POZINEG 1000

Indications

• Bacterial infections due to sensitive Gram-positive and Gram-negative bacteria
• Complicated urinary tract infections
• Acute pyelonephritis
• Hospital-acquired pneumonia
• Ventilator-associated pneumonia

Dosage

Adults: By intravenous infusion: 1 g every

Mechanism of action

Cefepime disrupts bacterial cell walls by binding to and inhibiting transpeptidases known as penicillin-binding proteins (PBPs), which are critical for the synthesis of the peptidoglycan layer. This action leads to the lysis and death of susceptible microorganisms. Cefepime exhibits strong binding affinity for PBP-3 and PBP-1 in Escherichia coli and Pseudomonas aeruginosa, and PBP-2 in E. coli and Enterobacter cloacae.

Pharmacodynamics

Cefepime has a broad range of activity against various Gram-negative bacteria, including Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa, as well as Gram-positive bacteria such as Staphylococcus aureus (methicillin-susceptible strains), Streptococcus pneumoniae, Streptococcus pyogenes, and Viridans group streptococci. It is more stable against beta-lactamases compared to third-generation cephalosporins and is less likely to induce resistance mechanisms in bacteria.

Pharmacokinetics

Cefepime is well-absorbed when administered intravenously or intramuscularly. It has a volume of distribution of 0.2 to 0.3 L/kg and is primarily eliminated through the kidneys, with a half-life of approximately 2 hours in patients with normal renal function. Dose adjustments are necessary for patients with renal impairment to prevent accumulation and potential toxicity.

Adverse effects

• Anemia
• Hypotension
• Electrolyte imbalance
• Thrombocytosis
• Gastrointestinal disorders
• Anxiety
• Constipation
• Insomnia
• Angina pectoris
• Arrhythmias
• Dyspnoea
• Genital pruritus
• Paraesthesia
• Seizure

Precautions

• Monitor renal function in patients with renal impairment
• Use with caution in patients with a history of antibiotic-associated colitis
• Caution in patients with known allergies to beta-lactam antibiotics

Pregnancy

Manufacturer advises to use only if potential benefit outweighs risk, with toxicity observed in animal studies.

Breast-feeding

Manufacturer advises avoiding use due to lack of available information.

Storage

Store in a cool, dry place, protected from light. Follow specific storage instructions as indicated on the product label.

Formulations

• Injection, powder for solution for infusion (1 g and 2 g vials)
• Injection, powder for solution for infusion (500 mg and 1 g vials)

Indications

• Pain relief
• Fever reduction
• Treatment of respiratory conditions
• Management of inflammation
• Cough relief
• Antibiotic therapy

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines tailored to paediatric populations, as dosages will depend on the formulation and active ingredients used in the mixture.

Adults: Refer to specific drug combinations for appropriate dosing recommendations, as dosages will vary widely based on the active ingredients included.

Mechanism of action

The mechanism of action of a mixture depends on the specific active ingredients included. For instance, if the mixture consists of an analgesic and an anti-inflammatory, the analgesic may work by inhibiting cyclooxygenase enzymes, thus reducing prostaglandin synthesis, while the anti-inflammatory may reduce inflammation through modulation of immune cell activity. The synergistic effects can enhance overall therapeutic outcomes.

Pharmacodynamics

Pharmacodynamics of mixtures varies based on the components involved. Each ingredient may exert its pharmacological effects through different pathways, leading to a combined effect that is often greater than the sum of individual drugs. This can involve interactions at receptor sites, modulation of enzyme activity, or alteration of metabolic pathways, improving clinical outcomes for patients.

Pharmacokinetics

Pharmacokinetics of drug mixtures is influenced by the individual pharmacokinetic profiles of each constituent. This includes absorption rates, distribution volumes, metabolism pathways, and elimination half-lives. The presence of multiple active ingredients can lead to altered absorption due to interactions, changes in protein binding, or competition for metabolic enzymes. Understanding these dynamics is crucial for optimizing dosing regimens and minimizing potential adverse effects.

Pregnancy

The safety of this mixture during pregnancy has not been established. Use only if the potential benefits outweigh the risks.

Breast-feeding

Caution is advised when using this mixture while breastfeeding. Consult a healthcare professional for guidance.

Storage

Store in a cool, dry place, away from direct sunlight and moisture. Ensure that the container is tightly closed.

Mechanism of action

Cefepime is a bactericidal cephalosporin with a mode of action similar to other beta-lactam antibiotics. Cefepime disrupts bacterial cell walls by binding and inhibiting transpeptidases known as penicillin-binding proteins (PBPs), which are enzymes involved in the final stages of peptidoglycan layer synthesis. This results in the lysis and death of susceptible microorganisms. Cefepime has a broad spectrum of _in vitro_ activity that includes both Gram-positive and Gram-negative bacteria. Cefepime has affinity for PBP-3 and PBP-1 in _Escherichia coli_ and _Pseudomonas aeruginosa_, as well as PBP-2 in _E. coli_ and _Enterobacter cloacae_.

Pharmacodynamics

Cefepime is a fourth-generation cephalosporin antibiotic. It is active against Gram-negative bacteria such as _Enterobacter_ spp., _Escherichia coli_, _Klebsiella pneumoniae_, _Proteus mirabilis_ and _Pseudomonas aeruginosa_, and Gram-positive bacteria such as _Staphylococcus aureus_ (methicillin-susceptible isolates only), _Streptococcus pneumoniae_, _Streptococcus pyogenes_ and Viridans group streptococci. Compared to third-generation cephalosporins, cefepime has an extended Gram-negative coverage. Whereas other cephalosporins are degraded by plasmid- and chromosome-mediated beta-lactamases, cefepime is stable and not significantly hydrolyzed by these enzymes. Cefepime is also a poor inducer of type 1 beta-lactamases and, therefore, a good alternative against bacteria resistant to third-generation cephalosporins. In animal models of infection, the time that the unbound plasma concentration of cefepime exceeds the minimum inhibitory concentration (MIC) of infecting organisms has been shown to correlate with treatment efficacy. It has been suggested that cefepime can cross the inflamed blood-brain barrier. This, along with its ability to inhibit γ-aminobutyric acid (GABA), could lead to the neurotoxic effects observed in some of the patients treated with cefepime.