The main concerns with the use of aminoglycoside antibiotics are nephrotoxicity and ototoxicity. In their article, the authors find a rate of aminoglycoside associated nephrotoxicity of 58% in intensive care unit icu patients who received gentamicin or amikacin and noted that mortality in these patients was higher than in patients without acute kidney injury aki 45% versus 29%. The protekt study tested the hypothesis that rosuvastatin can inhibit aminoglycosideinduced nephrotoxicity in children with cystic fibrosis cf. We read with interest the study by oliveira and colleagues.
Aminoglycoside resistance mechanisms were determined in 11,079 of these isolates by the correlation of resistance phenotypes to 12 aminoglycosides and dna hybridisation with up to 19 resistance genes. The epidemiology of tubular disorders is unclear as a standard. Aminoglycoside antibiotics are water soluble, eliminated primarily by the kidney 100% of the dose is normally excreted unchanged in the urine, have negligible protein binding, have a small volume of distribution 0. The 6rs of drug induced nephrotoxicity bmc nephrology. Sep 07, 2014 download fulltext pdf aminoglycosideinduced nephrotoxicity article pdf available in journal of pharmacy practice 276 september 2014 with 1,253 reads. Sep 30, 2012 the probability of nephrotoxicity occurrence. Lopeznovoa1,2, yaremi quiros1,2, laura vicente1,2, ana i. Aminoglycoside antibiotics are frequently employed in the treatment of serious infections caused by aerobic gram negative bacilli. More side effects increased nephrotoxicity change in the drug metabolism 4. The use of these potent antibacterial agents is limited by the risks of ototoxicity and nephrotoxicity. Pathophysiologic mechanisms of selected types of nephrotoxicity. David humes, 1 1 veterans administration medical center, ann arbor, michigan veterans administration medical center ann arbor michigan medical service, veterans.
Aminoglycosides have long been one of the commonest causes of druginduced nephrotoxicity. However, 50 years after the discovery of the first ag streptomycin, nephrotoxicity is still very difficult to predict and avoid. The onset of nephrotoxicity is delayed in the oda group p 0. Aminoglycoside antibiotics are clearly nephrotoxic in humans, but since they are also highly efficacious in the treatment of serious infections cause we use cookies to enhance your experience on our website. The pathogenesis of aminoglycoside nephrotoxicity is still evolving despite extensive worldwide investigations. Pdf aminoglycosides are among the oldest antibiotics available to treat serious infections caused by primarily, gramnegative bacteria. Clinical and pharmacokinetic characteristics of aminoglycoside nephrotoxicity in 201 critically ill patients jerome j.
Aminoglycoside dosages and nephrotoxicity springerlink. Aminoglycoside nephrotoxicity american journal of medicine. Pdf aminoglycoside nephrotoxicity revisited researchgate. However, these investigations have facilitated the identification of several inhibitors of aminoglycoside nephrotoxicity. Definition, structure these are group of natural and semisynthetic antibiotics having polybasic amino groups linked glycosidically to two or more animosugar 3. The model is a powerful tool to represent and describe the influence of the dosage regimen on aminoglycoside nephrotoxicity. Several factors, in cluding the underlying health of the patient, cri teria used to define nephrotoxicity, and the spe cific. In skeletal muscle, aminoglycosides block both the l. Aminoglycoside antibiotics maintain a leading role in antibacterial therapy of severe gramnegative infections despite nephrotoxicity complicating 10% to 20% of therapeutic courses. Experimental studies in healthy human volunteers indicate aminoglycosides cause proximal tubular damage in most patients, but rarely, if ever, cause glomerular or tubular dysfunction. Aminoglycoside use in intensive care units and aminoglycoside.
Aminoglycoside ag nephrotoxicity is a wellknown occurrence. The epidemiology of aminoglycoside induced nephrotoxicity is not fully understood. Kaloyanides division of nephrology and hypertension department of medicine, school of medicine state university of new york at stony brook stony brook, new york, 11 7948152. Block of ms channels occurs in the submillimolar range k d 200. The protekt study tested the hypothesis that rosuvastatin can inhibit aminoglycoside induced nephrotoxicity in children with cystic fibrosis cf. Nephrotoxic effects of aminoglycosides on the developing kidney. These two points have led to numerous reports evaluating oncedaily dosing of aminoglycosides in which the cumulative dose for a 24hour period would be administered as a single dose. Dec 27, 2019 aminoglycoside nephrotoxicity aminoglycosides preferentially affect the proximal tubular cells. Modification of experimental aminoglycoside nephrotoxicity.
