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Highlights from the 6th Western Pacific Congress of Chemotherapy and Infectious Diseases
Kuala Lumpur, Malaysia, November 29-December 3, 1988

CONTENTS

Introduction

Levofloxacin: Leader Among Respiratory Fluoroquinolones

Levofloxacin Significantly More Effective Than Other Commonly Used Agents

Cost-effective Switch Regimen Demonstrated for Ofloxacin/Levofloxacin

Levofloxacin: Wide Spectrum of Activity and Excellent Penetration into Ear, Nose and Throat Tissues

Introduction

The 6th Western Pacific Congress of Chemotherapy and Infectious Diseases (6th WPCCID), held in Malaysia from November 29 to December 3, was universally described as an exciting meeting, presenting the most recent information available on the optimal management of many of the most common disorders facing infectious disease specialists. Presentations were of a uniformly high standard, with eminent speakers from throughout Asia, the United States and Europe attending to keep up-to-date with the rapidly changing face of infectious disease treatment. Of particular interest were the numerous reports on levofloxacin, which is beginning to establish a prominent niche for itself, particularly in regard to respiratory tract infections (RTIs). Levofloxacin has been confirmed as an extremely effective, well tolerated and a more cost-effective alternative than many other agents when dealing with these infections. The following summarizes a few of the many studies that were presented in an effort to clarify the role of this exceedingly useful antimicrobial.

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Levofloxacin: Leader Among Respiratory Fluoroquinolones

The fluoroquinolones are now widely recognized as one of the most important classes of antibiotics, with levofloxacin at the forefront of these agents. Due to the additional advantages possessed by levofloxacin, it is being hailed as a leader in the treatment of RTIs with numerous reports confirming the efficacy of this agent. Of particular interest was a symposium focusing on levofloxacin, highlighting its major advantages which include an excellent antibacterial spectrum covering Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, and other RTI-related pathogens (Table 1).

Table 1. Sensitivity of common respiratory bacterial pathogens to levofloxacin
Table_1

In addition, levofloxacin has improved pharmacokinetic and pharmacodynamic properties which make it a better agent than many other available, and is associated with a low level of adverse reactions and drug-drug interactions. While resistance among respiratory pathogens to beta-lactams has been increasing, this is not a problem for levofloxacin which acts at a different target site in the bacteria compared to penicillins. Levofloxacin achieves excellent plasma antimicrobial concentration after intravenous or oral administration, and reaches extremely high concentrations in the lungs and respiratory tissues (Table 2).

Table 2. The concentrations of levofloxacin in serum and BALF
Table_2

In the epithelial lung fluid, the penetration is 3-12:1 compared with 0.25:1 for beta-lactams, and 10:1 for macrolides. In alveolar macrophages, fluoroquinolones penetrate up to 34 times higher than serum levels, while beta-lactams are consistently below plasma levels. Another important characteristic of levofloxacin is that it acts with concentration-dependent killing, thereby achieving a more rapid bactericidal effect. Due to its high bioavailability, it is very easy to switch from intravenous to oral therapy. In addition, because it has a long half-life of six hours with a long postantibiotic effect, it can be given once daily. These features ensure that compliance is high, and costs are reduced by shortening duration of hospitalization.

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Levofloxacin Significantly More Effective Than Other Commonly Used Agents

The efficacy of levofloxacin in refractory and recurrent lower respiratory tract infections (LRTIs) was studied in a trial in which 60 patients were randomized to receive either levofloxacin 300 mg twice daily for 7-10 days, or azithromycin 0.5 g once daily for 7-10 days. The total efficacy was 90% in the levofloxacin group, and this was significantly higher than that for azithromycin group which only achieved a very low 63.4% total efficacy rate (p < 0.01) (Table 3).

Table 3. Comparison of efficacy and bacterial eradication following levofloxacin or azithromycin therapy in RTI
Table_3

In addition, other clinical results confirmed that levofloxacin was as effective as cefuroxime axetil in the treatment of LRTI. Patients were randomized to receive either levofloxacin 200 mg twice daily, or cefuroxime axetil 500 mg twice daily, both for 5-14 days. Clinical response demonstrated that the levofloxacin patients achieved an efficacy rate of 92.86% (13 of 14 patients) and the cefuroxime axetil patients had an 85.71% efficacy rate (12 of 14 patients).

