Study of renal parameter changes by intraperitoneal injection of amikacin and cefotaxime in albino rats
Keywords:
Amikacin, Cefotaxime, Blood urea nitrogen, Serum creatinineAbstract
Background: Amikacin and cefotaxime are excreted by renal mechanisms and have ability to influence the structure and/or function of kidneys. In the present study, an attempt has been made to assess the nephrotoxic effects of amikacin, cefotaxime, and their combination.
Methods: A total of 10 albino rats (180-210 g) were included in each of four groups. Group A (control group) received i.p. 2 ml/kg/day of normal saline, Group B received i.p. 15 mg/kg/day of amikacin, Group C received i.p. 100 mg/kg/day of cefotaxime, and Group D received i.p. amikacin and cefotaxime daily for 4 weeks. Blood urea nitrogen (BUN) and serum creatinine were estimated at 1st, 14th, 28th day during i.p. administration then at 6th and 18th month during follow-up. Data obtained were expressed as mean±standard deviation and analyzed using the analysis of variance.
Results: At 1st day, 14th day, 28th day, 6th month, 18th month, mean blood urea and serum creatinine in Group A were 20.37±0.08, 20.42±0.10, 20.48±0.09, 20.38±0.10, 20.45±0.07 and 0.50±0.067, 0.49±0.096, 0.48±0.075, 0.49±0.034, and 0.48±0.045, respectively; in Group B were 20.31±0.06, 24.08±0.50, 25.68±0.57, 22.60±0.09, 21.52±36 and 0.50±0.07, 0.65±0.093, 0.78±0.097, 0.63±0.08, 0.56±0.063, respectively; in Group C were 20.11±0.06, 23.84±0.08, 25.11±0.46, 22.50±0.78, 21.14±0.65 and 0.52±0.073, 0.69±0.063, 0.83±0.081, 0.69±0.062, 0.57±0.52, respectively; in Group D were 20.70±1.55, 26.32±1.1, 29.90±0.98, 26.05±1.6, 23.44±1.0 and 0.53±0.045, 0.90±0.084, 1.04±0.14, 0.91±0.045, 0.89±0.048 respectively. Mean BUN and serum creatinine were normal in Group A, but increase was highly significant in Group B, C, and D during drug administration but decreased during follow-up. In Group D, the mean level remained above the normal range till 18th month.
Conclusions: Rise in BUN and serum creatinine was highly significant when the amikacin was combined with cefotaxime during i.p. administration as well as during follow-up. It concluded that these drug combinations may be harmful to the kidney, and gradually, it can lead to permanent renal damage.
Metrics
References
Noone P, Pattison JR, Shafi MS. Acute renal failure after high doses of gentamicin and cephalothin. Lancet. 1973;1(7816):1387-8.
Tune BM, Fravert D. Cephalosporin nephrotoxicity. Transport, cytotoxicity and mitochondrial toxicity of cephaloglycin. J Pharmacol Exp Ther. 1980;215(1):186-90.
Bennett WM, Singer I, Coggins CJ. A guide to drug therapy in renal failure. JAMA. 1974;230(11):1544-53.
Bennett WM, Muther RS, Parker RA, Feig P, Morrison G, Golper TA, et al. Drug therapy in renal failure: dosing guidelines for adults. Part I: antimicrobial agents, analgesics. Ann Intern Med. 1980;93(1):62-89.
Luft FC, Kleit SA. Renal parenchymal accumulation of aminoglycoside antibiotics in rats. J Infect Dis. 1974;130(6):656-9.
Luft FC, Patel V, Yum MN, Kleit SA. Nephrotoxicity of cephalosporin-gentamicin combinations in rats. Antimicrob Agents Chemother. 1976;9(5):831-9.
Bobrow SN, Jaffe E, Young RC. Anuria and acute tubular necrosis associated with gentamicin and cephalothin. JAMA. 1972;222(12):1546-7.
Schultze RG, Winters RE, Kauffman H. Possible nephrotoxicity of gentamicin. J Infect Dis. 1971;124 Suppl: S145-7.
Fillastre JP, Laumonier R, Humbert G, Dubois D, Metayer J, Delpech A, et al. Acute renal failure associated with combined gentamicin and cephalothin therapy. Br Med J. 1973;2(5863):396-7.
Noone P, Parsons TM, Pattison JR, Slack RC, Garfield-Davies D, Hughes K. Experience in monitoring gentamicin therapy during treatment of serious gram-negative sepsis. Br Med J. 1974;1(5906):477-81.
