Autor: Nermin Sefić
While the world focuses on the threat of future viral pandemics, a slower but equally serious threat is developing in the background of the modern healthcare system — growing bacterial resistance to…
While the world focuses on the threat of future viral pandemics, a slower but equally serious threat is developing in the background of the modern healthcare system — growing bacterial resistance to antibiotics that underpin nearly every branch of modern medicine, from simple surgical procedures to cancer treatment and organ transplantation.
Antimicrobial resistance is a natural evolutionary process — bacteria surviving exposure to an antibiotic pass their resistance to subsequent generations, while susceptible bacteria die off. This process, while inevitable to some degree, is dramatically accelerated by excessive and inappropriate antibiotic use — in human medicine, where antibiotics are often prescribed for viral infections against which they have no effect, and in livestock farming, where antibiotics are used en masse not only to treat disease but also as a routine feed additive to promote animal growth.
This excessive use creates enormous evolutionary pressure that accelerates the development of resistant strains considerably faster than would naturally occur, while simultaneously the pharmaceutical industry develops fewer and fewer new antibiotics due to economic challenges specific to this drug category.
Developing new antibiotics faces a unique economic challenge that doesn't exist in the same way for other drug categories. Unlike drugs for chronic diseases used long-term, generating sustained revenue, antibiotics are typically used short-term to treat acute infections, and new, most advanced antibiotics are deliberately held back as a "last line of defense," used only when all other options fail, precisely to slow resistance development against them.
This medically sound practice of conserving the most advanced antibiotics creates a paradoxical economic incentive — pharmaceutical companies investing hundreds of millions in developing a new antibiotic face a market where that product, if successful, will be deliberately used sparingly to preserve its effectiveness, making return on investment considerably more uncertain than for drugs intended for broad, continuous use. The result is a dramatic decline in the number of new antibiotics reaching market over prior decades, despite growing clinical need for them.
Antimicrobial resistance knows no national borders — resistant bacterial strains developing in one part of the world can quickly spread globally through international travel, trade, and migration. This global interconnection means that one country's efforts to reduce its own antibiotic use, however valuable, cannot fully protect that country from importing resistant strains developed elsewhere.
Countries with less strict regulation of antibiotic use, particularly in livestock farming, and with more limited capacity for infection surveillance and control in hospital settings, represent particularly worrying hotspots for developing and spreading resistant strains, creating a global public health risk that extends beyond those individual countries' borders.
Growing antibiotic resistance threatens to undermine fundamental achievements of modern medicine in ways that often remain insufficiently recognized by the broader public. Surgical procedures considered routine today, including hip replacement, cesarean section, and many other interventions, rely on the ability to effectively treat postoperative infections with antibiotics. Chemotherapy for cancer treatment often temporarily weakens a patient's immune system, making them vulnerable to infections that could become fatal without effective antibiotics.
A world where antibiotics become significantly less effective wouldn't just be a world with more deaths from infections easily curable today, but also a world where many other medical interventions we now take for granted would become considerably riskier, potentially setting medicine back decades in terms of routine-procedure safety.
Addressing the antimicrobial resistance crisis requires a coordinated multi-level approach — more judicious use of existing antibiotics through better diagnostics distinguishing bacterial from viral infections, stricter regulation of antibiotic use in livestock, new economic models decoupling antibiotic development profitability from sales volume to correct the existing perverse incentive, and continued investment in researching new antimicrobial strategies, including alternatives to traditional antibiotics like bacteriophage therapy.
Several countries and international organizations are experimenting with "subscription" models for new antibiotics, where governments pay pharmaceutical companies a fixed fee for a new antibiotic's availability, regardless of actual sales volume, precisely to remove the economic incentive for overselling that conflicts with medically sound, conservative use.
The hospital environment presents particularly fertile ground for developing and spreading resistant bacterial strains, combining a high concentration of immunocompromised patients, intensive antibiotic use, and close physical contact facilitating bacterial transfer between patients. Hospital-acquired infections caused by strains like MRSA (methicillin-resistant Staphylococcus aureus) or carbapenem-resistant enterobacteria represent a growing challenge for hospital systems worldwide, with infection rates varying significantly depending on the quality of local infection-control protocols and hygiene practice.
While public discussion of antimicrobial resistance often focuses on antibiotic use in human medicine, agricultural use, particularly in intensive livestock farming, represents a comparable, if not greater, total burden of global antibiotic use. Routine antibiotic use in animal feed, not to treat disease but as a routine additive promoting faster animal growth, creates massive, continuous evolutionary pressure driving resistant-strain development in livestock populations, which can then transfer to humans through direct contact, meat consumption, or environmental contamination from livestock waste.
Global surveillance systems tracking the emergence and spread of new resistant strains in real time represent a key early-warning tool enabling health systems to react before a new resistant strain spreads massively.
The World Health Organization's (WHO) latest report on antibacterial agents in clinical development, released in 2024, reveals a more nuanced picture than a simple decline story. The number of antibacterial agents in clinical development rose from 80 in 2021 to 97 in 2023 — growth that at first glance looks encouraging. But WHO itself warns in the same report that despite this growth, there remains an "urgent need for new, innovative agents for serious infections," particularly against pathogens identified on WHO's 2024 bacterial priority pathogen list.
