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Highlights from the 29th World Conference of the International Union against Tuberculosis and Lung Diseases
Bangkok, Thailand, November 23-26, 1998

CONTENTS

Introduction

Fluoroquinolones: Drugs of Choice in Respiratory Tract Infections

The Way Forward

Levofloxacin: Leading the Field of Respiratory Treatment

Clinical Reports Highlight Efficacy of Levofloxacin Over Competitors

Introduction

Image_1The 29th World Conference of the International Union against Tuberculosis and Lung Diseases (29th IUATLD/UICTMR): Global Congress on Lung Health was held in Thailand from November 23-26, 1998. As the premier meeting for all involved in the field of tuberculosis and lung disease, this was a "must-attend" event, with a rich and varied scientific program. Experts joined from around the world to discuss the latest findings covering basic and clinical research, as well as technical and social issues relevant to this important medical field. The aim of the meeting was to present data in a setting where open debate was actively encouraged, leading to tangible results in the prevention and treatment of lung disease.

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Fluoroquinolones: Drugs of Choice in Respiratory Tract Infections

One of the most stimulating symposia looked at the role of levofloxacin in treating respiratory tract infections (RTIs). Dr Nalinee Aswapokee, Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Siriraj Hospital, Bangkok, Thailand, provided an excellent overview, in which she clearly outlined the role of the fluoroquinolones in treating RTI. She noted that LRTI is one of the leading causes of morbidity and mortality, making it imperative that effective and safe therapeutic regimens are developed. Such effective regimens are becoming more difficult to administer due to the changes in agents responsible for community-acquired pneumonia (CAP), and increasing resistance patterns. This has been highlighted by the increase greater than 60 times in incidence of drug-resistant Streptococcus pneumoniae (DRSP).

Image_2At the same time, most RTIs need to be treated empirically, with the doctor unaware of the causative pathogen, emphasising the need to have adequate surveillance data for all countries and regions. Dr Aswapokee noted that, in general, the etiological diagnosis is established in less than 50% of CAP cases, and the clinical features do not confidently predict the microbial etiology in the majority of cases. The most common cause of CAP is S. pneumoniae, and Haemophilus influenzae with severe pneumonia likely to be due to S. pneumoniae or Legionella spp. The likelihood of atypical pathogens causing the infection also needs to be considered, with Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella spp. as common causes of CAP in lteq 30%, lteq 18%, and lteq 14% of cases, respectively.

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The Way Forward

One agent able to overcome these problems is levofloxacin, which exerts an amazing coverage of key respiratory pathogens, including enhanced activity against S. pneumoniae and DRSP (Tables 1-2).

Table 1. Activities against RT pathogens*
Table_1

Table 2. Activities against drug-resistant S. pneumoniae
Table_2

In addition, levofloxacin possesses a favorable pharmacokinetic profile, with extremely high penetration into respiratory tissues and fluids. Not content with such high bioavailability, levofloxacin also has the advantage of penetrating intracellularly and reaches high concentrations in alveolar macrophages (Table 3).

Table 3. Clinical pharmacokinetics
Table_3

Other pharmacokinetic features include its long half-life with extended postantibiotic effect (PAE), allowing it to retain its efficacy when given in a once-daily dosage. The usefulness of these features have been confirmed in clinical trials, demonstrating the excellent efficacy of levofloxacin in treating CAP and acute exacerbations of chronic bronchitis (AECB).

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Levofloxacin: Leading the Field of Respiratory Treatment

Dr Mary Ip, Division of Respiratory and Critical Care Medicine, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, continued the theme of clinical efficacy in a presentation. She described optimal treatment of chronic bronchial infections, looking specifically at acute exacerbations of bronchiectasis. Dr Ip stressed that new treatments for these infections are required as oral beta-lactams are now significantly less effective due to the many pathogens now producing beta-lactamase. In patients with associated cystic fibrosis, the most commonly isolated micro-organism in the early stages is Staphylococcus aureus, while later, Pseudomonas aeruginosa dominates. In non-cystic fibrosis cases, S. pneumoniae and H. influenzae are the most commonly identified pathogens. However, several recent studies demonstrate that the microbial profile has changed and Gram-negatives are being seen more frequently, including P. aeruginosa. In the past, anti-pseudomonal agents have necessitated intravenous administration, but were associated with higher treatment costs and reduced tolerability. Levofloxacin, however, is effective in managing these infections orally: a fact confirmed in a recent prospective, double-blind, randomized study.

