Aminoglycosides, mortality and increase of serum-creatinine in patients with bacteraemia given appropriate empirical therapy. A Danish hospital-based cohort study

Abstract number: 1733_884

Schønheyder H., Freundlich M., Pedersen L., West H., Thomsen R.

Objectives: Aminoglycoside (AG)-b-lactam combination therapy has been discouraged after the appearance of metaanalyses which did not find significant advantages compared to b-lactam monotherapy. Whether this conclusion is valid to all patient groups is questionable and therefore we examined the association between AG therapy, mortality and increased serum-creatinine in patients with bacteraemia given appropriate empirical antibiotic therapy.

Methods: Cohort study based on prospective registration of bacteraemias 1996–2002 at a Danish hospital. AG+b-lactam was the recommended empirical therapy for severe sepsis. We identified 1,257 patients, 969 of whom received gentamicin or tobramycin (AG cohort), while 288 patients who were not exposed to AGs formed the non-AG cohort. We performed Cox regression analysis to compare mortality rates adjusted for potential confounders including comorbidity; the association between AG therapy and an increase of serum-creatinine >45 mmol/L was analysed by logistic regression.

Results: The cumulative 30-day mortality in the AG cohort was 17.3% vs. 18.1% in the non-AG cohort (adjusted mortality rate ratio (MRR) 1.02; 95% CI 0.74–1.39). For patients alive after 30 days the cumulative mortality 31–180 days after the bacteraemia was 20.3% in the AG cohort vs. 12.3% in the non-AG cohort (adj. 31–180 day MRR 1.72; 95% CI 1.15–2.55). AG therapy was associated with lower 30-day mortality in patients with an abdominal focus (adj. 30-day MRR 0.52; 95% CI 0.24–1.10) or a urinary tract focus (adj. 30-day MRR 0.48; 95% CI 0.22–1.08), but with a worse prognosis in patients with a respiratory tract focus (adj. 30-day MRR 2.06; 95% CI 0.93–4.53). The higher mortality associated with AG therapy beyond day 30 was observed for all major foci except for the urinary tract where the MRR was close to one. Serum-creatinine concentration was available at baseline in 983 (78.2%) patients and repeated measurements within 14 days in 422. An increase of serum-creatinine >45 mmol/L was observed less often in AG treated patients (5.9% vs. 15.0%, adjusted OR 0.54; 95% CI 0.26–1.15).

Conclusion: Among patients with bacteraemia given appropriate empirical therapy, AG therapy was neither associated with increased 30-day mortality nor risk of rising serum-creatinine. AG therapy was associated with a survival benefit during the first weeks of infection in patients with a urinary tract or an abdominal focus. The long-term outcome warrants further consideration.