Nephrotoxicity amikacin

Gamba G, Contreras AM, Cortes J, Nares F, Santiago Y, Espinosa A, Bobadilla J, Sanchez GJ, Lopez G, Valadez A, Pena JC. Elypoalbuminemia as a risk factor for amikacin nephrotoxicity. La Revista de Investigacion Clinica 1990 42(3) 204-209. 

However, it is important to note that the addition of nephrotoxic agents, such as amphotericin B, aminoglysides (e.g., gentamicin, tobramidn, or amikacin), and non-steroidal anti-inflammatory drugs (NSAIDs e.g., naproxen, ibuprofen, or ketorolac) may potentiate the nephrotoxic effects of the calcineurin inhibitors. 

Amikacin/ kanamycin Adults See footnote8 Children 15-30 mg/kg per day intravenous or intramuscular as a single daily dose Ototoxicity, nephrotoxicity Baseline audiogram, vestibular testing, Romber testing and SCr Monthly assessments of renal function and auditory or vestibular symptoms... 

Renal toxicity - Renal toxicity may be characterized by decreased creatinine clearance, cells or casts in the urine, decreased urine specific gravity, oliguria, proteinuria, or evidence of nitrogen retention. Renal damage is usually reversible. The relative nephrotoxicity of these agents is estimated to be Kanamycin = Amikacin = Gentamicin = Tobramycin Streptomycin. 

Like all aminoglycosides, amikacin is nephrotoxic and ototoxic (particularly for the auditory portion of the eighth nerve). Serum concentrations should be monitored. Target peak serum concentrations for an every-12-hours dosing regimen are... 

It is important to monitor peak and trough plasma levels (see p. 20) of gentamicin, tobramycin, netilmicin, and amikacin to avoid concentrations that cause dose-related toxicities (Figure 31.7). [Note Peak levels are defined as those obtained 1/2 to 1 hour after infusion. Trough levels are obtained immediately before the next dose.] Patient factors, such as old age, previous exposure to aminoglycosides, gender, and liver disease, tend to predispose patients to adverse reactions. The elderly are particularly susceptible to nephrotoxicity and ototoxicity. 

The same spectrum of toxicity (ototoxicity and nephrotoxicity) is shared by all members of the group, The more important and frequent interactions are pharmacodynamic. Streptomycin and gentamicin produce predominantly vestibular effects, whereas amikacin, kanamycin and neomycin primarily affect auditory function. All are rapidly excreted by the kidney,... 

After administration of the recommended doses of amikacin for 10 days, renal damage probably occurs in less than 10% of cases. Limited data support the view that amikacin is less nephrotoxic than other aminoglycosides, possibly because of lower binding affinity to proximal tubular cells or reduced potential to cause phospholipidosis (SEDA-20,236). In several prospective randomized studies the liability of amikacin to cause nephrotoxicity was no greater than that of gentamicin or tobramycin (6-8). In a prospective study there was significantly lower nephrotoxicity with amikacin 15 mg/kg/day (4% toxicity) compared with netilmicin 7 mg/kg/day (12%) (9). As with other aminoglycosides, renal toxicity is reversible in most cases (10). 

Nephrotoxicity occurred in five of 195 patients who received amikacin (15 mg/kg/day) with either cefepime (2 g bd) or ceftazidime (2 g tds) (5). In two patients the deterioration in renal function was mild and resolved without withdrawal of amikacin. In the three other patients, renal insufficiency necessitated drug withdrawal two of these patients recovered, but one died with sepsis, and renal function was still abnormal at the time of death. 

Lane AZ, Wright GE, Blair DC. Ototoxicity and nephrotoxicity of amikacin an overview of phase II and phase III experience in the United States. Am J Med 1977 62(6) 911-18. 

Hottendorf GH, Gordon LL. Comparative low-dose nephrotoxicities of gentamicin, tobramycin, and amikacin. Antimicrob Agents Chemother 1980 18(1) 176-81. 

Isepamicin is similar to amikacin but has better activity against strains that produce type I 6 -acetyltransferase. It can cause nephrotoxicity, vestibular toxicity, and ototoxicity. However, it is one of the less toxic of the aminoglycosides (1). The antibacterial spectrum of isepamicin includes Enterobacteriaceae and staphylococci anaerobes, Neisseriae, and streptococci are resistant (1). Isepamicin was as effective and safe as amikacin in the treatment of acute pyelonephritis in children and might prove an advantageous alternative in areas with a high incidence of resistance to other aminoglycosides (2). 

In a retrospective cost analysis, the records of 527 patients with acute leukemia were studied (11). They had been treated in a multicenter, randomized trial for febrile neutropenia with ceftazidime and amikacin plus either teicoplanin (6 mg/kg in a single dose n — 275) or vancomycin (30 mg/kg/day in 2 doses n — 252). Qinical responses were equivalent. Again the higher acquisition costs for teicoplanin were counterbalanced by the lower incidence of adverse events and easier administration, resulting in overall similar costs for both regimens. A total of 8% of patients treated with vancomycin reported adverse events compared with 3.2% of patients treated with teicoplanin. Rashes occurred in 6.0 versus 1.4% respectively. Nephrotoxicity, ototoxicity, fever, and hypotension occurred in very few patients. 

Results from animal studies indicate that while furosemide enhanced cephaloridine nephrotoxicity no increased renal toxicity was observed by combining of piperacillin with furosemide [142]. Latamoxef and flo-moxef may decrease nephrotoxicity of vancomycin by inhibiting its uptake into the kidney [146,147]. The results of a retrospective study including renal transplant patients indicate that aztreonam can be safely administered with cyclosporine [148]. Combination therapy with ampicillin/aztreonam in neonates showed a lower renal toxicity than in the group with concurrent administration of oxacillin/ amikacin [149]. 

Jongejan HTM, Provost AP, Molenar JC. Potentiation of cis-dlammlnedichloroplatinlum nephrotoxicity by amikacin In rats. Cancer Chemother Pharmacol 1988 22 178-80. 

Although all aminoglycosides possess the ability to induce nephrotoxicity, differences exist in the nephrotoxic potential of the various drugs. Neomycin and gentamicin are the most potent nephrotoxi-cant aminoglycosides, while amikacin and netilmicin are the least nephrotoxic aminoglycosides. Other aminoglycosides are intermediate in nephrotoxic potential. 

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