Infectious Disease and the Development of new antibiotics

Infectious diseases are now the second major cause of death worldwide and the third leading cause of death in developed countries. The global market for antibiotic sales is set to rise
to $ 40.3 billion by 2015.

This will be propelled by intensive research in new areas of treatment and the emergence of new drug classes. The oversubscription of antibiotics, particularly in hospitals since the 1960s has caused a steep rise in the rates of bacterial resistance. This means that existing antibiotics are no longer effective in all cases and treatment options for certain micro-organisms have become scarce, particularly with the Gram negatives. Currently, the majority of anti-infective substances developed by industry lack innovation, underlining the need for new innovative approaches.
Methicillin-resistant Staphylococcus aureas (MRSA) affects more than 94,000 people and kills nearly 19,000 in the US every year. In the EU about 25,000 patients die every year from infections from multi-drug resisting bacteria. Such infections result in health-care costs and lost productivity totalling at least £1.5 billion per year.

Sealife’s initial target market for its compounds aims:

• To address upcoming Linezolid resistance in 2020 with its treatment for systemic application of SSSI,
  Endocarditis, Healthcare-Associated Pneumonia MRSA induced sepsis.
• To address Mupirocin resistance in MRSA for the development of innovative topical wound disinfection
  and nasal decontamination products.
• To address the need to discover and develop new antibiotics targeting Gram negative infections
  particularly against Pseudomonas aerugenosa, Klebsiella & Acinetobacter sp.

A recent study by the National Nosocomial Infections Surveillance (NNIS) System (part of the Centres for Disease Control (CDC) in the USA) showed that 63% of all Staphylococcus infections were resistant to treatment, representing an 11% increase over the previous five years.
More disturbing is the thought that within a few years, all clinical isolates of Staphylococcus aureus infections will be classed as community – associated methicillin resistant.
The ability of bacteria to readily evade any form of established therapy remains a constant in antimicrobial treatment and pathogens that are resistant to one or more antibiotics are emerging and spreading worldwide.
There is no doubt that the treatment for these and other emerging infections must be the development and use of novel antibiotic therapies.

Yet it would seem that prospects for replacing current antimicrobial drugs are poor. According to a report Bad Bugs, No Drugs: No ESKAPE! published in January, 2009, by the Infectious Diseases Society of America (IDSA), only a single new antibacterial – doripenem – has been approved in the USA since 2006. All other antibiotics coming to the market are usually re-engineered me too drugs e.g. 5th generation cephalosporins that do not solve the issues of cross resistance.
A recent EU report was similarly bleak – just 15 antibacterial drugs that offer a potential benefit over existing drugs are in development, and only five have reached phase 3 clinical trials.
Furthermore pharmaceutical companies may not perceive the development of antimicrobial drugs to be attractive – owing perhaps to a clinical need restricted to short courses of therapy, and the likelihood that the drugs’ useful lives will be truncated by resistance.

On Nov 20, 2009, the Infectious Diseases Society of America challenged the USA and EU to develop ten new licensed antibiotics within the next 10 years (by 2020) dubbed the 10 x ’20 Initiative. This call followed a summit held on Nov 2009 in Washington, DC, at which US President Barack Obama and Swedish Prime Minister Fredrik Reinfeldt, representing the EU, established a transatlantic task force to encourage research and development of new antimicrobial drugs.
Though this target seems unrealistic, it could create much needed momentum in antimicrobial development.
A global strategy is badly needed to enact the 10 x ’20 Initiative and create a stable research infrastructure for anti microbial development, for example in determining how much money will be available, who will provide it, and how academic and company researchers will work together to surmount obstacles in drug development.
Although a number of new anti-Gram positive antibacterial agents are likely to be introduced soon for clinical use, they will not represent a quantum leap in the ability to effectively treat these human pathogens. Antibacterials are the only class of therapeutic in which drugs of last-resort have become first-line therapy.

New classes of antimicrobials with novel mechanisms of action and new approaches to increasing the effectiveness of traditional antimicrobials are urgently needed.

Our research has shown that the unique qualities of marine derived chemical scaffolds to provide Sealife with a strong platform for the development of new first in class small molecule medical breakthrough drugs of the future.