Klastersky J, Henri A, Hensgens C, Daneau D. Gram-negative infections in cancer. Study of empiric therapy comparing carbenicillin-cephalothin with and without gentamicin. JAMA. 1974;227(1):45-8.
Klastersky J, Debusscher L, Weerts-Ruhl D, Prevost JM. Carbenicillin, cefazolin, and amikacin as an empiric therapy for febrile granulocytopenic cancer patients. Cancer Treat Rep. 1977;61(8):1433-9.
Klastersky J, Cappel R, Daneau D. Therapy with carbenicillin and gentamicin for patients with cancer and severe infections caused by gram-negative rods. Cancer. 1973;31(2):331-6.
Klastersky J. Treatment of severe infections in patients with cancer. The role of new acyl-penicillins. Arch Intern Med. 1982;142:1984-7.
Cohen B, Saginur R, Clecner B, Mendelson J, Kavalec E. Double-blind comparative trial of once – versus twice-daily netilmicin therapy in severe acute urinary tract infections. Curr Ther Res. 1985;38(6):880-4.
Kosek JC, Mazze RI, Cousins MJ. Nephrotoxicity of gentamicin. Lab Invest. 1974;30(1):48-57.
Neu HC, Labthavikul P. Antibacterial activity and beta-lactamase stability of ceftazidime, an aminothiazolyl cephalosporin potentially active against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1982;21(1):11-8.
Bailey RR. Renal failure in combined gentamicin and cephalothin therapy. Br Med J. 1973;2:776.
Kucers A, McK Bennett N. The Use of Antibiotics. 3rd edition. Public Health. 1980;94(3):206-7.
Klastersky J, Hensgens C, Debusscher L. Empiric therapy for cancer patients: comparative study of ticarcillin-tobramycin, ticarcillin-cephalothin, and cephalothin-tobramycin. Antimicrob Agents Chemother. 1975;7(5):640-5.
Craig WA, Welling PG, Jackson TC, Kunin CM. Pharmacology of cephazolin and other cephalosporins in patients with renal failure. J Infect Dis. 1973;128:347-53.
Barza M. The nephrotoxicity of cephalosporins: an overview. J Infect Dis 1978;137 Suppl: S60-73.
Child KJ, Dodds MG. Mechanism of urinary excretion of cephaloridine and its effects on renal function in animals. Br J Pharmacol Chemother 1966;26(1):108-19.
Atkinson RM, Currie JP, Davis B, Pratt DA, Sharpe HM, Tomich EG. Acute toxicity of cephaloridine, an antibiotic derived from cephalosporin C. Toxicol Appl Pharmacol. 1966;8(3):398-406.
Kleinknecht D, Jungers P, Fillastre JP. Letter: nephrotoxicity of cephaloridine. Ann Intern Med. 1974;80(3):421-2.
Burland WL, Simpson K, Samuel PD. Combining cephaloridine and streptomycin for the treatment and prophylaxis of neonatal infections. Postgrad Med J. 1970;Suppl:85-9.
Harrison WO, Silverblatt FJ, Turck M. Gentamicin nephrotoxicity: failure of three cephalosporins to potentiate injury in rats. Antimicrob Agents Chemother. 1975;8(2):209-15.
Cohen L, Lapkin R, Kaloyanides GJ. Effect of gentamicin on renal function in the rat. J Pharmacol Exp Ther. 1975;193(1):264-73.
Tvedegaard E. Letter: interaction between gentamicin and cephalothin as cause of acute renal failure. Lancet. 1976;2(7985):581.
Benveniste R, Davies J. R-factor mediated gentamicin resistance: a new enzyme which modifies aminoglycoside antibiotics. FEBS Lett. 1971;14(5):293-96.
Burton JR, Lichtenstein NS, Colvin RB, Hyslop NE Jr. Acute renal failure during cephalothin therapy. JAMA. 1974;229:679-82.
Flandre O, Damon M. Experimental Study of Nephrotoxicity of Gentamicin in Rats, First International Symposium on Gentamicin, Basel, Schwabe and Co; 1967. p. 47-61.
Fanning WL, Gump D, Jick H. Gentamicin- and cephalothin-associated rises in blood urea nitrogen. Antimicrob Agents Chemother. 1976;10(1):80-2.
Opitz A, Herrmann I, van Herrath D, Schaefer K. Acute renal failure following gentamicin-cephalosporin association therapy. Med Welt. 1971;11:434-8.
Hansen MM, Kaaber K. Nephrotoxicity in combined cephalothin and gentamicin therapy. Acta Med Scand. 1977;201(5):463-7.
