indication

Topical uses include treatment for superficial eye infections caused by susceptible bacteria (used in combination with other antiinfectives), treatment of otitis externa caused by susceptible bacteria, treatment or prevention of bacterial infections in skin lesions, and use as a continuous short-term irrigant or rinse to prevent bacteriuria and gram negative rod bacteremia in abacteriuric patients with indwelling catheters. May be used orally to treat hepatic encephalopathy, as a perioperative prophylactic agent, and as an adjunct to fluid and electrolyte replacement in the treatment of diarrhea caused to enteropathogenic E. coli (EPEC).

pharmacology

Neomycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.

mechanism of action

Aminoglycosides like neomycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically neomycin binds to 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.

toxicity

LD50 = 200 mg/kg (rat). Because of low absorption, it is unlikely that acute overdosage would occur with oral neomycin. However, prolonged administration could result in sufficient systemic drug levels to produce neurotoxicity, ototoxicity and/or nephrotoxicity. Nephrotoxicity occurs via drug accumulation in renal proximal tubular cells resulting in cellular damage. Tubular cells may regenerate despite continued exposure and nephrotoxicity is usually mild reversible. Neomycin is the most toxic aminoglycoside agent, which is thought to be due to its large number of cationic amino groups. Otoxocity occurs via drug accumulation in the endolymph and perilymph of the inner ear causing irreversible damage to hair cells in the cochlea or summit of ampullar cristae in the vestibular complex. High frequency hearing loss is followed by low frequency hearing loss. Further toxicity may cause retrograde degeneration of the auditory nerve. Vestibular toxicity may result in vertigo, nausea and vomiting, dizziness and loss of balance.

biotransformation

Neomycin undergoes negligible biotransformation after parenteral administration.

absorption

Poorly absorbed from the normal gastrointestinal tract. Although only approximately 3% of neomycin is absorbed through intact intestinal mucosa, significant amounts may be absorbed through ulcerated or denuded mucosa or if inflammation is present.

half life

2 to 3 hours

route of elimination

The small absorbed fraction is rapidly distributed in the tissues and is excreted by the kidney in keeping with the degree of kidney function.

drug interactions

Cefotaxime: Increased risk of nephrotoxicity

Cefotetan: Increased risk of nephrotoxicity

Cefoxitin: Increased risk of nephrotoxicity

Ceftazidime: Increased risk of nephrotoxicity

Ceftriaxone: Increased risk of nephrotoxicity

Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Due to the potential for additive or synergistic toxicities (including both nephrotoxicity and neuromuscular blockade) between colistimethate and the aminoglycoside antibiotics, this combination should be avoided whenever possible. If these agents must be used together, patients' renal and neuromuscular function should be monitored closely.

Tacrolimus: Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Neomycin. Use caution during concomitant therapy.

Ticarcillin: Ticarcillin may reduce the serum concentration of Neomycin. Ticarcillin may inactivate Neomycin in vitro and the two agents should not be administered simultaneously through the same IV line.