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Antibiotic Resistance
Introduction
Antibiotic resistance is the capacity of bacteria to survive and proliferate despite exposure to antibiotics that would typically inhibit their growth or eliminate them. Resistance develops through various mechanisms, including genetic mutations, production of enzymes that degrade antibiotics, efflux pumps, horizontal gene transfer, and adaptive physiological changes. Resistance is typically identified through in vitro susceptibility testing. As a component of broader antimicrobial resistance (AMR), antibiotic resistance leads to treatment failure, prolonged illness, and heightened mortality worldwide.[1][CDC. About antimicrobial resistance. 2025][ECDC. Antimicrobial resistance (AMR). 2025]
Results from a 2016 national study estimated that approximately 30% of outpatient antibiotic prescriptions were inappropriate, underscoring widespread prescribing inefficiencies.[2] As of 2022, Centers for Disease Control and Prevention (CDC) surveillance data show that nearly 28% of outpatient antibiotic prescriptions are unnecessary. Moreover, 29.5% of these prescriptions involved broad-spectrum antibiotics classified under the World Health Organization (WHO) Watch category (from Access, Watch, Reserve antibiotic guidance), which are associated with a high risk of promoting resistance.[CDC. Core Elements of Hospital Antibiotic Stewardship Programs. 2025][CDC Antibiotic Use and Stewardship in the United States, 2024 Update: Progress and Opportunities. 2024] To address these challenges, antimicrobial stewardship programs have been widely endorsed by major health organizations, including the CDC, the Infectious Diseases Society of America, and the Society for Healthcare Epidemiology of America.[3][CDC. Core Elements of Hospital Antibiotic Stewardship Programs. 2025] These programs focus on optimizing antibiotic use through evidence-based prescribing protocols, interprofessional collaboration, and systematic review and auditing of prescribing practices.
Globally, antibiotic resistance is escalating rapidly. In 2021, bacterial antimicrobial resistance was linked to an estimated 4.71 million deaths, including 1.14 million directly caused by resistant infections.[4] While AMR-related mortality has decreased among children younger than 5, adults older than 70 have had more than an 80% increase in deaths attributed to AMR during the same timeframe.[4]
There is growing concern about increasing resistance in gram-negative pathogens, a paucity of new antibiotics in development, and the risk of significant adverse effects with existing antibiotics.[5] Antibiotic consumption has also grown substantially, from 29.5 billion to 34.3 billion defined daily doses between 2016 and 2023, a 16.3% increase.[6] This trend is most pronounced in low- and middle-income countries and is closely linked to inappropriate prescribing and over-the-counter antibiotic use.
Antimicrobial resistance places a massive financial strain on global healthcare systems, costing tens of billions of United States (US) dollars each year. If current trends continue, this figure is expected to surge into the hundreds of billions annually within the next 10 years. For instance, the World Bank projects up to $159 billion in yearly impact by 2050, while the O’Neill Review foresees a cumulative global loss of approximately $100 trillion by mid-century if no action is taken.[7][8][9] The estimated cost per individual resistant infection ranges from $100 to more than $20,000, depending on the pathogen and setting, as well as broader economic losses from reduced productivity and premature deaths.[10]
In the US, hospital-onset resistant infections increased by approximately 20% between 2021 and 2022, following the COVID-19 pandemic.[CDC. Antimicrobial Resistance Facts and Stats. 2025]. Particularly concerning is the emergence of Candida auris, a multidrug-resistant fungus, and cases have increased 5-fold since 2019.[11][CDC. Antimicrobial Resistance Facts and Stats. 2025.][CDC. About antimicrobial resistance. 2025][ECDC. Antimicrobial resistance (AMR). 2025] Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE pathogens) remain major causes of hospital-acquired infections and show rising resistance trends in some regions (eg, China).[12] Each year, more than 2.8 million antibiotic-resistant infections and over 35,000 related deaths occur in the US, mirroring global trends (see Table 1).[13][CDC. Antibiotic Resistance Threats in the United States, 2019. 2019] Without effective intervention, AMR is projected to claim up to 10 million lives annually by 2050, potentially totaling 39 million deaths over the next 25 years.[14]
