Antibiotic resistance: The growing threats and potential solutions

Understanding the mechanisms of antibiotic resistance

AR presents a major challenge to modern medicine, as nearly all approved antibiotics face resistance from one or more microorganisms. This resistance undermines antibiotic efficacy by enabling bacteria to evade or neutralize drug action through mechanisms generally classified as either intrinsic or acquired [Figure 1].^[24-26] While antibiotics typically target vital bacterial functions such as protein synthesis, DNA replication, and cell wall biosynthesis, bacteria have evolved diverse molecular strategies to counter them. These include target site modification, efflux pump activation, enzymatic inactivation, reduced membrane permeability, metabolic bypass, and biofilm formation.^[26-29] Understanding these mechanisms is critical for guiding antibiotic design, optimizing clinical application, and developing new drugs that can circumvent or suppress resistance.^[29-30]

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Figure 1:

Mechanism of antibiotic resistances.

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MDR in bacteria may result from chromosomal mutations or the acquisition of mobile genetic elements such as plasmids, integrons, and transposons, many of which carry multiple resistance genes.^[31-33] The enzyme β-lactamase, for example, hydrolyzes β-lactam antibiotics, rendering them ineffective. Resistance to such enzymes can be managed through the use of β-lactamase-stable drugs or inhibitors.^[28] In addition, efflux pumps actively expel antibiotics from bacterial cells and are often regulated in response to environmental triggers.^[34-36] Their contribution to resistance can be countered using efflux pump inhibitors.^[37] Alarmingly, bacteria have evolved to exploit antibiotics as nutrient sources rather than therapeutic threats.^[38,39] The emergence of resistance is thus driven by a combination of genetic adaptability and environmental pressure, making it a formidable challenge in clinical settings.^[38,40]

Factors contributing to the rise of resistance

Numerous biological and environmental factors contribute to the emergence and spread of resistance. These include spontaneous gene mutations, HGT, phenotypic adaptation, and biofilm formation.^[41] The following subsections expand on the primary molecular mechanisms involved in resistance development.

Biofilm formation

Biofilm, as illustrated in Figure 2, is a group of microorganisms attached to a surface, which can form on both inert and living surfaces. Biofilm formation is an important factor in protecting bacterial cells from antibiotic treatment.^[56] During biofilm formation, bacterial strains and species cooperate, using cell-to-cell communication, known as quorum sensing, facilitated by signaling molecules.^[54] The biofilm formation practically involves these dynamical processes, which comprise:

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Figure 2:

Steps in biofilm formation. EPS (extracellular polymeric substances) are secreted to promote attachment and maturation. Source (Saucer et al., 2022).

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1. Conditioned surface attachment by bacteria (this is an initial stage, which is reversible)

2. Irreversible attachment (the cell adheres and accumulates, forming clusters)

3. Development of early biofilm structure (micro-colonies are formed from the coordinated community)

4. Biofilm maturation at this stage, a mature three-dimensional biofilm structure is formed

5. Matrix detachment of cells to free form (at this final stage, the mature biofilm detaches into individual bacterial cells again).^[57,58]

Biofilm-associated bacteria are intrinsically more resistant to antibiotics than their planktonic counterparts due to a combination of interrelated mechanisms [Figure 3]. First, the extracellular polymeric substance matrix of the biofilm acts as a physical barrier that impedes the penetration of antibiotics, limiting their access to the bacterial cells embedded within the biofilm structure.^[59,60] In addition, biofilms create a highly heterogeneous microenvironment, characterized by gradients in nutrients and oxygen. These gradients lead to the development of metabolic variability among the bacterial population, with some cells entering a dormant or slow-growing state in which antibiotics are significantly less effective.^[59,61] Quorum sensing further contributes to this resilience by facilitating coordinated gene expression, thereby enhancing bacterial survival strategies and promoting resistance traits.^[61,62] Moreover, phenotypic diversity within the biofilm contributes to differential susceptibility, where certain subpopulations remain sensitive to antibiotics while others exhibit full resistance, further complicating eradication efforts.^[59,60]

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Figure 3:

Mechanism of antibiotic resistance in biofilm. Arrows indicate decreased antibiotic penetration through the biofilm matrix and the resulting slow diffusion. Source (Abebe, 2020).

