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

29 March, 2018

A new generation of fluoroquinolone treatment has begun with the advent of the high-dose, short-course levofloxacin regimen. It may seem to many working in the field of infectious diseases that over the last decade the development of new fluoroquinolones has been matched by the subsequent dismissal of many of these agents from general use. However, one agent has remained constant throughout this time. As competitor agents arrive and then fall by the wayside, levofloxacin remains a valuable member of the physician’s armamentarium, providing reliable, effective and safe treatment for a wide range of infections. Now the utility of this agent has been further enhanced by the development of a 750 mg dose that provides excellent clinical and microbiological success while, at the same time, allowing administration in a short five-day schedule that possesses advantages of greater compliance, cost-effectiveness and the potential to halt the increase in resistance. To summarize the role of this new regimen, Penetrationinterviewed Lala M. Dunbar, Albert Lauro Chair and Professor of Medicine/Emergency Medicine at Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America. Professor Dunbar has been at the forefront of clinical research into the use of high-dose, short-course levofloxacin and was able to use her in-depth knowledge of infectious diseases and antibiotic strategies to provide a comprehensive overview of this exciting new formulation.



Q01 What are the pharmacokinetic features of the 750 mg levofloxacin dose that make it an attractive therapeutic strategy in comparison to the 500 mg dose?
Q02 The relative potencies of the fluoroquinolones can be assessed according to pharmacodynamic factors. Could you comment on this?
Q03 How does the 750 mg levofloxacin dose compare to other fluoroquinolone regimens in terms of achieving these targets?
Q04 What is the antibacterial coverage provided by high-dose levofloxacin, and for what clinical diseases is it indicated?
Q05 How does the antibacterial activity of high-dose levofloxacin compare to other fluoroquinolones?
Q06 Could you comment on the fluoroquinolone coverage of Pseudomonas aeruginosa?
Q07 Could you discuss the role of this high-dose, short-course therapeutic strategy in the treatment of CAP?
Q08 What were the clinical success rates according to pathogen?
Q09 How important are atypical pathogens in the etiology of CAP?
Q10 How effective was 750 mg levofloxacin in treating CAP caused by atypical respiratory pathogens?
Q11 It has been reported that using the high-dose levofloxacin regimen there is a faster resolution of symptoms. Could you comment on this?
Q12 The lower 500 mg dose has been useful in providing easy switch from IV to PO therapy. Does the high-dose regimen also provide a convenient transition from IV to PO therapy and what benefits in clinical management does this option provide?
Q13 How do you decide which patients with CAP should be admitted?
Q14 What role does this high-dose, short-course therapy have in treating acute bacterial sinusitis?
Q15 Does the high-dose, short-course levofloxacin have a role to play in the treatment of cUTI?
Q16 Could you comment on the use of the high-dose, short-course levofloxacin schedule in special patient subgroups such as the elderly or those with renal impairment?
Q17 There is a lot of data available demonstrating the tolerability and safety of the levofloxacin 500 mg schedule. Could you comment on the safety of the 750 mg dose in preclinical and clinical trials?
Q18 Could you comment on the safety of levofloxacin compared to other fluoroquinolones?
Q19 Could you comment on the problem of resistance and how should this problem be managed?
Q20 It has been proposed that another advantage of using the high-dose, short-course levofloxacin regimen is its potential to reduce the emergence of antibacterial resistance. Could you discuss whether this is a likely benefit of using this strategy?
Q21 Have there been any changes in levofloxacin resistance trends over the past decade of use?
Q22 How do the resistance rates to levofloxacin compare to those reported for other antimicrobial agents in regard to common respiratory tract pathogens?
Q23 Do you know if resistance rates among the fluoroquinolones have changed?
Q24 Do the differing antimicrobial agents have different mechanisms responsible for resistance?
Q25 What is the role of efflux in fluoroquinolone resistance?
Q26 A common problem encountered in optimizing antimicrobial therapy is maintaining compliance. Does this regimen provide any benefits in this regard?
Q27 Is there any cost-effective implications associated with this regimen?
Q28 What issues would you like to see further investigated in regard to the high-dose strategy?