Infection
Update

Chronic obstructive pulmonary disease (COPD) is one of the most frequent respiratory adult infections in the developed world and in the United States alone, around 16 million people are diagnosed annually. It is the fourth leading cause of death and its annual mortality has been predicted to increase from 2.25 million deaths in 1990 to 4.5 million deaths in 2020. Acute exacerbations of COPD (AECOPD) can cause respiratory failure which is one of the main causes of death in such patients.
  Because of the potential seriousness of the infection and its major financial implications, such as the costs associated with hospitalization and days lost from work, physicians need to have a rapid treatment which is both safe and effective.
  Over the last twenty years, the fluoroquinolones have established themselves as very powerful antibiotics with a wide spectrum of activity. Their antibacterial activity is concentration-dependent, meaning that the higher the dose, the more rapid and efficient is the bacterial killing. They also exhibit excellent respiratory tract penetration. In particular, levofloxacin has been shown to be very safe and effective with excellent pharmacodynamic and pharmacokinetic properties. Its relatively low incidence of side effects means that it can be given as a daily dose of 750 mg producing a high cure rate in a relatively short period, typically 5 days. Its safety profile is so good that, if the clinical situation warrants it, 1,000 mg levofloxacin daily is possible. Using high doses for short periods limits the total exposure to drug and potentially, may help to combat the emergence of bacterial resistance.


Question

Q01 Chronic respiratory tract infections, including acute bacterial exacerbations of chronic bronchitis (ABECB) and acute exacerbations of COPD (AECOPD) are a common and pervasive problem, associated with significant morbidity. Could you comment on the rationale for using antimicrobials to treat such patients?
Q02 When choosing an antimicrobial agent for treating ABECB, what features do you look for, and what are the features of levofloxacin that make it a useful agent in this setting?
Q03 You recently have reported the results of a study investigating 750 mg QD levofloxacin for 5 days in ABECB (7). Why did you feel there was a need for this high-dose therapy?
Q04 Could you describe the study design?
Q05 How did you define ABECB in this study?
Q06 What were the patient demographic features of those entered into the study? Were these different in any way to the general population that a general physician would expect to treat?
Q07 What were the predominant pathogens identified in the study as causing the exacerbation?
Q08 What are the resistance rates for the most common ABECB pathogens and is this changing? If so, what trends in resistance patterns have been noted, and what global differences have been noted in resistance patterns?
Q09 What impact does resistance patterns among respiratory tract infection (RTI) pathogens have on the use of fluoroquinolones such as levofloxacin?
Q10 What was the bacterial eradication like with levofloxacin and how did this compare to the results found with amoxicillin-clavulanate or other comparator agents?
Q11 Could you comment on the use of symptom resolution as the endpoint of your study?
Q12 You used a shorter duration of therapy with levofloxacin - what was your rationale for this?
Q13 Was the shorter course therapy effective compared to the longer 10 day amoxicillin-clavulanate therapy?
Q14 How was the high dose levofloxacin therapy tolerated? Was there any difference between the tolerability of the usual 500 mg dose from this newer 750 mg schedule?
Q15 Could you comment on the safety profile of levofloxacin compared to other fluoroquinolones as well as other antimicrobials used in this setting?
Q16 What were the benefits associated with using this levofloxacin treatment schedule in ABECB patients?
Q17 Could you comment on the advantages/disadvantages of levofloxacin compared to other agents, apart from amoxicillin-clavulanate in the treatment of ABECB (e.g., cefuroxime axetil, clarithromycin, other fluoroquinolones)?
Q18 Were you able to identify any factors associated with increased risk of treatment failure in this group of patients? How would you stratify ABECB patients to ensure the optimum treatment is given to each group?
Q19 What are the most commonly accepted treatment guidelines for this group of patients and could you briefly summarize the general consensus on managing ABECB patients?
Q20 Has the role of fluoroquinolones such as levofloxacin in treating RTI changed over the last decade and what do you expect its role to be in the next ten years?
Q21 In addition to ABECB, in what other clinical situations would you recommend using a high dose (750 mg or greater) of levofloxacin?

References

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