Nephrotoxicity, defined as a 50% or greater fall in calculated creatinine clearance, developed in 30 patients 14. Prospective cohort studies of aki have documented the frequency of druginduced nephrotoxicity to be approximately 1426% in adult populations. Follow the links to read common uses, side effects, dosage details and. Nephrotoxicity and agents responsible nephrotoxic injury is damage to one or both kidenys that result from exposure to a toxic substance.
To date, no model has completely described the pharmacodynamic behavior of ag nephrotoxicity, even though the mechanism of this toxicity has been widely studied 4, 7, 15, 27. Nephrotoxicity occurs once the aminoglycoside is freely filtered by the glomerular filtration barrier and is reabsorbed in the s1 and s2 segments of the proximal renal tubule. Nevertheless, by multivariate discriminant analysis they found that age was a significant discriminant factor, and that it was the most important factor identified before aminoglycoside treatment was initiated. Common vitamins and supplements to treat aminoglycoside. Risk factors for nephrotoxicity in patients treated with. The aminoglycoside enters the cytosol and accumulates in organelles such as the mitochondria, golgi complex, and the nucleus. Download fulltext pdf aminoglycosideinduced nephrotoxicity article pdf available in journal of pharmacy practice 276 september 2014 with 1,253 reads. Plaut2 departments of pharmaceutics,1 medicine,2 and surgery,3 schools of pharmacy1 and medicine,23 state university of new york at buffalo. Smith, aminoglycoside nephrotoxicity in humans rev infect dis 5. Clinical trials of aminoglycosides in seriously ill patients indicate that the relative risk for developing acute renal failure. In this forum, i will summarize the renal handling of the aminoglycosides, the pathogenetic mechanisms of nephrotoxicity, and the clinical aspects of aminoglycoside induced acute renal failure.
Risk of nephrotoxicity with combination vancomycin. The relative insensitivity of immature rats to aminoglycosideinduced nephrotoxicity in vivo and the comparative nephrotoxicity. Although aminoglycoside induced nephrotoxicity has been the subject of multiple studies, the short and longterm effect of aminoglycosides administration on the developing kidney of the fetus or premature newborn has not yet been determined. Clinical application of this model might make it possible to adjust aminoglycoside dosage regimens by taking into account both the efficacies and toxicities of the drugs. As the use of aminoglycosides became more widespread, the toxic effects of these agents, most notably ototoxicity and nephrotoxicity, became more apparent. Nephrotoxicity is one of the most important side effects and therapeutical limitations of aminoglycoside antibiotics, especially gentamicin. Noting that carbenicillin protects against aminoglycoside nephrotoxicity in rats even more than does cepha lothin, they suggested that all 3lactamantibiotics confer protection, but thatcephalosporins. Aminoglycosideinduced nephrotoxicity in children springerlink.
Although aminoglycosideinduced nephrotoxicity has been the subject of multiple studies, the short and longterm effect of aminoglycosides administration on the developing kidney of the fetus or premature newborn has not yet been determined. Aminoglycoside nephrotoxicity and creatinine clearance. New insights into the mechanism of aminoglycoside nephrotoxicity. Aminoglycoside nephrotoxicity revisited article pdf available in journal, indian academy of clinical medicine 84. Lopeznovoa 1 2 yaremi quiros 1 2 laura vicente 1 2 ana i. It has been hypothesized that aminoglycosideinduced nephrotoxicity might be prevented by using pentoxifylline, which has antioxidant and antiin ammatory effects and improves microcirculation. The nephrotoxicity risk scores of 61 patients were determined using parameters suggested by moore et al. Aug 05, 2015 nephrotoxicity and agents responsible nephrotoxic injury is damage to one or both kidenys that result from exposure to a toxic substance. Although a clear recognition of the patient and treatmentrelated risk factors, combined with the onceaday schedule and effective monitoring procedures, have definitely improved the situation over what prevailed in the early 1980s, we are still short of having brought the safety of. Manifestations of and risk factors for aminoglycoside. Modeling, simulation, and control article pdf available in antimicrobial agents and chemotherapy 473.
