Study objectives: To evaluate the efficacy and tolerability of levofloxacin (L) as monotherapy in patients with severe community-acquired pneumonia (CAP) in comparison with therapy using a combination of cefotaxime (C) plus ofloxacin (O).
Design: Prospective, randomized 1:1, comparative, open, parallel-group study.
Setting: Multinational study with 149 sites.
Patients: A total of 398 randomized patients who had been admitted to the ICU with severe CAP without shock, including 308 patients in a modified intent-to-treat population and 271 patients in the per-protocol (PP) population (L group, 139 patients; C + O group, 132 patients).
Interventions: Therapy with levofloxacin (500 mg IV, q12h) vs therapy with a C + O combination (C, 1g IV, q8h; O, 200 mg IV, q12h) for 10 to 14 days.
Measurements and results: The main end point was the clinical efficacy at the end of treatment (ie, the test-of-cure [TOC] visit). The statistical hypothesis was the noninferiority of L therapy to C + O therapy with a 2.5% alpha risk (unilateral) and a 15% maximum set difference. At the TOC visit, a clinical success was observed in 79.1% of patients (L group) and 79.5% of patients (C + O group) in the PP population (difference, -0.4%; 95% confidence interval [CI], -10.79 to 9.97% without adjustment for simplified acute physiology score [SAPS] II at inclusion; difference, -0.3%; 95% CI, -10.13 to 9.58% with adjustment for SAPS II). A satisfactory bacteriologic response was present in 73.7% of L group patients and 77.5% of C + O group patients, including responses of 75.7% and 70.3%, respectively, in the L group and C + O group in the Streptococcus pneumoniae-documented population. In the safety analysis, 20 patients in the L group (10.3%) and 16 patients in the C + O group (8.0%) experienced at least one adverse event that was considered to be treatment-related.
Conclusion: L therapy was at least as effective as the combination therapy of C + O in the treatment of a subset of patients with CAP requiring ICU admission. This conclusion cannot be extrapolated to patients requiring mechanical ventilation or vasopressors (ie, those patients in shock).