A Multicenter, Randomized Study Comparing the Efficacy and Safety of Intravenous and/or Oral Levofloxacin versus Ceftriaxone and/or Cefuroxime Axetil in Treatment of Adults with Community-Acquired Pneumonia

Abstract

Five hundred ninety patients were enrolled in a prospective, multicenter, randomized trial comparing the efficacy and safety of 7 to 14 days of levofloxacin treatment with that of ceftriaxone and/or cefuroxime axetil in the management of community-acquired pneumonia in adults. Patients received either intravenous and/or oral levofloxacin (500 mg once daily) or the comparative agents, parenteral ceftriaxone (1 to 2 g once to twice daily) and/or oral cefuroxime axetil (500 mg twice daily). Erythromycin or doxycycline could be added to the comparator arm at the investigator's discretion. The decision to use an intravenous or oral antimicrobial agent for initial therapy was made by the investigator. Clinical and microbiological evaluations were completed at the baseline, during treatment, 5 to 7 days posttherapy, and 3 to 4 weeks posttherapy. Four hundred fifty-six patients (226 given levofloxacin and 230 administered ceftriaxone and/or cefuroxime axetil) were evaluable for clinical efficacy. Streptococcus pneumoniae and Haemophilus influenzae were isolated in 15 and 12%, respectively, of clinically evaluable patients. One hundred fifty atypical pathogens were identified: 101 were Chlamydia pneumoniae, 41 were Mycoplasma pneumoniae, and 8 were Legionella pneumophila. Clinical success at 5 to 7 days posttherapy was superior for the levofloxacin group (96%) compared with the ceftriaxone and/or cefuroxime axetil group (90%) (95% confidence interval [CI] of ؊10.7 to ؊1.3). Among patients with typical respiratory pathogens who were evaluable for microbiological efficacy, the overall bacteriologic eradication rates were superior for levofloxacin (98%) compared with the ceftriaxone and/or cefuroxime axetil group (85%) (95% CI of ؊21.6 to ؊4.8). Levofloxacin eradicated 100% of the most frequently reported respiratory pathogens (i.e., H. influenzae and S. pneumoniae) and provided a >98% clinical success rate in patients with atypical pathogens. Both levofloxacin and ceftriaxone-cefuroxime axetil eradicated 100% of the S. pneumoniae cells detected in blood culture. Drug-related adverse events were reported in 5.8% of patients receiving levofloxacin and in 8.5% of patients administered ceftriaxone and/or cefuroxime axetil. Gastrointestinal and central and peripheral nervous system adverse events were the most common events reported in each treatment group. In conclusion, these results demonstrate that treatment with levofloxacin is superior to ceftriaxone and/or cefuroxime axetil therapy in the management of community-acquired pneumonia in adults.

Efficacy and safety of levofloxacin in the context of other contemporary fluoroquinolones: a review

“…These studies usually have reported clinical cure rates Ͼ90%. 4,5 For levofloxacin, cure rates in mild to moderate CAP have ranged from 94% to 98%, 4,5,32 and in severe disease, 87%. 33 These studies have shown that levofloxacin compares favorably with ceftriaxone.…”

“…Two trials 32,33 of IV-PO switch therapy compared levofloxacin with ceftriaxone followed by PO cephalosporin therapy. One study, 32 a large series in predominantly ambulatory patients (half initially treated in the hospital), reported clinical success at 1 week after therapy in 96% of patients receiving levofloxacin (217/ 226), compared with 90% after cephalosporin therapy (ceftriaxone/cefuroxime axetil) (207/230).…”

“…35 CAP caused by atypical pathogens also responds well to levofloxacin therapy. In these trials, [32][33][34][35] beta-lactam comparators usually were supplemented by additional macrolide therapy, whereas levofloxacin was used alone. In the large trial 32 in predominantly ambulatory patients, clinical success rates of levofloxacin monotherapy in treating M pneumoniae (19/19 patients) and C pneumoniae (46/47 patients) infections were 100% and 98%, respectively.…”

“…In these trials, [32][33][34][35] beta-lactam comparators usually were supplemented by additional macrolide therapy, whereas levofloxacin was used alone. In the large trial 32 in predominantly ambulatory patients, clinical success rates of levofloxacin monotherapy in treating M pneumoniae (19/19 patients) and C pneumoniae (46/47 patients) infections were 100% and 98%, respectively. An overview metaanalysis 36 of results in 191 atypical infections reported a 96% response rate with levofloxacin therapy (94% for comparators [ceftriaxone, cefuroxime axetil, and amoxicillin/clavulanic acid]), Mycoplasma infections responded in 100% of cases, Chlamydia in 96%, and Legionella in 92% (vs 83% with comparator agents).…”

Comparative efficacy of levofloxacin and ceftriaxone in the treatment of community acquired pneumonia in children

“…Bradley et al [5] in their comparative study of levofloxacin in the treatment of children with community-acquired pneumonia showed that cure rate of levofloxacin was 94.3% whereas cure rate of comparator group (0.5 to <5 years: amoxicillin/ clavulanate or ceftriaxone; > or =5 years: clarithromycin or ceftriaxone with clarithromycin or erythromycin lactobinate) was 94%. File et al [12] in their comparative study of intravenous and/or oral levofloxacin (500 mg once daily) or the comparative agents, parenteral ceftriaxone (1 to 2 g once to twice daily) and/or oral cefuroxime axetil (500 mg twice daily) in treatment of adults with community-acquired pneumonia showed that clinical success rate of levofloxacin (96%) is superior to ceftriaxone and/or cefuroxime axetil (90%) in the management of adult with CAP. Cure rate of levofloxacin in these mentioned studies support the present study.…”