Abstract
The aminoglycosides are bactericidal drugs whose primary effect is irreversible inhibition of bacterial protein synthesis. Aminoglycoside efficacy is dependent on the presence of oxygen and the existence of the proper electrochemical gradient on each side of the cell membrane. Drug resistance to aminoglycosides can develop at several different sites of drug action. Aminoglycosides primarily are effective against the aerobic gram-negative bacilli, including most Pseudomonas species. Addition of clindamycin or metronidazole to drug regimens that include aminoglycosides adds anaerobic coverage. Aminoglycosides and β-lactam antibiotics are synergistic at many points in their activity, and addition of a β-lactam adds gram-positive coverage to drug regimens. Aminoglycosides are not absorbed well from the gastrointestinal tract and usually are administered either intravenously or intramuscularly. They are excreted almost exclusively by renal filtration. Only about 10% of an absorbed aminoglycoside dose is bound to plasma proteins, so liver disease has virtually no effect on aminoglycoside distribution. Aminoglycoside toxicities include ototoxicity and nephrotoxicity; drug hypersensitivity is rare. The combination of gentamicin plus penicillin or ampicillin is excellent therapy for chorioamnionitis in cases of vaginal delivery. Gentamicin plus clindamycin is one of two regimens recommended by the Centers for Disease Control and Prevention for parenteral treatment of pelvic inflammatory disease. This combination also is effective against most polymicrobial postoperative infections. Streptomycin may be used in the treatment of tuberculosis and other mycobacterial infections. The wholesale price of aminoglycosides, particularly gentamicin, is relatively low compared to other antibiotics. Once-daily aminoglycoside dosing has been introduced recently into the clinical setting. Animal studies indicate that this new regimen is equally effective when compared with divided dosing and appears to have lower toxicity in immunocompetent patients. Advantages of once-daily dosing of aminoglycosides include decreased toxicity, increased efficacy, and decreased cost.
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