FOSTYL SUPER wsp

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

Indications

• Acidity regulator
• Stabilizing agent in pharmaceutical formulations
• Potential use in metabolic processes

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations, as pediatric dosing should be based on individual clinical scenarios.

Adults: Refer to specific guidelines for formulations containing tartarate, as dosing may vary based on the therapeutic context.

Mechanism of action

Tartarate acts as a salt that can influence the solubility and stability of various pharmaceutical compounds. It is known to interact with calcium ions and may affect the crystallization processes of certain compounds. In metabolic pathways, tartarate may participate in the citric acid cycle, contributing to energy production and various enzymatic reactions.

Pharmacodynamics

The pharmacodynamics of tartarate are largely related to its role as a buffering agent and stabilizer in formulations. It does not have direct pharmacological effects in the way that active drugs do but can influence the solubility and bioavailability of co-administered medications. Its effects on metabolic pathways can indirectly influence physiological responses.

Pharmacokinetics

The pharmacokinetics of tartarate, particularly potassium tartrate, involve absorption in the gastrointestinal tract, where it dissociates into potassium and tartrate ions. These ions can be absorbed and utilized in various biochemical processes. Excretion primarily occurs via the kidneys. The pharmacokinetic profile may vary based on the formulation and route of administration.

Indications

• Bacterial infections in livestock
• Respiratory infections
• Enteritis caused by various pathogens
• Mycoplasma infections

Dosage

Children: For paediatric dosing, refer to the BNF for Children for appropriate dosing information based on age and weight.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated, as doses may vary.

Mechanism of action

Tylosin inhibits peptide bond formation by binding to the 50S ribosomal subunit of bacteria, blocking the aminoacyl-tRNA from entering the ribosome and thus halting protein synthesis. This inhibition acts as a slow-binding, slowly reversible process, and the interaction with the ribosome is characterized by a significant degree of irreversibility, which is crucial for its antibiotic properties.

Pharmacodynamics

Tylosin exhibits bacteriostatic activity, meaning it inhibits bacterial growth rather than directly killing bacteria. Its effectiveness is particularly notable against certain strains of bacteria that are resistant to other antibiotic classes. The irreversibility of its action on the ribosome contributes to its long-lasting effects against bacterial infections.

Pharmacokinetics

After administration, tylosin is absorbed and distributed throughout the body. It is metabolized in the liver and excreted primarily in the bile, with some renal excretion. The half-life of tylosin can vary based on the route of administration and the species being treated. It is important to monitor for potential accumulation in cases of renal impairment.

Pregnancy

There is insufficient data on the use of tylosin during pregnancy. It should only be used if the potential benefits outweigh the risks.

Breast-feeding

It is not known whether tylosin is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Tylosin tartrate tablets
• Tylosin injectable solution
• Tylosin oral suspension

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.

Mechanism of action

The inhibition of peptide bond formation by tylosin, a 16-membered ring macrolide, was studied in a model system derived from Escherichia coli. In this cell-free system, a peptide bond is formed between puromycin (acceptor substrate) and AcPhe-tRNA (donor substrate) bound at the P-site of poly(U)-programmed ribosomes. It is shown that tylosin inhibits puromycin reaction as a slow-binding, slowly reversible inhibitor. Detailed kinetic analysis reveals that tylosin (I) reacts rapidly with complex C, i.e., the AcPhe-tRNA. poly(U).70S ribosome complex, to form the encounter complex CI, which then undergoes a slow isomerization and is converted to a tight complex, CI, inactive toward puromycin. These events are described by the scheme C + I <==> (K(i)) CI <==> (k(4), k(5)) CI. The K(i), k(4), and k(5) values are equal to 3 microM, 1.5 min(-1), and 2.5 x 10(-3) min(-1), respectively. The extremely low value of k(5) implies that the inactivation of complex C by tylosin is almost irreversible. The irreversibility of the tylosin effect on peptide bond formation is significant for the interpretation of this antibiotic's therapeutic properties; it also renders the tylosin reaction a useful tool in the study of other macrolides failing to inhibit the puromycin reaction but competing with tylosin for common binding sites on the ribosome. Thus, the tylosin reaction, in conjunction with the puromycin reaction, was applied to investigate the erythromycin mode of action. It is shown that erythromycin (Er), like tylosin, interacts with complex C according to the kinetic scheme C + Er <==> (K(er)) CEr <==> (k(6), k(7)) C*Er and forms a tight complex, CEr, which remains active toward puromycin. The determination of K(er), k(6), and k(7) enables us to classify erythromycin as a slow-binding ligand of ribosomes