Fight Resistance - Pharmaceutical Executive

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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


But as alarming as these figures are, there's reason to think drug resistance is much more extensive—and much faster growing—in the developing world. Overall figures are difficult or impossible to come by. But consider the following:

  • In South Asia, multidrug-resistant strains of S. typhi, the organism that causes typhoid fever, have emerged: In a 1994 study, typhoid fatality rates approached 10 percent—close to the 12.8 percent recorded pre-antibiotics. And the situation is worsening: Another study showed 56 percent of isolates in South Asia were reported to be methicillin-resistant. In Vietnam, penicillin is no longer effective in 60 to 70 percent of the population affected with Streptococcus pneumoniae—a top killer—and resistance to third-generation cephalosporins is also increasing. When it comes to treating typhoid in Vietnam, there is almost total resistance to all first- and second-line antibiotics.
  • During the Rwandan genocide, shigellosis ripped through the refugee camps in Zaire, killing 20,000 in the first month alone. Previously, cheap antibiotics were effective against the disease. Now, throughout much of Africa, Shigella bacteria have grown resistant to four first-line antibiotics—ampicillin, tetracycline, cotrimoxazole, and chloramphenicol—and resistance to ciproflaxacin is increasing.
  • Many sexually transmitted diseases in Asia have become a death sentence with the rapid rise of resistance to fluoroquinolones. In Hong Kong, for example, the rate of resistance to ciprofloxacin has grown from 18 percent of gonorrhea patients in 1997 to 73 percent in 2003. During that same time period, fluoroquinolone resistance in Africa increased from 17 percent to 38 percent.
  • In KwaZulu-Natal, South Africa, one outbreak of XDR-TB killed 74 patients within a matter of weeks, sparking fears that XDR-TB could spread rapidly—and lethally.

"There are a lot of questions about, How did that happen?" says Margaret Riley, professor of biology at the University of Massachusetts, Amherst. "The easy answer is, 'We abused and overused antibiotics.' And that, of course, is true. We have used too much per patient, too much per year, too much per country—too much in just about any measure, and we're using it in agriculture and things of the sort."

Already, 20 million people in developing countries die each year from infections and parasitic diseases, according to the World Health Organization (WHO). That number will only grow as a high rate of AMR combines with a high rate of infections in warm, unhygienic living conditions to create a medical nightmare of infections with no cure.


Total Approved Antibacterials: US
There's a name for that nightmare: the "post-antibiotic age," an idea that has been kicked around for several decades. In the developed world, the concept has galvanized physicians, who are slowly changing their indiscriminate prescribing of antimicrobial drugs, says William Schaffner, MD, Vanderbilt University's chairman of preventive medicine.

But in the developing world, the post-antibiotic age may already be here.

The Never-Ending Story: Man vs. Bacteria

Throughout much of history, humans have been at the mercy of bacteria-borne illnesses. In the Middle Ages, plague and leprosy killed millions. Penicillin, discovered in 1928 and first used successfully in patients in 1941, was startlingly effective against infection. But if the public in the 1950s hoped that the battle against bacteria was over, they were wrong.

The explanation was Darwinian survival of the fittest. Bacteria multiply quickly. Under optimal conditions, a single bacterium can produce a billion offspring in a day. And they mutate rapidly; recent research suggests bacteria undergo genetic changes a thousand times more frequently than anyone had suspected. So while penicillin could kill off many of the bacteria involved in a given infection, it often would leave behind other strains—strains resistant to penicillin—that eventually proliferated and spread through the population.

Over the years, a pattern emerged. Bacteria developed resistance to a given antibiotic. Companies developed new antibiotics that selected for new resistant phenotypes. The length of time an antibiotic could be viable depended on the drug and the extent of patients' abuse—the resistance problem was exacerbated when they took their drugs for too short a time or at too low a dose, increasing the likelihood that microbes would adapt and spread, rather than be killed. (See Intervals to Resistance chart.)

Antibiotics used to be big business. By the 1980s, the market for third- and fourth-generation cephalosporins was growing nearly 30 percent a year. But the glut of competition—and the ability to use vancomycin, the "drug of last resort," for tricky infections—ultimately made the market seem unattractive for companies, even saturated. The industry began to focus on more profitable chronic conditions.


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