Global surveillance efforts are expanding in response to this threat. The WHO Global Antimicrobial Resistance Surveillance System, launched in 2015, provides standardized international data on antimicrobial resistance trends to inform policy. In 2024, the United Nations General Assembly reaffirmed worldwide commitments to stewardship, innovation, and equitable access to effective antimicrobials.[15][WHO. Global antibiotic resistance surveillance report 2025. 2025] [CDC. Antibiotic Resistance Threats in the United States, 2019. 2019]
Table 1. Annual Infection Burden by Organism in the United States (Adapted From CDC and IDSA Estimates)
|
Organism |
Estimated Infections/Year |
Estimated Deaths/Year |
|
Carbapenem-resistant Enterobacterales |
13,100 |
1100 |
|
Methicillin-resistant Staphylococcus aureus |
323,700 |
10,600 |
|
Vancomycin-resistant Enterococci |
54,500 |
5400 |
|
Drug-resistant Pseudomonas aeruginosa |
32,600 |
2700 |
|
Multidrug-resistant Acinetobacter species |
8500 |
700 |
Function
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Function
Mechanisms and Evolutionary Pathways of Resistance
Antibiotic use imposes selective pressure that drives bacteria to develop survival strategies, making resistance an escalating public health threat. The misuse and overuse of antibiotics in medicine, agriculture, and the environment greatly amplify this pressure.[16][17][18] Bacterial resistance can be either intrinsic to an organism or acquired through genetic change, often via spontaneous mutation or horizontal gene transfer.[19] Bacteria may also transiently display resistance (adaptive resistance) in response to external stimuli.
Evolutionary Categories of Resistance
- Intrinsic resistance: Some bacterial species possess inherent structural or biochemical traits that confer natural resistance to certain drugs. For example, Mycoplasma species lack a cell wall and are intrinsically resistant to β-lactam antibiotics.[20] Leuconostoc and Pediococcus species exhibit intrinsic resistance because their cell wall precursors lack the vancomycin-binding sites, rendering the antibiotic ineffective.[21]
- Acquired resistance: Bacteria initially susceptible to an antibiotic can develop resistance through chromosomal mutations or by acquiring resistance genes from other organisms. For instance, Mycobacterium tuberculosis can develop rifampin resistance through mutations in the ribonucleic acid (RNA) polymerase gene.[19][20] Other forms of acquired resistance include:
- Genetic mutation: Spontaneous mutations may alter antibiotic target sites, reduce drug binding, or decrease cell permeability. A clinically relevant example is a mutation in the dihydrofolate reductase gene that confers trimethoprim resistance in Escherichia coli and Haemophilus influenzae.[22]
- Horizontal gene transfer: Resistance genes can spread between bacteria through transformation, transduction, or conjugation. This is exemplified by the global dissemination of methicillin-resistant S aureus via acquisition of the mecA gene on the staphylococcal cassette chromosome mec, a mobile genetic element.[23][24]
- Adaptive resistance: Bacteria develop transient resistance in response to environmental pressures, such as the expression of efflux pumps or the formation of biofilms. The resistance appears to dissipate upon removal of the external stressor. For example, the temporary development of the MexXy-OprM efflux pump is implicated in Pseudomonas aeruginosa resistance.[25]
Mechanistic Basis of Resistance
- Enzymatic inactivation: Bacteria may produce enzymes (eg, β-lactamases, carbapenemases) that chemically inactivate antibiotics by hydrolyzing critical structural elements (eg, the β-lactam ring).[20][26]
- Target site modification: Alterations in antibiotic binding sites, such as mutations in penicillin-binding proteins, ribosomal 23S rRNA, or DNA gyrase, can reduce drug affinity. This mechanism underlies resistance to macrolides, fluoroquinolones, glycopeptides, and other classes of antibiotics.[20][27]
- Reduced permeability and efflux: Bacteria can restrict intracellular drug levels by decreasing outer membrane permeability (eg, loss of porin channels) or by actively pumping drugs out via efflux transporters. These strategies are common in gram-negative bacteria and confer resistance to agents such as aminoglycosides, tetracyclines, and fluoroquinolones.[19][20]
- Metabolic bypass: Some organisms evade an antibiotic’s effect by bypassing the targeted metabolic pathway. For example, bacteria resistant to sulfonamides or trimethoprim often use alternative folate synthesis pathways to circumvent inhibition.[19][27]
