Linezolid Versus Ceftriaxone/Cefpodoxime in Patients Hospitalized for the Treatment of Streptococcus pneumoniae Pneumonia

Intravenous (i.v.) to oral linezolid (600 mg twice daily for both, with optional aztreonam) and a cephalosporin regimen (i.v. ceftriaxone 1 g twice daily followed by oral cefpodoxime 200 mg twice daily) were compared for the treatment of community-acquired pneumonia (CAP), with emphasis on patients with Streptococcus pneumoniae. This multicenter, randomized, open-label trial was conducted in 27 countries in 6 continents. Efficacy was assessed 12-28 d following treatment. Clinical and laboratory safety assessments were evaluated; isolates for microbiologic assessments were identified primarily by sputum or blood culture. In all treated patients (linezolid, n = 381; ceftriaxone/cefpodoxime, n = 366), linezolid had a higher clinical cure rate than ceftriaxone/cefpodoxime (83.0% vs. 76.4%, respectively; p = 0.040). S. pneumoniae was isolated in 73.2% (186/254) of patients at baseline, with similar eradication rates in the linezolid and ceftriaxone/cefpodoxime groups (88.7% vs. 89.9%, respectively; p = 0.830). Linezolid had a superior clinical cure rate (93.1% vs. 68.2%; p = 0.021) in patients with S. pneumoniae bacteremia. Logistic regression analyses revealed that linezolid-treated patients with bacteremia, pleural effusion, cardiac comorbidities, diabetes or abnormal white blood cell counts had significantly better outcomes than cephalosporin-treated patients. Both regimens were well tolerated, although the incidence of drug-related adverse events was higher in the linezolid group than in the ceftriaxone/cefpodoxime group (21.3% vs. 11.2%, respectively; p = 0.0002). In summary, empiric i.v./oral linezolid was more effective than ceftriaxone/cefpodoxime in patients hospitalized with CAP, with comparable cure rates in S. pneumoniae pneumonia and higher cure rates in pneumonia complicated by bacteremia.