The understanding of aminoglycoside nephrotoxicity therefore has substantial clinical relevance. Patients receiving gentamicin 25 or tobramycin 29 were evaluated in a randomized, prospective, doubleblind study. Recovery from aminoglycoside nephrotoxicity with continued drug administration. It has been hypothesized that aminoglycoside induced nephrotoxicity might be prevented by using pentoxifylline, which has antioxidant and antiin ammatory effects and improves microcirculation. Traditionally, aminoglycoside nephrotoxicity has been considered to result mainly from tubular damage. Department of veterans, affairs medical center northport, new york. Aminoglycoside nephrotoxicity and age annals of internal. Aminoglycosides are excreted by glomerular filtration at a rate proportional to the serum concentration. Despite rigorous patient monitoring, nephrotoxicity appears in 1025% of therapeutic courses. Aminoglycosideinduced nephrotoxicitya focus on monitoring. Aminoglycoside nephrotoxicity in 201 critically ill. The use of concomitant penicillins and changes in dosing strategy seem to be particularly exciting new leads toward elimination of clinical aminoglycoside nephrotoxicity.
Bank, role of tubular obstruction in acute renal failure due to gentamicin kidney int 24. They estimated renal function from a calculated creatinine clearance and concluded that a high initial creatinine clearance is associated with an increased risk. A randomised controlled trial of rosuvastatin for the. Nephrotoxins are chemicals displaying nephrotoxicity. Acute kidney injury is a relatively common complication of therapy with the aminoglycoside antibiotics, with a rise in the plasma creatinine concentration of more than 0. Aminoglycoside nephrotoxicity kidney international. Previous studies have shown that vaninduced nephrotoxicity may be alleviated in vivo by cilastatin imipenem cilastatin simultaneous treatment. In the combined populations, nephrotoxicity developed in 59 17. Aminoglycoside induced nephrotoxicity article pdf available in journal of pharmacy practice 276 september 2014 with 1,253 reads how we measure reads. Model for predicting nephrotoxicity in patients treated. Aminoglycoside nephrotoxicity in humans clinical infectious. In this forum, i will summarize the renal handling of. Aminoglycoside antibiotics are positively charged molecules that interact with both membrane lipids and ion. Aminoglycosides are concentrationdependent, bactericidal agents that undergo active transport into the cell where they inhibit protein synthesis on the 30s subunit of the bacterial ribosome.
Nephrotoxicity is a significant concern in pediatrics with 16% of hospitalized aki events being attributable primarily to a drug. All had their vancomycin and aminoglycoside serum concentrations controlled by a clinical pharmacokinetics service. Pathogenesis of nephrotoxicity of cephalosporins and. These agents are freely filtered by the glomeruli and quickly taken up by the proximal tubular epithelial cells, where they are incorporated into lysosomes after first interacting with phospholipids on the brush border membranes. The use of aminoglycoside ag antibiotics has declined over the past 15 years primarily due to comparable potency of other antimicrobials and the nephrotoxicity potential of ag drugs. Thirteen patients 21% could not be scored because their initial creatinine clearances exceeded the upper limit of the nomogram. Nephrotoxic effects of aminoglycosides on the developing. Aminoglycoside nephrotoxicity aminoglycosides preferentially affect the proximal tubular cells. Aminoglycoside antimicrobial drugs, notably gentamicin and amikacin, constitute some of the best choices for treatment of severe gramnegative infections. The clinical usefulness of these inhibitors must still be established. Aminoglycosides are freely filtered across the glomerulus.
The lowest level of nephrotoxicity was observed when aminoglycosides were administered at 1. Maneuvers ready to be tested for effectiveness in the clinical use of these drugs are highlighted. Nephrotoxicity of antimicrobials and antibiotics advances. Patients at highest risk of druginduced nephrotoxicity are those with one or more of the following. New york, new york the high incidence of associated nephrotoxicity represents an important concern in the use of aminoglycoside antibiotics, which have been im plicated as one of the primary causes of drug induced acute renal failure.
The clinical utility of a published nomogram to predict. However, resurgence in the use of ag antimicrobials is occurring due to multidrugresistant gramnegative nosocomial infections. However, these definitions pose challenges since a 50% increase in scr may not have high specificity for dikd since the underlying disease being treated as well as other aki risk factors could be. Pdf aminoglycosides remain dependable antibactericidal agents.
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