Comparative efficacies and tolerabilities of intravenous azithromycin plus ceftriaxone and intravenous levofloxacin with step-down oral therapy for hospitalized patients with moderate to severe community-acquired pneumonia

Treat Respir Med. 2004;3(5):329-36. doi: 10.2165/00151829-200403050-00006.


Objective: To compare the efficacy and tolerability of ceftriaxone plus azithromycin with those of levofloxacin in the treatment of hospitalized patients with moderate to severe community-acquired pneumonia (CAP).

Design: Randomized, open-label multicenter trial with 1 : 1 treatment allocation in an inpatient setting.

Patients: 212 male or female inpatients with a clinical diagnosis of CAP were included in the study. In each treatment group >50% of patients had a pneumonia severity index of IV or V.

Interventions: Open-label treatment with either intravenous (IV) ceftriaxone 1g and IV azithromycin 500 mg daily or IV levofloxacin 500 mg daily. Patients who improved clinically were switched to oral follow-on therapy with either azithromycin 500 mg/day or levofloxacin 500 mg/day. At the clinician's discretion, oral cefuroxime axetil was added to the treatment regimen of patients who received oral azithromycin if a macrolide resistant pneumococcal isolate was documented.

Results: Overall, both study treatments were well tolerated. Favorable clinical outcomes in clinically evaluable patients were demonstrated in 91.5% of patients treated with ceftriaxone plus azithromycin and 89.3% (95% CI -7.1%, 11.4%) of patients treated with levofloxacin at the end of therapy visit and in 89.2% and 85.1% (95% CI -6.7%, 14.8%) patients, respectively, at the end of study visit. Bacteriological eradication rates for both treatments were equivalent with the exception of Streptococcus pneumoniae; 44% of isolates were eradicated with levofloxacin compared with 100% of isolates with ceftriaxone plus azithromycin.

Conclusions: As acknowledged by international CAP treatment guidelines, the combination of a third-generation cephalosporin and a macrolide is at least as efficacious as monotherapy with a fluoroquinolone with enhanced anti-pneumococcal activity, for hospitalized patients with moderate to severe CAP. Combined medication with a macrolide and third-generation cephalosporin may be preferred over fluoroquinolones as first-line therapy of hospitalized patients with CAP to minimize the development of multiresistant nosocomial Gram-negative bacilli.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Azithromycin / administration & dosage
  • Canada
  • Ceftriaxone / administration & dosage
  • Community-Acquired Infections / drug therapy
  • Community-Acquired Infections / pathology
  • Drug Administration Schedule
  • Female
  • Germany
  • Humans
  • Infusions, Intravenous
  • Levofloxacin
  • Male
  • Ofloxacin / administration & dosage
  • Pneumonia, Bacterial / drug therapy*
  • Pneumonia, Bacterial / pathology
  • Severity of Illness Index
  • Treatment Outcome
  • United States


  • Anti-Bacterial Agents
  • Levofloxacin
  • Ceftriaxone
  • Azithromycin
  • Ofloxacin