Neomycin, also known as framycetin, is an aminoglycoside antibiotic that displays bactericidal activity against Gram-negative aerobic bacilli and some anaerobic bacilli where resistance has not yet arisen. It is generally not effective against Gram-positive bacilli and anaerobic Gram-negative bacilli. Neomycin comes in oral and topical formulations, including creams, ointments, and eyedrops. Neomycin belongs to the aminoglycoside class of antibiotics that contain two or more amino sugars connected by glycosidic bonds. Neomycin was discovered in 1949 by microbiologist Selman Waksman and his student Hubert Lechevalier at Rutgers University. Neomycin received approval for medical use in 1952. Rutgers University was granted the patent for neomycin in 1957.
Discovery Neomycin was discovered in 1949 by the microbiologist Selman Waksman and his student Hubert Lechevalier at Rutgers University. It is produced naturally by the bacterium Streptomyces fradiae. Synthesis requires specific nutrient conditions in either stationary or submerged aerobic conditions. The compound is then isolated and purified from the bacterium.
Medical uses Neomycin is typically applied as a topical preparation, such as Neosporin (neomycin/polymyxin B/bacitracin). In 2023, the topical combination of neomycin with dexamethasone and polymyxin B (neomycin/polymyxin B/hydrocortisone) was the 260th most commonly prescribed medication in the United States, with more than 1 million prescriptions. The antibiotic can also be administered orally, in which case it is usually combined with other antibiotics. Neomycin is very poorly absorbed from the gastrointestinal tract and mostly stays in the gut, exiting with feces. It has been used as a preventive measure for hepatic encephalopathy and hypercholesterolemia. By killing bacteria in the intestinal tract, Neomycin keeps ammonia levels low and prevents hepatic encephalopathy. Orally administered neomycin has also been used to reduce the risk of post operative infection following gastrointestinal surgery and to treat small intestinal bacterial overgrowth. Neomycin has good activity against Gram-positive and Gram-negative bacteria, but is ototoxic and nephrotoxic (damaging to kidney function) at doses required to inhibit bacteria even when compared to other aminoglycosides. It is thus not used systemically. Its only use as an injection is when neomycin is included, in small quantities, as a preservative in some vaccines – typically 25 μg per dose.
Spectrum Similar to other aminoglycosides, neomycin has excellent activity against Gram-negative bacteria and is partially effective against Gram-positive bacteria. It is relatively toxic to humans, with allergic reactions noted as a common adverse reaction (see: hypersensitivity). Physicians sometimes recommend using antibiotic ointments without neomycin, such as Polysporin. The following represents minimum inhibitory concentration (MIC) susceptibility data for a few medically significant Gram-negative bacteria.
Enterobacter cloacae: >16 μg/ml Escherichia coli: 1 μg/ml Proteus vulgaris: 0.25 μg/ml Waksman and Lechevalier originally noted that neomycin was active against streptomycin-resistant bacteria as well as Mycobacterium tuberculosis, the causative agent for tuberculosis.
Side effects In 2005–06, Neomycin was the fifth-most-prevalent allergen in patch test results (10.0%). It was named Allergen of the Year in 2010. Like other aminoglycosides, neomycin has been shown to be ototoxic, causing tinnitus, hearing loss, and vestibular problems in a small number of patients. Neomycin affects the cochlea, which is found in the inner ear. Hearing loss is caused by ear hair cell death, which occurs in response to treatment with neomycin. Routes known to lead to ototoxicity include rectal, parenteral, intrapleural, topical, and oral. Although cases of ototoxicity via the oral route are most commonly associated gastrointestinal inflammation or renal impairment, there have been cases where people with normal function in these organs developed ototoxicity after prolonged use. Patients with existing tinnitus or sensorineural hearing loss are advised to speak with a healthcare practitioner about the risks and side effects prior to taking this medication. Neomycin is also a known GABA gamma-Aminobutyric acid antagonist and can be responsible for seizures and psychosis, at least in animal models.
Mechanism of action
Activity Neomycin's antibacterial activity stems from its binding to the 30S subunit of the prokaryotic ribosome, where it inhibits prokaryotic translation of mRNA. Neomycin also exhibits a high binding affinity for phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid component of cell membranes.
Resistance Neomycin resistance is most commonly conferred by a kanamycin kinase gene; the resultant enzyme inactivates the antibiotic by attaching a phosphate group. This gene is variously known as APH (aminoglycoside 3' phosphotransferase) or neo. Currently, research is being performed to understand if derivatives of neomycin can have the same antibiotic effects while still being effective against neomycin-resistant bacteria. Other neomycin-inactivating enzymes also exist. Specific versions of the neo gene are commonly included in DNA plasmids used to establish stable mammalian cell lines expressing cloned proteins in culture. Although neomycin does not disrupt the eukaryotic ribosome, the related G418 inhibits both prokaryotic and eukaryotic ribosomes and is inactivated by APH/neo. As a result, G418 makes neo a selectable marker usable in both eukaryotes and prokaryotes: by adding it to a cell culture, cells not expressing the marker are killed. Many commercially available protein expression plasmids use this approach.
Chemistry
… excerpt ends here. Continue reading the full article.
