POLYGYNAX VIRGO

Indications

• Oral candidiasis
• Perioral fungal infections
• Oropharyngeal candidiasis

Dosage

Children: 100,000 units by mouth 4 times a day, usually for 7 days, continued for 48 hours after lesions have resolved.

Adults: 100,000 units by mouth 4 times a day, usually for 7 days, continued for 48 hours after lesions have resolved.

Mechanism of action

Nystatin is a channel-forming ionophore that binds to ergosterol, a sterol found in fungal cell membranes, creating membrane-spanning pores. This disrupts the membrane's integrity, resulting in the leakage of intracellular components and loss of electrochemical gradients essential for cell function, leading to cell death.

Pharmacodynamics

Nystatin exhibits both fungistatic and fungicidal activity against a wide range of yeasts and yeast-like fungi, particularly _Candida albicans_. Resistance is minimal with _Candida albicans_ but may develop in other _Candida_ species. It is ineffective against bacteria, protozoa, or viruses and has significant systemic toxicity, limiting its use to topical and oral applications.

Pharmacokinetics

Nystatin is poorly absorbed from the gastrointestinal tract, which allows it to exert its effects locally within the gut and oral cavity. Because of its limited systemic absorption, it is primarily used for local treatment of fungal infections. The drug is not metabolized systemically and is excreted unchanged in the feces.

Contra-indications

• Infants with impaired swallowing
• Acute porphyrias

Adverse effects

• Abdominal distress
• Angioedema
• Diarrhoea
• Face oedema
• Nausea
• Sensitisation
• Skin reactions
• Stevens-Johnson syndrome
• Vomiting

Precautions

• Caution in patients with acute porphyrias
• Use with care in patients with a history of hypersensitivity to nystatin or other polyene antifungals

Pregnancy

Nystatin is generally considered safe in pregnancy; however, it should be used only if clearly needed and prescribed by a healthcare provider.

Breast-feeding

Nystatin is excreted in breast milk but is considered safe for use during breastfeeding as it is poorly absorbed systemically.

Storage

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

Formulations

• Nystatin oral suspension 100,000 units/ml
• Nystatin tablets
• Nystatin capsules

Indications

• Bowel sterilization before surgery
• Hepatic coma
• Topical infections caused by susceptible organisms

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: By mouth: 1 g every 1 hour for 4 hours, then 1 g every 4 hours for 2–3 days. For hepatic coma: Up to 4 g daily in divided doses usually for 5–7 days.

Mechanism of action

Neomycin sulfate binds to the 30S ribosomal subunit of bacteria, leading to the misreading of mRNA and the inhibition of protein synthesis. This disrupts the production of essential proteins needed for bacterial growth and function, ultimately resulting in cell death.

Pharmacodynamics

Neomycin demonstrates bactericidal activity against susceptible bacteria. Its efficacy is enhanced in alkaline environments, which is why it is often used in combination with other agents for surgical prophylaxis. The drug is primarily effective against a range of gram-negative organisms, including Escherichia coli and Klebsiella species, but also has some activity against gram-positive organisms.

Pharmacokinetics

Neomycin is poorly absorbed from the gastrointestinal tract, and its systemic absorption is minimal when administered orally. In cases of systemic use, such as intramuscular or intravenous administration, neomycin is distributed widely in the body but is primarily excreted unchanged in the urine. The elimination half-life varies but is generally around 2 to 3 hours in individuals with normal renal function. Monitoring of serum concentrations is essential to prevent toxicity, especially in patients with renal impairment.

Adverse effects

• neurotoxicity
• ototoxicity
• nephrotoxicity
• allergic reactions
• skin rashes
• hearing loss

Interactions

• other nephrotoxic drugs
• loop diuretics
• neuromuscular blocking agents

Precautions

• monitor renal function
• use cautiously in patients with hearing impairment
• avoid concurrent use with other ototoxic medications
• ensure adequate hydration

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use caution; neomycin can be absorbed systemically and may affect the nursing infant.

Storage

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

Formulations

• oral tablets
• topical ointments
• injectable solutions

Indications

• Bacterial infections caused by aerobic organisms
• Topical treatment of skin infections

Mechanism of action

Neomycin binds to specific proteins and 16S rRNA within the 30S ribosomal subunit of susceptible bacteria. This binding interferes with the decoding site, causing misreading of mRNA and leading to the incorporation of incorrect amino acids into polypeptides. As a result, nonfunctional or toxic peptides are produced, and polysomes are disrupted into nonfunctional monosomes. Neomycin's bactericidal action is characterized by its ability to irreversibly bind to the 30S ribosomal subunit, thereby inhibiting bacterial protein synthesis.

Pharmacodynamics

Neomycin is primarily active against aerobic bacteria and is not effective against fungi, viruses, or most anaerobic bacteria. It mediates its bactericidal effects by inhibiting protein synthesis, which suppresses bacterial growth and survival. Following oral administration, neomycin exhibits a duration of bactericidal activity lasting between 48 to 72 hours. It is particularly useful in treating infections caused by strains of E. coli and Klebsiella, and it also acts to reduce colonic bacterial populations in patients with hepatic coma.

Pharmacokinetics

Neomycin is poorly absorbed from the gastrointestinal tract when taken orally, which limits its systemic availability and enhances its utility in targeting colonic bacteria. It is generally not used parenterally due to its potential for nephrotoxicity and ototoxicity. The duration of action following oral administration can last from 48 to 72 hours, and it is primarily excreted unchanged in the urine. Caution should be exercised when using neomycin in patients with renal impairment, as the risk of toxicity increases.

