Interaction between gentamicin and mycophenolate mofetil in experimentally induced pyelonephritis

Acute pyelonephritis (APN) is an inflammatory disease that leads to kidney malfunction. The objective of this investigation was to evaluate the impact of gentamicin (GEN) and ceftriaxone (CEF) alone and in combination with mycophenolate mofetil (MMF) on experimentally induced APN. Forty two Wistar male rats were assigned into seven groups +APN, APN +GEN, APN+CEF, APN+MMF, APN+GEN+MMF and APN+CEF+MMF. APN was induced by injecting E. coli in the left kidney. The control and +APN groups were treated with normal saline while the other APN groups received GEN, CEF, or MMF alone and/or in combination for 2 weeks. The elevated total white blood cells count and increased level of creatinine and blood urea nitrogen (BUN) in +APN groups returned to normal levels following 14 days treatment with GEN and CEF. Co-administration of GEN with MMF could not recover the APN-induced changes and resulted in a significant (P < 0.05) elevation of creatinine and BUN levels. Histopathological studies supported the biochemical findings as GEN and CEF alone could partly restore the APN-induced degeneration and leukocytic infiltration; however, the combination therapy of GEN plus MMF failed to reduce the APN-induced damages. The antibacterial susceptibility test demonstrated that the strain of E. coli used in this study was susceptible to GEN and CEF and the combination therapy did not change the antibacterial potency. These findings suggest that co-administration of GEN with MMF in APN may enhance kidney damage and the adverse effects of combination therapeutic regimen could be related partly to incompatibility of these compounds.