Aminoglycoside antibiotics toxicity

Williams, P.D., Hottendorf, G.H. and Bennett, D.B. (1986a). Inhibition of renal membrane binding and nephrotoxicity of aminoglycosides. J. Pharmacol. Exp. Ther. 237 919-925. Williams, P.D., Laska, D.A. and Hottendorf, G.H. (1986b). Comparative toxicity of aminoglycoside antibiotics in cell cultures derived from human and pig kidney. In Vitro Toxicol. 1 23-32. 

C) The 3-lactam antibiotics prevent toxic effects of the aminoglycoside antibiotics. 

It is an aminoglycoside antibiotic used only as luminal amoebicide and has no effect against extra intestinal amoebic infections. It is less toxic than other agents, but it should be used cautiously in patients with significant renal disease and with gastrointestinal ulcer. 

The aminoglycoside antibiotics are discussed in Chapter 45. Kanamycin has been used for treatment of tuberculosis caused by streptomycin-resistant strains, but the availability of less toxic alternatives (eg, capreomycin and amikacin) has rendered it obsolete. 

Chloramphenicol (9) is liable to breakdown by chloramphenicol acetyl-transferases [185]. Fluoro derivatives (57, 58) resist enzymatic attack but little has been heard of these, apparently because of their toxicity [319], Aminoglycoside antibiotics (AGACs) may be chemically modified by AMEs. Some derivatives (e.g. amikacin, 43) are more recalcitrant than others, e.g. kanamycin (42) (see Figure 4.2). Other enzyme-resistant AGACs of low toxicity are needed. 

Additive renal toxic effects may occur with immunosuppressants (e.g. azathioprine, ciclosporin, tacrolimus), ACE inhibitors, penicillamine, irinotecan and aminoglycoside antibiotics. A deterioration of renal function may even occur after the topical use of NSAIDs. Guidelines are variable for the use of NSAIDs with differing degrees of renal function, as assessed by creatinine clearance measurements. 

The enzyme resistance shown by BB-K8 is thought to be due to a blocking effect caused by the a-hydroxybutyric acid side chain. This appears to be a promising area of research but the toxicity problems associated with aminoglycoside antibiotics have still to be overcome. 

There are many circumstances in which a fixed drug dose is likely to be ineffective or toxic in a significant number of individuals, e.g. cytotoxic chemotherapy, aminoglycoside antibiotics. It is usual then to calculate the dose according to body weight. Adjustment according to body surface area is also used and may be more appropriate, for this... 

In rats, ototoxicity caused by gentamicin or tobramycin was amehorated by melatonin, which did not interfere with the antibiotic action of the aminoglycosides (70). The free radical scavenging agent alpha-lipoic acid has previously been shown to protect against the cochlear adverse effects of systemically administered aminoglycoside antibiotics, and in a recent animal study it also prevented cochlear toxicity after the administration of neomycin 5% directly to the round window membrane over 7 days (71). 

John JF Jr. What price success The continuing saga of the toxic therapeutic ratio in the use of aminoglycoside antibiotics. J Infect Dis I988 I58(I) I-6. 

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