Levofloxacin demonstrates concentration-dependent bactericidal activity most closely related to the pharmacodynamic parameters of the ratio of area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) and the ratio of peak plasma concentration (C(max)) to MIC. Increasing the dose of levofloxacin to 750 mg exploits these parameters by increasing peak drug concentrations, allowing for a shorter course of treatment without diminishing therapeutic benefit. This was demonstrated in a multicenter, randomized, double-blind investigation that compared levofloxacin dosages of 750 mg per day for 5 days with 500 mg per day for 10 days for the treatment of mild to severe community-acquired pneumonia (CAP). In the clinically evaluable population, the clinical success rates were 92.4% (183 of 198 persons) for the 750-mg group and 91.1% (175 of 192 persons) for the 500-mg group (95% confidence interval, -7.0 to 4.4). Microbiologic eradication rates were 93.2% and 92.4% in the 750-mg and 500-mg groups, respectively. These data demonstrate that 750 mg of levofloxacin per day for 5 days is at least as effective as 500 mg per day for 10 days for treatment of mild-to-severe CAP.
This is the first prospective clinical trial in which patients with acute bacterial exacerbation of chronic bronchitis have been stratified by degree of underlying illness.Uncomplicated patients were randomised to levofloxacin 750 mg once daily (q.d.) for 3 days or azithromycin q.d. for 5 days. Complicated patients were randomised to levofloxacin 750 mg q.d. for 5 days or amoxicillin 875 mg/clavulanate 125 mg twice daily for 10 days.Regardless of therapy, complicated patients demonstrated lower clinical and microbiological success than uncomplicated patients. Clinical success for clinically evaluable patients was similar for levofloxacin and azithromycin (93.0 versus 90.1%, respectively), and levofloxacin and amoxicillin/clavulanate (79.2 versus 81.7%, respectively). For microbiologically evaluable patients, clinical response to levofloxacin for 3 days was superior to azithromycin for 5 days (96.3 versus 87.4%, respectively), and levofloxacin for 5 days was similar to amoxicillin/ clavulanate for 10 days (81.4 versus 80.9%, respectively). Microbiological eradication was superior for levofloxacin for 3 days compared with azithromycin for 5 days (93.8 versus 82.8%, respectively), and similar for levofloxacin and amoxicillin/clavulanate for 10 days (81.4 versus 79.8%, respectively).In conclusion, levofloxacin 750 mg for 3 days was comparable to azithromycin for 5 days for uncomplicated patients with acute bacterial exacerbation of chronic bronchitis, while 5 days of 750 mg levofloxacin was comparable to 10 days of amoxicillin/clavulanate for complicated acute bacterial exacerbation of chronic bronchitis.
The 750-mg, 5-day course of levofloxacin was at least as effective as the 500-mg, 10-day regimen for atypical CAP. Additionally, the 750-mg, short-course levofloxacin therapy may reduce total antimicrobial drug usage and more rapidly relieve pneumonia symptoms.
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