The Aminoglycoside Antibiotics antibiotics

The Aminoglycoside Antibiotics

antibiotics

Streptomycin, Kanamycin, Gentamicin, Neomycin, Framycetin and Tobramycin

These have similar chemical structures, pharmacological actions and adverse effects. They are not absorbed and for systemic treatment must be given by injection.

The outstanding property of streptomycin is its bactericidal effect on the tubercle bacillus. It is given in conjunction with para-aminosalicylic acid (PAS) and ionized and this triple therapy prevents the emergence of resistant strains. For long-term therapy the daily dose of streptomycin should not exceed 1 g. The chemotherapy of tuberculosis is discussed later on. Its use in infections due to Gram-negative bacilli is restricted by the rapid development of bacterial resistance. When infective endocarditis is due to an organism relatively resistant to penicillin, such as Strept. faecalis, good results may be obtained by combining streptomycin with large doses of benzylpenicillin or ampicillin.

Kanamycin is active against many Gram-negative bacilli and resistance develops much more slowly than with streptomycin. It should be reserved for the treatment of serious infection such as peritonitis or bacteraemia due to Gram-negative bacteria, e.g. Esch. coli or Proteus species. It is also used in the treatment of gonorrhoea due to organisms of reduced penicillin sensitivity.
The dose should not normally exceed 250 mg six-hourly by intramuscular injection.

Gentamicin has a range of activity similar to kanamycin but has the very important additional advantage of being effective against Ps. aeruginosa (Ps. pyocyanea). It is also active against penicillin-resistant staphylococci but inactive against streptococci and most anaerobic organisms. The dose depends on renal function and the age and weight of the patient. Up to 5 mg per kilogram body weight per 24 hours in divided doses is required for serious infections but 2 mg per kg is sufficient for uncomplicated urinary tract infections. Tobramycin is a new aminoglycoside which is more active than gentamicin against Ps. pyocyanea and is possibly less ototoxic.

Neomycin is too toxic to be given parenterally but local applications containing neomycin are used in infections of the skin and eye. Neomycin is used for the pre-operative preparation of the large bowel and also in hepatic encephalopathy to reduce the numbers of colonic bacteria.

ADVERSE EFFECTS (Aminoglycoside)

The outstanding toxic effect of all the aminoglycosides is on the eighth cranial nerve. With streptomycin and gentamicin the vestibular division is initially affected with resultant vertigo and incoordination. Later, deafness may also occur. Kanamycin tends to cause deafness first while neomycin is much too ototoxic for systemic use. The ototoxicity of the aminoglycosides is directly proportional to the age of the patient, the serum level of the antibiotic and the duration of administration. The aminoglycosides are principally excreted from the body by the kidneys and the risk of ototoxicity is increased if there is any impairment of renal function. Consequently these antibiotics must be given with great caution to any patient with renal disease and where possible serum levels of the antibiotic should be monitored and the dose adjusted accordingly. Sensitivity rashes and fever occur in about 5 per cent of patients treated with streptomycin. Desensitization is indicated if it is essential to continue with the antibiotic. Application of neomycin to the skin may cause hypersensitivity.

Cycloserine

Cycloserine is a bactericidal antibiotic used in the treatment of urinary tract infections due to Esch. coli. The adult dose is 250 mg orally twice daily for a fortnight. Overdosage or normal dosage in the presence of impaired renal function may cause drowsiness or epilepsy. Recurrent urinary tract infection with Esch. coli may be prevented by long-term treatment with 125-250 mg cycloserine on alternate days.

The Polymyxins

The most important member of this group of antibiotics is polymyxin E (Colistin). It is bactericidal against many Gram-negative bacilli and all strains of Ps. aeruginosa.

Colistin sulphomethate. This is given by intramuscular injection in a dose of 1-3 million units eight-hourly depending on the weight of the patient and renal function. Colistin is sometimes prescribed orally in Esch. coli gastroenteritis of infants but the principal indication is pseudomonas infections of the renal tract. All polymyxins are nephrotoxic and may also cause paraesthesiae and dizziness although these side-effects are rare with colistin.

Nitrofurantoin and Nalidixic Acid

These two unrelated chemotherapeutic agents are indicated only for the treatment of infections of the urinary tract and are not effective in other conditions. They are active against the common Gram-negative bacilli such as Esch. coli and Proteus and are administered by mouth. The dose of nitrofurantoin is 100 mg three or four times a day and that of nalidixic acid 1 g three times a day. Nausea and vomiting are common during nitrofurantoin therapy while photo-sensitivity skin reactions occasionally occur with nalidixic acid. Both drugs are potentially neurotoxic. Nitrofurantoin can cause peripheral neuropathy especially if there is renal failure and nalidixic acid may produce increase in intracranial pressure in babies. (The Aminoglycoside Antibiotics)