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In addition, biofilms promote HGT due to the close proximity of cells, enabling frequent plasmid and integron exchange.^[54,55] The matrix itself, often described as a biological “superglue,” supports cell adhesion and shields the community from immune responses and environmental stressors.^[63,64] Biofilm formation also upregulates genes involved in resistance mechanisms, such as efflux pumps and antibiotic-degrading enzymes, further compounding treatment difficulties.^[65]

Importantly, cells released from mature biofilms can retain acquired resistance traits, making them potent disseminators of AMR in the environment or host.^[65] AR is further reinforced by structural modifications in cellular organelles targeted by antibiotics – such as the cell wall, ribosomes, nucleic acid polymerases, and folate synthesis pathways – which reduce drug susceptibility.^[66,67] Therefore, disrupting biofilm development at early stages is a critical target for emerging antibiofilm and antimicrobial strategies.^[68]

Agricultural use

The extensive use of antibiotics in agriculture has significantly contributed to the rise in AR, as observed in recent studies.^[47] One major factor is the application of organic manure derived from the waste and remains of humans and animals, which exposes plants to antibiotics. In agricultural practices, antibiotics are often used to promote growth and improve feed efficiency by altering gut microbiota – such as by enhancing vitamin synthesis, reducing microbial competition, and modifying rumen metabolism.^[73] However, this non-therapeutic use, particularly in livestock and poultry, contributes significantly to the selection and spread of AR bacteria within agricultural ecosystems.^[74]

The increase in anthropogenic activities, including manure from antibiotic-treated animals and the application of fertilizers, has turned the soil into a reservoir for AMR.^[75] These activities contribute to the persistence and spread of antibiotic-resistant genes and microbial contaminants in the soil through evolutionary processes and multiplication within hosts^[74] [Figure 4]. The mechanisms of AR in animals are similar to those in humans, as resistance genes can be transferred horizontally through mobile genetic elements.^[76] As a result, agriculture has become a critical platform for the development and dissemination of AR.

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Figure 4:

Antibiotic resistance in agricultural production. WWTP (wastewater treatment plant) effluent contributes to contamination of aquatic sources. Source (Iwu et al., 2020).

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Health implications

The emergence of resistance carries health implications affecting patient outcomes and healthcare practices at large. A primary consequence is the heightened morbidity and mortality linked to infections that were easily managed. Infections caused by antibiotic-resistant bacteria such as MRSA and carbapenem-resistant Enterobacteriaceae (CRE) lead to more complications, extended illnesses, and higher death rates. According to the WHO, drug-resistant infections caused approximately 4.95 million deaths in 2019, with 1.27 million of those deaths directly attributed to AMR.^[83]

Patients suffering from antibiotic-resistant infections often experience extended hospital stays, higher healthcare costs, and an increased likelihood of further medical complications.^[84-87] These infections can lead to severe conditions, such as sepsis or organ failure, requiring intensive medical care and prolonged recovery periods.^[77] In addition, the use of more potent antibiotics to treat resistant infections can have additional side effects, further complicating patient recovery, as highlighted by both the WHO and Nature.^[87]

Cancer patients are particularly vulnerable to AR. Those undergoing chemotherapy have weakened immune systems, making them more susceptible to infections. The increased frequency of infections undermines preventive treatments’ effectiveness, often necessitating stronger and more toxic medications. This not only raises the risk of side effects but also complicates cancer treatment plans, potentially affecting the overall success of therapies and increasing mortality rates.^[88]

In healthcare settings, AR complicates infection control. Hospitals and clinics encounter additional difficulties in preventing the spread of bacteria that resist treatment. This involves implementing stricter infection control measures, such as isolating patients with infections, improving cleaning and disinfection practices, and ensuring hand hygiene. The increased use of equipment (personal protective equipment) and other infection control strategies adds to the workload and cost in healthcare facilities.^[89] Persistent outbreaks of bacteria can result in transmission within healthcare environments, posing a continuous risk to patient safety. The emotional toll on patients and healthcare workers is another aspect of resistance. Patients dealing with infections that resist treatment often face heightened anxiety and stress because of uncertainty about treatment outcomes and the potential for complications.^[90] On the other hand, healthcare professionals experience the pressure of handling infections that are hard to treat, limited treatment choices, and the emotional weight of negative patient outcomes. This mental strain can impact the wellness and job satisfaction of healthcare workers, making the management of antibiotic infections even more complex.^[89,90]

