Double-Blind Comparison of the Nephrotoxicity and Auditory Toxicity of Gentamicin and Tobramycin

Abstract

Two hundred fifty-eight patients with suspected sepsis were treated with tobramycin or gentamicin in a prospective, randomized, double-blind trial. One hundred forty-six patients received nine or more doses, had serial determinations of serum creatinine, and were evaluated for nephrotoxicity; 91 were able to cooperate with audiometry and were evaluated for auditory toxicity. Auditory toxicity developed in five of 47 (10 per cent) given gentamicin and five of 44 (11 per cent) given tobramycin. Nephrotoxicity developed in 19 of 72 (26 per cent) given gentamicin and nine of 74 (12 per cent) given tobramycin (P less than 0.025). The severity of the nephrotoxicity was not different; the mean increase in creatinine was 1.3 mg per 100 ml (114.9 mumol per liter) in both groups. Both the tobramycin and gentamicin groups had a similar mean age, initial serum creatinine level, total dose, serum aminoglycoside level, and duration of therapy. We conclude that tobramycin causes nephrotoxicity less frequently than does gentamicin.

Increased renal DNA synthesis in vivo after administration of low doses of gentamicin to rats

“…Healthy volunteers (<40 years of age) have shown no significant alteration of kidney function upon a 10-day exposure to gentamicin (29). Conversely, elevation of serum creatinine was seen in 10 to 37% of ill patients (average age, >60 years) treated for the same time period or less (7,26,30). Other situations in which kidney regeneration rates might differ from normal would be worthy of investigation.…”

Evidence That Antibiotics Bind to Human Mitochondrial Ribosomal RNA Has Implications for Aminoglycoside Toxicity

“…The majority of adverse effects reported during treatment with gentamicin and kanamycin A, both paromamine-derived aminoglycosides, are similar to the symptoms exhibited in mitochondrial dysfunctions and include renal, auditory, and muscular disorders in both humans and animals (23)(24)(25)(26)(27)(28)(29). More acute symptoms are associated with the treatment with gentamicin (27,30,(63)(64)(65)(66)(67)(68).…”

“…Therapeutic use of aminoglycosides can produce side effects in which mitochondrial dysfunctions are observed in human and animal renal, auditory, and muscular disorders (23)(24)(25)(26)(27)(28)(29)(30). However, the biochemical effects of aminoglycosides on human cytoplasmic and human mitochondrial H69 have as yet to be studied.…”

Cystic fibrosis, aminoglycoside treatment and acute renal failure: the not so gentle micin

“…A concomitant survey of prescribing practices showed that, actually, more CF centres prescribed tobramycin than gentamicin, suggesting that the increased incidence of ARF with gentamicin reflected true increased nephrotoxicity of this drug rather than just prescribing patterns. And, indeed, there is previous evidence for increased toxicity of gentamicin in the general population [19]. Moreover, resistance to gentamicin has been found in the majority of Pseudomonas aeruginosa identified in patients with CF in the UK and many other countries, making it a poor choice not only because of side effects [20,21].…”