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| Clinical data | |
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| Trade names | Neo-rx |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682274 |
| Routes of administration | Topical,oral |
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| Pharmacokinetic data | |
| Bioavailability | None |
| Protein binding | N/A |
| Metabolism | N/A |
| Eliminationhalf-life | 2 to 3 hours |
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| ChEMBL | |
| ECHA InfoCard | 100.014.333 |
| Chemical and physical data | |
| Formula | C23H46N6O13 |
| Molar mass | 614.650 g·mol−1 |
| 3D model (JSmol) | |
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 N Y (what is this?) (verify) | |
Neomycin is anaminoglycosideantibiotic that displays bactericidal activity againstGram-negative aerobicbacilli and some anaerobic bacilli where resistance has not yet arisen. It is generally not effective againstGram-positive bacilli and anaerobic Gram-negative bacilli. Neomycin comes in oral and topical formulations, including creams, ointments, and eyedrops. Neomycin belongs to theaminoglycoside class of antibiotics that contain two or moreamino sugars connected byglycosidic bonds.
Neomycin was discovered in 1949 by microbiologistSelman Waksman and his student Hubert Lechevalier atRutgers University. Neomycin received approval for medical use in 1952.[1] Rutgers University was granted the patent for neomycin in 1957.[2]
Neomycin was discovered in 1949 by the microbiologistSelman Waksman and his student Hubert Lechevalier atRutgers University. It is produced naturally by the bacteriumStreptomyces fradiae.[3] Synthesis requires specific nutrient conditions in either stationary or submerged aerobic conditions. The compound is then isolated and purified from the bacterium.[4]
Neomycin is typically applied as atopical preparation, such as Neosporin (neomycin/polymyxin B/bacitracin). 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 forhepatic encephalopathy andhypercholesterolemia. 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 followinggastrointestinalsurgery.[5]
Waksman and Lechevalier originally noted that neomycin was active against streptomycin-resistant bacteria as well asMycobacterium tuberculosis, the causative agent fortuberculosis.[6] Neomycin has also been used to treatsmall intestinal bacterial overgrowth. Neomycin is not administered via injection, as it is extremelynephrotoxic (damaging to kidney function) even when compared to otheraminoglycosides. The exception is when neomycin is included, in small quantities, as a preservative in some vaccines – typically 25 μg per dose.[7]
In 2022, the combination of neomycin withdexamethasone andpolymyxin B was the 274th most commonly prescribed medication in the United States, with more than 800,000 prescriptions.[8][9]
Similar to other aminoglycosides, neomycin has excellent activity againstGram-negative bacteria and is partially effective againstGram-positive bacteria. It is relatively toxic to humans, with allergic reactions noted as a common adverse reaction (see:hypersensitivity).[10] Physicians sometimes recommend using antibiotic ointments without neomycin, such asPolysporin.[11] The following representsminimum inhibitory concentration (MIC) susceptibility data for a few medically significant Gram-negative bacteria.[12]
In 2005–06, Neomycin was the fifth-most-prevalent allergen inpatch test results (10.0%).[13] It was namedAllergen of the Year in 2010.[14] Neomycin is also a known GABAgamma-Aminobutyric acid antagonist and can be responsible for seizures and psychosis.[15] Like other aminoglycosides, neomycin has been shown to beototoxic, causingtinnitus, hearing loss, andvestibular problems in a small number of patients. Neomycin affects the cochlea, which is found in the inner ear.[16] Hearing loss is caused by ear hair cell death, which occurs in response to treatment with neomycin.[16] 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.[citation needed]
Neomycin's antibacterial activity stems from its binding to the 30S subunit of the prokaryoticribosome, where it inhibits prokaryotic translation of mRNA.[17]
Neomycin also exhibits a high binding affinity for phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid component of cell membranes.[18]
Neomycin resistance is conferred by either one of twokanamycin kinase genes.[19] Genes conferring neomycin-resistance are commonly included in DNAplasmids used to establish stable mammaliancell lines expressing cloned proteins in culture. Many commercially available protein expression plasmids contain aneo-resistance gene as aselectable 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.[20]
Neomycin was first isolated from theStreptomyces fradiae andStreptomyces albogriseus in 1949 (NBRC 12773).[21] Neomycin is a mixture of neomycin B (framycetin); and itsepimer 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.[6] It is also thermostable and soluble in water (while insoluble in organic solvents).[6] Neomycin has good activity againstGram-positive andGram-negative bacteria, but isototoxic. Its use is thus restricted to the oral treatment of intestinal infections.[22]
Neomycin B is composed of four linked moieties:D-neosamine, 2-deoxystreptamine (2-DOS),D-ribose, andL-neosamine.[citation needed]
Neomycin A, also called neamine, containsD-neosamine and 2-deoxystreptamine. Six genes are responsible for neamine biosynthesis: DOIS gene (btrC, neo7); L-glutamine:DOI aminotransferase gene (btrS, neo6); a putative glycosyltransferase gene (btrM, neo8); a putative aminotransferase (similar to glutamate-1-semialdehyde 2,1-aminomutase) gene (btrB, neo18); a putative alcohol dehydrogenase gene (btrE, neo5); and another putative dehydrogenase (similar to chorine dehydrogenase and related flavoproteins) gene (btrQ, neo11).[23] A deacetylase acting to remove the acetyl group on N-acetylglucosamine moieties ofaminoglycoside intermediates (Neo16) remains to be clarified (sequence similar to BtrD).[24]
Next is the attachment of theD-ribose viaribosylation of neamine, using 5-phosphoribosyl-1-diphosphate (PRPP) as the ribosyl donor (BtrL, BtrP);[25] glycosyltransferase (potential homologues RibF, LivF, Parf) gene (Neo15).[26]
Neosamine B (L-neosamine B) is most likely biosynthesized in the same manner as the neosamine C (D-niosamine) in neamine biosynthesis, but with an additionalepimerization step required to account for the presence of the epimeric neosamine B in neomycin B.[27]
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.[28]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.[28] Neomycin C can undergo enzymatic synthesis from ribostamycin.[29]
Standard grade neomycin is composed of several related compounds includingneomycin A (neamine), neomycin B (framycetin), neomycin C, and a few minor compounds found in much lower quantities. Neomycin B is the most active component in neomycin followed by neomycin C and neomycin A. Neomycin A is an inactive degradation product of the C and B isomers.[30] The quantities of these components in neomycin vary from lot-to-lot depending on the manufacturer and manufacturing process.[31]
Aminoglycosides such as neomycin are known for their ability to bind to duplex RNA with high affinity.[32] The association constant for neomycin with A-site RNA is in the 109 M−1 range.[33] However, more than 50 years after its discovery, its DNA-binding properties were still unknown. Neomycin has been shown to induce thermal stabilization of triplex DNA, while having little or almost no effect on the B-DNA duplex stabilization.[34] Neomycin was also shown to bind to structures that adopt an A-form structure, triplex DNA being one of them. Neomycin also includes DNA:RNA hybrid triplex formation.[35]
