isepamicin and Kidney-Failure--Chronic

Piperacillin inactivation of the aminoglycosides isepamicin and gentamicin in 12 chronic hemodialysis patients was assessed. Six subjects each received isepamicin (7.5 mg/kg of body weight) or gentamicin (2 mg/kg) alone and in combination with piperacillin (4 g every 12 h for four doses). Isepamicin and gentamicin concentrations in plasma and urine were monitored over 48 h after each dose and analyzed by high-performance liquid chromatography and fluorescence polarization immunoassay, respectively. The pharmacokinetics of isepamicin were not significantly altered during combination treatment with piperacillin. The total body clearance (3.79 +/- 0.71 versus 3.94 +/- 1.05 ml/min), the steady-state volume of distribution (0.19 +/- 0.04 versus 0.18 +/- 0.03 liter/kg), and the terminal elimination half-life (47.91 +/- 7.20 versus 45.08 +/- 10.34 h) were not significantly altered in the presence of piperacillin. In contrast, the terminal elimination half-life (47.68 +/- 20.58 versus 35.67 +/- 11.18 h) of gentamicin was significantly reduced when gentamicin was given with piperacillin. The total body clearance (4.26 +/- 3.07 versus 4.89 +/- 1.94 ml/min) and the steady-state volume of distribution (0.19 +/- 0.04 versus 0.20 +/- 0.04 liter/kg) of gentamicin were not significantly altered during combination therapy; however, the nonrenal clearance of gentamicin administered in combination with piperacillin (3.56 +/- 0.38 ml/min) increased significantly compared with that of gentamicin (2.03 +/- 0.50 ml/min) given alone. The results of this study suggest that no additional dosage adjustment of isepamicin during concomitant therapy with piperacillin in hemodialysis patients is necessary. However, this does not preclude the need for appropriately ex vivo-handled specimens for monitoring isepamicin concentrations in plasma to ensure therapeutic efficacy and prevent toxicity. Furthermore, additional dosage adjustments may be necessary when gentamicin is used concomitantly with piperacillin, on the basis of the significant in vivo inactivation that takes place in end-stage renal disease patients.

Topics: Adult; Gentamicins; Half-Life; Humans; Kidney Failure, Chronic; Piperacillin

Though the pathogenic significance and the reservoir of Ewingella americana have not been clarified, this organism has caused several pathogenic infections, especially in immunocompromised patients. We report a pneumonia in a patient with chronic renal failure, who had chronic rejection of transplanted kidney. E. americana was identified to be the pathogen of pneumonia with clinical symptoms and signs and radiological examination. As soon as he was treated with ceftriaxone and isepamicin, clinical improvement was followed with no further growth of E. americana or other pathogenic isolates from sputum culture. This suggests to be the case of pneumonia caused by E. americana for the first time in the Korean literature.

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Enterobacteriaceae; Enterobacteriaceae Infections; Gentamicins; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Pneumonia; Sputum; Time Factors

Topics: Aged; Gentamicins; Half-Life; Humans; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Renal Dialysis

The disposition of isepamicin, an investigational aminoglycoside antibiotic, was evaluated in 30 subjects with various degrees of renal function. The subjects were divided into five groups: those with normal renal function (creatinine clearance [CLCR], greater than 80 ml/min/1.73 m2), those with mild renal insufficiency (CLCR, 50 to 80 ml/min/1.73 m2), those with moderate renal insufficiency (CLCR, 30 to 49 ml/min/1.73 m2), those with severe renal insufficiency (CLCR, 5 to 29 ml/min/1.73 m2), and those maintained on hemodialysis (CLCR, less than 5 ml/min/1.73 m2). Subjects on hemodialysis were studied both during hemodialysis and during an interdialytic period. The volumes of distribution of isepamicin were not significantly different among the five groups of patients. The total body clearance (CLP) and renal clearance (CLR) of isepamicin significantly decreased as CLCR decreased. The CLP of isepamicin and CLCR were significantly related [(COP = 0.391.[CLCR] + 1.83; r2 = 0.878)]. Nonrenal clearance of isepamicin did not differ between groups. Hemodialysis augmented the CLP of isepamicin by approximately 25-fold. The amount of isepamicin recovered in the dialysate was 60.6 +/- 15.8% of the dose administered. The maximal rebound of the isepamicin concentration in plasma after cessation of hemodialysis was observed at 0.78 +/- 0.7 h. Concentrations in plasma increased 32.7 +/- 22.9% over that measured at the end of hemodialysis. These data indicate that dosage adjustments are necessary in subjects with decreased renal function.

Topics: Adult; Aged; Female; Gentamicins; Humans; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Renal Dialysis