Economic and public health impact of AR

AR imposes substantial burdens on both the economy and global public health. Patients with resistant infections often require longer hospital stays, more complex treatments, and higher healthcare expenditures.^[91] The WHO has reported that treating resistant infections is significantly more expensive than managing non-resistant cases, with one study estimating that AMR adds approximately $1,383– $30,093 per patient due to longer hospital stays and the need for second- or third-line treatments, underscoring the substantial economic burden.^[84,92,93]

On a macroeconomic scale, the World Economic Forum warns that AR could reduce global GDP by 1.1–3.8% by 2050, potentially resulting in trillions of dollars in losses due to decreased productivity, increased mortality, and healthcare strain.^[94] Sectors such as agriculture are also affected – resistant infections in animals reduce productivity, increase veterinary costs, and pose trade and food security risks.

Public health systems face immense pressure. Resistant infections complicate the treatment of diseases such as tuberculosis and gonorrhea, especially in vulnerable populations such as the elderly, immunocompromised individuals, and patients undergoing chemotherapy or organ transplants.^[95] These challenges are further magnified in low- and middle-income countries, where limited access to diagnostics, quality healthcare, and effective antibiotics widens health disparities.^[83]

The growing threat also undermines confidence in healthcare systems and poses challenges for modern medicine, which relies heavily on antibiotics for infection control in surgeries, cancer treatment, and intensive care. Combating AR thus requires a coordinated global response – emphasizing responsible antibiotic use, robust surveillance, investment in research and development, and equitable access to healthcare and public education.^[96]

Developing new antibiotics

The primary strategies for developing new antibiotics to combat resistance include modifying existing antibiotics, discovering new antibiotics from unique sources, and identifying new antibiotics from small-molecule libraries.

Modifying the chemical structure of existing antibiotics can help bypass resistance mechanisms. For example, omadacycline, a modified tetracycline, overcomes common resistance mechanisms such as efflux pumps and ribosomal protection.^[101] It is structurally related to older tetracyclines such as tetracycline, doxycycline, and minocycline but exhibits improved activity against resistant pathogens that have developed mechanisms limiting the efficacy of these earlier agents.^[102,103] Similarly, modifications to vancomycin have led to the creation of synthetic analogs that are effective against vancomycin-resistant bacteria.^[104-106] New antibiotics have also been developed by attaching a catechol-type siderophore to a cephalosporin core, enhancing its stability against β-lactamases. A prominent example is cefiderocol, a siderophore-cephalosporin conjugate that utilizes iron transport systems to enter Gram-negative bacteria and remains stable against most β-lactamases, including metallo-β-lactamases.^[107]

The traditional method of discovering antibiotics often involves screening natural sources such as plants, soil actinomycetes, and marine environments. For instance, catechols from plants are known to inhibit microbial enzymes, and compounds derived from marine fungi and bacteria have shown activity against resistant strains like MRSA.^[108,109] In addition, insect-derived antimicrobial peptides, like thanatin, exhibit potent activity against drug-resistant bacteria.^[110]

New antibiotics can also be discovered through screening small-molecule libraries, which contain thousands of synthetic compounds with different appendages and molecular skeletons.^[111] While the chances of a new compound becoming an approved drug are low (1 in 10,000), large libraries increase the likelihood of finding promising candidates. For example, a compound screened from a library of 167,405 molecules inhibited the growth of antibiotic-resistant Gram-positive bacteria by targeting an enzyme critical for their growth.^[78] This compound targets lipoteichoic acid synthase, a key enzyme required for the growth of Gram-positive bacteria.^[112] In addition, small-molecule libraries, which contain thousands of synthetic compounds with diverse structures, can be used to discover new antibiotics. While the chances of any given compound becoming an approved drug are low, the use of large libraries increases the possibility of finding promising new leads.^[78,112]

Alternative therapies

Aside from the use of drugs developed from natural microbiomes, small drug libraries, and modification of existing drugs, other alternative strategies to combating AR are the use of bacteriophage and probiotic therapy.

Probiotic therapy

Probiotics are microorganisms that, when administered in adequate amounts, provide health benefits to the host.^[120] The most common probiotic species include Lactobacilli and Bifidobacteria, although other genera such as E. coli, Saccharomyces cerevisiae var. boulardii, and Bacillus coagulans are also widely used.^[120] New species such as Akkermansia muciniphila, Eubacterium hallii, and Faecalibacterium prausnitzii are being investigated for their potential probiotic benefits.

