Fight Resistance - Pharmaceutical Executive


Fight Resistance
Doomsayers predict that the post-antibiotic age is coming. But rising rates of antimicrobial resistance show that in many parts of the world, it is already here.

Pharmaceutical Executive

The decoding of the Haemophilus influenzae genome in 1995 engendered a concentrated but brief interest in bacteriology. The pharma industry saw new opportunity in target-based approaches to antibiotic discovery, and companies plunged into high-throughput screening campaigns of candidate genes. GlaxoSmithKline, for example, invested $70 million in this approach—but walked away with no leads. A literature review found that 34 other companies also came up empty-handed. Even today, nearly 15 years after the emergence of bacterial genomics, there are no promising antibiotic pipeline candidates derived from this strategy.

"The target-based approach was and has been a complete and absolute failure—there's no other way to state it," says Thomas Evans, head of infectious diseases at the Novartis Institutes for BioMedical Research. "It's clear that approach, which almost every big company took and some are still taking, makes perfect sense and should have worked—but it's not going to."

Dr. Anthony Fauci, director of NIAID, says antimicrobial resistance is a big problem, but many developing countries have more pressing concerns, and resistance is "a luxury to deal with."
With fewer Big Pharma companies investing in antibiotics, there's been fewer antimicrobial drugs. This documented decrease has brought the problem of antimicrobial resistance to a head, given that we once again face infectious diseases with no cure.

Despite the seriousness of AMR, it hasn't topped officials' agendas. "My perception is that resistance is the least of their worries," says Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases, part of the National Institutes of Health. "The developing world has so many other big challenges that resistance is a luxury to deal with. You know, they'll take any antibiotics that are available—even if they have to deal with resistance—because right now that can't be at the forefront."

The problem with that reasoning is that Africa and Asia—and other parts of the developing world that are highly prone to infectious diseases—can't afford the steep slide into resistance. AMR can deliver what amounts to a crushing blow to societies that are already disproportionately suffering. The agents most affected are inexpensive, older antimicrobials, which in many cases are all that are available or affordable. But new therapies—for example, the treatment for MDR-TB—can be a hundred times more expensive than standard therapies. And that's just for one disease. "The estimated monetary cost of antimicrobials required to treat a resistant N. gonorrheae infection is 2 to 7 times greater than a nonresistant infection," APUA's Sosa writes. "This multiple is 10 to 11 times for shigellosis in adults and as much as 11 to 90 times for resistant Streptococcus pneumoniae."

What's more, AMR is hurting current treatment efforts and helping to destroy precious infrastructure in the developing world. For example, a recent study in the Lancet reported that 70 percent of pathogens found in hospital nurseries in developing countries are resistant to the antibiotics ampicillin and gentamicin. However, those are precisely the drugs WHO recommends to treat children for this purpose.

One has to look only as far as the protocol for TB in the less-developed world to see how resistance can affect outcomes. "If a TB patient fails on antibiotics, they'll just repeat the course," says Kari Stoever, director of the Albert B. Sabin Vaccine Institute and executive secretary of the Global Network for Neglected Tropical Disease Control. "And if they don't have the drugs due to pricing, distribution, whatever the reason, then after two trials of a standard antibiotic, that patient will just be turned away."


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