The Pharmaceutical Journal Vol 264 No 7084 p284
February 19, 2000 Clinical

Encouraging results for "first new class of antibiotic for over 30 years"

A new drug which may be useful in treating hospital-acquired infections is currently awaiting approval to be marketed worldwide. Developed by Pharmacia & Upjohn, linezolid represents the first new class of antibiotic to be introduced for more than 30 years, says the company. The new class is known as the oxazolidinones which have a novel mechanism of action that involves inhibition of bacterial protein synthesis at an earlier stage than other antibacterial agents. Data from linezolid's phase III trials were presented for the first time in the UK at a press briefing on February 15 (and to the Hospital Infection Society on February 16) by Dr Mark Wilcox (consultant and senior lecturer in medical microbiology, Leeds General infirmary) and Dr Matthew Dryden (consultant microbiologist, Royal Hampshire County hospital, Winchester). The phase III trial programme was designed to compare linezolid with current therapies in the treatment of bacterial infections. These included different forms of pneumonia, skin and soft tissue infections and infections caused by antibiotic-resistant Gram-positive bacteria (methicillin-resistant staphylococcal infections and vancomycin-resistant enterococcal infections).

Hospital-acquired MRSA infection with septicaemia, from a peripheral line injection

Dr Dryden said that data from the phase III trials indicated a clinical cure rate for linezolid of around 90 per cent in fighting community-acquired pneumonia and skin and soft tissue infections. For more difficult to manage infections, such as hospital-acquired pneumonia and for infections that could be resistant to currently available antibiotics, the clinical cure rate ranged from 66-89 per cent. The results in all cases were similar to the comparator agents in the studies.
Dr Dryden added that linezolid was well tolerated and, as it was effective orally, treatment could be continued in the community.
Pharmacia & Upjohn says that results from the phase III and earlier phase II studies indicate that oxazolidinones have activity against resistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis, penicillin- and cephalosporin-resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus.
Speaking at the press briefing, Dr Wilcox described the problem of antibiotic resistance and hospital-acquired infections, which accounted for more than 5,000 deaths each year in England and Wales. "Antibiotic resistance is causing growing concern in UK hospitals and these [linezolid] data are encouraging. New drugs with novel modes of action, such as linezolid, may play an important role in tackling the problem of resistance," commented Dr Wilcox.
Last month a report published by the Public Health Laboratory Service (PHLS) and the London School of Hygiene estimated that hospital-acquired infections cost the NHS around £1bn a year in England alone. The proportion of S aureus strains reported to the PHLS that are methicillin-resistant has increased from 1.7 per cent in 1990 to 34 per cent in 1999 (British Medical Journal 2000;320:213), although MRSA is generally still sensitive to vancomycin.
An application for the licensing of linezolid in the UK was submitted to the Medicines Control Agency in November, 1999. The company hopes to have gained a licence by June, 2000.