Neomycin
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. The antibiotic can also be administered orally, in which case it is usually combined with other antibiotics. Neomycin is not absorbed from the gastrointestinal tract and 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. Due to its poor GI tract absorption, orally administered neomycin has also been used to reduce the risk of post operative infection following gastrointestinal surgery.Waksman and Lechevalier originally noted that neomycin was active against streptomycin-resistant bacteria as well as Mycobacterium tuberculosis, the causative agent for tuberculosis. Neomycin has also been used to treat small intestinal bacterial overgrowth. Neomycin is not administered via injection, as it is extremely nephrotoxic even when compared to other aminoglycosides. The exception is when neomycin is included, in small quantities, as a preservative in some vaccines – typically 25 μg per dose.
In 2023, the combination of neomycin with dexamethasone and polymyxin B was the 260th most commonly prescribed medication in the United States, with more than 1million prescriptions.
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. Physicians sometimes recommend using antibiotic ointments without neomycin, such as Polysporin. The following represents minimum inhibitory concentration 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
Side effects
Molecular biology
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, a phospholipid component of cell membranes.
Resistance
Neomycin resistance is conferred by either one of two kanamycin kinase genes. Genes conferring neomycin-resistance are commonly included in DNA plasmids used to establish stable mammalian cell lines expressing cloned proteins in culture. Many commercially available protein expression plasmids contain a neo-resistance gene as a selectable marker.Currently, research is being performed to understand if derivatives of neomycin have the same antibiotic effects while still being effective against neomycin-resistant bacteria.
Biosynthetic pathway
Neomycin was first isolated from the Streptomyces fradiae and Streptomyces albogriseus in 1949. Neomycin is a mixture of neomycin B ; and its epimer neomycin C, the latter component accounting for some 5–15% of the mixture. It is a basic compound that is most active with an alkaline reaction. It is also thermostable and soluble in water. Neomycin has good activity against Gram-positive and Gram-negative bacteria, but is ototoxic. Its use is thus restricted to the oral treatment of intestinal infections.Neomycin B is composed of four linked moieties: D-neosamine, 2-deoxystreptamine, D-ribose, and L-neosamine.
Neomycin A, also called neamine, contains D-neosamine and 2-deoxystreptamine. Six genes are responsible for neamine biosynthesis: DOIS gene ; L-glutamine:DOI aminotransferase gene ; a putative glycosyltransferase gene ; a putative aminotransferase gene ; a putative alcohol dehydrogenase gene ; and another putative dehydrogenase gene. A deacetylase acting to remove the acetyl group on N-acetylglucosamine moieties of aminoglycoside intermediates remains to be clarified.
Next is the attachment of the D-ribose via ribosylation of neamine, using 5-phosphoribosyl-1-diphosphate as the ribosyl donor ; glycosyltransferase gene.
Neosamine B is most likely biosynthesized in the same manner as the neosamine C in neamine biosynthesis, but with an additional epimerization step required to account for the presence of the epimeric neosamine B in neomycin B.
Neomycin B and C are 23-carbon molecules with a four-ring structure. Three of the rings are six-membered, and one is five-membered.
Neomycin B and Neomycin C are stereoisomers of each other and differ by only one stereocenter one giving the R conformation and the other giving the S conformation.
Neomycin C can undergo enzymatic synthesis from ribostamycin.