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Vancomycin does not enhance amikacin-induced tubular nephrotoxicity in children
M P Goren1, D K Baker, J L Shenep
1Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38101-0318.
Abstract:
A three-drug antibiotic regimen including vancomycin and amikacin has been recommended as effective treatment in clinical settings in which Gram-positive bacteremias are a serious problem. To determine if vancomycin potentiates the tubular proteinuria associated with amikacin therapy, we studied febrile, neutropenic children with leukemia who were treated with either amikacin (800 mg/m2/day) and ticarcillin-clavulanate or with vancomycin (1.2 g/m2/day), amikacin and ticarcillin. Tubular proteinuria was assessed in 14 children by monitoring the excretion of total urinary protein and two other sensitive indicators of nephrotoxicity, the renal tubular enzymes N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase, in sequential 8-hour urine collections during 7 days of antimicrobial therapy. There were no significant differences between the two treatment groups in excretion of the three marker proteins when values were compared on any day of therapy or for the entire 7-day course. Nor did we observe any significant changes in either serum creatinine concentrations or amikacin clearance rates in the larger study group of 101 children from which these patients were drawn. Although amikacin was subclinically nephrotoxic, the addition of vancomycin to amikacin therapy did not enhance clinical or tubular nephrotoxicity in these children.
Insights
Vancomycin did not increase kidney damage in children receiving amikacin for Gram-positive bacteremia. This study found no enhanced tubular proteinuria or nephrotoxicity when vancomycin was added to amikacin therapy.
Area of Science:
- Pharmacology
- Nephrology
- Pediatric Oncology
Background:
- Gram-positive bacteremias pose significant clinical challenges.
- Vancomycin and amikacin are key antibiotics for treating serious bacterial infections.
- Potential for drug-drug interactions, particularly nephrotoxicity, requires careful evaluation.
Purpose of the Study:
- To investigate whether vancomycin potentiates amikacin-induced tubular proteinuria.
- To assess the combined nephrotoxic effects of vancomycin and amikacin in febrile, neutropenic children with leukemia.
Main Methods:
- Studied febrile, neutropenic children with leukemia receiving amikacin plus ticarcillin-clavulanate or vancomycin, amikacin, and ticarcillin.
- Monitored urinary excretion of total protein, N-acetyl-beta-D-glucosaminidase, and alanine aminopeptidase over 7 days.
- Assessed serum creatinine concentrations and amikacin clearance rates in a larger cohort.
Main Results:
- No significant differences in urinary protein excretion between treatment groups.
- No significant changes in serum creatinine or amikacin clearance rates observed.
- Amikacin demonstrated subclinical nephrotoxicity, but vancomycin did not exacerbate it.
Conclusions:
- The addition of vancomycin to amikacin therapy did not enhance clinical or tubular nephrotoxicity in this pediatric patient population.
- This finding is crucial for optimizing antibiotic regimens in immunocompromised children with bacteremia.