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HEALTH: The hunt for new antibiotics
LONDON, 29 June 2012 (IRIN) - Almost one in every five deaths worldwide occurs as a result of infection
, but many bacterial illnesses will become incurable as the efficacy of current antibiotic drugs wanes, according to the World Health Organization (WHO
"The world is on the brink of losing these miracle cures," WHO announced in 2011. It sounded like the farewell to a generation of familiar, dependable antibiotics after more than half a century of service.
In some countries that brink has already been crossed, said Laura Piddock, director of the UK-based initiative, Antibiotic Action
, and founder of the Antimicrobial Agents Research Group at the UK’s Birmingham University.
For too long people have taken for granted that there will be antibiotics to kill the bacteria, but the bacteria have been mutating to develop defences against those very same antibiotics.
Streptococcus pneumoniae is a major cause of pneumonia, among many other serious infections. Escherichia coli, or E. coli, is a leading cause of diarrhoeal diseases. Staphylococcus aureus (S. aureus) is responsible for many ailments, from minor skin infections to pneumonia, meningitis, toxic shock syndrome and sepsis.
“Whereas resistance has been addressed for the past four decades by experts in the industrialized world, studies describing the problem and the public health situation in the developing world have lagged behind,” noted a recent book
by the Alliance for the Prudent Use of Antibiotics, at the US-based Tufts University.
As drugs take longer to cure illnesses or are no longer effective, even minor infections can become deadly, wrote a representative from the global pharmaceutical company, GlaxoSmithKline (GSK).
Poor hygiene speeds up the spread of antibiotic resistance. Taking antibiotic drugs excessively, inappropriately or in the wrong dosage gives bacteria a chance to alter their DNA and adapt to evade the effective ingredients in drugs.
In Indonesia, a local study
found that antibiotics are prescribed for nearly 80 percent of childhood respiratory and stomach illnesses - even for ones caused by viruses, which cannot be treated by antibiotics.
With increasing resistance to antibiotics, the need to find replacements is becoming more urgent. “I think governments, industry and scientists do appreciate the problem,” said Brad Spellberg of the US-based Infectious Diseases Society of America Antimicrobial Availability Task Force. “What most governments have thus far lacked is the political will to act on the problem.”
Even with political will, scientific progress is slow, partly because designing an antibiotic that effectively treats a range of bacterial illnesses can be more difficult than finding a vaccine that prevents infection by targeting one specific disease.
As a result, the research pipeline for antibiotics is “virtually dry” GSK noted. “There has been a significant reduction in antibiotic research over the past 15-20 years. Only two classes of antibiotics [oxazolidinones and cyclic lipopeptides
] have been developed and launched in the last 30 years.”
“The low-hanging fruit has been plucked - the easy-to-discover antibiotics have been discovered,” said Spellberg. “Each new generation of antibiotics becomes progressively more difficult to discover and develop, taking longer, costing more
, and being [financially] more risky than prior generations [of antibiotics].”
Antibiotics are usually used for days or weeks, unlike treatment that can last for months or years as in the case of chronic illnesses such as cancer and diabetes. When available, new antibiotics are used as little as possible, and only when patients fail to respond to existing treatments. As a result, new antibiotics offer lower returns on investment, GSK pointed out.
Regulatory hurdles for testing and approval have also hindered progress. In the last decade the Food and Drug Administration (FDA), the drug regulatory agency in the US - where most antibiotic trials take place - has changed its rules on clinical trials. “The result has been confusion… Companies are not sure how to do clinical trials to make FDA statisticians happy,” Spellberg told IRIN. “There is a substantially higher risk now of failing to get antibiotics approved by the FDA, even if phase III clinical trials are successfully completed.”
Efforts underway to boost antibiotic discoveries include the Generating Antibiotic Initiatives Now
(GAIN) Act in the US, expected to pass later in 2012, while the European Union (EU) recently launched a public-private partnership
between public research organizations and pharmaceutical companies to encourage appropriate antibiotic use, monitor bacterial resistance, and boost research.
The EU plan is expected to cost US$280.6 million, nearly 50 percent of which is being provided by the Brussels-based Innovative Medicines Initiative, with the remainder coming from collaborators’ in-kind contributions of expertise and drugs.
Pharmaceutical companies can also spur action. GSK, for example, has urged more public-private partnerships. “There needs to be a fundamentally different approach, with companies, public institutions and academia working together and sharing information to re-stimulate research.”