Novel antibiotics: Regional research is (half) the solution

What you need to know

• Antibiotic resistance is increasing globally, and new drugs are needed to overcome the dangers of microbes that evade essential treatments.
• Middle-and-lower income countries are threatened by some of the most resistant bacteria.
• Local drug development may have a bonus benefit for global health outcomes.

There is a dire need for new antibiotics amid growing antimicrobial resistance (AMR), especially in low-and-middle income countries.

That's why in India, drug makers like Wockhardt are trialing new antibiotics against pathogens that show signs of AMR.

Given the rapid advancement with tailor-made therapeutics — as demonstrated most successfully with mRNA vaccines during the COVID-19 pandemic — some might expect the same quick process can be achieved by drugmakers to produce new antibiotics.

But it's not that simple. It takes more time and is more costly to develop and produce antibiotics than vaccines.

Antibiotics are very complex. Unlike vaccines, which are tailored to specific viruses, antibiotics are designed to target multiple bacteria, many of which have different ways of resisting treatment.

"With antibiotics, you're potentially targeting 8-10 pathogens, and each of these pathogens cause infections in different settings — some in hospital [Ed.: such as "superbugs"], some in the home — and each one of these pathogens has a different resistance mechanism, too," said Mahesh Patel, a chief scientific officer at Indian pharmaceutical company, Wockhardt.

Advantages of a regional approach to developing new antibiotics

Pharmaceutical companies in lower and middle-income regions are taking a localized approach — testing so-called "candidate" antibiotics locally, where there is a specific need among communities they know well.

In South Africa and Brazil, the focus is on neonatal sepsis in hospital settings, where antibiotics no longer work, or treatments for gonorrhea and other sexually transmitted infections (STIs).

In India, it's those hospital superbugs.

Sachin Bhagwat, also a chief scientific officer at Wockhardt, says the regional approach can have a positive impact on global public health.

"What's important in terms of the science is that Indian pathogens, Indian bacteria, represent one of the highest levels of resistance in the world," Sachin said.

When they profile their antibiotics against local bacterial, "the advantage is that that drug would automatically be effective against pathogens globally, because we've already tested them against one of the highest levels of resistance in India, and the levels of resistance tends to be lower in other regions," said Sachin. 

The challenges of regional antibiotic development

The process for global approval for any new medical product, whether it's an antibiotic, vaccine or drug to treat other diseases or conditions, is dominated by the US Federal Drug and Food Administration (FDA), and the European Medicines Agency (EMA).

But that poses a challenge for companies like Wockhardt, which aim to bring drugs to market in the regions they test them.

That means Wockhardt has to run two studies at the same time: one aimed at local priorities, among patients in local or regional communities, and another that prioritizes global regulations.

"We should try to make sure we prioritize those antibiotics which we really know are going to address the priority pathogens and where we're seeing the greatest burden of the disease, in terms of infections," said Seamus O'Brien, R&D Director at the Global Antibiotic Research and Development Partnership.

GARDP collaborates with regional teams, for example in South Africa and Brazil, to understand AMR and develop ways to fight it.

Each location has its own challenges.

India, for instance, has a strong manufacturing base for generic drugs. In Africa, however, O'Brien says groups conducting "discovery and exploratory research"  need more support. That includes improving local data about co-morbidities that can affect the ability of antibiotics to work.

Which pathogens pose the greatest threat in regional settings?

Among the most important AMR targets are carbapenem-resistant bacteria.

In Latin America, it appears that bacteria resistant to carbapenem antibiotics have different resistance mechanisms than similar bacteria found in Africa and Asia. Two pathogens are of particular concern: Acinetobacter baumannii and Enterobacter species.

"Those two pathogens are concerning from a Latin American perspective and there is a trend for increasing resistance,” said O'Brien.

Bacterial STIs, such as chlamydia, gonorrhea, and syphilis, are increasingly resistant to antibiotics. Some other bacteria, which are not typically known as STIs but can be transmitted sexually, such as shigella and Neisseria species, are also concerning.

Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa  cause a range of common yet potentially fatal illnesses, such as pneumonia, bloodstream infections (Sepsis), urinary tract infections, and "superbug" hospital-acquired infections.

Edited by: Matthew Ward Agius