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Cost-effective Switch Regimen Demonstrated for Ofloxacin/Levofloxacin

A randomized comparative, parallel-group trial was reported, assessing chronic obstructive pulmonary disease (COPD) patients with acute infections treated with either ofloxacin intravenously 400 mg twice daily, or intravenous ceftazidime 2 g every eight hours for at least three days. Depending on clinical improvement, they were then switched to oral therapy of either levofloxacin 300 mg twice daily, or ceftibuten 400 mg once daily. Results showed that the clinical success ("cure" plus "improved") for ofloxacin/levofloxacin was 97% compared to 93% for the cephalosporin group (Table 4).

Table 4. Comparison of RTI treatment using ofloxacin/levofloxacin versus ceftazidime/ceftibuten
Table_4

An economic analysis of this data demonstrated that the levofloxacin regimen was much more cost-effective.

Further evidence was presented supporting the efficacy of oral levofloxacin versus intravenous ceftazidime in the treatment of patients with bronchiectasis. Patients admitted with acute exacerbation were randomized to receive 10 days of either oral levofloxacin 400 mg twice daily, or ceftazidime 1 g intravenously thrice daily. The 24-hour sputum volume score improved from 97.9 to 31.2, and from 63.2 to 24.7 for levofloxacin and ceftazidime, respectively; sputum purulence score improved from 3.44 to 2.07, and 4.05 to 1.78; cough score from 2.2 to 1.06, and 2.2 to 0.8; and dyspnea score improved from 2.01 to 0.8, and 1.7 to 0.6. These results confirm that levofloxacin is as effective as parenteral ceftazidime in the empirical management of patients with acute exacerbations of bronchiectasis. This corresponds to a significant advantage for levofloxacin in terms of decreasing medical manpower, reducing costs, and markedly improving patient acceptability.

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Levofloxacin: Wide Spectrum of Activity and Excellent Penetration into Ear, Nose and Throat Tissues

Sinusitis is one of the major problems facing clinicians working in ear, nose and throat (ENT). Another study randomized 28 patients to receive levofloxacin 500 mg once daily, and 28 patients to receive amoxicillin-clavulanate 500/125 mg thrice daily. In the levofloxacin group, 12 patients were cured, 13 reported improvement and three patients failed therapy. In the amoxicillin-clavulanate group, 16 recovered and 10 improved.

Adding to this data, was a large single-blind, randomized, clinical trial comparing the efficacy and safety of levofloxacin versus amoxicillin-clavulanate (co-amoxiclav) in the treatment of sinusitis. In this trial, levofloxacin was given as a 500 mg once-daily dose, while amoxicillin-clavulanate was given as 625 mg thrice daily. An independent ENT physician and radiologist who were blinded to the treatment evaluated the clinical and radiological response after 14 days of treatment. A total of 90 patients were included in the study, with 44 randomized to the levofloxacin arm, and 46 randomized to receive amoxicillin-clavulanate arm. Clinical response, based on the physicians evaluation, was similar for the two groups (11 "excellent", 16 "good", and 7 "fair" for the levofloxacin group compared to 10 "excellent", 22 "good", 6 "fair" and 4 poor in the amoxicillin-clavulanate group). Levofloxacin consistently achieved equivalent or better results, proving its efficacy in the field of ENT (Figure 1).

Figure 1. Efficacy assessment on symptoms response
Figure_1

In addition to presentations regarding infections of the respiratory tract, there were a range of presentations outlining the clinical efficacy and safety of levofloxacin in treating other disorders, including those of the urinary tract, gastrointestinal and nervous systems. One of the major advantages of levofloxacin which was stressed time and time again was its excellent spectrum of activity, with very low resistance. This is of great importance, as resistance to other agents such as beta-lactams, macrolides and penicillin continues to rise. Continued surveillance of isolates throughout the world is necessary to ensure that management focuses on prescribing effective agents such as levofloxacin, rather than those which are ineffective due to high resistance rates.

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