FOCIN CAPSULES

Indications

• Acute uncomplicated lower urinary tract infections

Mechanism of action

Fosfomycin exerts its bactericidal effects by covalently binding to a cysteine in the active site of the UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) enzyme. This inhibition prevents the enzyme from catalyzing the condensation of phosphoenolpyruvate (PEP) with UDP-N-acetylglucosamine (UNAG), disrupting the production of the peptidoglycan precursor UDP-N-acetylmuramic acid (UDP-MurNAc) and ultimately interfering with bacterial cell wall synthesis. Fosfomycin enters bacterial cells via the L-alpha-glycerophosphate system and the hexose-6-phosphate transporter system. Additionally, it reduces bacterial adhesion to epithelial cells in the urinary and respiratory tracts.

Pharmacodynamics

Fosfomycin is primarily used for treating urinary tract infections but is also effective against various difficult-to-treat strains of bacteria. It has demonstrated the ability to act synergistically with other antibiotics, which enhances its efficacy against clinically relevant pathogens. The drug has low cross-resistance with other antibiotics due to its unique mechanism of action. Furthermore, fosfomycin possesses immunomodulating properties, influencing cytokine responses and enhancing neutrophil activity against pathogens. It effectively penetrates biofilms, reducing microbial load and altering biofilm structure.

Pharmacokinetics

Fosfomycin is administered intravenously and has a bioavailability that can vary depending on the formulation. It is primarily eliminated through renal excretion, with a clearance that may be affected by renal function. The drug's half-life and distribution in body tissues can vary, and monitoring of renal function is advised during treatment, especially in patients with compromised renal function.

Adverse effects

• Abdominal pain
• Diarrhoea
• Headache
• Nausea
• Vomiting
• Skin reactions
• Dizziness
• Vulvovaginal infection
• Antibiotic associated colitis

Precautions

• Monitor electrolytes and fluid balance with intravenous use
• Caution in patients with cardiac insufficiency, elderly patients, hyperaldosteronism, hypernatraemia, hypertension, and pulmonary oedema
• Severe hepatic impairment requires caution

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk-no information available.

Breast-feeding

Present in milk in small amounts, but absorption from gastrointestinal tract is negligible.

Storage

Store in a cool, dry place away from direct sunlight. Follow specific storage instructions on the label.

Formulations

• Fomicyt 2g powder for solution for infusion vials
• Fomicyt 4g powder for solution for infusion vials

Mechanism of action

Fosfomycin exerts its bactericidal effects by binding covalently to a cysteine in the active site of the UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) enzyme, rendering it inactive. By preventing MurA from catalyzing the condensation of phosphoenolpyruvate (PEP) with UDP-N-acetylglucosamine (UNAG), fosfomycin inhibits the production of the peptidoglycan precursor UDP N-acetylmuramic acid (UDP-MurNAc). Ultimately, the first step of bacterial cell wall synthesis is disrupted. In _Escherichia coli_, fosfomycin gains entry into bacterial cells via two mechanisms: the L-alpha-glycerophosphate system and the hexose-6-phosphate transporter system. Fosfomycin also has important effects on cell adhesion. For example, the adhesion of bacterial cells to urinary epithelial cells is reduced in the presence of fosfomycin. The adhesion of _Streptococcus pneumoniae_ and _Haemophilus influenzae_ to respiratory epithelial cells is also reduced

Pharmacodynamics

Although used primarily to treat urinary tract infections, fosfomycin has been shown to act synergistically with other antibiotics against clinically relevant bacteria. There is also growing interest in the potential of fosfomycin to treat more complex infections since it has retained activity against many difficult-to-treat strains of bacteria including methicillin-resistant _Staphylococcus aureus_ (MRSA) and multidrug-resistant enterobacteria. Further, since fosfomycin has a unique and singular mechanism of action, the risk of cross-resistance with other antibiotics is low. Fosfomycin also demonstrates immunomodulating properties. For example, the antibiotic may influence components of the acute inflammatory cytokine response and enhances neutrophil phagocytic destruction of pathogens. Fosfomycin penetrates biofilms effectively and is capable of not only reducing or eliminating microorganisms in biofilms but can also alter the biofilm structure.