Gested that neomycin had a direct toxic action Ototoxicity.

a brief review of the occurrence of deafness after the use of neomycin by a variety of routes Complete loss of eighth cranial nerve function with total deafness ,vertigo and nystagmus in a 9 year old girl was attributed to systemic absorption of neomycin following its topical application with dimethyl sulphoxide Three patients became deaf and developed acute renal failure, and i also developed muscular weakness and apnoea after their orthopaedic wounds had been irrigated with solution containing neomycin. Treatmen included haemodialysis. Of 13 patiens with liver disease who had been given neomycin by nouth,6 developed irreversible deafness. Total doses ranged from 84 to 4500g . Neomycin could cause deafness when used to irrigate wounds and burn by inhalation for bronchiectasis and by application in ear. The committee on Safety of Medicines had issued a warning on the use of aerosol preparation of neomycin. Deafness had occurred following the such of preparation in the treatment of extensive skin damage from burns and other cause. A reminder of the increase risk of drug-incuded deafness in patients with perforation of the tympanic membrane when otitits externa is treated topically with preparation containing aminoglycoside antibiotics such framycetin and neomycin. It is important ensure that there is no perforation before such preparation are prescribed. Overdosage : a patient who wainadvertently given 6 g of neomycin by intramuscular injection for hepatic coma developed anuria but was managed succesfully by haemodialysis. A fatality preceded by deafnessin a patient inadvertently given 8 g of neomycin intramuscularly instead of by mouth. Treatment of adverse effects. Patients who develop renal failure may be treated with haemodialysis of peritoneal dialysis although the rate of removal of neomycin is slow. The neoromuscular blocking activity of neomycin may sometimes be reversed by niostigmine or a calcium salt and corticosteroids has been given to sensitivity reactions. Precaution Neomycin is contra-indicated for intestinal desinfection when an obstruction is present and in patients with a know historyof allergy to neomycin . It should be used with great care in patients with kidney or liver disease and in those with impaired hearing. The opical use of neomycin in patient with extensive skin damage or perforated tympanic membrane may result im deafness (see advarse effect, above). The parenteral use of neomycin is no longer recomended. Intraperitoneal instillationof neomycin may precipitaterespiratory paralysis in patients who have received neuromuscular blocking agants. Prolonged local use should be avoided as it may lead to skin sensitisation. Neomycin by mouth and possibibly the parenteral administration of other aminoglycosides such as gentamicin, might cause immediate skin sensitivity reactions in patients previously sensitised by the topical use of neomycin.

As with streptomycin, neomycin should be used with caution in patients receiving other drugs with neuromuscular blocking activity, anticoagulants, anti-emetic and other drugs which are atotoxic. Neomycin taken by mouth has been reported to impair the absorption of other drugs includng phenoxymethylpenicilinand digoxin the efficacy of oral contraceptives might be reduced. A 7 month old child who had reciived six 100-mg doses of neomycin on the day before anticipated surgery developed respiratory ndepression and cyanosis after saline enema possibly due increased absorption of neomycin caused by the enema. A recommendation that the dose of neomycin for topical treatment should not exceed 1g daily for 7 days. Higher or more prolonged dosage would appear to be ototoxic Effect on blood estimations neomycin could interfere biologically with chemical estimation for cholestrol in the blood to produce erroneous lowered result Interaction for reports of other compounds affecting fae antimicrobial activity of neomycin, see antimicrobial action below. Pregnancy and neonate. Deafness in the infant of a mother given neomycin during pregnancy has been reported. Antimikrobial action. Neomycin has a mode of action and spectrumof activity similar to those of streptomycin sulphate and kanamycin sulphate. It is bactericidal and effective against staphylococci and a wide range of gram negative bacteria including Eschericia Coli, Klebsiella, Haemophilis influenza, Proteus, Salmonella and Shigella. Mycobacterium tuberculosis is sensitive. Neomycin is most active in alkaline media. The minimum inhibitory concentration of Neomycin have been reported to range from 0,5 to 8 g/ml. Diminished activity in concentration of 30 g or more/ml heparin decreased in vitro the antibacterial effect of Neomycin 1g per ml against Stapylococcus aureus Aspirin decreased the antibacterial effect in vitro of neomycin sulphate against Staph aureus and E coli For reports of various compounds decreasing the activity of neomycin, see above under loss of activity Enhanced activity Sensitivity studies carried out on Staph aureus and Pseudomonas aeruginosa demonstrated that caffeine and theophylline enchanced the antimicrobial activity of neomycin against these organisms in vitro Resistance to neomycin and the other aminoglycoside antibiotic, apart from streptomycin is acquired slowly. It is ofteb associated with the plasmid-mediated production of bacterial enzymes. Frequent and long-term use has led to resistant staphylococci Absorption and Fate. Neomycin is poorl absorbed from the alimentary tract, about 97% of an orally administered dose being excretes unchanged in the faeces. Doses of 3 to 4 g by mounth produce

peac plasma concentration of up to 4g per ml absorption is similae after administration by enema. It is however rapidly absorbed after intramuscular injection, doses of 0,5 to 1 g producting a plasma concentration of about 20g per ml. Absorption has also been reported to occur from the peritoneum, respiratory tract, bladder, wounds and inflamed skin. Onceneomycin is absorbed it is rapidly excreted by the kidneys in active form; 30 to 50% of a parenteral does has been detected in the urine. Use, Neomycin sulphate is administered topically in the treatmentof infection of the skin and eye due to susceptible staphylococci and other organisms. Neomycin undecenoate or sulphate is used in ear drops. To prevebt the development of resistant strains, another antibacterial agent such a bacitracin, polymixin B or chlorhexidine is sometimes used in conjunction with neomycin. A cream containing neomycin sulphate and chlorhexidine hydrochloride has been used for application to the nostrils in the treatment of staphylococcal nasal carries but resistant organisms have development. Because neomycin sulphate is poorly absorbed from the gastro intestinal tract,it has been given by mouth for the suppression of bacterial growth in the intestine before abdominal surgery although the development of ressistant organisms may be encouraged and supra infebtion may occur it is used similar,with other antibcterial agents in neutropenic patients.Neomycin is given to patients with hepatic encephalopathy to suppress ammonia forming bacteria in the gastro intestinal tract and may also be used in the treatment of infective diarrhoea caused by escherichia coli.