The Silent Pandemic: Antibiotic Resistant Superbugs

Authored by: Venkat Rao

The Nevada Public Health officials recently reported a case of a women who died in Reno from an infection that could not be treated with any antibiotic available in the United States. Testing showed the superbug had spread throughout her system fending off 26 different antibiotics used to treat her.

Antimicrobial resistance (AMR) to commonly used antibiotics accounts for nearly 5 million deaths annually and is currently the leading cause of death worldwide. Just for comparison, as of today, the total number of deaths associated with COVID-19 pandemic over the past three years combined is estimated to be 6.78 million globally. It is noteworthy, that the pandemic related death statistic covers a three-year period, whereas the annual deaths due to antimicrobial resistance is nearly 5 million and according to published estimates will rise to 10 million by 2050.

According to a recent CDC report, just in 2020 alone, more than 29,400 people died due to infection from antibiotic-resistant superbug infections, nearly 40 percent of which were acquired in hospitals. Extensive use of antibiotics to manage hospital infections during the first year of COVID-19 pandemic attributed as the main reason for the more than 15% increase in antibiotic-resistant infections in the United States.

Antimicrobial resistance is a serious health security threat globally and a major public health challenge that has gradually expanded both in its complexity and magnitude with very limited countermeasures available on hand for health professionals and public health officials.

Antimicrobial resistance has steadily contributed to preventable deaths, extended length of stay at the hospital, excessive additional costs due to testing and treatments with generally poor outcomes in vast majority of cases.

In a recent study, researchers estimated the public health disease burden in 204 countries for 23 pathogens and a total of 88 drug combinations used to treat these pathogens. Using a study approach that directly addresses the differences between disease burden associated with resistance and burden attributable to resistance, they concluded a median of 1.27 million deaths in 2019 directly attributable to resistance, which is the combined total of global HIV (680,000) and malaria deaths (627,000). In other words, the number of deaths attributable to drug resistance is greater than the deaths from two major global communicable diseases, malaria and HIV, and ranks only behind tuberculosis in terms of global mortalities. Countries with poor public health infrastructure also carry a much larger share of AMR burden and mortality. For example, AMR attributable death rates in western sub-Sharan Africa was 27.3 deaths per 100,000, whereas it was 6.5 deaths per 100,000 in Australia.

By any metric, AMR is a silent global pandemic in progress and it is unclear why this serious global problem has received so little attention from the policy makers and public health agencies, except in select scientific forums and research publications. Recognizing the serious public health threat posed by the AMR, a recent report describes four antibiotic-resistant pathogens of global concern, Staphylococcus aureus, Klebsiella pneumoniae, non-typhoidal Salmonella and Mycobacterium tuberculosis, for which antibiotic-resistant strains are reported from all over the world, making them the "face" of the global AMR problem.

A broad range of antibiotics are ineffective to treat common infections in Neonatal intensive, such as Staphylococcal species which account for over 60 percent of infections, and it has become very difficult, or sometimes impossible to treat numerous outbreaks of methicillin-resistant Staphylococcal aureus (MRSA) at these facilities.

According to a new US Department of Agriculture report from the National Antimicrobial Resistance Monitoring System (NARMS), multi-drug resistant Salmonella has increased in the food-producing animals. Data analyzed over the past 6 years on chicken, swine, and cattle product samples reveal resistance to critically important antibiotics in current use such as Ciprofloxacin, Ceftriaxone and Trimethoprim-Sulfamethoxazole.

The challenge with AMR is that only a limited number of antimicrobial agents are in development, which limits the prospect for new and more effective medical countermeasures, forcing clinicians and public health officials to find alternative approaches aimed at preventing the origin and spread of drug-resistant pathogens. These include advocacy to optimize the use of currently available antimicrobial agents and instituting rigorous infection control measures at healthcare facilities, daycare centers, schools, athletic centers and hospitals, where the risks are higher for contracting drug-resistant infection. Pharmacists with education and training on drugs used to infectious diseases could play a key role in antibiotic resistance awareness and promote infection control practices.

The puzzling nature of the problem is that despite several global initiatives to contain the surge of antibiotic resistance the rate of increase in annual deaths continues to rise. Researchers believe there are unknown factors contributing to the rise of antimicrobial resistance pandemic. With only limited data available for the parts of the world where the infectious diseases burden is high it is very difficult to assess the global scope and scale of the antimicrobial resistance pandemic.

Assessing the adverse economic impact of antimicrobial resistance, the World Bank estimates that by 2050 the global Gross Domestic Product (GDP) could decline up to four percent, and the livestock sector which accounts for a large chunk of economic activity could shrink up to 11 percent driving 28 million people into extreme poverty globally. Like in most case, the developing nations of the world are likely to face the most economic damage if current trend in antimicrobial resistance goes unchecked.

According to the World Bank estimates, an additional annual investment of $9 billion globally in the One Health initiative on human and animal health could accrue benefits to the tune of $20 trillion, a more than 100 times return on investment. It is easy to understand how the World Bank views the cost-benefits in terms of return on investment, although the rea; benefits are direct measures of gains in global health, health security, and infection control. Echoing a similar concern on the growing threat of superbugs, a recent report from the Organization for Economic Cooperation and Development (OECD) concluded that superbugs constitute a $65 billion threat to the US healthcare system if current trends remain unchecked and will lead to 30,000 deaths annually linked to antimicrobial resistance. However, with investment as meager as just $2 per person per year on a comprehensive public health budget estimates are that we could avert three out of four deaths attributable to superbugs.

Where would such investment go to combat superbugs? Public health officials have embarked on comprehensive strategy that goes beyond the confines of the hospital to include promotion of hygiene and sanitation among healthcare workers, avoid over prescription of antibiotics either by delaying or entirely eliminate where alternative countermeasures exist, launch a diagnostic system to test patients rapidly for drug resistant bacterial and viral infections, and launch public health awareness campaign on the threat of superbugs and public health hygiene and behavioral measures to counter the biggest threat to modern healthcare system.

A prescient quote from Margaret Chang, former director of the World Health Organization captures the serious health security threat of antimicrobial resistance, “Some experts say we are moving back to the pre-antibiotic era. No. This will be a post-antibiotic era. In terms of new replacement antibiotics, the pipeline is virtually dry. A post-antibiotic era means, in effect, an end to modern medicine as we know it. Things as common as strep throat or a child's scratched knee could once again kill.”

If unabated, the silent pandemic of antimicrobial resistance will impose in near certain terms unbearable health and economic consequences globally far exceeding the ongoing crisis of COVID-19 pandemic.