The World Is Not Prepared For Terrifying Superbugs

It’s more than resistant bacterial superbugs that should scare us. Only a few months after the Wellcome Trust’s dire report on growing antibiotic resistance and the looming “post-antibiotic era,” a new report stresses that it is not just bacteria we need to worry about. Viruses and parasites are showing growing resistance to antimicrobials as well, and countries are ill-equipped to deal with this.

While there is growing awareness of increasing resistance among healthcare-associated bacteria like carbapenem resistant enterobacter (CRE) and methicillin resistant Staph aureus, especially in the U.S. and Europe, this new report, “Worldwide country situation analysis: Response to antimicrobial resistance,” adds an important global perspective.

Klebsiella and wbc - by David Dorward, PhD, NIAID

Some of the report’s key findings:

Only a quarter of the 133 countries surveyed have a national plan to fight antimicrobial (all microbial infections, not just bacteria) resistance.

Monitoring for antibiotic resistance is infrequent due to many factors, including under-equipped and under-trained laboratories, poor data collection and poor communication. I saw this vividly illustrated in northern India, where we researched tuberculosis. Sputum cultures were rarely done, only after someone had failed therapy. Cultures were sent to a reference lab and seemed to inevitably come back as “contaminated specimen; unable to process,” weeks or months later. Sensitivity tests took months. The result was doctors treating TB outside of guidelines, based on their clinical experience. While well-intentioned, the physicians’ lack of microbiology data information on which to base decisions likely helped  fuel the emergence of multi-drug resistant (MDR) and extremely drug resistant (XDR) TB in the region.

Without adequate lab identification and sensitivity testing, surveillance, and communication, emerging patterns of resistance are missed, and unnecessarily broad spectrum antibiotics are often needlessly used.

Many antibiotics and other antimicrobials are readily available over-the-counter. Patients are unaware that antibiotics don’t treat viral infections, again consuming antibiotics unnecessarily. Treatment guidelines are often lacking. Again, the OTC sales are poorly tracked.

An additional problem, particularly in developing countries, is that access to high-quality medications may be limited, leading to drugs without enough active ingredient and subtherapeutic dosing. Counterfeit drugs are a significant problem, particularly with antimalarials.

Many basic resources are very limited in many countries, contributing to nosocomial (healthcare-acquired) infections. Soap and clean water are often lacking, let alone hand sanitizers, gowns, and gloves.

Resistant organisms are then readily spread by global trade, travel and tourism, as illustrated by the emergence of NDM-1 bacteria in the U.S. and Europe in patients who acquired the highly resistant strain of carbapenem-resistant Enterobacteriaceae in India.

As I noted in recent posts, a major contributor to drug resistance in the environment is pharma manufacturers dumping antibiotics into wastewater. Agricultural farms pose another huge problem, with 80% of antibiotics sold in the U.S. going to livestock. The global use in livestock is projected to increase by as much as 67% over the next 15 years. Antibiotic-resistant bacteria are being spread from cattle yards through dust laden with excrement and are widely dispersed by drought and wind. Finally, there were reports in recent news that herbicides like Monsanto’s dicamba (Kamba) and glyphosate (Roundup), and 2,4-dichlorophenoxyacetic acid (2,4-D), can cause resistance in some bacteria.

Why care?

Infections from drug resistant organisms have a much higher death rate, varying with the type of organism. Antibiotic resistant bacteria cause at least 23,000 deaths and more than 2 million illnesses ⁠in the U.S. annually, according to the CDC. Because patients often receive ineffective antibiotics, they might stay infectious for a long time, exposing many other people and fueling the spread.

For example, there were 480,000 new cases of MDR-TB globally in 2013, and XDR-TB has spread to at least 100 countries. WHO estimates that 3.5% of new TB cases and 20.5% of previously treated TB cases are MDR-TB, but there are wide differences in rates, with Russia leading with >18% drug-resistant TB.

Drug resistant TB in new cases - courtesy WHO

Artemesin-resistant malaria is a growing threat in Southeast Asia, having been detected throughout the area, and now encroaching on India. With no other effective therapies and no new drugs on the horizon, deaths from malaria will be rising.

Gonorrhea (GC) infects 541 young women per 100,000 in the U.S. and slightly fewer men. Gonorrhea has become highly resistant to each of the antibiotics previously used to treat it: sulfonilamides, penicillin, tetracycline, and fluoroquinolones, such as ciprofloxacin. By 2006, 13.8% of isolates exhibited resistance to ciprofloxacin, so recommendations changed. An oral cephalosporin, cefixime, was recommended, but now there is too much resistance to that antibiotic as well. Currently, CDC’s STD treatment guidelines recommend dual therapy with ceftriaxone (an injectable cephalosporin) and either azithromycin or doxycycline to treat all uncomplicated GC. An additional change in technology makes detecting resistant GC more complicated. Previously, GC was grown on routine culture plates, and sensitivity testing was done routinely.

Now testing is commonly done with a nucleic acid amplification test (NAAT), which detects genetic material of the organism without a culture. It is a faster test, but antibiotic sensitivities can’t be done—a serious downside in monitoring for resistance.

Per WHO, “in 2013, 12.9 million people living with HIV were receiving antiretroviral therapy globally, of which 11.7 million were in low- and middle-income countries.” Levels of HIV drug resistance were ~5% in 2010. Since then, resistance to anti-retroviral drugs has increased up to 22% in some areas.

The more common influenza virus has developed resistance to amantidine, making it useless, and prompting the recommendation to use oseltamivir (Tamiflu) or zanamivir (Relenza) instead. (Cynics would suggest that lobbying also played a role). In 2013-14, a 2% resistance to oseltamivir was found; this will undoubtedly grow.

The WHO report highlights the growing emergence of resistance to a variety of microorganisms, including viruses, parasites, and fungi in addition to the bacteria we more often worry about. There is an urgent need for better and more rapid diagnostics, particularly for TB, and for more widespread sensitivity testing and global surveillance. Most countries are ill-equipped to do this, fueling the spread of resistant organisms. All this is occurring at a time when pharmaceutical companies are withdrawing from antimicrobial drug development because it is not as profitable for them as drugs for chronic diseases.

As I noted last week in discussing antibiotic shortages, “We cannot rely on a profit-based model to fix this. It appears that alleviating shortages will require government intervention. What might make the most sense is the creation of a public health agency responsible for the development and production of products that are of public health importance but may not be financially viable from a profit driven standpoint. With growing emergence of resistant organisms, antibiotic drug shortages will become a more threatening problem.” This week’s report from WHO reiterates the need for a different model.

Source: Forbes Health