Aminoglycoside treatment and mortality after bacteraemia in patients given appropriate empirical therapy: a Danish hospital-based cohort study

Abstract

OBJECTIVES: The effectiveness and safety of aminoglycoside (AG)/beta-lactam combination therapy has been questioned in several meta-analyses. We examined the association between AG combination therapy and mortality and increase in serum creatinine in adult patients with bacteraemia given appropriate empirical antibiotic therapy. METHODS: Historical cohort study based on prospective registration of bacteraemias in a Danish hospital 1996-2002. AG + beta-lactam was the recommended empirical therapy for severe sepsis. We identified 1,257 patients, of whom 969 received gentamicin or tobramycin (AG cohort); 288 patients not given AGs formed the non-AG cohort. We used Cox regression analysis to compare adjusted mortality rates; the association between AG therapy and increase in serum creatinine was analysed by logistic regression. RESULTS: The cumulative 30 day mortality in the AG cohort was 17.3% versus 18.1% in the non-AG cohort [adjusted mortality rate ratio (MRR) 1.02; 95% CI 0.74-1.39]. The adjusted 31-180 day MRR in the AG cohort was 1.72 (95% CI 1.15-2.55). AG therapy was associated with lower 30 day mortality in patients with an abdominal focus (adjusted 30 day MRR 0.52; 95% CI 0.24-1.10) or a urinary tract focus (adjusted 30 day MRR 0.48; 95% CI 0.22-1.08), but with a worse prognosis in patients with a respiratory tract focus (adjusted 30 day MRR 2.06; 95% CI 0.93-4.53). An increase in serum creatinine of >or=45 micromol/L was observed similarly often in AG- and non-AG-treated patients [14.1% versus 12.4%, adjusted odds ratio 1.06; 95% CI 0.63-1.79]. CONCLUSIONS: Among patients with bacteraemia receiving appropriate empirical coverage, AG combination therapy was not associated with increased 30 day mortality and only a modest risk of raised serum creatinine. The longer-term prognosis should, however, be explored further.