Aminoglycosides

By | 2011-05-09

This group includes streptomycin, dihydrostreptomycin, neomycin, framycetin, gentamicin, paromomycin, amikacin, tobramycin, and apramycin. All are bactericidal and active against Gram-negative organisms and some Gram-positive organisms, but not streptococci. Amikacin, gentamicin, and tobramycin are active against Pseudomonas aeruginosa. Aminoglycosides are taken up into bacteria by an oxygen-dependent process and are therefore inactive against anaerobic bacteria. They are more active in alkaline media, which is of particular importance when treating urinary infections. Aminoglycosides show synergism with beta-lactam antibacterials. Bacteria may rapidly acquire resistance to these antibiotics. Enteric bacteria may gain the ability to produce a range of aminoglycoside-inactivating enzymes particularly if a sub-therapeutic dose is given. The different members of the group vary in their susceptibility to these inactivating enzymes.

The aminoglycosides are not absorbed from the gastrointestinal tract following oral administration; therefore this route is used for the treatment of gastro-intestinal infections and hepatic encephalopathy. The treatment of systemic infections, including invasive enteric organisms, requires that the drug is administered by injection. Aminoglycosides are poorly distributed into body compartments such as the brain, cerebrospinal fluid, and the eye. Elimination is solely by renal excretion.

The important side-effects of aminoglycosides are vestibu-lar or auditory ototoxicity, and nephrotoxicity. Risk of toxicity following systemic administration varies with different members of the group. Neomycin is particularly toxic to the auditory and renal systems. Streptomycin and dihydrostreptomycin are ototoxic and gentamicin is ototoxic and nephrotoxic. Due to their potential nephrotoxic effect, they should be used with care and for short periods of time. The toxic effects on the kidney vary with the individual drugs but dosing regimens that have short interdosing intervals are more likely to cause damage to the kidneys than dosing regimens where long interdosing intervals are used. As these drugs kill by a concentration-dependent mechanism, giving the daily dose once rather than dividing and giving it every 8 hours is also more likely to be successful since higher peak concentrations of the drug will be achieved by the former method. If there is renal impairment, an alternative drug should be chosen. If this is not possible, the interdosing interval should be increased on the basis of the animal’s plasma-creatinine concentration (see Prescribing in renal impairment) and the plasma levels of the drug should be monitored. The trough drug concentration should be measured just before the next dose is given to ensure that, in the case of gentamicin, it has fallen below 1 micro-gram/mL to avoid toxicity.

Simultaneous administration with other potentially ototoxic drugs such as loop diuretics should be avoided (see Drug Interactions). Aminoglycosides may impair neuromuscular transmission particularly if used peri-operatively in association with anaesthesia. They should not be given to animals with myasthenia gravis. These drugs are well absorbed from the peritoneal cavity and instillation during surgery may result in drug overdose and transient respiratory paralysis.

AMIKACIN

Indications. Amikacin-sensitive infections

Dose: See Prescribing for reptiles

Prescription-only medicine: @ Amikacin (Non-proprietary) UK

Injection, amikacin (as sulfate) 250 mg/mL

Prescription-only medicine: (0) Amikin (Bristol-Myers Squibb) UK

Injection, amikacin (as sulfate) 50 mg/mL, 250 mg/mL

APRAMYCIN

Indications. Apramycin-sensitive infections

Contra-indications. Cats, myasthenia gravis, see notes above

Side-effects. Ototoxicity, nephrotoxicity, see notes above

Warnings. Caution in renal impairment; Drugs Interactions – aminoglycosides; aminoglycosides may cause hypersensitivity reactions in operators following injection, inhalation, ingestion, or skin contact

Dose:

Calves: by addition to drinking water, milk, or milk replaces 20-40 mg/kg daily

Lambs: by mouth, 10 mg/kg daily

Pigs: by addition to drinking water, 7.5-12.5 mg/kg daily

or 5 g/100 litres drinking water

by addition to feed, 100 g/tonne feed

Piglets: by mouth, 10-20 mg/kg daily

Poultry: by addition to drinking water, 25-50 g/100 litres

Medicated feedingstuff prescription: Apralan G200 (Elanco) UK

Premix, apramycin (as sulfate) 200 g/kg, for pigs

Withdrawal Periods.

Pigs: slaughter 14 days

Prescription-only medicine: Apralan Oral Doser (Elanco) UK

Mixture, apramycin (as sulfate) 20 mg/unit dose, for lambs, piglets; dose applicator (1 unit dose = 1.1 mL)

Withdrawal Periods.

Lambs: slaughter 35 days.

Piglets: slaughter 28 days

Dose:

Piglets: 1-2 unit doses daily

Lambs: 1 unit dose/2 kg body-weight

Prescription-only medicine: Apralan Soluble Powder (Elanco) UK

Oral powder, for addition to drinking water, milk, or milk replacer, apramycin (as sulfate) 1 g, 50 g, 1 kg, for calves, pigs, poultry (measure provided = apramycin 5 g with 50-g bottle, apramycin 25 g with 1-kg bag)

Withdrawal Periods.

Calves: slaughter 28 days.

Pigs: slaughter 14 days.

