Nephrotoxicity of vancomycin and aminoglycoside therapy separately and in combination

There is conflict by evidence as to whether therapy with vancomycin plus an aminoglycoside is more nephrotoxic than therapy with either agent alone. Here we report the results of a prospective, non-randomized, open-label study of the incidence of nephrotoxicity in elderly patients who received vancomycin alone (32 patients) or an aminoglycoside alone (67 patients) or in combination (37 patients). The mean (95% confidence limits) incidence of nephrotoxicity, defined as an increase of > or = 44.2 mumol/L in the serum creatinine, was 19% (5-32%) in patients receiving vancomycin alone, 24% (10-38%) in patients receiving vancomycin plus an aminoglycoside, and 12% (4-20%) in patients receiving an aminoglycoside alone (P > 0.05 for all comparisons). The corresponding absolute increases of the serum creatine were 20.3 +/- 23.0 mumol/L (-24.8 to +65.4 mumol/L), 37.1 +/- 53.0 mumol/L (-67.2 to +140.4 mumol/L), and 22.1 +/- 31.8 mumol/L (-40.7 to +94.6 mumol/L). The absolute increase was significantly greater (P < 0.05) in patients receiving vancomycin plus an aminoglycoside than in patients receiving an aminoglycoside alone. A meta-analysis of seven previously published studies combined with our data revealed that the incidence of nephrotoxicity associated with combination therapy is 13.3 +/- 3.1% (7.3-19.4%) greater than therapy with vancomycin alone (P < 0.01) and 4.3 +/- 1.4% (1.6-7.0%) greater than therapy with an aminoglycoside alone (P < 0.05). The clinical relevance of this finding may be limited in that the mean duration of antimicrobial therapy in three of the studies was greater than 21 days.