Tobramycin nephrotoxicity. A prospective clinical study

Coca, António; Martínez, Alberto; Soriano, E; Bladé, J; Segura, Fernando; Ribas-Mundó, M

doi:10.1136/pgmj.55.649.791

Cited by 8 publications

(6 citation statements)

References 35 publications

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“…Serum creatinine, the most widely used marker of aminoglycoside nephrotoxicity is considered to be insensitive (69). This insensitivity is shared by serum beta-2 microglobulin (70), and albuminuria (71). In a recent study, urinary concentration of beta-2 microglobulin was used as a tubular marker and it was found to be more sensitive than serum creatinine.…”

Section: Nephrotoxicitymentioning

confidence: 99%

Clinical Pharmacokinetics, Toxicity and Cost Effectiveness Analysis of Aminoglycosides and Aminoglycoside Dosing Services

Mathews

Bailie

1987

J Clin Pharm Ther

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This article reviews the clinical pharmacokinetics, clinical toxicity and cost-effectiveness analysis of aminoglycosides and of dosing services for aminoglycosides. The reader is referred elsewhere for a review of the pharmacology, antimicrobial spectrum of activity and clinical use of these drugs.A critique of the more commonly used methods of aminoglycoside dosage determinations is included, based on the inter-individual variation in aminoglycoside disposition parameters. The advantages and disadvantages of arbitrary, predictive, and pharmacokinetic methods of dosing determination are summarized. Justification for the routine determination of serum aminoglycoside concentrations is reviewed.We review the lack of standardization of definitions for aminoglycosideassociated nephrotoxicity in published studies, and studies which illustrate these differences are highlighted. Evidence for the association between serum aminoglycoside concentrations and nephrotoxicity is examined. Ototoxicity is similarly reviewed.The concept of cost-effectiveness analysis is examined extensively in this review. We discuss the literature concerning the cost benefit analysis of drug dosing services.

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Section: Nephrotoxicitymentioning

confidence: 99%

Clinical Pharmacokinetics, Toxicity and Cost Effectiveness Analysis of Aminoglycosides and Aminoglycoside Dosing Services

Mathews

Bailie

1987

J Clin Pharm Ther

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“…When patients exhibiting nephrotoxicity were com- pared with those without nephrotoxicity, there were no differences with respect to age, sex ratio, duration of therapy, total dose, initial creatinine levels, peak and trough aminoglycoside levels, source of infection, and concurrent drug therapy. When patients with abnormally high levels of aminoglycoside were excluded from the comparison, nephrotoxicity appeared in 6.1% of the patients on tobramycin and in DISCUSSION Although toxicities of tobramycin and amikacin have been extensively studied previously (9,10,18,21,24), they have never been compared in a prospective'randomized trial involving an unselected group of patients (21). Similar rates of nephrotoxicity (ca.…”

Section: Resultsmentioning

confidence: 99%

Comparison of the nephrotoxicity and auditory toxicity of tobramycin and amikacin

Gatell¹,

Miguel²,

Zamora³

et al. 1983

Antimicrob Agents Chemother

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A total of 157 patients were treated with tobramycin or amikacin in a controlled prospective randomized trial. Dosages were adjusted to renal function according to a nomogram. Trough and peak aminoglycoside levels were available at the end of the trial. Of the above total, 113 recipients of nine or more doses of tobramycin or six or more doses of amikacin, without other apparent cause of renal failure, were evaluated for nephrotoxicity. Thirty-six patients were evaluated for auditory toxicity. The patients in groups evaluated for either nephrotoxicity or auditory toxicity were similar with respect to intensity and etiology of bacterial disease, concurrent exposure to other antimicrobial drugs, a,ge and sex distribution, initial serum creatinine level, and total dose and duration of antimicrobial therapy. Nephrotoxicity of similar severity developed in 4 of 59 (6.8%) recipients of tobramycin and in 7 of 54 (13.1%o) recipients of amikacin (P > 0.05). Mild auditory toxicity developed in 3 of 19 (15.7%) recipients of tobramycin and in 2 of 17 (11.7%) recipients of amikacin (P > 0.05). When patients with abnormally high mean trough or peak aminoglycoside levels were excluded from comparison, nephrotoxicity was 6.12 and 5.12% (P > 0.05) and auditory toxicity was 17.6 and 7.69%6 (P > 0.05) in the groups given tobramycin and amikacin, respectively, We conclude that the nephrotoxicity and auditory toxicity of amniacin and tobramycin are not significantly different and that such toxicities are indeed infrequent events when the dosages of these drugs are adjusted to hold blood levels within the safe boundaries suggested by the studies of others.

