WSJ: The next generation of antibiotics

Researchers look for new substances to mix with antibiotics

Researchers are developing new strategies to combat bacteria that existing antibiotics are unable to fight, testing new substances that could boost antibiotics' killing power and leveraging genetic sequencing to develop deadlier drugs, the Wall Street Journal's Shirley Wang reports.

When antibiotics fail

Antibiotic resistance is a growing problem across the globe. Two million people each year are infected with antibiotic-resistant bacteria, and 23,000 die as a result, according to CDC.

U.K. health chief: The antibiotic 'apocalypse' is nigh

Antibiotics naturally lose their effectiveness as bacteria builds up resistance, but antibiotic development by pharmaceutical companies slowed sharply after about 1990 because the drugs are less profitable than others in treating chronic diseases, according to Wang. "Antibiotics have a finite lifetime because resistance is inevitable…therefore, there's always a need to innovate," says Michael Fischbach, a bioengineering professor at the University of California-San Francisco (UCSF).

Targeting E. coli, MRSA, and more

Researchers from Boston University and Harvard University are developing antibiotics to target a family of bacteria living in the gut—Enterobacteriaceae—which includes E. coli. In 1998, there was one known case in which a patient became infected with antibiotic-resistant bacteria from this family; today, there are about 9,000 cases a year, including 610 related deaths.

Enterobacteriaceae are particularly hard to kill because they possess an outer cell wall that prevents many antibiotics from penetrating. Scientists have found that trace amounts of silver make the bacteria's outer walls more permeable, allowing the common antibiotic vancomycin to work against E. coli.

Meanwhile, Merck researchers are developing treatments that target an enzyme called beta-lactamase that lives in certain bacteria, such as those that cause pneumonia, and neutralizes antibiotics. Merck researchers have managed to kill about 97% of such antibiotic-resistant bacteria by adding an enzyme-inhibiting agent called MK-7655.

Synthetic Biologics is also targeting the beta-lactamase enzyme by adding a modified version of the enzyme to antibiotics, prompting the drug to break down when it reaches the bowel, where Clostridium difficile can build, but keeping the drug intact in the bloodstream. The new process would allow larger doses of antibiotics to be administered without the patient suffering typical side effects, such as gastrointestinal problems.

Another group of researchers, led by Fischbach, has found that a handful of new antibiotics prevent methicillin-resistant Staphylococcus aureus (MRSA) bacteria from making a person ill by effectively disarming the bacteria without killing it (Wang, Wall Street Journal, 12/16).

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