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."
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.
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."
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."