Study of renal parameter changes by intraperitoneal injection of amikacin and cefotaxime in albino rats

Suhail Ahmad, Roquiya Begum, Manish Kumar


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.


Amikacin, Cefotaxime, Blood urea nitrogen, Serum creatinine

Full Text:



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.