The 2026 IDSA Guidance for treatment of antimicrobial resistant Gram-negative infections has been published in the last few days. Although the authors explicitly state that their Guidance focuses on clinical practice in the United States, a global survey undertaken by Abi Manesh and ADVANCE-ID Network (NUS) showed that the IDSA Guidance is the most widely used guidance document around the world. This includes low- and middle-income countries (LMICs) where the burden of antimicrobial resistant Gram-negative infections is highest. This creates huge problems - for example, the 2026 IDSA Guidance preferred options for carbapenem-resistant Acinetobacter (sulbactam-durlobactam) and for NDM-producing Enterobacterales (aztreonam-avibactam and cefiderocol) are not available in LMICs, with the exception of China. ADVANCE-ID Network (NUS) has shown that the 28-day mortality of patients with carbapenem-resistant Acinetobacter and CRE when treatment does not include these IDSA preferred antibiotics exceeds 50%. At the FDA Antimicrobial Drug Advisory Committee Meeting assessing sulbactam-durlobactam in April 2023, Committee Member Richard A. Murphy MD insightfully asked "has the sponsor thought about access to the drug in low-income countries outside of the US, Europe"? The sad reality is that while the small companies left in antibiotic development can think about access, there is ZERO possibility that they can actually afford to provide access to LMICs. Money flowing to small companies for the pre-clinical and clinical development of innovative antibiotics (thank you CARB-X, AMR Action Fund, Wellcome Trust, Novo Nordisk, Gates Foundation, BARDA and others) even if they are targeted at the AMR issues of LMICs, is not going to help these companies provide timely access of their products to LMICs. Something needs to change to allow access to the most appropriate antibiotics for AMR in LMICs. There is effort from Global Antibiotic R&D Partnership (GARDP) and the antibiotic industry in India and China (largely for their domestic purposes), but who else is going to create change to provide access to LMICs for the antibiotics currently recommended in the United States? Will anything have changed when the IDSA 2028 and 2030 Guidance is released?
Peter Beyer
1mo
Thank you, David, for spelling this out so clearly! We do hope to demonstrate that working with generic companies and other partners you can built a new business model and extent access to high burden countries
Karen Bush
1mo
An idealistic solution would be for a global foundation/organization to maintain a stockpile of first-line antibiotics for serious infections (purchased at market prices) and to make these drugs available to LMICs for a nominal charge. In today's world, this is probably untenable.
Rienk Pypstra
1mo
Indeed, the business model for AMR antibiotics fails even for drugs that made it to the FDA finish. This is not a question of inadequate science nor of lack of evidence. Rather, it is a matter of regulatory fragmentation and cost control, which prevent return on investment for R&D and commercialisation efforts. Cudos to all initiatives promoting alternative financial pull incentives, and aiming to reduce regulatory barriers (e.g. granting global access on the basis of one major regulatory authority approval)!
Sameeh M. Salama
1mo
Thank you David Paterson, for shedding light on this important and vastly neglected issue. It’s a chicken-and-egg problem: to fix access, we first need to fix the broken antibiotic market. How can a small company be expected to develop and ensure access to new antibiotics in LMICs when we struggle to bring them into and generate a sustainable return from larger markets? Antibiotic developers are asked to invest hundreds of millions of dollars, only to see appropriate stewardship limit sales. That is exactly why meaningful pull incentives are essential. Many G20 countries are still debating what level of incentive is needed to bring developers back to the field. The PASTEUR Act remains one of the most important potential pull incentives because of the meaningful financial reward it could provide. Yet, we are still waiting. No sustainable innovation, no sustainable access
I fully agree dear David. CRAB and CREs are particularly challenging in LMICs where we have ZERO access to the new drugs. Access must be addressed. Hub and spoke models might be one way to go until more drastic things happen.
An important and timely perspective. Evidence-based guidelines must be accompanied by equitable access to recommended therapies. Without improving global availability of novel antimicrobials, the gap between guideline recommendations and real world practice in LMICs will continue to widen.
Pramod Kashid
1mo
Important perspective David Paterson. 100 % agree . Global guidelines can only improve outcomes when patients can actually access the recommended treatments. Ensuring equitable access to effective antimicrobials, particularly in LMICs, must be a global priority in tackling AMR.
SustainAct-AMR
1mo
Crucial perspective, David Paterson. It highlights a painful paradox: global guidelines driving clinical expectations, but market dynamics preventing equitable access to drugs like sulbactam-durlobactam and aztreonam-avibactam in LMICs. Addressing the 50%+ mortality rate requires global push/pull incentives and licensing frameworks tailored for small biotech, not just country-by-country commercial strategy.
Barbara Brenner
1mo
Sure: They will have to include bacteriophages. Magistral preps, pharmaceutical quality, no GMP. And they‘d better speed up!
I completely agree, David. As long as we continue to treat antimicrobial resistance as a series of local or regional problems rather than as a global pandemic, we are unlikely to develop effective and equitable solutions for LMICs. Guidelines can only improve outcomes if the recommended therapies are actually accessible. Otherwise, the gap between evidence and clinical reality will continue to widen, leaving clinicians to manage some of the most resistant infections without the tools considered standard elsewhere. AMR requires the same level of global coordination, investment, and commitment that we have seen for pandemics. Without that shift in mindset, I fear that by the time the 2028 and 2030 IDSA Guidance is published, access in many LMICs will still be the exception rather than the rule.