Effects of Antimicrobial Agents on Renal Function in Patients Administered Vancomycin Hydrochloride

Abstract-Vancomycin hydrochloride (VCM) has a potent bactericidal activity against Gram positive bacteria, especially, Methicillin-resistant Staphylococcus aureus (MRSA). In the clinical situation, patients infected with not only with MRSA, but also with Gram negative bacterium or fungi are encountered. Because VCM has an adverse reaction of nephrotoxicity, we examined the nephrotoxicity and drug interactions of VCM and some antibiotics and antifungus agents in rabbits. We have already reported on the attenuation of nephrotoxicity by VCM with imipenem/cilastatin sodium, flomoxef sodium, fosfomycin sodium or minocycline hydrochloride, but no attenuation with ceftazidime, cefpimizole sodium or fluconazol. In this study, we investigated the renal function and VCM clearance in MRSA-infected patients, and compared our findings with those in the patients coadministered antimicrobial agents which decreased the nephrotoxicity of VCM in rabbits (decreasing group, n=23) and the patients coadministered the drugs which didn't decrease the nephrotoxicity in rabbits or administered VCM alone (non-decreasing group, n=22). No significant differences were observed regarding age, serum creatinine, BUN, serum potassium, total protein, albumin, WBC and CRP at the starting time of VCM-treatment, VCM doses, period of VCM treatment, and serum VCM concentrations (peak, trough) between the decreasing group and the non-decreasing group. However, the serum creatinine levels in the nondecreasing group were significantly higher than those of the decreasing group at 2 weeks after the VCM theatment. In addition, the serum creatinine levels at the end of the VCM treatment in the non-decreasing group were higher than those of the dereasing group.However, no significant differences were observed in the VCM clearance and BUN between the decreasing group and the non-decreasing group, even though the serum creatinine in the nondecreasing group significantly increased. The high ratio of cancer in our patients (decreasing group n=12, non-decreasing group n=15) may have influenced our resuls. Further investigations are needed to estimate whether or not antimicrobial agents may influence the renal functions in VCM administered patients.