Comparison of levofloxacin (L) and cefotaxime (C) combined with ofloxacin (O) for treatment of severe community-acquired pneumonia (CAP) in the intensive care unit
© BioMed Central Ltd. 2004
Published: 15 March 2004
To evaluate, in patients with severe CAP requiring ICU admission, the efficacy and tolerance of L (500 mg/12 hours) given intravenously (+ oral route) during 10–14 days as a monotherapy in comparison with an intravenous combination of C (1 g/8 hours) and O (200 mg/12 hours).
Patients included in this phase IV, prospective, multicenter, multinational, open, and randomized (1:1) study exhibited a severe CAP defined by usual criteria. The statistical hypothesis was a noninferiority of L to C + O with a 2.5% a-risk (bilateral) and a 15% maximum set difference.
In the modified intent-to-treat and the per-protocol (PP) populations, there were 308 (L: 149; C + O: 159) and 271 patients (L: 139; C + O: 132), respectively. The main patients characteristics were similar in both groups. Mean age = 59.6 ± 16.7 years, male gender = 68.2%. Mean SAPS II values at inclusion were 34.0 ± 15.8 (L) and 33.0 ± 13.7 (C + O). Mechanical ventilation, during the first 2 days of inclusion was required in 53.5% (L) vs 56.2% (C + O) patients. At least one causal organism was identified in 55.0% (L) vs 54.1% patients (C + O). Blood cultures were positive in 24.4% (L) and 22.1% (C + O) documented patients. Streptococcus pneumoniae (47.6% patients) and Haemophilus spp. (23.8% patients) were the predominant pathogens followed by Staphylococcus aureus (6.0%), atypicals (7.1%), and enterobacteriaceae (8.9%).
The clinical success rates, at end of treatment, in the PP population were 79.1% (L) vs 79.5% (C + O). The difference (diff.) was -0.4% and the 95% confidence interval (CI) was [-10.8% to 9.97%]. At the follow-up visit, 21–45 days after the end of the treatment, the clinical success rates were 68.8% (L) vs 70.9% (C + O) (diff. = -2.1%; 95% CI = [-14.5% to 10.25%]). Bacteriological responses were favorable in 73.7% (L) vs 77.5% (C + O) patients. In pneumococcal CAP, favorable responses occurred in 75.7% and 70.3%, respectively. Incidence of death was 12.2% (L) vs 16.7% (C + O) (P = 0.3).
In the safety analysis (n = 395 patients), no difference was found between groups. Twenty patients in group L (10.3%) and 16 in group C + O (8.0%) presented at least one adverse event (AE) considered as treatment-related (P = 0.42). The treatment was withdrawn following the occurrence of an AE considered as treatment-related in 2.6% (L) vs 2.0% (C + O) patients (P = 0.75).
Levofloxacin (500 mg twice daily dose) is at least as efficacious as the cefotaxime (1 g three times daily) + ofloxacin (200 mg twice daily) combination for the antibiotic therapy of patients with a severe CAP hospitalized in an ICU, with success rates around 80%.