In the United States, infections from NDM-producing carbapenem-resistant Enterobacterales have surged by 460% between 2019 and 2023, according to new federal data, turning a once-rare “nightmare bacteria” into a rapidly growing threat. That spike captures how quickly antimicrobial resistance is shifting and why experts warn of a looming superbug crisis that could wipe out millions of lives if current trends continue. I focus here on what has changed, what the best evidence says about the burden and economic risk, and where policy and innovation still fall short, without relying on hype.
The Current Scale of the Superbug Threat
The definitive U.S. baseline comes from the CDC, which estimates more than 2.8 million antimicrobial-resistant infections and more than 35,000 deaths every year in the United States. That same analysis classifies resistant organisms into urgent, serious, concerning, and watch list categories, treating carbapenem-resistant Enterobacterales as one of the most worrisome threats because they are hard to treat and spread in healthcare settings. The CDC also notes that the burden rises further when related threats linked to antibiotic use, such as Clostridioides difficile, are included.
Globally, the scale is even starker. A Landmark GRAM study in the Lancet estimates about 4.95 m deaths associated with bacterial AMR in 2019 and about 1.27 m deaths directly attributable to bacterial AMR, with pathogens such as Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae among the leading contributors. The World Health Organization has responded by publishing a list that Defines priority pathogens for research and control, placing carbapenem-resistant Enterobacterales in a “critical” tier because of their resistance to last-line antibiotics and their ability to spread through hospitals and long-term care facilities.
Pandemic Setbacks and Recent Surges
When COVID-19 hit, progress against resistance stalled. A detailed review from the CDC documents that deaths from antimicrobial-resistant infections commonly associated with healthcare rose in 2020, at the same time that infection prevention programs were stretched and laboratory testing throughput fell. The agency explains that these operational strains likely contributed to more resistant infections in hospitals and nursing homes, even as routine surveillance activities were disrupted.
Newer data show that the problem did not simply revert once the initial pandemic wave eased. A Post-pandemic update from the CDC finds that hospital-onset infections from seven key healthcare-associated threats remained above 2019 levels in 2021 and 2022, and that reported clinical Candida auris cases rose sharply over that period. In parallel, an Official CDC newsroom release describes how NDM-producing carbapenem-resistant Enterobacterales infections surged 460% from 2019 to 2023, based on peer-reviewed methods that examined clinical and screening data, signaling a rapid expansion of a particularly dangerous form of CRE.
Independent experts say the true picture may be even more concerning because of gaps in surveillance. A Major news investigation into the CDC and Annals NDM CRE findings reports that some U.S. states lack routine testing for these organisms, and that limited screening can cause small official numbers to understate the real spread. Those interviews describe how incomplete state-level coverage and testing limitations leave public health officials uncertain about how widely NDM CRE has already moved beyond hospitals into other settings.
Why This Crisis Matters: Health and Economic Toll
On the health side, antimicrobial resistance is already killing on a scale comparable to major infectious diseases. The same Landmark GRAM work in the Lancet estimates 4.95 m deaths associated with bacterial AMR in 2019, with 1.27 m of those deaths directly attributable to resistance rather than to the underlying infections alone. The analysis also shows that resistant infections cut across age groups and clinical syndromes, affecting bloodstream infections, respiratory disease and intra-abdominal infections, which complicates routine care for conditions that used to be straightforward to treat.
The economic stakes are similarly severe. A modelling report from the World Bank titled “Drug Resistant Infections: A Threat to Our Economic Future” warns that unchecked resistance could push global GDP losses by 2050 into a range comparable to the 2008 financial crisis. That Drug Resistant Infections analysis also projects that up to about 28 million people could be pushed into extreme poverty by 2050 in its high-impact scenario, underscoring how AMR may deepen inequality by hitting low-income populations hardest through longer illnesses, higher healthcare costs and reduced productivity.
