Comparison of levofloxacin and cefotaxime combined with ofloxacin for ICU patients with community-acquired pneumonia who do not require vasopressors.
OBJECTIVE
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).


METHODS
Prospective, randomized 1:1, comparative, open, parallel-group study.


METHODS
Multinational study with 149 sites.


METHODS
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).


METHODS
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.


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.


CONCLUSIONS
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).
Service de Réanimation Médicale et Maladies Infectieuses, Hôpital G. Chatiliez, 135 rue du Président Coty, 59208 Tourcoing, France. oleroy@ch-tourcoing.fr
Olivier
O
Leroy
Pierre
P
Saux
Jean-Pierre
JP
Bédos
Evelyne
E
Caulin
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002439:Cefotaxime / Q000008:administration & dosage*; D016009:Chi-Square Distribution; D017714:Community-Acquired Infections / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage*; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D011446:Prospective Studies; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin; D002439:Cefotaxime