bacteria. The combination therapy leads to a synergistic effect, improving the overall therapeutic outcome.

Pharmacokinetics

Sulbactam is generally well absorbed when administered intravenously. Its distribution is widespread throughout body tissues, and it is known to cross the blood-brain barrier to some extent. Sulbactam is primarily excreted unchanged in the urine, with a half-life of approximately 1 hour, necessitating regular dosing to maintain effective levels in the bloodstream.

Contra-indications

• Hypersensitivity to sulbactam or any component of the formulation
• Severe allergic reactions to beta-lactam antibiotics

Adverse effects

• Allergic reactions, including rash, pruritus, and anaphylaxis
• Gastrointestinal disturbances, such as diarrhea, nausea, and vomiting
• Hematologic reactions, including thrombocytopenia and eosinophilia
• Liver enzyme elevations
• Renal impairment

Interactions

• May enhance the effects of warfarin, leading to increased risk of bleeding
• Potential interaction with probenecid, which may inhibit renal excretion of sulbactam
• Concurrent use with other antibiotics may lead to altered efficacy

Precautions

• Use with caution in patients with a history of penicillin allergy
• Monitor renal function in patients with pre-existing renal impairment
• Caution in patients with severe hepatic impairment
• Evaluate for signs of superinfection with prolonged use

Pregnancy

Sulbactam is classified as pregnancy category B. Animal reproduction studies have not shown a risk to the fetus, but there are no well-controlled studies in pregnant women.

Breast-feeding

Sulbactam is excreted in breast milk; caution should be exercised when administered to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Protect from freezing.

Formulations

• Sulbactam injection for intravenous or intramuscular use
• Combination formulations with beta-lactam antibiotics, such as ampicillin-sulbactam

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.