Antibiotic resistance kills an estimated 700,000 people each year worldwide, and some experts predict that number to reach 10 million by 2050 if efforts are not made to curtail resistance or develop new antibiotics. Despite an urgent need for these drugs, the once-robust development pipeline for antibiotics now produces little more than a trickle of compounds. As of September 2016, about 40 new antibiotics were in clinical development for the US market, compared with hundreds of cancer drugs.
|Bacterium or bacterial family (and antibiotics it resists)||Typical effects|
|1||Acinetobacter baumannii (carbapenem)||Hospital infections|
|2||Pseudomonas aeruginosa (carbapenem)||Hospital infections|
|3||Enterobacteriaceae (carbapenem) ESBL-producing||Hospital infections|
|4||Enterococcus faecium (vancomycin)||Hospital infections|
|5||Staphylococcus aureus (methicillin, vancomycin)||Skin infections, pneumonia, bloodstream infections|
|6||Helicobacter pylori (clarithromycin)||Infection can lead to stomach ulcers and cancer|
|7||Campylobacter spp. (fluoroquinolone)||Diarrhoea|
|9||Neisseria gonorrhoeae (cephalosporin, fluoroquinolone)||Gonorrhea|
|10||Streptococcus pneumoniae (penicillin-non-susceptible)||Pneumonia|
|11||Haemophilus influenzae (ampicillin)||Childhood pneumonia, meningitis, bloodstream infections|
|12||Shigella spp. (fluoroquinolone)||Diarrhoea|
ESBL, extended-spectrum β-lactamase. Bacteria that produce this enzyme are resistant to certain classes of antibiotics.
Gram-negative bacteria, which take the top three spots on the WHO list, pose a particular challenge. These microbes have a double cell membrane, which makes it difficult for drugs to gain entry in high enough concentrations to kill them off. We need to work out how we can get compounds to breach that barrier, says Kim Lewis, a biochemist at Northeastern University in Boston, Massachusetts.
On the financial side, several new initiatives aim to make antibiotic development more appealing. The US 21st Century Cures Act, signed into law in December 2016, includes a streamlined approval pathway for antibiotics that treat life-threatening infections. Last year also saw the launch of CARB-X, a public–private partnership funded by the United States and the United Kingdom that aims to stimulate preclinical development of new antibiotics.
Incentives such as these might help to spark activity, but Michael Gilmore, director of Harvard Medical School’s Infectious Disease Institute in Boston, worries that any system that relies on profit-driven drug companies to develop new antibiotics is doomed to fail. “The bottom line is that the economic model doesn’t work,” Gilmore says.