Poultry: slaughter 7 days, should not be used in birds producing eggs for human consumption

FRAMYCETIN SULFATE

(Framycetin sulphate)

Indications. Framycetin-sensitive infections, in particular acute bovine mastitis with systemic involvement

Contra-indications. Cats, myasthenia gravis, see notes above; hypersensitivity to framycetin or other aminoglycosides; concurrent cephalosporins

Side-effects. Ototoxicity, nephrotoxicity, see notes above

Warnings. Caution in renal impairment; Drugs Interactions – (aminoglycosides); concomitant use of calcium borogluconate at parturition advised because aminoglycosides may cause hypocalcaemia; aminoglycosides may cause hypersensitivity reactions in operators following injection, inhalation, ingestion, or skin contact

Dose: Dairy cattle: by intramuscular injection, 5 mg/kg twice daily for up to 3 days

Prescription-only medicine: Framomycin 15% Injection (Novartis) UK

Injection, framycetin sulfate 150 mg/mL, for dairy cattle

Withdrawal Periods.

Cattle: slaughter 49 days, milk 56 hours

GENTAMICIN

Indications. Gentamicin-sensitive infections

Contra-indications. Pregnant animals, concurrent use of other drugs that may induce ototoxicity or nephrotoxicity

Warnings. Care in renal impairment

Dose: Horses: by intravenous injection, 6.6 mg/kg once daily

Dogs, cats: by subcutaneous or intramuscular injection, 5 mg/kg twice daily for 24 hours then once daily

Prescription-only medicine: Pangram 5% (Bimeda) UK

Injection, gentamicin 50 mg/mL, for dogs, cats

NEOMYCIN SULFATE

(Neomycin sulphate)

Indications. Neomycin-sensitive infections; hepatic encephalopathy

Contra-indications. Cats, myasthenia gravis, foals manifesting signs of toxaemia, see notes above

Side-effects. Ototoxicity, nephrotoxicity, see notes above

Warnings. Caution in renal impairment or urinary obstruction; Drugs Interactions – (aminoglycosides); aminoglycosides may cause hypersensitivity reactions in operators following injection, inhalation, ingestion, or skin contact, operators should wear suitable protective clothing

Dose:

Horses: hepatic encephalopathy, see section 3.6.3

Lambs: see preparation details

Pigs: by addition to drinking water, 11 mg/kg body-weight; 12.5 g/100 litres

by addition to feed, 11 mg/kg body-weight; 230 g/tonne feed

Dogs, cats: bacterial infections, 11 mg/kg daily in divided doses

Hepatic encephalopathy

Poultry: by addition to drinking water, 11 mg/kg by addition to feed, 230 g/tonne feed

Prescription-only medicine: @ Neomycin (Non-proprietary) UK

Tablets, neomycin sulfate 500 mg

Prescription-only medicine: Neobiotic Soluble Powder 70% (Pfizer) UK

Oral powder, for addition to drinking water or feed, neomycin sulfate 700 mg/g, for pigs, broiler chickens

Withdrawal Periods.

Pigs: slaughter 14 days.

Chickens: slaughter withdrawal period nil

Medicated feedingstuff prescription: Neomycin Premix (Pfizer) UK

Premix, neomycin sulfate 100%, for pigs, broiler chickens

Withdrawal Periods.

Pigs: slaughter 14 days.

Chickens: slaughter withdrawal period nil

Prescription-only medicine: Orojet N (Fort Dodge) UK

Oral liquid, neomycin sulfate 70 mg/unit dose, for lambs (1 unit dose = 1 mL)

Withdrawal Periods. Slaughter 28 days

Dose:

Lambs: 1 unit dose/5 kg body-weight

PAROMOMYCIN

Indications. Paromomycin-sensitive infections

Dose: See Prescribing for amphibians

Paromomycin (Available from IDIS, UK)

Paromomycin preparations are not available in the UK. To obtain a supply, the veterinarian should obtain a STA from the VMD

STREPTOMYCIN

Indications. Streptomycin-sensitive infections

Warnings. Excessive or prolonged administration can lead to balance and hearing impairment

Dose: Horses, cattle, sheep, goats: by intramuscular injection, 10 mg/kg daily

Dogs, cats: by intramuscular injection, 25 mg/kg daily

Prescription-only medicine: Devomycin (Norbrook) UK

Injection, streptomycin sulfate 250 mg/mL, for horses, cattle, sheep, goats, dogs, cats

Withdrawal Periods. Should not be used in horses intended for human consumption.

Cattle: slaughter 14 days, milk 2 days.

Sheep, goats: slaughter 14 days, should not be used in sheep, goats producing milk for human consumption

With Dihydrostreptomycin

Prescription-only medicine: Devomycin-D (Norbrook) UK

Injection, dihydrostreptomycin sulfate 150 mg, streptomycin sulfate 150 mg/ mL, for horses, cattle, sheep, goats, dogs, cats

Withdrawal Periods. Should not be used in horses intended for human consumption.

Cattle: slaughter 21 days, milk 2 days. Sheep, goats: slaughter 21 days, should not be used in sheep, goats producing milk for human consumption

Dose:

Horses, cattle, sheep, goats: by intramuscular injection, 1 mL/30 kg daily

Dogs, cats: by intramuscular injection, 1 mL/12 kg daily

TOBRAMYCIN

Indications. Tobramycin-sensitive infections

Dose: See Prescribing for reptiles and Prescribing for exotic birds

Prescription-only medicine:® Tobramycin(Non-proprietary) UK

Injection, tobramycin (as sulfate) 40 mg/mL

Prescription-only medicine:® Nebcin (King) UK

Injection, tobramycin (as sulfate) 10 mg/mL, 40 mg/mL