The Way Forward: High-Dose, Short-Course Levofloxacin Leads the Field

29 March, 2018

Question 4

What is the antibacterial coverage provided by high-dose levofloxacin, and for what clinical diseases is it indicated?

Levofloxacin has a broad spectrum of activity covering many Gram-positive and Gram-negative pathogens, including penicillin resistant S. pneumoniae as well as atypical bacteria. The 750 mg short-course regimen has been approved in the United States for treating acute bacterial sinusitis, community-acquired pneumonia (CAP), complicated urinary tract infections (cUTIs) and acute pyelonephritis (AP), caused by the following pathogens: S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, H. parainfluenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. One of the driving forces behind the development of the 750 mg dose of levofloxacin was use of PK/PD models to identify regimens associated with good clinical outcomes and to identify regimens that will suppress the emergence of resistant organisms – a process known as Monte Carlo simulation studies (9, 12, 13). In vitro pharmacokinetic models have also been used to evaluate the pharmacodynamics of 750 and 500 mg doses of levofloxacin against 4 ciprofloxacin resistant S. pneumoniae isolates. In this model, the 750 mg dose was rapidly bactericidal against all 4 strains with eradication of organisms within 30 hours (14). Information derived from studies such as these provided an important impetus for development of the 750 mg dose.