Probiotic bacteria offer several health benefits by enhancing the ability to control pathogenic bacteria. These benefits include improving intestinal barrier function, reducing bacterial adherence to cells, promoting co-aggregation, and producing organic acids that inhibit pathogenic bacteria.^[121] Many probiotics also produce antimicrobial substances [Figure 5] such as short-chain fatty acids, hydrogen peroxide, nitric oxide, and bacteriocins, which help them compete with other microorganisms in the gastrointestinal tract and may inhibit pathogenic bacteria.^[122]

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Figure 5:

Effect of bacteriophage and probiotic on pathogenic bacteria.

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The WHO and Food and Agriculture Organization (FAO) recommend probiotics as a complementary strategy to reduce antibiotic use and support gut health, particularly in infection prevention and recovery. Probiotics may lower the risk of antibiotic-associated diarrhea and secondary infections, helping reduce antibiotic consumption and slow resistance development.^[123,124]

They also restore microbial balance after antibiotic use, limiting the spread of resistant bacteria. In agriculture, probiotic use is emerging as an alternative to prophylactic antibiotics, particularly in livestock, aligning with broader efforts to reduce reliance on antibiotics and combat AMR.^[125]

Mechanisms of action of metal complexes against bacteria

Metal complexes have emerged as a promising strategy in addressing AR due to their diverse and unique mechanisms of action. Unlike traditional organic antibiotics that often target a single pathway, metal-based compounds can attack bacteria through multiple modes. These include releasing active molecules inside the cell, disrupting key biological processes through ligand exchange, or producing reactive oxygen species (ROS) through photoactivation.^[133]

Research has shown that many metal complexes function similarly to catalytic drugs, either by generating toxic compounds within bacterial cells or by depleting vital cellular components.^[134,135] Their three-dimensional structures also enable them to interact with biological targets in ways that flat, organic molecules often cannot – an advantage linked to greater effectiveness in past studies.^[136] Furthermore, metal fragments are now being explored in drug discovery due to their ability to cover more diverse chemical space.^[137]

Some metal complexes can bind directly to bacterial DNA – such as cisplatin, which forms stable adducts – interfering with replication and function.^[138] Others act by mimicking essential metal ions that bacteria use, disrupting enzymes or cell signaling. Additional mechanisms include redox-active complexes that damage cells by generating ROS, and photoactivatable metal compounds used in therapies like photodynamic therapy (PDT).^[138]

While certain metal-based antibiotics have shown similar resistance patterns to traditional drugs, several studies have reported that bacteria do not readily develop resistance to metal complexes, even after repeated exposure.^[139-141] For example, antimicrobial PDT (aPDT) works by generating ROS that damages multiple cellular targets simultaneously, making it very difficult for bacteria to adapt or resist. So far, no conclusive evidence suggests that bacteria can develop resistance to Apdt.^{[120,142,143]}

Although further research is needed, the current findings suggest that metal complexes may offer a powerful alternative to conventional antibiotics, with a lower risk of resistance development. Several metal-based agents – such as silver (Ag) nanoparticles, gallium, Cu(II), ruthenium, and gold complexes – are under early investigation for their broad-spectrum activity and unique mechanisms, including DNA binding and enzyme inhibition.^[144,145] Some have shown efficacy against MDR bacteria such as P. aeruginosa, S. aureus, and E. coli, with ongoing studies aiming to improve their safety and selectivity.^[144,146]

Examples of metal complexes used in combating antibiotic-resistant bacteria

Metal-based compounds have significantly contributed to medicinal chemistry through the development of therapies targeting a range of pathogens, including antibiotic-resistant bacteria.^[133] In recent years, research into the antimicrobial properties of metal complexes has accelerated, revealing their potential as alternative or adjunct therapies in the fight against AMR.^[147] A growing body of research has demonstrated that metal ions such as Cu, Zn, Ag, cobalt (Co), and nickel (Ni) possess intrinsic antimicrobial properties. When these metals are formulated into coordination complexes, they can not only exhibit standalone antibacterial activity but also enhance the pharmacological efficacy of existing antimicrobial agents.

