ZINFORO

Indications

• Complicated skin and skin structure infections
• Community-acquired pneumonia
• Infections caused by methicillin-resistant Staphylococcus aureus (MRSA)

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing recommendations.

Adults: Refer to specific guidelines and protocols for adult dosing based on the type and severity of the infection.

Mechanism of action

Ceftaroline exerts its antibacterial effects by binding to penicillin-binding proteins (PBPs) located within the bacterial cell wall. This binding inhibits bacterial cell wall synthesis, leading to cell lysis and death. Ceftaroline has a high affinity for PBP2a, a unique protein found in MRSA, which allows it to overcome resistance mechanisms that other beta-lactam antibiotics cannot.

Pharmacodynamics

Ceftaroline demonstrates time-dependent bactericidal activity. Its efficacy is related to the time that the drug concentration remains above the minimum inhibitory concentration (MIC) of the target pathogen. The drug exhibits a broad spectrum of activity against both aerobic and anaerobic bacteria, with particular strength against Gram-positive organisms.

Pharmacokinetics

Ceftaroline is administered intravenously and has a volume of distribution of approximately 20 L. It is primarily eliminated by the kidneys, with about 85% of the dose excreted unchanged in urine. The half-life of ceftaroline is around 2.5 hours. Dose adjustments may be necessary in patients with renal impairment.

Contra-indications

• Hypersensitivity to cephalosporins or any component of the formulation

Adverse effects

• Nausea
• Diarrhea
• Rash
• Headache
• Abdominal pain
• Hypersensitivity reactions
• Elevated liver enzymes
• Neutropenia

Interactions

• Probenecid may increase serum concentrations of cetaroline
• Anticoagulants may have increased risk of bleeding

Precautions

• Use with caution in patients with a history of severe allergic reactions to penicillins
• Monitor for signs of Clostridium difficile-associated diarrhea
• Renal impairment may require dose adjustments

Pregnancy

Category B. Animal studies have not shown any harm, but there are no adequate studies in pregnant women. Use only if clearly needed.

Breast-feeding

Excreted in human milk. Caution is advised; consider potential benefits versus risks.

Storage

Store at 2-8 degrees Celsius. Protect from light. Do not freeze.

Formulations

• Injectable powder for reconstitution

Indications

• Uncomplicated urinary tract infections
• Complicated urinary tract infections
• Prophylaxis in urinary tract surgery

Dosage

Children: Refer to specific dosing guidelines based on the BNF for Children.

Adults: Refer to specific dosing guidelines based on the BNF.

Mechanism of action

Fosfomycin acts by irreversibly inhibiting the enzyme MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), which is involved in the first step of bacterial cell wall synthesis. This inhibition prevents the formation of peptidoglycan, an essential component of bacterial cell walls, leading to bacterial cell death.

Pharmacodynamics

Fosfomycin demonstrates bactericidal activity, particularly against rapidly dividing bacteria. The drug is effective against a variety of pathogens, including Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa. The pharmacodynamic properties include time-dependent killing, with effectiveness being related to the duration of time that the drug concentration exceeds the minimum inhibitory concentration (MIC) for the target organism.

Pharmacokinetics

Fosfomycin is administered orally or intravenously and is well absorbed from the gastrointestinal tract. Its bioavailability is approximately 30% following oral administration. The drug is widely distributed in body tissues and fluids, including urine, where it achieves high concentrations. Fosfomycin is minimally metabolized, primarily excreted unchanged in the urine. The elimination half-life is approximately 4 to 5 hours, and renal function plays a significant role in its elimination.

Contra-indications

• Hypersensitivity to fosamil or any of its excipients
• Severe renal impairment
• Pregnancy

Adverse effects

• Headache
• Dizziness
• Nausea
• Diarrhea
• Hypotension
• Elevated liver enzymes
• Rash

Interactions

• Concomitant use with other antihypertensives may enhance hypotensive effects
• Potential interactions with drugs that affect renal function
• Caution with medications that can increase the risk of nephrotoxicity

Precautions

• Monitor renal function regularly during treatment
• Use with caution in patients with a history of cardiovascular disease
• Caution in elderly patients due to potential for increased sensitivity

Pregnancy

Fosamil is contraindicated during pregnancy due to potential harm to the fetus.

Breast-feeding

It is not known whether fosamil is excreted in human milk. Caution should be exercised when administered to a nursing mother.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Injectable solution