- Substrate production: Bacteria can increase the production of substrates that compete with antibiotics for binding sites or inhibit their action. For example, S aureus can increase p-aminobenzoic acid production to overwhelm sulfamethoxazole's binding to dihydrofolate synthetase, thereby allowing bacterial folate synthesis and replication to continue.[28][29][30]
- Biofilm formation and stress adaptation: Bacteria in biofilms embed themselves in a protective extracellular matrix that limits antibiotic penetration. Within biofilms, bacteria can enter dormant states or activate stress responses, making them less susceptible to antibiotics. This contributes to persistent, chronic infections that are difficult to eradicate.[31][32]
Multidrug-resistant (MDR) organisms often harbor multiple resistance mechanisms simultaneously, frequently on mobile genetic elements, which greatly complicates treatment. Infections with MDR bacteria are associated with higher morbidity and mortality, as well as increased healthcare burdens.[16][23] Addressing this growing threat demands a comprehensive strategy that encompasses robust antimicrobial stewardship, enhanced surveillance of resistance trends, stringent infection prevention measures, and sustained investment in the development of novel antibiotics.[27][33] As part of this effort, global funding frameworks for AMR research have been developed, including through the Global Fund, the United Kingdom's Global AMR Innovation Fund, and the Global AMR R&D Hub.[The Global Fund. Antimicrobial Resistance. 2024][The Global AMR Innovation Fund. 2025][WHO. Incentivising the development of new antibacterial treatments 2024. 2024]
Issues of Concern
The equilibrium between antibiotic development and the emergence of resistance has shifted precariously, posing a significant threat to effective treatment. The worldwide spread of organisms such as vancomycin-resistant Enterococcus, methicillin-resistant Staphylococcus aureus, and MDR gram-negative bacilli underscores the urgent need for stewardship to preserve the effectiveness of existing drugs.[24][34] Inappropriate antibiotic prescribing was driven by diagnostic uncertainty or patient demand, which further accelerates resistance. For example, giving amoxicillin for a viral illness such as infectious mononucleosis provides no benefit and can precipitate adverse reactions, including antibiotic-induced rash.[35]
Moreover, the overuse of antibiotics in agriculture continues to amplify resistance among human pathogens.[17][18] Exacerbating the issue is stagnation in antibiotic innovation, with few new classes introduced over the past 2 decades, especially against gram-negative organisms, highlighting the urgent need for renewed investment in novel antimicrobial agents.[5][36] Recognizing these gaps, the WHO has identified urgent research priorities in AMR, including the development of rapid diagnostics, optimization of antibiotic use, and a deeper understanding of resistance transmission dynamics.[37]
Clinical Significance
Antibiotic resistance has profound clinical and public health implications. Infections caused by resistant organisms often last longer, require second-line (or more toxic) therapies, prolong hospitalization, and result in higher mortality rates than infections caused by susceptible strains.[16][33][38] For example, an inhibition zone diameter of 20 mm or greater with a 1-μg oxacillin disk on Mueller-Hinton agar with 5% sheep blood is considered indicative of Streptococcus pneumoniae susceptibility to penicillin.[39] However, if the inhibition zone is greater than 20 mm, susceptibility cannot be confirmed; further testing and reconsideration of penicillin-based therapy may be required based on the minimum inhibitory concentration. Inappropriate antibiotic use also increases the risk of complications such as Clostridioides difficile colitis and hypersensitivity reactions.
Beyond individual patients, widespread resistance undermines infection control efforts and can lead to hospital outbreaks. In the community, the proliferation of MDR bacteria limits treatment options for common infections. Economically, AMR imposes high costs on healthcare systems due to prolonged care needs, increased investigations and interventions, more expensive alternative drugs, diversion of staffing and resources (including personal protective equipment), and higher intensive care unit admission rates. Antibiotic resistance also incurs broader societal costs from lost productivity and premature deaths.[10][33] These societal costs have downstream impacts, including increased out-of-pocket healthcare expenses for patients and decreased access to healthcare, which place substantial strain on taxpayer-funded healthcare systems.