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“…This insensitivity is shared by all other markers of the glomerular function such as the serum concentration of |I2m (46), albuminuria [7] or the direct estimation of the glomerular filtration rate [46], and these are not as easy to estimate. An increase in serum amino glycoside level may reflect an impairment of renal func tion [6,26,35,47] due to a cause other than nephrotoxicity [5,36,39] and erroneously lead to the institution of a therapeutic alternative fora severe, and potentially lifethreatening infection [34,36,39], Tissular accumulation of aminoglycosides may be directly measured or inferred from a mathematical formula [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

“…It is highly specific, allowing one to differentiate serum creatinine increase due to a nephrotoxicity from other causes of creatinine increases [36][37][38], It is however less sensitive than tubular markers and difficult to use in a routine fashion [38]. Finally, urinary casts [7,17,36,41] and urinary elimina tion of tubular brush border [9,10,28,48] and lysosome [9,31,48] enzymes and low molecular weight proteins [2,5,14,18,21,29,36,[38][39][40]48] have been used as indicators of tubular aminoglycoside nephrotoxicity in experimental animals [1,3,10,31,49] and in man [5,9,14,18,21,28,36,[38][39][40]. p2m, one of the most widely used tubular markers of aminoglycoside nephrotoxicity in man [5,14,21,36,38,…”

Section: Discussionmentioning

confidence: 99%

“…Until recently, the clinical nephrotoxicity of amino glycosides has been compared using markers which ref lect the glomerular filtration rate [3,4,7,13,15,[22][23][24]33,34,43,44,46], Among them, serum creatinine is the simplest and most widely used [15,22,24,33,43,44]. Tubular markers such as beta-2-microglobulin (P2m) [5,14,21,36,[38][39][40] and other low molecular weight proteins [2,18,21,29,48], and brush border [9,10,28,48] and lysosomal enzymes [9,31,48] of the renal epithelial tubu lar cells are earlier and more sensitive [5,9,17,18,21,31,39,40], Their clinical usefulness, however, is not fully established [2,34,...…”

Section: Introductionmentioning

confidence: 99%

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Tobramycin and Amikacin Nephrotoxicity

Gatell¹,

SanMiguel²,

Zamora³

et al. 1985

Nephron

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108 patients who received tobramycin or amikacin could be evaluated for nephrotoxicity in a prospective randomized trial. Both groups had similar illnesses, and causative agents, concurrent drug administration, ages, sex ratios, initial serum creatinine and aminoglycoside levels and total dose and duration of therapy. Using urinary concentration of β₂microglobulin (β₂m) as a marker, nephrotoxicity was detected in 13 (22.4%) of 58 patients given tobramycin and 13 (26%) of 50 given amikacin (n.s.). Using serum creatinine as a marker, nephrotoxicity was detected in 3 (5.2%) of 58 patients given tobramycin and in 7 (14%) of 50 given amikacin (n.s.). The whole group of 108 patients was used to compare the usefulness of serum creatinine levels versus urinary concentration of β₂m. An elevation of serum creatinine was detected in 10 of 108 patients (9.3%). In 5 of these 10 patients the β₂m remained normal, suggesting a functional renal failure. In 21 of the 108 patients (19.4%) the β₂m increased while the serum creatinine remained normal, suggesting an aminoglycoside nephrotoxicity which would have remained undetected if only serum creatinine had been measured. In the remaining patients (77 of the 108; 71.3%) serum creatinine and urinary concentration of β₂m both remained normal throughout the treatment. In conclusion no statistically significant differences were found between tobramycin and amikacin nephrotoxicity. Urinary β₂m is more sensitive than serum creatinine and furthermore it allows one to differentiate aminoglycoside nephrotoxicity from functional renal failure.

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Tobramycin nephrotoxicity. A prospective clinical study

Cited by 8 publications

References 35 publications

Clinical Pharmacokinetics, Toxicity and Cost Effectiveness Analysis of Aminoglycosides and Aminoglycoside Dosing Services

Clinical Pharmacokinetics, Toxicity and Cost Effectiveness Analysis of Aminoglycosides and Aminoglycoside Dosing Services

Comparison of the nephrotoxicity and auditory toxicity of tobramycin and amikacin

Tobramycin and Amikacin Nephrotoxicity

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