Aminoglycoside toxicity - a review of clinical studies published between 1975 and 1982

Abstract

The present survey of aminoglycoside nephro- and ototoxicity covers approximately 10,000 patients reported on in clinical trials published between 1975 and 1982. Included in the survey were clinical trials with at least 15 patients evaluable for nephro and/or ototoxicity provided relevant data were given on methodology, patient material and aminoglycoside dosage. Each publication was evaluated by both investigators and relevant data entered into a chart. One hundred and forty-four published trials were surveyed; 139, 63 and 34 for renal, cochlear and vestibular side effects, respectively. Frequencies were calculated as number of patients with side effect of total number of evaluated patients. In the average overall figures toxicity labelled by respective authors as 'definitely', 'probably' and 'possibly' related to study drug is included. When available, frequencies of toxicity 'definitely' and 'probably' related to study drug were analysed separately. The average daily dosages of gentamicin, tobramycin, netilmicin and amikacin were 3.9, 3.8, 5.2 and 15.4 mg/kg, respectively. The average frequencies of nephrotoxicity for gentamicin and tobramycin were 14.0 and 12.9%, respectively, and of netilmicin and amikacin 8.7 and 9.4%, respectively. The average frequency of cochlear toxicity was 13.9% for amikacin, 8.3 and 6.1% for gentamicin and tobramycin, respectively, and 2.4% for netilmicin. The material available for evaluation of vestibular toxicity was considerably smaller. The average frequencies for gentamicin, tobramycin and amikacin were similar (3.2 to 3.7%) while netilmicin again exhibited a somewhat lower figure (1.4%). The overall figures and the clinical ranking that they imply were basically substantiated when prospective comparative trials were analysed separately. However, some inconsistencies go unexplained: for example the frequency of gentamicin nephrotoxicity was markedly higher in trials where it was compared to tobramycin (20 trials) than when it was compared to netilmicin (16 trials).

Evaluation of methods to estimate glomerular filtration rate versus actual drug clearance in patients with chronic spinal cord injury

“…Overestimation of GFR results in dosing renally cleared medications higher than recommended, and this could lead to supratherapeutic vancomycin and AG serum levels leading to adverse drug effects and/or toxicity. [5][6][7] In the nephrology arena, a more recently developed equation, the Modification of Diet in Renal Disease equation (MDRD), has been widely used to estimate GFR. [8][9] Moreover, a new equation, the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI), has been proposed to more accurately estimate GFR compared with MDRD.…”

Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo

“…However, the clinical use of aminoglycosides is limited to life-threatening infections because of serious ototoxic (4−14% of patients receiving aminoglycosides) and nephrotoxic (9−14%) side-effects (Kahlmeter and Dahlager, 1984). In mammals, including humans, ototoxicity is a serious, and mostly permanent, side-effect of aminoglycoside therapy, whereas nephrotoxicity is often acute and reversible.…”

Premature stop codons involved in muscular dystrophies show a broad spectrum of readthrough efficiencies in response to gentamicin treatment

“…3 Moreover, this antibiotic is currently used in human therapy against bacterial infections, and its pharmacokinetics properties and side effects are well characterized. 17 However, one cannot exclude that a long-term use of gentamicin may induce other types of side effects due to generalized readthrough of normal termination codons. DMD, the most common X-linked fatal genetic disease, is a degenerative disorder of striated muscle caused by reduction or absence of the protein dystrophin, and affects approximately 1 in 3500 newborn males.…”