Ketek (telithromycin) is more active than several commonly used antibiotics against resistant community-acquired lower respiratory tract infections, according to Protekt US (Prospective Resistant Organism Tracking and Epidemiology of the Ketolide Telithromycin) studies presented at the 98th Annual American Thoracic Society (ATS) International Conference.

The data show that Ketek remained active against Streptococcus pneumoniae isolates- the bacteria strain most associated with respiratory tract infections - that were resistant to penicillin and newer macrolide antibiotics. Bacterial resistance is an increasing problem in the United States; over the last two decades S. pneumoniae isolates with resistance to ß-lactam antibiotics - such as penicillins and cephalosporins - and macrolides have spread rapidly across the United States.

"This study data shows that Ketek may be a valuable treatment for community-acquired lower respiratory infections," said Charles Stratton, MD, Vanderbilt University School of Medicine and lead Protekt US investigator. "This is particularly important given the rise in resistance to commonly used antibiotics."

The Protekt US surveillance study was conducted using isolates of S. pneumoniae and H. influenzae collected from 207 medical centers across the United States during the 2000-2001 respiratory season. A total of 4,709 isolates of S. pneumoniae and 1,895 isolates of H. influenzae were studied.

The study results conclude that Ketek is the most active agent against S. pneumoniae, inhibiting 99.7% of S. pneumoniae isolates by = 1 mg/L. By comparison, gatifloxacin, penicillin, erythromycin, clarithromycin and azithromycin were susceptible at 98.6%, 48.5%, 70.0%, 70.2% and 69.8% of S. pneumoniae isolates respectively. S. pneumoniae, while resistant to penicillins, macrolides, and fluorquinolones, remained highly susceptible to Ketek.

In the study, Ketek was found to be four times more active than erythromycin or clarithromycin, eight times more active than penicillin, amoxicillin/clavulanate, cefuroxime or azithromycin, 16 times more active than gatifloxacin, tetracycline and co-trimoxazole, and 64 times more active than levofloxacin and linezolid based on the MIC values.

Study results also demonstrated that of the 1,895 H. influenzae isolates studied, 26.4% were b-lactamase-producers - a major bacterial defense mechanism against antibiotics. Ketek activity, however, was unaffected by the production of b-lactamase.

To date, telithromycin has been examined in nine randomized, double-blind, comparator-controlled clinical trials. The most common adverse events reported included diarrhea, nausea, dizziness and vomiting. The majority of adverse events were mild to moderate in intensity.

In June 2001, Aventis Pharmaceuticals received an approvable letter from the U.S. FDA for the use of telithromycin for the following indications: community-acquired pneumonia (CAP), acute bacterial exacerbations of chronic bronchitis (AECB) and acute bacterial sinusitis (ABS). The FDA said the drug was not approvable for the treatment of tonsillitis/pharyngitis.

Protekt US is one of the largest surveillance studies in the United States, evaluating in its first year more than 17,000 pathogens in more than 206 sites across 44 states. The study was initiated in 2000 and was designed to monitor the spread of resistant phenotypes and genotypes of the major RTI pathogens across the nation. It is an ongoing study that is a branch of a larger international study called Protekt, which altogether includes more than 500 centers in 35 countries worldwide.

TABLE

Advair Diskus 250/50

FP 250

Advair Diskus 250/50

FP 250

One hour post-dose

One hour post-dose

8.5 hours post-dose

8.5 hours post-dose

Day One

-11.4 +/- 1.5 %*

-20.0 +/- 1.7%

-14.6% +/- 1.5%*

-19.7% +/- 1.7%

Week Four

-10.9 +/- 1.5%*

-18.4 +/- 1.8%

-12.4% +/- 1.5%*

-18.7 +/- 1.7%

In addition, Advair Diskus 250/50 also provided significantly greater improvements in morning peak expiratory flow over one to four weeks compared with FP 250 (19.2 L/min vs. 6.3 L/min; p=.027) and in the percent of rescue-free days (15.8 percent vs. 7.6 percent; p=.024).

Advair Diskus is indicated for the long-term, twice-daily, maintenance treatment of asthma in patients 12 years of age and older. It is not indicated for the relief of acute bronchospasm. Advair Diskus does not replace fast-acting inhalers for the treatment of sudden symptoms and should not be taken more than twice a day. People switching from an oral steroid like prednisone to Advair Diskus, which contains an inhaled steroid, need to be especially careful. While adjusting to the switch, a person may not be as able to heal after surgery, infection, or serious injury. Advair should be used with caution in patients with cardiovascular disorders. Some patients may experience an increase in blood pressure or heart rate or change in heart rhythm.

Advair is not indicated for the prevention of exercise-induced bronchospasm. Patients who are receiving Advair twice daily should not use salmeterol for prevention of exercise-induced bronchospasm, or for any other reason. Patients should see their doctor if their asthma does not improve.

Advair Diskus was developed and marketed by GlaxoSmithKline, one of the world's leading research-based pharmaceutical and health care companies.