Silver-based complexes, notably Ag(I)-N-heterocyclic carbene complexes, have shown potent activity against resistant bacterial strains such as MRSA, P. aeruginosa, and E. coli, in addition to antifungal activity against Candida albicans.^[148-151] Similarly, Cu(II) complexes, particularly those incorporating Schiff bases and other chelating ligands, have demonstrated significant bactericidal effects. These complexes are known to act by inducing oxidative stress and disrupting bacterial membranes, with documented efficacy against E. coli, Klebsiella pneumoniae, and Bacillus subtilis strains.^[152-155]

Zn(II) and Co(III) complexes have also garnered attention due to their ability to inhibit bacterial β-lactamase enzymes – key contributors to AR in many pathogens.^[156] Furthermore, recent findings by Olagboye et al. highlight the dual antibacterial and antifungal properties of Ni(II) and manganese (II) barbitone complexes, which exhibit robust activity against both Gram-positive and Gram-negative bacterial strains.^[157] Although some metal-based compounds, such as Cu(II)-TBZH, have been primarily investigated for their antifungal potential,^[158] the broader literature increasingly supports their integration into antibacterial drug development pipelines.

Collectively, these metal-based agents offer unique, multi-targeted mechanisms of action that not only enhance antimicrobial potency but also reduce the likelihood of resistance development. As such, they represent a valuable addition to the therapeutic arsenal against MDR organisms.

Concept and importance of the One Health approach

The growing impact of zoonotic (transmitted from animals to humans) infections on human and animal health has been brought to light by recent worldwide illness occurrences.^[184] It additionally seems clear that environmental changes, such as population expansion, climate change, agricultural intensification, and human encroachment into wildlife habitats, are what cause the formation of these zoonotic diseases^[185,186] and that human and animal populations are at risk due to environmental contamination with harmful chemicals and other dangers.^[187,188] International organizations, including the WHO, the World Organization for Animal Health (OIE), and the FAO of the United Nations, have recognized One Health as a critical component of disease control and prevention strategies.^[189]

One Health strategies aimed at combating AMR primarily focus on reducing antibiotic use in food animals. While establishing a direct causal link is complex, systematic reviews and meta-analyses have shown associations between reduced antibiotic use in food animals and decreased AMR, particularly in animals, with some evidence of limited human impact. These findings highlight significant research gaps that need further exploration.^[190]

Case studies and examples of One Health initiatives

Several case studies illustrate the effectiveness of the One Health approach in tackling emerging infectious diseases, promoting global collaboration, and addressing pressing public health challenges.

One of the earliest and most significant examples is the outbreak of Severe Acute Respiratory Syndrome (SARS), which emerged in 2002 as the first major transmissible novel disease of the 21^st century. SARS underscored the urgency of a globally coordinated response to emerging health threats and revealed the potential for unidentified zoonotic pathogens to arise from wildlife at any time and place. The epidemic exposed vulnerabilities in national and international preparedness systems and highlighted the critical need for improved alert mechanisms, transparent information sharing, and rapid response capacities. It epitomized the foundational principles of the One Health approach by demonstrating that large-scale outbreaks require multidisciplinary and international cooperation.^[191]

The global response to the emergence of H5N1 avian influenza further reinforced the value of the One Health framework. Concerns about its pandemic potential led the United Nations Secretary-General to appoint a UN Systems Coordinator for Avian and Animal Influenza, facilitating collaboration between major international organizations, including the WHO, FAO, OIE, UNICEF, the World Bank, and numerous national health ministries. This coalition launched the International Ministerial Conferences on Avian and Pandemic Influenza, which played a vital role in improving global surveillance, risk communication, and pandemic preparedness efforts.^[192]

The Global Health Security Agenda (GHSA) provides another compelling example of One Health in action. Launched to strengthen global capacity to prevent, detect, and respond to infectious disease threats, the GHSA focuses on the interconnectedness of human, animal, and environmental health. It has fostered cross-sectoral collaboration and led to the development of more robust surveillance systems and response mechanisms, ultimately enhancing global public health security.^[192,193]

The 2009 H1N1 influenza pandemic again demonstrated the importance of integrated, cross-sector responses. Public health officials, veterinarians, and environmental scientists worked collaboratively to monitor the outbreak and implement effective control strategies. This One Health-oriented coordination facilitated a better understanding of the virus’s transmission patterns and enabled timely interventions, thereby limiting the pandemic’s overall impact.^[194]

