Highlights from the 20th International Congress of Chemotherapy
Sydney, Australia, June 29-July 3, 1997
The 1997 International Congress of Chemotherapy (ICC) provided a comprehensive range of sessions catering to the needs of all infectious disease experts. The international flavour of the meeting was upheld with more than 340 invited speakers from around the world participating in a range of plenary sessions, symposia, state-of-the-art lectures and workshops. Topical issues covered included emerging diseases, antibiotic resistance and optimal treatment strategies aimed at effectively dealing with a range of respiratory tract infections (RTI).
Levofloxacin was the topic of numerous preclinical and clinical studies presented, with results confirming that levofloxacin possesses an excellent antibacterial spectrum of activity, penetrates into tissues extremely well and is very safe for the treatment of a wide range of infections. In particular, results from clinical trials reported at the meeting strongly support the use of levofloxacin for the treatment of infections of the upper and lower respiratory tract.
Levofloxacin - Demonstration of Comprehensive Antibacterial Activity
RTI continue to provide a challenge to physicians with the development of resistance to ß-lactams leading to a reappraisal of current therapy. Levofloxacin, as well as being extremely effective in treating RTI, has been shown to have with no cross resistance to penicillins, cephalosporins or macrolides. In vitro study results assessing levofloxacin versus other antibiotics against 202 isolates of Streptococcus pneumoniae were reported by Dr. K. Thomson, USA. He confirmed that levofloxacin was superior to ciprofloxacin, ofloxacin, erythromycin, penicillin, amoxicillin, loracarbef, cefaclor, cefpodoxime, ceftriaxone and trimethroprim-sulfamethoxazole (TMP-SMX) (Table 1). Among the fluoroquinolones, levofloxacin was the most potent with 98% of all isolates inhibited by 2 µg/ml. Levofloxacin was also superior to the ß-lactams, erythromycin and TMP-SMX, as it was equally active against penicillin-susceptible and -resistant strains.
Table 1. In vitro activity of levofloxacin, ofloxacin, and comparison agents against 202 recent clinical isolates of Streptococcus pneumoniae
Clinical Results Support Levofloxacin's In Vitro Success
These in vitro results have been shown to correspond to excellent clinical efficacy with a range of studies confirming the superiority of levofloxacin in the treatment of RTI. Included among these studies was an evaluation of levofloxacin 500 mg once-daily orally for 7 to 10 days in the treatment of adults with community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB), presented by Dr. Alsagaff, Indonesia. Forty patients received 500 mg once-daily producing a success rate of 95%, a quick defervescence in temperature and a shortened hospital stay. All causative pathogens were eradicated. An added benefit associated with levofloxacin is its oral administration which is more cost-effective and better accepted by patients.
Oral Levofloxacin as Effective as Intravenous Cephalosporin
A study presented by Dr. Yoo, Korea, compared the efficacy and safety of oral levofloxacin 200 mg levofloxacin t.i.d. with intravenous cefamandole (CFM) 1.0 g t.i.d in the management of 21 patients with AECB. Levofloxacin achieved a 90% effective rate compared to 85.7% for cefamandole. Microbiological eradication rate achieved by levofloxacin was also higher than that for cefamandole (Figure 1). These results highlighted that levofloxacin is a safe and effective oral antibiotic that can be used in AECB, providing an oral option which is comparable to intravenous second generation cephalosporins.
Figure 1. Microbiologic Eradication and Clinical Success Rate
Levofloxacin Produces Better Results Than Amoxicillin-Clavulanic Acid
Further evidence supporting the wide clinical usefulness of levofloxacin was provided by Dr. Hou, China. Thirty LRTI cases received levofloxacin 300 mg b.i.d. for 7-14 days while 30 others received amoxicillin-clavulanic acid 2.4 g intravenously every 8 hours for 7-14 days. Sixty patients with urinary tract infections (UTI) were randomised to receive either levofloxacin 300 mg given once-daily for 7-10 days or amoxicillin-clavulanic acid 1.2 g intravenously every 8 hours for 7-10 days. Acute gonorrhoea cases were treated with a single 300 mg dose of levofloxacin, while the other infections received 300 mg either once- or twice-daily for 7-14 days.
Results confirmed that levofloxacin achieved significantly higher clinical effective rates than amoxicillin-clavulanic acid for both LRTI and UTI cases. In regard to LRTI, the overall efficacy rate for levofloxacin was 90% compared to 63.3% for amoxicillin-clavulanic acid. The rates of bacterial eradication of levofloxacin were also significantly higher than that of amoxicillin-clavulanic acid in both LRTI and UTI (p < 0.05).
Excellent cure and efficacy rates were achieved for patients with gonorrhoea, typhoid fever and skin and soft tissue infections (SSTI). Not only was levofloxacin effective, but it was demonstrated to be far better tolerated by patients than amoxicillin-clavulanic acid, with an adverse effect rate for levofloxacin of 3.8% compared to 21.7% for amoxicillin-clavulanic acid. These very positive results add to the rapidly growing scientific evidence confirming the benefits provided by levofloxacin in the treatment of many infections.
UTI - A Major Indication for Levofloxacin
The efficacy and safety of levofloxacin (200 mg b.i.d. PO for 7-14 days) was compared to ciprofloxacin (200 mg IV b.i.d. for 7-14 days) in the treatment of complicated UTI in a study presented by Dr. Hong, China. Levofloxacin achieved a 78.2% (18/23) bacterial eradication rate while ciprofloxacin only achieved a 57.1% (12/21) eradication rate. These bacteriological results translated into improved clinical efficacy for levofloxacin, which achieved a cure rate of 76.7% compared to 63.3% for ciprofloxacin (Table 2).
Table 2. Compare the results of levofloxacin with ciprofloxacin
Excellent Safety Profile Confirmed for Levofloxacin
Results from a three year post-marketing surveillance data on levofloxacin in Japan were reported by M. Sawada, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan. In the phase IV study, adverse drug reactions (ADR) associated with levofloxacin were reported in only 203 from 16,158 cases. The most frequently reported ADR (> 0.05% incidence rate) are shown in Figure 2. Dr. Sawada noted that the rate of ADR was not dependent on daily dose and concluded that the incidence rate of ADR in the phase IV study on levofloxacin was 1.3%. This was described as a very acceptable level, particularly compared with other fluoroquinolones.
Figure 2. Distribution of ADRs in Phase IV Study
Levofloxacin - Highly Effective for Typhoid Fever
A trial in which 80 patients with Salmonella typhi infection were randomised to receive either levofloxacin or cefixime was performed by Dr. Zheng, China, demonstrated remarkable efficacy for levofloxacin, with a cure and total effective rate of 97.5% (39/40) and 100%, respectively (Table 3). In comparison the cefixime group was less effective, achieving a cure and total effective rate of 90%. No relapse or recurrence were observed during the three months follow-up period. Bacteriological assessment revealed a bacterial eradication rate for levofloxacin of 100% covering both S. typhi and S. paratyphi A. In contrast cefixime eradication rate was lower at 90%. It was concluded from these excellent results that levofloxacin is highly effective for the treatment of typhoid and paratyphoid fever. It has the features of high clinical cure and effective rates, high bacterial eradication rates as well as a shortened antifebrile time, easy administration, and no relapse or recurrence.
Table 3. Comparison of the clinical effectiveness between two randomized groups