Gentamicin is active against aerobic Gram-negative bacilli including Escherichia coli, Enterobacter, Klebsiella, Proteus (indole negative and positive) and Pseudomonas aeruginosa. In the best-guess treatment of septicaemia, gentamicin should be combined with a p-lactam antibiotic or an antianaerobic agent, e.g. metronidazole, or with both. Gentamicin is a drug of choice for serious Gram-negative septicaemia and it is effective in combination for abdominal and pelvic sepsis. In streptococcal and enterococcal endocarditis gentamicin is combined with benzyl-penicillin, in staphylococcal endocarditis with an antistaphylococcal penicillin, and in enterococcal endocarditis with ampicillin (true synergy is seen provided the enterococcus is not highly resistant to gentamicin).
Dose is 3-5 mg/kg body weight per day (the highest dose for more serious infections) either as a single dose or in three equally divided doses. The rationale behind single dose administration is to achieve high peak plasma concentrations (10-14 mg/1, which correlate with therapeutic efficacy) and more time at lower trough concentrations (16 h at < 1 mg/1, which are associated with reduced risk of toxicity). Therapy should rarely exceed 7 days. Patients with cystic fibrosis eliminate gentamicin rapidly and require higher doses. Gentamicin applied to the eye gives effective corneal and aqueous humour concentrations.
Tobramycin is similar to gentamicin; it is more active against most strains of Pseudomonas aeruginosa and may be less nephrotoxic. It is commonly administered via a nebulizer for treatment of infective exacerbations of cystic fibrosis caused by pseudomonads or Enterobacteriaceae.
Amikacin is mainly of value because it is more resistant to aminoglycoside-inactivating bacterial enzymes than is gentamicin. Since it is more costly, amikacin is reserved for treatment of infections with gentamicin-resistant organisms. Peak plasma concentrations should be kept between 20-30 mg/1 and trough concentrations below 10 mg/1.
Netilmicin is a semisynthetic aminoglycoside which is active against some strains of bacteria that resist gentamicin and tobramycin; evidence suggests that it may be less oto- and nephrotoxic.
Neomycin is principally used topically for skin, eye and ear infections and, by some, to reduce the bacterial load in the colon in preparation for bowel surgery, or in hepatic failure. Enough absorption can occur from both oral and topical use to cause eighth cranial nerve damage, especially if there is renal impairment.
Framycetin is similar to neomycin in use and in toxicity.
Streptomycin, superseded as a first-line choice for tuberculosis, may be used to kill resistant strains of the organism.
Spectinomycin is active against Gram-negative organisms but its clinical use is confined to gonorrhoea in patients allergic to penicillin, or to infection with gonococci that are (3-lactam drug resistant. The steady growth of resistant gonococci, particularly P-lactamase-producing strains, suggests that spectinomycin will continue to have a significant role in this disease, although resistance to it is reported.
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