At the national level, Kenya has implemented a One Health initiative to combat the growing threat of AMR. The country developed a national AMR training curriculum for healthcare workers, which has been widely adopted and implemented across 19 countries.^[195] Kenya’s National Action Plan reflects a One Health strategy, although implementation faces challenges due to decentralized healthcare and funding gaps.^[196] The country has established multiple coordination mechanisms for zoonoses, AMR, aflatoxicosis, and pesticide-related health threats but lacks an overarching coordination structure.^[197] To address this, experts recommend expanding the Zoonotic Disease Unit into a broader One Health Office. In addition, the Fleming Fund consortium in Kenya has supported AMR surveillance efforts across animal and human health sectors, including antimicrobial stewardship training and capacity building.^[198]

Together, these case studies illustrate the transformative power of the One Health approach in addressing a wide range of global health challenges. From emerging infectious diseases to the escalating problem of AMR, these examples underscore the importance of interdisciplinary collaboration, strengthened surveillance, and coordinated response strategies. The success of One Health initiatives across diverse contexts confirms its critical role in improving public health outcomes, enhancing global preparedness, and delivering sustainable solutions to complex health threats. This highlights why, despite increased efforts, the pipeline for new antibiotics from major pharmaceutical and biotechnology companies remains limited.^[177]

Nanotechnology

Nanotechnology offers transformative potential in combating AR through the development of nanoscale materials and systems with novel antimicrobial capabilities. One key application involves antimicrobial nanoparticles – such as those composed of Ag, gold, or Zn oxide – which inherently exhibit bactericidal activity. These nanoparticles can disrupt bacterial membranes, generate ROS, and interfere with essential metabolic functions. Owing to their small size, they can efficiently penetrate bacterial cells, thereby enhancing efficacy against resistant strains.^[199] Beyond intrinsic antimicrobial action, nanotechnology also enables the development of nano-carriers for antibiotic delivery. These include liposomes, dendrimers, and polymeric nanoparticles, which can encapsulate antibiotics, protect them from enzymatic degradation, and deliver them specifically to infection sites. Such targeted delivery enhances drug bioavailability, reduces off-target effects, and minimizes the likelihood of resistance development.^[200] Another critical advantage is the ability of nanomaterials to disrupt biofilms – protective matrices that render bacteria particularly resilient to antibiotics. By penetrating these biofilms and releasing antimicrobials directly at the infection site, nanoparticles can dismantle biofilm structures, thereby restoring or enhancing antibiotic effectiveness.^[201]

Combination therapies

Combination therapies represent another innovative avenue for addressing AR. These strategies involve the use of multiple therapeutic agents – either multiple antibiotics or antibiotics paired with non-antibiotic compounds – to achieve greater antimicrobial efficacy and limit resistance emergence. For instance, synergistic antibiotic combinations, which involve drugs with complementary mechanisms of action, can yield effects that exceed the sum of their individual activities. This not only improves therapeutic outcomes but also reduces the selection pressure for resistance.^[202] In addition, antibiotics can be co-administered with adjuvants – non-antibiotic compounds that enhance their effectiveness. Common examples include beta-lactamase inhibitors, which protect beta-lactam antibiotics from enzymatic degradation and thereby restore their potency against resistant organisms.^[203] A further promising approach is the integration of bacteriophages – viruses that specifically infect and kill bacteria – into treatment regimens. Phage therapy, especially when used in conjunction with antibiotics, offers the advantage of precision targeting of resistant bacterial strains and improved biofilm disruption, thereby enhancing antibiotic penetration and efficacy.^[204]

Precision medicine approaches

Precision medicine introduces a paradigm shift in infectious disease treatment by tailoring interventions to individual patients based on genetic, microbial, and pharmacological factors. One application is genomic profiling of pathogens, where advanced sequencing technologies are used to detect resistance genes. This allows clinicians to select antibiotics with the highest likelihood of success, thereby reducing reliance on broad-spectrum agents and limiting resistance selection.^[205] Another emerging strategy involves microbiome analysis. By understanding the composition and dynamics of the patient’s microbiota, clinicians can implement interventions – such as the use of probiotics or prebiotics – to preserve microbial balance and prevent colonization by resistant organisms.^[206] Finally, personalized antibiotic dosing, guided by pharmacokinetic and pharmacodynamic modeling, ensures that each patient receives the optimal drug concentration to maximize bacterial eradication while minimizing toxicity and the development of resistance. This approach is especially valuable for populations with variable drug metabolism, including children, the elderly, and patients with co-morbidities.^[207]