ANTIMICROBIAL AGENTS AND CHEmoTHERAPY, Sept. 1978, p. 318-321 0066-4804/78/0014-0318$02.00/0 Copyright © 1978 American Society for Microbiology
Pharnacology of Intraperitoneal Cefazolin Undergoing Peritoneal Dialysis
Vol. 14, No. 3
Prind in U.S.A.
Patients
DONALD KAYE,l* NORMA WENGER," 2 AND BRAJESH AGARWAL2 Department ofMedicine, The Medical College of Pennsylvania,' and The Medical College of Pennsylvania
Medical Service of the Philadelphia Veterans Administration Hospital,2 Philadelphia, Pennsylvania 19129 Received for publication 8 May 1978
Cefazolin was added to dialysis fluid in nine patients with renal failure undergoing peritoneal dialysis with 2 liters/h per exchange. With 50 mg/liter (three patients), the first measurable mean serum concentration was 3.7 ,ug/ml (range, 2.4 to 4.9 ,ug/ml) after three exchanges and was 30.3 ug/ml (range, 13.3 to 44.3 ,ug/ml) after 24 exchanges. After 18 to 24 more exchanges without cefazolin, the mean serum concentration was 12.3 itg/ml (range, 3.8 to 24.6 iLg/ml). The mean concentration in the dialysis outflow was 26.9 sg/ml (range, 2.5 to 58.5 ,ug/ml). With 150 mg/liter (six patients), the mean serum concentration was 5.2 ,ug/ml (range, 3.6 to 7.8 ,ug/ml) after the first exchange and 8.4 (range, 6.1 to 14.0 1&g/ml), 15.0 (range, 8.2 to 23.5,ug/ml), and 71.9 (range, 26.2 to 142.1 ,ug/ml) ,ug/ml after the second, third, and twenty-fourth exchanges, respectively. After 17 to 24 more exchanges without cefazolin, the mean serum concentration was 38.2 ,ug/ml (range, 15.4 to 65.7 ,tg/ml). The mean concentration in the dialysis outflow was 71.4 ug/ml (range, 21.9 to 150.8 ug/ml). After 1 g of cefazolin was given intraperitoneally with no more dialysis, serum concentrations rose by a mean of 62.5 ,ug/ml (rangy, 18.9 to 107.8 ,tg/ml). The maximum rise occurred within 2 h with two-thirds of the rise occuning within 30 min. During the subsequent 22 h levels dropped to 65.4% of the peak. There have been no reports on the pharmacology of cefazolin after intraperitoneal injection. The present study was undertaken in patients undergoing peritoneal dialysis to evaluate serum and dialysis outflow concentrations after intraperitoneal administration of cefazolin. MATERIALS AND METHODS
cavity. Two patients received 1 g in 100 ml (these had been dialyzed with 50 mg of cefazolin per liter); two patients received 1 g in 50 ml (these had been dialyzed with 150 mg/liter); and four patients received 1 g in 25 ml (these had been dialyzed with 150 mg/liter). Serum and dialysate were obtained before the first dialysis containing cefazolin, and sera and portions of dialysate were obtained periodically during dialysis, the sera being drawn immediately at the end of a 1-h exchange. Sera and dialysates were studied for the first through fifth, the tenth, and the twenty-fourth (last) cefazolin-containing exchanges; the twentyeighth exchange; and the last exchange. After the 1-g intraperitoneal dose of cefazolin, serum was obtained at 30 min and at 1, 2, 4, 8, and 24 h. Sera and dialysates were stored at -20°C until analyzed by an agar diffusion technique with paper disks (7). Pooled uremic human serum was used for the standard curves for the serum levels, and dialysate was used for the curves for the dialysate levels. These standard curves did not differ in slope or y intercept from curves using pooled normal human serum and saline, respectively. All levels were run on at least quadruplicate disks.
Nine patients undergoing their first peritoneal dialysis for renal failure were studied. All of the patients had creatinine clearances of less than 5 mil/min. None had evidence of infection, and none had recently received antimicrobial agents. Dialysis consisted of a 2-liter exchange each hour, containing a mixture of sodium chloride, calcium chloride, magnesium chloride, sodium lactate, and dextrose 1.5% or 4.25% with potassium chloride (Dianeal, (Travenol Laboratories, Inc., Deerfield, Ill.). After running the fluid into the peritoneal cavity in 10 min, it was allowed to remain for 30 min and then emptied rapidly. After a first exchange without cefazolin, cefazolin in a concentration of 50 mg/liter (three patients) er 150 mg/liter (six patients) was added to the dialysis fluid for 24 exchanges. After the 24 exchanges with fluid containing cefazolin (48 liters in 24 h), dialysis RESULTS was continued for an additional 17 to 24 exchanges With concentrations of 50 mg/liter in the diwithout cefazolin, the duration being determined by the clinical indications for dialysis. After the last ex- alysis fluid (100 mg/h), a mean serum concenchange, 1 g of cefazolin in 25, 50, or 100 ml of saline tration ± standard deviation (SD) of 3.7 ± 1.0 solution was instilled into and left in the peritoneal ,tg/ml (range, 2.4 to 4.9 ,ug/ml) was achieved in 318
319 all three patients by the end of the third ex- 15.0 ± 6.5 pg/ml, respectively, with ranges of 6.1 change contining cefazolin (Fig. 1). Two of the to 14.0 ,ug/ml and 8.2 to 23.5 pAg/ml. The serum three patients had nonmeasurable serum con- levels subsequently increased to a mean peak of centrations (
Pharnacology of Intraperitoneal Cefazolin Undergoing Peritoneal Dialysis
Vol. 14, No. 3
Prind in U.S.A.