Global Policy Responses and Commitments
Governments have formally recognized the danger for nearly a decade. A Foundational Global Action Plan adopted by the World Health Assembly in 2015 Provides the five strategic objectives that still guide policy: improving awareness, strengthening surveillance and research, reducing infection incidence, optimizing antimicrobial use in human and animal health, and investing in new medicines, diagnostics and vaccines. Those objectives have shaped national action plans and underpinned efforts to expand stewardship programs and infection prevention measures in hospitals and clinics.
More recently, political leaders have tried to attach concrete targets to those broad goals. An Official record from the United Nations reports that Member States agreed to scale up action on AMR, including a commitment to reduce global deaths associated with bacterial AMR by 10% by 2030 from a 2019 baseline of 4.95 m associated deaths. A separate High-level summary of the UNGA AMR declaration explains that world leaders at UNGA framed AMR as a cross-sectoral issue touching health, agriculture and the environment, and called for catalytic funding to help countries meet those mortality and stewardship targets.
Tracking whether these promises translate into real-world change depends on surveillance. The Authoritative GLASS program from WHO Provides AMR estimates for 2023 across 93 infection type, pathogen and antibiotic combinations, drawing on more than 23 million bacteriologically confirmed cases. GLASS also follows resistance trends for 16 of those combinations from 2018 to 2023, giving policymakers a way to judge whether national action plans and global commitments are bending the curve in the right direction.
The Innovation Gap and Pipeline Challenges
Even as resistance climbs, the supply of new antibiotics remains thin. A recent Authoritative WHO review of the antibiotic pipeline Supports the concern that very few candidates target the organisms on its priority pathogen list, particularly those in the critical tier such as carbapenem-resistant Enterobacterales. That report relies on systematic assessment and evaluation of each candidate’s novelty and likely clinical value, and concludes that most products in development are variations on existing classes rather than truly new mechanisms that could outpace emerging resistance.
Forecasting work suggests that the consequences of this innovation gap could intensify over the coming decades. A Forecast-focused analysis from GRAM and IHME on AMR projects that tens of millions of deaths could occur between 2025 and 2050 if current trajectories hold and effective countermeasures are not scaled up. Those projections are based on systematic modelling of long-run trends rather than anecdotal reports of drug shortages, but they still depend on assumptions about future treatment practices, infection control and access to existing antibiotics.
Uncertainties and Paths Forward
Despite the detailed numbers, significant uncertainties remain. The Useful for reporting on NDM CRE surveillance gaps notes that some state health departments lack the resources or mandates to test widely for these organisms, which means official counts may miss early spread into smaller hospitals, outpatient clinics or long-term care facilities. The CDC itself acknowledges in its Provides threat assessment and its Supports the pandemic-era report that limitations in data collection and laboratory capacity make it hard to capture the full burden, especially outside major healthcare systems.
Long-term economic and mortality projections also carry wide uncertainty bands, as the Economic modelling from the World Bank and the Use for GRAM forecasts both acknowledge. Outcomes by 2050 will depend on choices that governments, health systems and industry make over the next decade on stewardship, infection prevention and R&D incentives. The World Health Assembly plan and the UNGA AMR commitments point repeatedly to antimicrobial stewardship, better hygiene, vaccination and investment in new tools as the most evidence-based ways to slow resistance, but they stop short of specifying exactly how much funding individual countries will allocate or how quickly they will close the gaps highlighted by GLASS.
For readers, the path forward runs through those same priorities at a national and local level. Supporting policies that strengthen surveillance, back infection prevention in hospitals and nursing homes, and fund antibiotic and diagnostic innovation aligns with what WHO and Member States have already pledged to do, while also helping to close the gap between official targets and on-the-ground practice. The 460% rise in NDM CRE since 2019 shows how fast the situation can change; whether that becomes a contained warning shot or the opening phase of a wider superbug crisis will depend on how seriously governments, health systems and the public treat those commitments now.
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*This article was researched with the help of AI, with human editors creating the final content.
