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.
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).


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


METHODS
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.


METHODS
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.
Zervos
Marcus
M
William Beaumont Hospital, Royal Oak, Michigan, USA.
Mandell
Lionel A
LA
Vrooman
Peter S
PS
Andrews
Charles P
CP
McIvor
Andrew
A
Abdulla
Ramzan H
RH
de Caprariis
Pascal J
PJ
Knirsch
Charles A
CA
Amsden
Guy W
GW
Niederman
Michael S
MS
Lode
Hartmut
H
D000284:Administration, Oral; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D017963:Azithromycin / Q000008:administration & dosage; D002170:Canada; D002443:Ceftriaxone / Q000008:administration & dosage; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005858:Germany; D006801:Humans; D007262:Infusions, Intravenous; D064704:Levofloxacin; D008297:Male; D015242:Ofloxacin / Q000008:administration & dosage; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D002443:Ceftriaxone; D017963:Azithromycin; D015242:Ofloxacin