In response, national regulatory bodies have increasingly tied hospital funding to demonstrated antimicrobial stewardship activities. Examples include the Centers for Medicare and Medicaid Services (US), the National Health Service (United Kingdom), and the National Safety and Quality Health Service Standards (Australia).[40][41][ACSQHC. Antimicrobial Stewardship in Australian Health Care 2018. 2018] Without coordinated global action, infections that were once easily treatable may again become life-threatening, effectively turning back the clock to the preantibiotic era.[33]
Other Issues
Antimicrobial Stewardship Strategies and Guidelines
Core strategies for optimizing antibiotic use: Antimicrobial stewardship programs play a central role in curbing resistance, enhancing patient outcomes, and preserving the efficacy of existing antibiotics. Such ASP initiatives promote evidence-based prescribing and minimize inappropriate use through a variety of coordinated interventions.[3][42][CDC. Core elements of hospital antibiotic stewardship. 2025]
Key stewardship strategies include:
- Empiric therapy with de-escalation: Initiating antibiotics empirically for suspected bacterial infection, then narrowing or discontinuing therapy once culture and sensitivity results are available.
- Preauthorization of critical agents: Requiring approval from an infectious disease or stewardship expert before dispensing certain high-risk or broad-spectrum antibiotics.
- Prospective audit and feedback: Reviewing antibiotic prescriptions in real time and providing direct feedback and education to prescribers.
- Facility-specific guidelines: Developing local treatment protocols based on institutional resistance patterns (antibiograms) to guide empiric antibiotic choices.
- Optimized dosing: Using pharmacokinetic/pharmacodynamic principles to ensure adequate drug exposure (eg, extended infusions for β-lactams) while minimizing toxicity.
- Intravenous-to-oral conversion: Transitioning from intravenous to oral (IV to PO) antibiotics as soon as clinically appropriate to reduce hospital stay length and intravenous catheter–related complications.
- Clinical decision support: Implementing electronic health record tools (order sets, alerts) to assist clinicians in choosing and reviewing antibiotic therapy.
- Interdisciplinary collaboration: Involving a team of infectious disease clinicians, pharmacists, microbiologists, nurses, and infection control professionals in stewardship activities.
These strategies have proven effective in reducing overall antibiotic use, decreasing antibiotic-related adverse events, and lowering rates of C difficile infection and infections caused by MDR organisms.[3][13][36] Nevertheless, certain knowledge gaps persist. For example, results from a 2018 Cochrane review noted the absence of any randomized trials comparing continuous versus intermittent antibiotic prophylaxis in patients with bronchiectasis, highlighting the need for more robust evidence to inform specific stewardship practices.[13] In tandem with optimizing antibiotic use, rigorous infection control measures (eg, hand hygiene, environmental decontamination, and prudent use of invasive devices) are critical to preventing the spread of resistant organisms and augmenting stewardship efforts.[SHEA. Multisociety Guidance for Sterilization and High-level Disinfection. 2025]
Guideline-based stewardship frameworks: National and international guidelines have formalized best practices for antimicrobial stewardship. The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) issued joint guidelines in 2016, updated in 2018, on implementing hospital antimicrobial stewardship programs (ASPs), emphasizing interventions such as preauthorization of broad-spectrum agents, routine audit and feedback, rapid diagnostics, IV-to-PO conversion protocols, and reassessment of reported penicillin allergies. Recent updates to these guidelines encourage the use of biomarkers (eg, procalcitonin levels) to guide antibiotic decisions in critical care settings.[3]
The CDC introduced its Core Elements for Hospital Antibiotic Stewardship Programs in 2014, with updates in 2019 and 2024. This framework outlines 7 essential components for effective programs: hospital leadership commitment, accountability (identifying stewardship leaders), pharmacy expertise, action (interventions), tracking of antibiotic prescribing and resistance, regular reporting of outcomes, and education. Adherence to these core elements is now linked to quality standards by The Joint Commission and is required for reimbursement by the Centers for Medicare & Medicaid Services.[CDC. Core Elements of Hospital Antibiotic Stewardship Programs. 2025]
