Adult inpatients and outpatients with a diagnosis of community-acquired bacterial pneumonia were evaluated in 2 pivotal clinical studies. In the first study, 590 patients were enrolled in a prospective, multi-center, unblinded randomized trial comparing levofloxacin 500 mg once daily orally or intravenously for 7 to 14 days to ceftriaxone 1 to 2 grams intravenously once or in equally divided doses twice daily followed by cefuroxime axetil 500 mg orally twice daily for a total of 7 to 14 days. Patients assigned to treatment with the control regimen were allowed to receive erythromycin (or doxycycline if intolerant of erythromycin) if an infection due to atypical pathogens was suspected or proven. Clinical and microbiologic evaluations were performed during treatment, 5 to 7 days posttherapy, and 3 to 4 weeks posttherapy. Clinical success (cure plus improvement) with levofloxacin at 5 to 7 days posttherapy, the primary efficacy variable in this study, was superior (95%) to the control group (83%). The 95% CI for the difference of response rates (levofloxacin minus comparator) was [-6, 19]. In the second study, 264 patients were enrolled in a prospective, multi-center, non-comparative trial of 500 mg levofloxacin administered orally or intravenously once daily for 7 to 14 days. Clinical success for clinically evaluable patients was 93%. For both studies, the clinical success rate in patients with atypical pneumonia due to Chlamydophila pneumoniae, Mycoplasma pneumoniae , and Legionella pneumophila were 96%, 96%, and 70%, respectively. Microbiologic eradication rates across both studies are presented in Table 10.
|Pathogen||No. Pathogens||Bacteriological Eradication Rate (%)|
Community-Acquired Pneumonia Due to Multi-Drug Resistant Streptococcus pneumoniae
Levofloxacin was effective for the treatment of community-acquired pneumonia caused by multi-drug resistant Streptococcus pneumoniae (MDRSP). MDRSP isolates are isolates resistant to two or more of the following antibacterials: penicillin (MIC ≥2 mcg/mL), 2nd generation cephalosporins (e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/ sulfamethoxazole). Of 40 microbiologically evaluable patients with MDRSP isolates, 38 patients (95%) achieved clinical and bacteriologic success at post-therapy. The clinical and bacterial success rates are shown in Table 11.
|* One patient had a respiratory isolate that was resistant to tetracycline, cefuroxime, macrolides and TMP/SMX and intermediate to penicillin and a blood isolate that was intermediate to penicillin and cefuroxime and resistant to the other classes. The patient is included in the database based on respiratory isolate.† n = the number of microbiologically evaluable patients who were clinical successes; N = number of microbiologically evaluable patients in the designated resistance group.‡ n = the number of MDRSP isolates eradicated or presumed eradicated in microbiologically evaluable patients; N = number of MDRSP isolates in a designated resistance group.|
|Screening Susceptibility||Clinical Success||Bacteriological Success*|
|n/N †||%||n/N ‡||%|
|2nd generation Cephalosporin resistant||31/32||96.9||31/32||96.9|
|Trimethoprim/ Sulfamethoxazole resistant||17/19||89.5||17/19||89.5|
Not all isolates were resistant to all antimicrobial classes tested. Success and eradication rates are summarized in Table 12.
|Type of Resistance||Clinical Success||Bacteriologic Eradication|
|Resistant to 2 antibacterials||17/18 (94.4%)||17/18 (94.4%)|
|Resistant to 3 antibacterials||14/15 (93.3%)||14/15 (93.3%)|
|Resistant to 4 antibacterials||7/7 (100%)||7/7 (100%)|
|Resistant to 5 antibacterials||0||0|
|Bacteremia with MDRSP||8/9 (89%)||8/9 (89%)|
To evaluate the safety and efficacy of the higher dose and shorter course of levofloxacin, 528 outpatient and hospitalized adults with clinically and radiologically determined mild to severe community-acquired pneumonia were evaluated in a double-blind, randomized, prospective, multicenter study comparing levofloxacin 750 mg, IV or orally, every day for five days or levofloxacin 500 mg IV or orally, every day for 10 days.
Clinical success rates (cure plus improvement) in the clinically evaluable population were 90.9% in the levofloxacin 750 mg group and 91.1% in the levofloxacin 500 mg group. The 95% CI for the difference of response rates (levofloxacin 750 minus levofloxacin
500) was [-5.9, 5.4]. In the clinically evaluable population (31 to 38 days after enrollment) pneumonia was observed in 7 out of 151 patients in the levofloxacin 750 mg group and 2 out of 147 patients in the levofloxacin 500 mg group. Given the small numbers observed, the significance of this finding cannot be determined statistically. The microbiological efficacy of the 5-day regimen was documented for infections listed in Table 13.
|S. pneumoniae||19/20 (95%)|
|Haemophilus influenzae||12/12 (100%)|
|Haemophilus parainfluenzae||10/10 (100%)|
|Mycoplasma pneumoniae||26/27 (96%)|
|Chlamydophila pneumoniae||13/15 (87%)|
Levofloxacin is approved for the treatment of acute bacterial sinusitis (ABS) using either 750 mg by mouth x 5 days or 500 mg by mouth once daily x 10 to 14 days. To evaluate the safety and efficacy of a high dose short course of levofloxacin, 780 outpatient adults with clinically and radiologically determined acute bacterial sinusitis were evaluated in a double-blind, randomized, prospective, multicenter study comparing levofloxacin 750 mg by mouth once daily for five days to levofloxacin 500 mg by mouth once daily for 10 days.
Clinical success rates (defined as complete or partial resolution of the pre-treatment signs and symptoms of ABS to such an extent that no further antibiotic treatment was deemed necessary) in the microbiologically evaluable population were 91.4% (139/152) in the levofloxacin 750 mg group and 88.6% (132/149) in the levofloxacin 500 mg group at the test-of-cure (TOC) visit (95% CI [-4.2, 10] for levofloxacin 750 mg minus levofloxacin 500 mg).
Rates of clinical success by pathogen in the microbiologically evaluable population who had specimens obtained by antral tap at study entry showed comparable results for the five- and ten-day regimens at the test-of-cure visit 22 days post treatment (see Table 15).
|* Note: Forty percent of the subjects in this trial had specimens obtained by sinus endoscopy. The efficacy data for subjects whose specimen was obtained endoscopically were comparable to those presented in the above table.|
|Pathogen||Levofloxacin 750 mg x 5 days||Levofloxacin 500 mg x 10 days|
|Streptococcus pneumoniae*||25/27 (92.6%)||26/27 (96.3%)|
|Haemophilus influenzae*||19/21 (90.5%)||25/27 (92.6%)|
|Moraxella catarrhalis*||10/11 (90.9%)||13/13 (100%)|
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