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HOLDING BACK THE SUPERBUGS

Olivia Rose-Innes
Prof Andrew Whitelaw

Researchers grapple with resistance against antibiotics

While Covid-19 grabbed the spotlight in 2020, another, perhaps even more alarming, public health threat waits in the wings: antimicrobial resistance. At Stellenbosch University (SU), scientists from multiple disciplines are grappling the “superbugs”.
 
Antimicrobial resistance (AMR), when pathogenic microorganisms evolve to render medications ineffective, is a growing menace. One United Nations estimate links it to 700 000 global deaths annually – potentially 10 million by 2050.
 
The worst-case scenario: no effective antibiotic drugs left in the doctor's arsenal, and a world defenceless against “superbug” bacteria and other pathogens.
 
A looming post-antibiotic era
 
Do we face a return to the pre-1920s, with no effective drugs to fight infectious diseases?
 
We may be heading in that direction. “Certainly we’re seeing patients develop infections with organisms resistant to every available antimicrobic. We have to try a combination of drugs and hope the immune system rallies,” says Prof Andrew Whitelaw, Head of the Division of Medical Microbiology at SU’s Faculty of Medicine and Health Sciences.
 
While the threat is grave, the post-antibiotic era has not arrived, he explains: “Some individual patients are entering their own little post-antibiotic era, but we’re not there yet at a societal level. The concern is that it will come.”
 
Resistant strains aren’t necessarily more dangerous, Whitelaw points out, but they make choosing the right drug increasingly difficult. “When you don’t know the organism causing an infection, you make a best ‘guess’ with your knowledge of what’s prevalent, and what’s in your pharmacy. The more drugs the organism is resistant to, the more
difficult it is deciding on the right drug while waiting for lab results. The longer you delay, especially with severe infections, the worse the outcome.”
 
South Africans are still fortunate to have access to a range of broader spectrum antibiotics. But more poorly resourced African countries are showing marked increases in mortality from resistant bacterial infections, Whitelaw warns.
 
AMR’s knock-on effects
 
Antibiotics are critical not only for patients with acute infection – AMR has knock-on effects for other medical endeavours. Surgical procedures such as hip replacements and heart surgery, for example, depend on effective antibiotics, and AMR means more life-threatening post-operative complications and infections.
 
Oncologists are also increasingly concerned about AMR. Patients on chemotherapy have compromised immunity, and antibiotics are essential for managing otherwise fatal infections. The more resistant organisms there are, the higher this risk becomes.
 
Dearth of new antimicrobials
 
The AMR crisis is compounded by the fact that fewer new antimicrobial agents are being developed – primarily for economic reasons.
 
“The economic model of antimicrobials differs from that of drugs for chronic lifestyle diseases. You could take the same antidiabetic or anti-hypertensive for life,” Whitelaw explains. “Whereas, you might take an antibiotic for a few days. You don’t want to take it longer than necessary to avoid resistance developing, but using less means less
revenue for the manufacturers.”
 
While there are still some companies pursuing antibiotic research and development, this primarily involves repurposing or “tweaking” the structure of existing compounds rather than developing completely novel ones.
 
More encouragingly, the South African Medical Research Council and certain overseas funders have recently made research grant calls for identifying new molecules with antimicrobial activity.
 
SU’s antimicrobial stewardship
 
Antimicrobial stewardship aims to promote responsible antimicrobial use, particularly avoiding antibiotic misuse and overuse.
 
SU’s involvement in this global initiative is a collaborative effort by the disciplines of medical microbiology, immunology, adult infectious diseases, paediatric infectious diseases and clinical pharmacology, and includes patient management, training and research.
 
Antimicrobial experts deliver a consultative service, visiting Tygerberg Hospital’s intensive care units and selected wards to advise on interpreting laboratory results and making sound antibiotic choices – for the benefit of both the patient and the hospital ecosystem as a whole.
 
“Apart from direct patient monitoring and management, the aim is training around antibiotic challenges, and disseminating stewardship principles to healthcare staff to get these in place for the future,” Whitelaw explains.
 
Students also benefit from AMR education and training. Undergraduates receive lectures and multi-disciplinary tutorials, involving clinical microbiology, pharmacology and infectious diseases. This is offered at Tygerberg Hospital, and some regional and district hospitals for students at the Rural Clinical School based in Worcester. Even
during the Covid-19 lockdown, tutorials continued via online platforms.
 
AMR research
 
Much of SU’s AMR research supports the “One Health” approach, which recognises interconnections among humans, other living organisms and their shared environment.
 
This entails “going beyond human AMR to investigate AMR in the environment and agricultural settings,” says Whitelaw. One such project is seeking resistant Gram negative bacteria (for example E. coli) in river water and effluent.
 
Researchers are also collaborating with colleagues in Germany, Egypt and Kenya. “Locally we’re hoping to investigate resistance in livestock and farm workers, and compare resistance mechanisms and species with those in healthy community members, to see the extent of overlap,” says Whitelaw. “Then investigations into transmission across sectors are planned.”
 
Other collaborative studies with the Division of Infectious Diseases, the Department of  Paediatrics and the Division of Neonatology focus on mortality associated with bloodstream infections, and interventions to reduce these in neonates.
 
SU scientists are also interested in how AMR research intersects with Covid-19: how the pandemic has affected AMR and hospital-acquired infection rates, and the spectrum of organisms and infections present. For example, antibiotic use might have risen given increased hospitalisations. However, the increased emphasis on infection control and hand hygiene compliance could have helped combat hospital-acquired infections – and the lessons learned may be useful in the coming battles with AMR.
 
The worst-case scenario: no effective antibiotic drugs left in the doctors arsenal, and a world defenceless against “superbug” bacteria and other pathogens.
 
Photo credit: Damien Schumann