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Since the discovery of penicillin, almost every type of bacteria is becoming resistant to the antibiotic designed to treat it. According to the U.S. Centers for Disease Control and Prevention (CDC), at least 2 million people become infected with bacteria resistant to antibiotics and at least 23,000 people die each year in the U.S. as a direct result of these infections. Globally, at least 700,000 die each year from antibiotic-resistant infections.

If we fail to take the necessary precautions, they could kill some 10 million people a year by 2050. That’s one death every three seconds.

Medical professionals use the term “superbug” to refer to strains of bacteria that are resistant to several types of antibiotics. A superbug resistant to colistin – one of the last effective antibiotics for the treatment of highly resistant bacteria – was recently found in a patient in Pennsylvania with a urinary tract infection. She had not traveled outside the country in the previous five months so the superbug is unlikely to have been imported.

The emergence of a transferable gene that confers resistance to colistin antibiotic is alarming. The first transferrable gene for colistin resistance was identified in China in November 2015. Since that report, this colistin-resistant gene has been reported in Europe, Canada and the U.S.

What drives overuse?

Patient expectations help drive inappropriate prescribing; that is, patients ask for (or demand) antibiotics, even if they have illnesses that antibiotics cannot treat, like the common cold. It takes a minute to write a prescription, but it takes much longer to explain to a patient that an antibiotic is not necessary.

One study showed that despite clear evidence that antibiotics should never be prescribed for acute bronchitis, about 70 percent of bronchitis patients from 1996 to 2010 received prescriptions. Another study revealed that doctors prescribe antibiotics for sore throats, despite well-known evidence that they are generally of little help, for fear of damaging good relationships with patients (because patients expect to be prescribed antibiotics). Stiff competition between doctors for patients also drives antibiotic prescriptions, and certain doctors play a bigger role than others.

Most Americans understand that overuse of antibiotics can threaten their effectiveness, but only a minority agree that bacterial resistance is a serious problem, according to the results of a small survey reported in Open Forum Infectious Diseases. The survey also showed that around 40 percent mistakenly believe antibiotics are the best treatment for a cold.

Developing new antibiotics is essential

Reducing inappropriate and unnecessary use of antibiotics in hospitals and in agriculture will help ease the problem, but the best solution is to invest in the development of new antibiotics. Unfortunately, that’s not being done. It costs upward of $2 billion to develop one new drug. Because antibiotics have traditionally been cheap and patients don’t take them for very long, there’s no economic incentive for the drug companies to develop them.

The total market for antibiotics is relatively large – sales of about $40 billion a year – but only about $4.7 billion comes from sales of patented antibiotics. That’s about the same as yearly sales for one top-selling cancer drug. So it’s no wonder that firms are not investing in public health needs with commercial incentives.

With the dearth of novel antibiotics, scientific bottlenecks in the research and development pipeline need to be overcome. That requires identifying promising leads and collaboration between the pharmaceutical industry and the academic labs where research could be converted into new alternatives to tackle antibiotic resistance.

Encouraging the drug industry to make new antibiotics

Developers should be provided an opportunity to make a reasonable return from useful products. Interventions to make this possible would include advance market commitments and market-entry rewards.

In October 2015, the UK and China agreed to establish a global research and development fund to attract $1.5 billion for investment in research to reduce the spread of antimicrobial resistance. But, overall, there’s insufficient private and public investment in R&D focused on the problem. Harmonized regulations and clinical trial networks can also play an important role to lower R&D costs for drug developers.

Other ways to control or stop the spread of infections

•  Surveillance. Hospitals in developed countries – and some in developing ones – are heavily engaged in surveillance and active management of infection control. They have stepped up their efforts to quickly identify high-level drug resistances and respond to them so that their patients aren’t put at risk. Hospital antimicrobial stewardship programs may lower the use of drugs by almost 20 percent – nearly 40 percent in the intensive care unit – and they were tied to a slight drop in infection rates, according to a meta-analysis in Antimicrobial Agents and Chemotherapy.
•  Mapping the spread of antibiotic-resistant bacteria. The CDC is leading the effort to respond to the discovery of the colistin-resistent superbug in Pennsylvania by investigating the patient’s close contacts. The National Antimicrobial Resistance Monitoring System tracks antimicrobial resistance across bacteria discovered in food, animals, humans and meats. The U.S. Congress provided the CDC with $160 million this year to implement the National Action Plan for Combating Antibiotic-Resistant Bacteria. These labs will be able to detect resistant organisms recovered from human samples and new forms of antibiotic resistance – including mutations that allow bacteria to withstand last-resort drugs like colistin.
•  Vaccines. There is a need for innovation and investment in vaccines. Vaccines can reduce the need for antibiotic treatment and therefore lower the demand for therapeutic treatments. For example, increasing use of the pneumococcal conjugate vaccine could potentially avert 11.4 million days of antibiotic use in children age 5 years and younger – roughly a 47 percent reduction in the amount of antibiotics used to treat Strep pneumococcal cases.
•  New and better diagnostics. Rapid diagnostics could potentially reduce unnecessary and inappropriate use of antimicrobials in both humans and animals. Better diagnosis can also accelerate the recruitment of patients with multi-drug resistant infections into clinical trials and narrow the use of new antibiotics once on the market.
• CRISPR. Bacteriophages can be used to help make antibiotic-resistant bacteria more sensitive to the drugs. Teams at Rockefeller University and the Massachusetts Institute of Technology both employed the CRISPR (clustered, regularly interspaced short palindromic repeats)-Cas9 system to produce therapies that target the genes that made the bacteria resistant to antibiotics.

According to Lord Jim O’Neill, who led the Review on Antimicrobial Resistance, an urgent and massive global awareness campaign is needed to stop people from consuming antibiotics like sweets. Physicians and public health officials need to understand how patients understand risk when it comes to using antibiotics, and it’s important to educate patients about the differences between viruses and bacteria and the seriousness of bacterial resistance.

The use, overuse and misuse of antimicrobial drugs has created resistant strains of bacteria that could be a greater threat in poorer nations than in richer ones, due to the absence of monitoring and surveillance systems for drug resistance and lack of regulation. And if new antibiotics become available, they are likely to be expensive and unaffordable in the developing world.

In both rich and poor countries, resistant bacteria are costly and deadly. However, in rich countries, access to diagnostic laboratories, robust surveillance, disposable items and well-organized infection control teams slow the spread of resistant bacteria, while in poor countries some or all of these do not exist. In other words, underlying inequity further worsens antimicrobial resistance in resource-limited places.

Dr. Melvin Sanicas is the regional medical expert for Sanofi Pasteur in Asia, Japan and the Pacific region.

Photo: Microbiologist Kitty Anderson of the U.S. Centers of Disease Control and Prevention looks at a 96-well plate used for testing the ability of bacteria to grow in the presence of various antibiotics. Photo courtesy of the CDC.

Homepage photo credit: The U.S. Food and Drug Administration via Flickr.