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The rationale for higher dose levofloxacin for the treatment of serious infections

Abstract number: 1135_19

Kahn J., Davis N.

Background/Objective:  

Advances in medical care continue to be associated with improved survival rates and better patient quality of life. A consequence of these developments is an increased vulnerability to serious infection due to traditional pathogens (or commensals and relatively avirulent organisms) that may be resistant to multiple antimicrobial agents. There are few new antibacterial agents on the horizon. One strategy for dealing with this threat is to maximize the utility of each of our antibacterial drugs by dosing them more rationally. The purpose of this paper is to summarize the rationale for utilizing higher doses of levofloxacin in the management of serious infections.

Methods:  

We have reviewed and will report on all available data from subjects exposed to daily levofloxacin doses of 750 mg or more.

Results:  

After more than seven years of use in the US, levofloxacin has maintained its excellent susceptibility profile. Drug levels seen in infected patients are significantly higher than those achieved in healthy volunteers and enable coverage of organisms with higher MICs. Because of its concentration-dependent bactericidal activity, higher doses of levofloxacin increase the speed and thoroughness of bacterial eradication in vitro and can inhibit the emergence of fluoroquinolone resistance in studied organisms. Clinical trials with the 750 mg dose have been undertaken in complicated skin and skin structure infections, nosocomial pneumonia, and febrile neutropenia; results were at least equivalent to comparator agents. Use of this dose in community-acquired pneumonia and acute bacterial exacerbations of chronic bronchitis has allowed for more rapid resolution of symptoms and a shortening of the course of therapy. Dosing in healthy volunteers at does up to 1500 mg per day resulted in no significant alteration of the adverse event profile. Clinical trial data show that the safety of 750 mg daily is similar to the 250 and 500 mg forms.

Conclusion:  

Levofloxacin has documented efficacy and safety credentials at clinical doses of at least 750 mg once daily. At these higher doses, it is an attractive candidate for monotherapy of some serious infections or for combination therapy with such other agents as the carbapenems or 4th generation cephalosporins. Additional clinical trials using these approaches seem warranted.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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