EXBLIFEP

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

• Complicated urinary tract infections
• Complicated intra-abdominal infections
• Infections caused by ESBL-producing bacteria

Dosage

Children: Refer to the BNF for Children for specific dosing information in paediatric patients.

Adults: Refer to the BNF for specific dosing information in adults.

Mechanism of action

Enmetazobactam inhibits the action of extended-spectrum beta-lactamases (ESBLs), a group of bacterial serine beta-lactamases that hydrolyze third-generation cephalosporins. By doing so, it safeguards cefepime from degradation, thereby preserving its antibacterial activity and preventing the emergence of antibiotic resistance.

Pharmacodynamics

Enmetazobactam exhibits broad-spectrum antibacterial activity, effective against a wide range of both gram-positive and gram-negative bacteria. Its ability to inhibit ESBLs allows it to maintain efficacy in the presence of resistant bacterial strains.

Pharmacokinetics

The pharmacokinetic profile of enmetazobactam is not extensively detailed in the provided sources. However, like many beta-lactam antibiotics, it is presumed to have a distribution that allows penetration into various tissues. Further studies would be required to outline its absorption, distribution, metabolism, and excretion characteristics.

Pregnancy

There is limited information on the use of enmetazobactam during pregnancy. Consult relevant clinical guidelines and consider the risk-benefit ratio.

Breast-feeding

There is limited information on the excretion of enmetazobactam in human milk. Consult relevant clinical guidelines before use.

Storage

Store in a cool, dry place, protected from light. Do not freeze.

Formulations

• Injectable solution

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.

Mechanism of action

Extended-spectrum beta-lactamases (ESBLs) are a group of bacterial serine beta-lactamases that hydrolyze third-generation cephalosporins (3GC), leading to the development of 3GC-resistant bacteria. When used in combination with cefepime, enmetazobactam protects cefepime from degradation by ESBLs and prevents antibiotic resistance.

Pharmacodynamics

Enmetazobactam is an antibacterial agent that is active against most gram-positive and gram-negative bacteria.