The key nuance lies in the distinction between growth in the number of pipeline compounds and the actual innovativeness of those compounds. WHO assesses innovativeness against specific criteria — absence of known cross-resistance, a new target, a new mode of action, or a new drug class. By these stricter criteria, the vast majority of compounds in the current pipeline represent modifications of existing antibiotic classes, not genuinely new approaches that could bypass existing resistance mechanisms.
The most comprehensive analysis to date of antimicrobial resistance's global impact, published in The Lancet in 2022 and updated in 2024, estimates that resistance directly caused 1.27 million deaths in 2019 — more than HIV/AIDS or malaria that year — while antibiotic resistance was associated with an additional 4.95 million deaths in total. The analysis, covering 204 countries and territories, reveals three syndromes — lower respiratory infections, bloodstream infections, and abdominal infections — together accounted for nearly 79% of all deaths attributed to antimicrobial resistance, with lower respiratory infections alone responsible for over 400,000 directly attributable deaths.
Future projections are even more concerning. A Global Research on Antimicrobial Resistance (GRAM) project study estimates that between 1990 and 2050, more than 39 million people worldwide could die from antibiotic-resistant infections, with the annual number of direct deaths projected to rise to 1.91 million by 2050 — an increase of nearly 70% compared to 2022. Interestingly, the mortality pattern by age group is changing dramatically: deaths from antimicrobial resistance among children under five fell by 50% between 1990 and 2021, while simultaneously rising by more than 80% among people over 70 — a pattern researchers attribute to a combination of improved child public health and an aging global population becoming increasingly susceptible to treatment-resistant infections.
Rising resistance of gonorrhea to ceftriaxone — the last remaining effective first-line antibiotic for that sexually transmitted infection — offers a concrete, well-documented example of how quickly the theoretical threat of antimicrobial resistance can become a real, measurable clinical problem. According to UK Health Security Agency (UKHSA) data, the number of ceftriaxone-resistant gonorrhea cases in England has risen dramatically — 17 cases were recorded between January 2024 and March 2025, more than the total 16 cases recorded across all of 2022 and 2023 combined.
Particularly concerning is the rise in so-called XDR ("extensively drug-resistant") cases — infections resistant to both ceftriaxone and second-line azithromycin treatment, leaving a patient with practically no effective treatment options. Nine XDR cases were recorded in the same 15-month period, compared to just five over the prior two years. The first ceftriaxone-resistant gonorrhea case was detected in England in 2015, and a total of 42 cases have since been reported. Most cases are linked to travel to the Asia-Pacific region, where ceftriaxone resistance is more common, while transmission within England itself so far remains limited.
Dr. Katy Sinka, an epidemiologist and head of the UKHSA's sexually transmitted infection section, warned that "gonorrhea is becoming increasingly resistant to antibiotics, which could make it untreatable in future" — the direct clinical consequence would be the return of untreated complications like pelvic inflammatory disease and infertility, conditions that had for decades been routinely curable with simple antibiotic treatment. This case precisely illustrates the dynamic WHO warns about — a bacterium gradually, systematically developing resistance to each new antibiotic class as it's introduced, leaving an increasingly narrow range of remaining effective treatment options.
Bacteriophage therapy — using viruses that specifically infect and destroy bacteria — is experiencing a significant revival as a potential alternative to traditional antibiotics, particularly for infections resistant to all existing drugs. The largest multinational study to date, published in Nature Microbiology in 2024, tracked 100 consecutive cases of personalized phage therapy across multiple centers and countries, offering the most comprehensive insight yet into this approach's actual clinical application beyond individual case studies.
A concrete example illustrating this approach's potential is the case of Lynn Cole, a patient with Sjögren's syndrome who suffered for years from recurrent blood infections resistant to all available antibiotics. In June 2020, doctors at the University of Pittsburgh turned to experimental phage therapy as a last resort — an approach requiring careful testing to select an optimal phage against her specific bacteria, with a purification process reducing endotoxins to levels acceptable under FDA standards.
Despite these encouraging individual successes, phage therapy remains faced with significant regulatory and infrastructure challenges limiting its broader application. A 2023 analysis of phage therapy's status in Germany identified critical shortcomings including a lack of clinical trials, insufficient regulation, and a shortage of phages available for clinical use — currently the therapy is applied to a limited number of patients through individual, personalized treatment attempts, not as a standardized, widely available treatment. The European Pharmacopoeia only introduced a dedicated section (5.31) on phage therapy medicinal products in 2024, signaling that regulatory infrastructure is only now beginning to catch up with scientific progress.
The urgency of resolving these regulatory obstacles becomes clearer when viewed through OECD projections, which estimate resistance to last-resort antibiotics could more than double by 2035 compared to 2005 levels — underscoring the need for alternative approaches like phage therapy precisely at the moment when the traditional antibiotic development pipeline, as described earlier in this text, remains structurally insufficient to address the scale of crisis ahead.
Antimicrobial resistance represents one of the most serious, yet least publicly recognized threats to global public health. Unlike pandemics that unfold dramatically and visibly, resistance develops gradually, through millions of individual prescribing and antibiotic-use decisions worldwide, making it a challenge requiring the same long-term, coordinated global attention as climate change, but currently receiving considerably fewer resources and less attention relative to the actual level of risk it represents.
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Autor i urednička odgovornost: Nermin Sefić. Izdavač: GNK ASG d.o.o..
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