Increasing reliance on last resort antibiotics reveals worrying superbug trend among LMICs – new data published in Lancet Global Health

Increasing reliance on last resort antibiotics reveals worrying superbug trend among LMICs – new data published in Lancet Global Health

• New Lancet Global Health article from the University of KwaZulu-Natal and Nesta Challenges’ Longitude Prize shows five-year increase in bacterial resistance to last resort antibiotics in South Africa 
• Procurement of some ‘reserve’ antibiotics has increased nearly 650% between 2015 and 2020
• Authors propose a new antimicrobial subscription and pooled procurement mechanism to boost access to existing and new antibiotics and diagnostics in low- and middle-income countries (LMICs).

14 December 2021 (London) – New data published this week in Lancet Global Health exposes a worrying five-year trend in South Africa that reliance on last resort antibiotics is rapidly increasing as more bacteria develop resistance to the most common ‘access’ and ‘watch’ antibiotics – the first and second line of defence against bacterial infections.

The new research is published in an article, ‘Global access to existing and future antimicrobials and diagnostics: antimicrobial subscription and pooled procurement’, co-authored by Professor Sabiha Essack, South African Research Chair in Antibiotic Resistance and One Health and Professor in Pharmaceutical Sciences at the University of KwaZulu-Natal, and Daniel Berman, Director of Global Health and Longitude Prize at Nesta Challenges.

Examining the five-year trend of drug-resistant infections and the procurement of ‘watch’ and ‘reserve’ (i.e. last resort) antibiotics in South Africa’s public health system, the study found statistically significant increases in non-susceptibility (i.e. resistance) to meropenem and tigecycline for Klebsiella pneumoniae, increasing by approximately 215% and 332% respectively, from 2015 to 2019.

In addition, statistically significant increases in procurement of ‘watch’ (carbapenems) and ‘reserve’ (linezolid) antibiotics further indicates increasing reliance on these drugs due to escalating non-susceptibility to narrower-spectrum ‘access’ antibiotics. Procured quantities of last resort ‘watch’ antibiotic meropenem increased from 55.09kg in 2015 to 411.91kg in 2020, an increase of 647.7% in only five years. It demonstrates that clinicians are increasingly reliant on reserve antibiotics as bacterial infections develop resistance to multiple antibiotics.

The South African data highlights the importance of access to new antibiotics to address the dwindling efficacy of existing broad-spectrum, watch and reserve antibiotics, particularly for Gram-negative bacteria priority pathogens.

Professor Sabiha Essack, University of KwaZulu-Natal, said:
“The corroboration of non-susceptibility data and antibiotic procurement data demonstrates clearly the pace of change at which infections are developing resistance to our first and second lines of infection defence – ‘access’ and ‘watch’ antibiotics. The significant increase in the procurement and use of reserve antibiotics reveals that the drugs we have available to us as clinicians are becoming less effective at treating infections. This is not a situation unique to South Africa, it is a global trend that requires new mechanisms to ensure uninterrupted access to efficacious antimicrobials and diagnostics to ensure their appropriate use and stewardship.”  

The research is featured in a new paper published in Lancet Global Health proposing a novel approach to create a predictable low and middle-income country (LMIC) market to ensure access to products to address growing resistance and treatment failure. It describes how antimicrobial subscription and pooled procurement (ASPP) could be implemented as a multinational or regional mechanism in which countries (or states within a country), leverage their combined purchasing power for a portfolio of newer and future antimicrobials and diagnostic products. Based on multi-year subscription contracts that are negotiated on behalf of these aggregated (i.e. pooled) procurers, ASPP could reshape the LMIC market for essential antimicrobials and diagnostics. 

Daniel Berman, Director of Global Health and the Longitude Prize, Nesta Challenges said:
“Since markets in High Income Countries provide the best chance to recoup investments, the focus of test developers is on the 20% of the global population that live in these countries. This means that the parts of the world with the most urgent need for new point-of-care diagnostic tests are being overlooked. If we want to change the situation in LMICs, we need to create viable markets for these products. Antibiotic subscription and pooled procurement would have the dual benefit of making antimicrobial diagnosis and treatment accessible in countries with the highest levels of resistance, while stimulating engagement of producers in LMIC markets.”

INCENTIVISING NEW DIAGNOSTICS TO IMPROVE STEWARDSHIP

The Longitude Prize was launched in 2014 to incentivise a new generation of rapid diagnostic tests for bacterial infections. Traditional diagnostic tests require laboratory facilities and produce results in 2-3 days. It means doctors and clinicians (especially those in low- and middle-income countries) are often forced to prescribe antibiotics based on educated guesses rather than empirical evidence. Access to diagnostic testing is crucial to steward the antibiotics that we have available, and future drugs that may come to market to ensure a future where antibiotics continue to save lives.

The Longitude Prize will award £8 million to a new rapid, affordable, accurate point-of-care diagnostic test that can identify whether a bacterial infection is present and which antibiotic to prescribe. The final deadline to submit an application to win the Longitude Prize is September 2022. Currently 55 teams of innovators are actively developing diagnostic tests to win the prize. However, the Lancet paper’s findings demonstrate the need to focus on improving the attractiveness of diagnostic markets in LMICs. 

‘Global access to existing and future antimicrobials and diagnostics: antimicrobial subscription and pooled procurement’ is published in Lancet Global Health on 13 December 2021 and is authored by Professor Sabiha Essack (South African Research Chair in Antibiotic Resistance and One Health and Professor in Pharmaceutical Sciences at the University of KwaZulu-Natal) and Daniel Berman (Director of Global Health and Longitude Prize at Nesta Challenges), with Professor Sujith Chandy (Department of Pharmacology and Clinical Pharmacology, Christian Medical College, Vollore, India), Dr Balaji Veeraraghavan (Department of Clinical Microbiology, Christian Medical College, Vollore, India) Krishnee Moodley (Antimicrobial Research Unit, University of KwaZulu-Natal, Durban, South Africa) and Oliver Cansdell.