Dr Ip reported results from this clinical trial which assessed levofloxacin versus ceftazidime in the treatment of patients admitted to hospitals for acute exacerbations of bronchiectasis. Group I received levofloxacin 300 mg twice daily, and Group II received ceftazidime 1 g thrice daily. Patient characteristics and disease severity were the same for both groups. Pathogens were isolated in approximately 65% of cases, with Pseudomonas accounting for a half of all isolates. Both regimens resulted in satisfactory clinical response. Oral levofloxacin was equivalent or superior to parenteral ceftazidime with no serious side effects (Table 4).

Table 4. Comparative patient response in two groups day 10
Table_4

Dr Ip noted that levofloxacin provided the physician with an excellent treatment for these patients and could be given orally, thereby reducing costs and improving patient tolerability of the regimen.

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Clinical Reports Highlight Efficacy of Levofloxacin Over Competitors

New treatment recommendations for CAP was the topic of a stimulating lecture given by Dr James S. Tan, Head of the Infectious Disease Section, Northeastern Ohio Universities College of Medicine, Ohio, USA. He began by noting that recent developments in bacterial resistance have stimulated physicians to look again at the indications and guidelines for RTIs treatment. Over the last decade, increasing numbers of penicillin-resistant S. pneumoniae (PRSP) and beta-lactamase-producing H. influenzae, as well as Moraxella catarrhalis, have been isolated throughout the world. The situation is becoming even worse, as many of these pneumococci are resistant not only to penicillin, but also to cephalosporins, and are rapidly becoming resistant to other agents such as macrolides, clindamycin and tetracycline.

Levofloxacin's spectrum of activity encompasses this pathogen, moving it to the forefront of recommended strategies for treating these infections. It is effective against many of the multidrug-resistant pathogens and has excellent activity against different agents causing CAP. Compared to beta-lactams, levofloxacin has negligible PRSP resistance, and no resistance to H. influenzae and M. catarrhalis. In fact, results from the Tracking Resistance in the United States Today (TRUST) study show only 0.6% of S. pneumoniae are resistant to levofloxacin (Figure 1).

Figure 1. Susceptibility of Streptococcus pneumoniae (1996-1997)
Figure_1

Other significant features of levofloxacin include its activity against Legionella, Chlamydia and Mycoplasma. It also possesses advantages over other fluoroquinolones, including extremely high tissue penetration. Levofloxacin's mechanism of action results in a concentration-dependent killing, which maximizes the area under the curve above the MIC (AUIC), allowing an extremely effective once-daily regimen. Compared to other fluoroquinolones levofloxacin is far superior in this regard (Figure 2).

Figure 2. Fluoroquinolones area under the curve (AUC) values
Figure_2

Levofloxacin is also available in parenteral and oral formulations, and due to its excellent bioavailability, is readily switched from intravenous to oral therapy. Another important advantage cited by many patients is that levofloxacin is extremely well tolerated, leading to improved patient compliance.

Results from many clinical trials confirming the efficacy of this agent in RTIs have led to a surge in the use of levofloxacin. Most importantly, clinical experience has shown superiority over beta-lactams (ceftriaxone/cefuroxime) in CAP (Figure 3).

Figure 3. Levofloxacin community-acquired pneumonia
(File TM Jr., et al. Antimicrob Agents Chemother 1997; 41: 1965-1972)

Figure_3

Other favorable results have been published for a range of RTIs, including AECB and sinusitis.

While there is often debate about the advantages and disadvantages of various antimicrobials, the common view among physicians throughout the meeting was that levofloxacin provides an exceptionally effective and safe antibiotic. Therefore, the issue of judicious practices in prescribing this agent were stressed to ensure its usefulness for clinicians and patients well into the coming century.

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