Adverse effects

• Nephrotoxicity
• Ototoxicity
• Allergic reactions
• Diarrhea
• Nausea
• Vomiting

Interactions

• neomycin+digoxin: Unknown (decreases absorption)
• neomycin+sorafenib: Unknown (decreases exposure)

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during therapy
• Evaluate hearing function in long-term use

Pregnancy

Neomycin is classified as category D; it should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Neomycin is excreted in breast milk; caution should be exercised when administered to nursing mothers.

Storage

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

Formulations

• Topical ointment
• Cream
• Eye drops
• Oral tablets

Indications

• Pneumonia caused by multidrug-resistant gram-negative bacteria
• Septicemia caused by gram-negative bacteria
• Urinary tract infections caused by resistant organisms
• Skin infections caused by resistant gram-negative bacteria

Dosage

Children: Refer to BNF for Children for appropriate dosing in paediatric patients.

Adults: Refer to local guidelines or BNF for specific dosing recommendations based on the type and severity of infection.

Mechanism of action

Polymyxin exerts its antibacterial effect by disrupting the integrity of the bacterial cell membrane. It binds to the lipopolysaccharides and phospholipids in the outer membrane of gram-negative bacteria, leading to increased permeability and eventual cell lysis.

Pharmacodynamics

Polymyxin has a bactericidal effect against susceptible gram-negative organisms. Its action is concentration-dependent, with higher concentrations leading to a more significant bactericidal effect. Resistance can occur through modifications in the bacterial cell membrane components that reduce drug binding.

Pharmacokinetics

Polymyxin is poorly absorbed from the gastrointestinal tract and is typically administered parenterally (intravenously or intramuscularly) for systemic infections. It has a volume of distribution that suggests extensive tissue penetration but is primarily eliminated by the kidneys. Half-life varies based on renal function, and dose adjustments may be necessary in patients with renal impairment.

Adverse effects

• Nephrotoxicity
• Neurotoxicity
• Allergic reactions
• Respiratory distress
• Nausea
• Vomiting

Interactions

• Increased nephrotoxicity when used with other nephrotoxic agents such as aminoglycosides or cisplatin
• Potential for respiratory depression with neuromuscular blocking agents

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during therapy
• Consider the risk of neurotoxicity, especially with prolonged use

Pregnancy

Polymyxin is classified as category C. Its safety during pregnancy has not been established, thus it should only be used if clearly needed.

Breast-feeding

It is not known if polymyxin is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Protect from freezing.

Formulations

• Polymyxin B sulfate injection
• Polymyxin E (colistin) inhalation solution
• Topical formulations

Mechanism of action

Framycetin binds to specific 30S-subunit proteins and 16S rRNA, four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes. Like other aminoglycoside antibiotic drugs, neomycin inhibits bacterial ribosomes by binding to the 30S ribosomal subunit of susceptible bacteria and disrupting the translational machinery of bacterial protein synthesis. Bacterial translation is normally initiated by the mRNA binding to the 30S ribosomal subunit and subsequent binding with 50S subunit for elongation. Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/ A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy. ... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/

Pharmacodynamics

Framycetin is used for the treatment of bacterial eye infections such as conjunctivitis. Framycetin is an antibiotic. It is not active against fungi, viruses and most kinds of anaerobic bacteria. Framycetin works by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Framycetin is useful primarily in infections involving aerobic bacteria bacteria. Neomycin mediates its bactericidal action by inhibiting bacterial protein synthesis, thereby suppressing the growth and survival of susceptible bacteria. Following oral administration, the duration of bactericidal activity of neomycin ranged from 48 to 72 hours. By decreasing colonic bacteria that produce ammonia, neomycin was shown to be effective as an adjunctive therapy in hepatic coma to improve neurologic symptoms. Neomycin is active against both gram positive and gram negative organisms, including the major _E. coli_ species resident in the colon as well as the enteropathogenic forms of _E. coli_. It is also active against _Klebsiella_-_Enterobacter_ group. Resistant strains of _E. coli_, _Klebsiella_ and _Proteus spp_. may emerge from neomycin therapy. Neomycin has no antifungal activity and has some activity against some protozoa.

Mechanism of action

Nystatin is a channel-forming ionophore, meaning it exerts its therapeutic effect via formation of a membrane-spanning pore in the fungal plasma membrane. The formation of this pore results in a change in membrane permeability that allows for leakage of intracellular contents and the subsequent disruption of electrochemical gradients necessary for proper cell function. Selectivity for fungal cells over mammalian cells is due to nystatin’s greater binding affinity for ergosterol, a key sterol found in fungal cell walls, as opposed to its mammalian counterpart, cholesterol. Nystatin exerts its antifungal activity by binding to sterols in the fungal cell membrane. The drug is not active against organisms (e.g., bacteria) that do not contain sterols in their cell membrane. As a result of this binding, the membrane is no longer able to function as a selective barrier, and potassium and other cellular constituents are lost. ... /Antimicrobial/ agents that act directly on the cell membrane of the microorganism, affecting permeability and leading to leakage of intracellular compounds; these include ... the polyene antifungal agents nystatin ... which bind to cell-wall sterols ...

Pharmacodynamics

Nystatin is an antifungal that is both fungistatic and fungicidal in vitro against a wide variety of yeasts and yeast-like fungi. It exerts its antifungal effects via disruption of the fungal cell membrane. Resistance to nystatin is minimal in _Candida albicans_, but tends to develop in other species of _Candida_. Nystatin carries no significant activity against bacteria, protozoa, or viruses. It carries significant systemic toxicity and is currently unavailable in a formula appropriate for systemic use - its efficacy is currently restricted, therefore, to topical, oral, and gastrointestinal infections.