Tracking Susceptibility and Reducing Resistance - Fluoroquinolones at the Forefront in the Fight Against Bacterial Pathogens

29 March, 2018

Although the focus of infectious disease in 2009 has been the Influenzae A (H1N1) virus, physicians and patients must not forget bacterial pathogens continue as a major threat. Many bacterial complications of viral infections reinforce this message. Without effective antimicrobial cover, bacterial infections would seriously damage society and healthcare systems. Antibiotics were originally thought to be the end of infectious diseases, but some see the development of resistance and super-bugs as signalling the end of the antibiotic era. However, neither position is correct – infectious diseases remain although we have an armamentarium of effective antibiotics. To maintain their activity, we must continue collecting susceptibility and resistance data to determine the most effective evidence-based antimicrobial regimens. It is also essential to combat constantly evolving pathogens and we are fortunate to have the fluoroquinolones, which have become very important since their introduction in quinolone form in 1962. One of the most important is levofloxacin, available since the 1990s and still exceptionally active. Levofloxacin, also one of the safest fluoroquinolones, has remained effective by judicious use of appropriate regimens based on pharmacological parameters and susceptibility data. To examine the current activity of levofloxacin against common bacterial pathogens Penetration interviewed Rafael Cantón, Professor of Microbiology at the Hospital Universitario Ramón y Cajal, Madrid, Spain. Professor Cantón is the Clinical Data Coordinator of EUCAST (European Committee on Antimicrobial Susceptibility Testing) and an expert on antimicrobial surveillance. Professor Cantón gave an indepth summary of the current situation regarding fluoroquinolones, particularly levofloxacin resistance profiles, and compared these with other agents.


Q01 Could you comment on the pharmacokinetic/pharmacodynamic (PK/PD) properties of levofloxacin that make it a useful antimicrobial agent, with particular reference to respiratory tract infections?
Q02 How do clinicians use PK/PD data to ensure optimal dosage regimens?
Q03 Do the PK/PD features of levofloxacin change when given orally?
Q04 Do you have any data comparing PK/PD properties of levofloxacin with other fluoroquinolones and the influence on bacterial killing?
Q05 What are the PK/PD features of levofloxacin in special patient populations- for example, critically ill patients, elderly or those with renal impairment?
Q06 In addition to the above pharmacologic values, the concept of the mutant prevention concentration (MPC) has been suggested as useful for guiding the most appropriate use of antimicrobials. Could you discuss the role of MPC in determining fluoroquinolone treatment regimens?
Q07 Is the strategy of administering doses above the MPC also beneficial when treating other Gram-positive pathogens and Gram-negative pathogens such as Pseudomonas aeruginosa and Escherichia coli?
Q08 There are now two sides to antimicrobial treatment- a dose regimen that effectively treats a patient but also one that is more likely to avoid the development of resistance. In this regard monitoring of resistance is an integral aspect to maintaining antibacterial efficacy. You have been involved in important surveillance studies looking at S. pneumoniae isolates. Could you comment on the prevalence of penicillin resistant S. pneumoniae (PRSP)
Q09 What is the current situation in regard to macrolide resistance among S. pneumoniae?
Q10 What are the mechanisms responsible for causing macrolide resistance, and do these different mechanisms translate into different clinical resistance patterns around the globe?
Q11 Are there any temporal trends in regards to the relative incidence of the two major mechanisms of macrolide resistance [erm (B) and mef (A)]?
Q12 Could you describe the current situation in regard to fluoroquinolone resistance rates for the major respiratory tract pathogens?
Q13 What have been the trends in fluoroquinolone resistance over the past decade?
Q14 Could you comment on the activity of levofloxacin, macrolide or beta-lactam resistant S. pneumoniae?
Q15 Why do you think fluoroquinolone resistance among S. pneumoniae has remained relatively low and stable?
Q16 Could you discuss the use of levofloxacin against ciprofloxacin-resistant S. pneumoniae?
Q17 Are there any differences among the fluoroquinolones in terms of their ability to select for resistance?
Q18 How do the results from your surveillance study impact on treatment strategies aimed at dealing with infections caused by S. pneumoniae?
Q19 What future research do you think is needed in this area?