For the poorest countries, lack of access to antibiotics worsens resistance


With the growing threat of antimicrobial resistance (AMR) around the world, discussion has dominated the question of how overuse of antibiotics drives resistance and how it is made worse by the lack of new antibiotics to treat infections. drug resistant.

But one report today from the Access to Medicine Foundation suggests that in areas of the world that experience both the highest rates of infectious disease and the highest levels of antimicrobial resistance, limited access to antibiotics, including new products and off-patent drugs that have been around for decades is a neglected part of the problem. And there are a range of barriers that prevent many low- and middle-income countries (LMICs) from accessing these desperately needed medicines.

Yet it’s a topic that’s taken a back seat in conversations about overuse of antibiotics in humans and animals, a weak antibiotic pipeline, and a broken financial market for new antibiotics. That’s something Jayasree Iyer, PhD, CEO of the Access to Medicine Foundation, would like to see changed.

“Access is becoming so underrepresented in our discussion of drug resistance that we forget that people are dying from preventable infections even though we have an arsenal of drugs today,” Iyer told CIDRAP News. “So how do we save and protect these drugs, and how do we make sure that patients still get them when they have an infection? I think that has to come back on the radar when we talk about AMR.”

Limited access to generic and proprietary antibiotics

The report is based on research from the Access to Medicine Foundation Reference RAM 2021 report, which found that only a third of antibiotics and antifungals from 17 companies were covered by a strategy that could make these products more accessible in 102 resource-constrained countries. These strategies to make medicines not only available but also affordable include things like fair pricing agreements, technology transfers, voluntary licensing agreements, and patient assistance programs.

And this was not limited to new innovative antibiotics and antifungals, which are usually launched first in high-income countries. It also covers off-patent and generic antibiotics for common infections, such as amoxicillin, metronidazole and doxycycline.

“It was very disturbing to see how few generic drugs were actually associated with an access strategy,” said Fatema Rafiqi, PhD, research program manager for the Access to Medicine Foundation and co-author of the report. “These drugs were not entering these low- and middle-income countries, where there was a dire need.”

Although the inappropriate use of antibiotics is the main driver of AMR, lack of access to antibiotics can also promote increased resistance by allowing bacterial infections to spread unchecked and develop resistance through selection. natural. And if a patient doesn’t get the right antibiotic for a particular infection because that particular drug isn’t available or too expensive, pathogens resistant to suboptimal treatment can spread.

This is a particular problem in poor and resource-constrained countries in Africa which, according to GRAM’s landmark report, released earlier this year, are significantly affected by drug-resistant infections. This report estimated that 1.27 million deaths in 2019 were directly attributable to AMR in 2019, and that western sub-Saharan Africa had the highest rate of deaths from drug-resistant infections, at 27.3 per 100. 000 inhabitants. South Asia had the second highest death rate, with 21.5 per 100,000 directly attributable to AMR.

“Where you live can dictate which antibiotics you have access to, which can mean that the treatment you receive may not be the best indicated or available for your condition,” says the management program director Francesca Chiara, PhD, MPH, at the University of Minnesota Center for Infectious Disease Research and Policy, editor of CIDRAP News. “This fuels resistance, in turn increasing morbidity and mortality.”

The reasons for this limited access vary. Registering antibiotics and antifungals for marketing and sale in countries is resource-intensive, and companies may choose to register their products only in LRICs where they know demand is high. Antibiotic supply chains are fragile and fragmented, which can lead to shortages. And in some resource-poor countries, government officials simply lack data on the particular antibiotics needed.

“When there is no data and there is no understanding of the populations who do not have access to a particular medicine, it causes problems for pharmaceutical companies because they do not know who to supply and how,” Rafiqi said. “Governments and public health agencies are usually the ones who have to acquire and report this data, but of course in countries where there are very few resources and there is not this capacity, you will not get these informations.

Access to new patented antibiotics and antifungals that are increasingly needed to treat multi-drug resistant (MDR) infections is even more limited in LRICs. These new drugs are almost always classified, according to the World Health Organization (WHO) antibiotic classification system, as “standby” antibiotics that should only be used for multidrug-resistant infections with little or no other treatment options. These products are typically introduced in high-income countries that have a defined unmet need and antibiotic stewardship protocols in place.

Case studies shed light on access strategies

But several strategies for increasing access to antibiotics in LMICs are available to companies, the report explains.

These include enabling the local production of antibiotics, such as technology transfers, a process which involves pharmaceutical companies transferring knowledge about the manufacturing process of a certain drug to a manufacturer in a country where the drug is necessary. Another example is voluntary licensing, in which the patent holder of a drug allows a generic drug manufacturer in a country to produce the patented product at a lower cost.

“If your product is not being made available to patients around the world, then partnering with someone who has a good regional footprint and has the same quality standards as you is a very good idea, especially for patients. pharmaceuticals that are not that difficult to manufacture and can be scaled up quite easily and potentially offered at lower cost,” Iyer said.

The report also highlights several examples of pharmaceutical companies working with LMICs to improve access to their products. Among them is Sanofi, which used technology transfers to enable a local partner in Nigeria to produce the off-patent antibiotic metronidazole, which is mainly used in Nigeria for hospital-acquired and nosocomial infections and is on the Model List of Medicines WHO essentials. . This company now produces nearly half a million boxes of metronidazole per year for the Nigerian market.

Another example is provided by the Japanese pharmaceutical company Shionogi, which announced in 2021 a Partnership with the Global Partnership for Antibiotic Research and Development and the Clinton Health Initiative to increase access to cefiderocol, a new antibiotic for multidrug-resistant infections that have limited treatment options in LRICs.

Iyer suggested this is an important example, because Shionogi manufactures its drugs only in Japan and has no footprint in LMICs, and the production of cefiderocol is complex. This unique approach to improving access to new antibiotics in LMICs is therefore worth watching.

“Is that the route for any new product that comes out of the pipeline? Is that the only route? I think that’s an important thing to look at,” she said.

Other efforts to promote access

Further efforts to improve access to antibiotics and antifungals are underway. In May, Pfizer announced its “Deal for a Healthier World” initiativeunder which the company will provide access to all of its current and future patent-protected medicines on a not-for-profit basis to 45 PRITI.

This includes the combination antibiotic/beta-lactamase inhibitor ceftazidime-avibactam, which is used to treat complicated intra-abdominal infections, urinary tract infections and pneumonia.

Chiara said more efforts like these will be needed to address the access issue.

“Designing and implementing mechanisms to ensure access to all available antibiotic treatments when and where they are needed must be considered key priorities to stop the spread of resistance,” she said.


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