Antibiotic resistance sets the theme of ECCMID

The threat of emerging strains of bacteria with resistance to the current arsenal of drugs was the subject of intense focus as the 14th Annual European Congress on Clinical Microbiology and Infectious Diseases (ECCMID) got underway last week, reports Wai Lang Chu.

Delegates at ECCMID, held in Prague, heard preclinical data by drug companies revealing experimental treatments and subsequent potent activity against a range of clinically prevalent bacteria.

German pharmaceutical company Bayer announced new preclinical data detailing the activity of a new antibiotic class, the aminomethylcyclines (AMCs). The lead compound, a semi synthetic antibiotic compound for intravenous use called Bay 73-7388, is being studied to target a wide range of clinically prevalent infections.

Rising bacterial resistance, especially in hospitals, is becoming more difficult to treat increasing the urgency to discover novel agents from new classes.

Bay 73-7388, developed in conjunction with Paratek Pharmaceuticals, demonstrated broad activity against a wide variety of Gram-positive, Gram-negative, atypical and anaerobic bacteria.

Marcus Pickel, head of Bayer corporate communications said: "It's too early to draw specific conclusions but the in vivo/vitro studies against a range of clinical isolates showed promise."

"Additionally, the compound showed no cross-resistance to available classes of antibiotics. Assuming trials go well, the drug could be launched some time in 2008."

In a similar vein, Basilea Pharmaceutical also presented in vitro data which demonstrated the new drug, BAL9141 (the active component of prodrug BAL5788). This drug is the first of a variation of the cephalosporin class and has activity against MRSA (methicillin-resistant Staphylococcus aureus), an organism that causes particular problems in hospital-acquired infections.

The study evaluated the in vitro activity of BAL9141 and comparators towards beta-lactamase producing Gram-negative bacteria. The drug displayed effective activity against gram-negative bacteria producing various types of beta-lactamase. In addition to its anti-MRSA activity, BAL 9141 maintained the potent activity of previous generation cephalosporins and aztreonam.

Jutta Heim, Basilea's chief scientific officer said: "This data has demonstrated that BAL5788 exhibits a low propensity to select for endogenous resistance by methicillin-resistant staphylococci."

"This is an essential feature for any new antibiotic that may be used to treat such infections."

Swiss pharmaceutical firm Arpida showed off its latest drug. Iclaprim (formerly AR-100) is a broad spectrum diaminopyrimidine antibiotic that has been shown to exert antibacterial action through the inhibition of bacterial dihydrofolate reductase - an enzyme essential for bacterial growth.

A study of iclaprim's activity against Chlamydia trachomatis and C pneumoniae was performed at the State University of New York, Brooklyn. The results of which are published in Antimicrobial Agents and Chemotherapy (2004 May;48(5):1885-6).

The in vitro activities of iclaprim, azithromycin, and levofloxacin were tested against C trachomatis and C pneumoniae, with activity that rivalled azithromycin and topped levofloxacin.

Finally, a new class of antimycobacterial compounds was presented that could provide a promising lead candidate for low cost drugs to overcome Mycobacterium tuberculosis, the organism behind the disease commonly known as TB.

The conference was an opportunity for scientists from Moscow, Russia, to present findings after they synthesised a series of analogues from the new class of compound. The compounds were found to be therapeutically active after oral application in experimental mice.

Various analogues demonstrated high in vitro activity against M tuberculosis including clinical isolates and MDR strains. In addition, synthesis of the compounds was efficient and inexpensive.

Currently 10-15 million people in the US and 2.1 billion people worldwide are infected with the tubercle bacillus. More seriously, multi drug resistant tuberculosis (MDR-TB) is a specific form of drug-resistant TB resistant to isoniazid and rifampicin, the two most powerful anti-TB drugs.

While drug-susceptible TB can be cured within six months, forms of drug-resistant TB (such as MDR-TB) require extensive chemotherapy (that is also more toxic to patients) for up to two years.