Levofloxacin does not decrease mortality in Staphylococcus aureus bacteraemia when added to the standard treatment: a prospective and randomized clinical trial of 381 patients

Abstract

Objectives: To study whether levofloxacin, added to standard treatment, could reduce the high mortality and complication rates in Staphylococcus aureus bacteraemia.

Design: A prospective randomized multicentre trial from January 2000 to August 2002.

Setting: Thirteen tertiary care or university hospitals in Finland.

Subjects: Three hundred and eighty-one adult patients with S. aureus bacteraemia. Patients with meningitis, and those with fluoroquinolone- or methicillin-resistant S. aureus were excluded.

Interventions: Standard treatment (mostly semisynthetic penicillin) (n = 190) or that combined with levofloxacin (n = 191). Supplementary rifampicin was recommended if deep infection was suspected.

Main outcome measures: Primary end-points were mortality at 28 days and at 3 months. Clinical and laboratory parameters were analysed as secondary end-points.

Results: Adding levofloxacin to the standard treatment offered no survival benefit. Case fatality rates were 14% in both groups at 28 days, and 21% in the standard treatment and 18% in the levofloxacin group at 3 months. Levofloxacin combination did not differ from the standard treatment in the number of complications, time to defervescence, decrease in serum C-reactive protein concentration or length of antibiotic treatment. Deep infection was found in 84% of patients within 1 week following randomization with no difference between the treatment groups. At 3 months, the case fatality rate for patients with deep infection was 17% amongst those who received rifampicin versus 38% for those without rifampicin (P < 0.001, odds ratio = 3.06, 95% confidence intervals = 1.69-5.54).

Conclusions: Levofloxacin combined with standard treatment in S. aureus bacteraemia did not decrease mortality or the incidence of deep infections, nor did it speed up recovery. Interestingly, deep infections in S. aureus bacteraemia appeared to be more common than previously reported.