Patients
DONALD KAYE,l* NORMA WENGER," 2 AND BRAJESH AGARWAL2 Department ofMedicine, The Medical College of Pennsylvania,' and The Medical College of Pennsylvania
Medical Service of the Philadelphia Veterans Administration Hospital,2 Philadelphia, Pennsylvania 19129 Received for publication 8 May 1978
Cefazolin was added to dialysis fluid in nine patients with renal failure undergoing peritoneal dialysis with 2 liters/h per exchange. With 50 mg/liter (three patients), the first measurable mean serum concentration was 3.7 ,ug/ml (range, 2.4 to 4.9 ,ug/ml) after three exchanges and was 30.3 ug/ml (range, 13.3 to 44.3 ,ug/ml) after 24 exchanges. After 18 to 24 more exchanges without cefazolin, the mean serum concentration was 12.3 itg/ml (range, 3.8 to 24.6 iLg/ml). The mean concentration in the dialysis outflow was 26.9 sg/ml (range, 2.5 to 58.5 ,ug/ml). With 150 mg/liter (six patients), the mean serum concentration was 5.2 ,ug/ml (range, 3.6 to 7.8 ,ug/ml) after the first exchange and 8.4 (range, 6.1 to 14.0 1&g/ml), 15.0 (range, 8.2 to 23.5,ug/ml), and 71.9 (range, 26.2 to 142.1 ,ug/ml) ,ug/ml after the second, third, and twenty-fourth exchanges, respectively. After 17 to 24 more exchanges without cefazolin, the mean serum concentration was 38.2 ,ug/ml (range, 15.4 to 65.7 ,tg/ml). The mean concentration in the dialysis outflow was 71.4 ug/ml (range, 21.9 to 150.8 ug/ml). After 1 g of cefazolin was given intraperitoneally with no more dialysis, serum concentrations rose by a mean of 62.5 ,ug/ml (rangy, 18.9 to 107.8 ,tg/ml). The maximum rise occurred within 2 h with two-thirds of the rise occuning within 30 min. During the subsequent 22 h levels dropped to 65.4% of the peak. There have been no reports on the pharmacology of cefazolin after intraperitoneal injection. The present study was undertaken in patients undergoing peritoneal dialysis to evaluate serum and dialysis outflow concentrations after intraperitoneal administration of cefazolin. MATERIALS AND METHODS
cavity. Two patients received 1 g in 100 ml (these had been dialyzed with 50 mg of cefazolin per liter); two patients received 1 g in 50 ml (these had been dialyzed with 150 mg/liter); and four patients received 1 g in 25 ml (these had been dialyzed with 150 mg/liter). Serum and dialysate were obtained before the first dialysis containing cefazolin, and sera and portions of dialysate were obtained periodically during dialysis, the sera being drawn immediately at the end of a 1-h exchange. Sera and dialysates were studied for the first through fifth, the tenth, and the twenty-fourth (last) cefazolin-containing exchanges; the twentyeighth exchange; and the last exchange. After the 1-g intraperitoneal dose of cefazolin, serum was obtained at 30 min and at 1, 2, 4, 8, and 24 h. Sera and dialysates were stored at -20°C until analyzed by an agar diffusion technique with paper disks (7). Pooled uremic human serum was used for the standard curves for the serum levels, and dialysate was used for the curves for the dialysate levels. These standard curves did not differ in slope or y intercept from curves using pooled normal human serum and saline, respectively. All levels were run on at least quadruplicate disks.
Nine patients undergoing their first peritoneal dialysis for renal failure were studied. All of the patients had creatinine clearances of less than 5 mil/min. None had evidence of infection, and none had recently received antimicrobial agents. Dialysis consisted of a 2-liter exchange each hour, containing a mixture of sodium chloride, calcium chloride, magnesium chloride, sodium lactate, and dextrose 1.5% or 4.25% with potassium chloride (Dianeal, (Travenol Laboratories, Inc., Deerfield, Ill.). After running the fluid into the peritoneal cavity in 10 min, it was allowed to remain for 30 min and then emptied rapidly. After a first exchange without cefazolin, cefazolin in a concentration of 50 mg/liter (three patients) er 150 mg/liter (six patients) was added to the dialysis fluid for 24 exchanges. After the 24 exchanges with fluid containing cefazolin (48 liters in 24 h), dialysis RESULTS was continued for an additional 17 to 24 exchanges With concentrations of 50 mg/liter in the diwithout cefazolin, the duration being determined by the clinical indications for dialysis. After the last ex- alysis fluid (100 mg/h), a mean serum concenchange, 1 g of cefazolin in 25, 50, or 100 ml of saline tration ± standard deviation (SD) of 3.7 ± 1.0 solution was instilled into and left in the peritoneal ,tg/ml (range, 2.4 to 4.9 ,ug/ml) was achieved in 318
319 all three patients by the end of the third ex- 15.0 ± 6.5 pg/ml, respectively, with ranges of 6.1 change contining cefazolin (Fig. 1). Two of the to 14.0 ,ug/ml and 8.2 to 23.5 pAg/ml. The serum three patients had nonmeasurable serum con- levels subsequently increased to a mean peak of centrations (