In 2025, IDSA and SHEA released expanded guidance integrating antimicrobial stewardship with broader infection prevention and hospital hygiene initiatives. This systems-level approach underscores that optimizing antibiotic use should occur alongside robust infection control and environmental cleaning protocols to more effectively contain the spread of resistant organisms (see Table 2).[SHEA. Multisociety Guidance for Sterilization and High-level Disinfection. 2025][3]
Table 2. Antimicrobial Stewardship Guidelines
|
Issuing body |
Guideline |
Year (Updates) |
Key Features |
|
IDSA/SHEA |
ASP Implementation Guidelines |
2016 (2018) |
Preauthorization; prospective audit and feedback; intravenous-to-oral conversion; diagnostic stewardship; allergy assessment |
|
CDC |
Core Elements for Hospital ASPs |
2019 (2024) |
Leadership support; accountability and drug expertise; tracking and reporting; education (aligned with Centers for Medicare and Medicaid Services/Joint Commission standards) |
|
IDSA/SHEA |
Integrated Stewardship & Infection Control Framework |
2025 |
Hospital-wide integration of ASP with infection prevention and environmental decontamination practices |
Source: Adapted from CDC and IDSA stewardship guidance.[CDC. Core Elements of Hospital Antibiotic Stewardship Programs. 2025][SHEA.Multisociety Guidance for Sterilization and High-level Disinfection. 2025][3]
ASP, antibiotic stewardship programs; CDC, Centers for Disease Control; IDSA, Infectious Disease Society of America; SHEA, Society for Healthcare Epidemiology of America
Enhancing Healthcare Team Outcomes
Antibiotic resistance remains a formidable threat to modern healthcare, undermining many advances of the antibiotic era. In response, antimicrobial stewardship programs have become a cornerstone of efforts to combat resistance and improve patient outcomes. The 2024 IDSA clinical guidance provides organism-specific recommendations for managing infections due to resistant pathogens. For example, the guidelines recommend carbapenems (eg, meropenem or imipenem-cilastatin) over piperacillin-tazobactam for serious infections caused by extended-spectrum β-lactamase–producing Enterobacterales and advocate the use of rapid molecular diagnostics to expedite targeted therapy.[43][44]
Effective ASPs rely on an interprofessional team approach. Infectious disease clinicians, clinical pharmacists, microbiologists, infection control specialists, and information technology staff all collaborate to optimize antibiotic use in partnership with treating clinical teams. When well-implemented, stewardship programs result in more appropriate prescribing, lower rates of MDR organism infections and hospital-acquired infections, fewer antibiotic-related adverse events, shorter hospital stays, and reduced mortality.[43] Additionally, ASPs foster improved communication and shared decision-making among healthcare professionals and promote ongoing education in antimicrobial prescribing. Importantly, reducing unnecessary antibiotic exposure through stewardship is vital given the stagnation in new antibiotic development.[36]
Collaboration with public health units and reference laboratories can yield further advances in the monitoring and surveillance of AMR trends within populations, including imported cases of MDR organisms across state and international borders. In summary, antimicrobial stewardship is critical to preserving the effectiveness of existing antibiotics. By tailoring therapies to current resistance patterns and strengthening interdisciplinary collaboration, stewardship programs help ensure that effective antimicrobial treatments remain available for future patients.[36]
References
Yoo JH. Antimicrobial Resistance - The 'Real' Pandemic We Are Unaware Of, Yet Nearby. Journal of Korean medical science. 2025 May 19:40(19):e161. doi: 10.3346/jkms.2025.40.e161. Epub 2025 May 19 [PubMed PMID: 40390585]
Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM Jr, Finkelstein JA, Gerber JS, Hyun DY, Linder JA, Lynfield R, Margolis DJ, May LS, Merenstein D, Metlay JP, Newland JG, Piccirillo JF, Roberts RM, Sanchez GV, Suda KJ, Thomas A, Woo TM, Zetts RM, Hicks LA. Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011. JAMA. 2016 May 3:315(17):1864-73. doi: 10.1001/jama.2016.4151. Epub [PubMed PMID: 27139059]
Barlam TF, Cosgrove SE, Abbo LM, MacDougall C, Schuetz AN, Septimus EJ, Srinivasan A, Dellit TH, Falck-Ytter YT, Fishman NO, Hamilton CW, Jenkins TC, Lipsett PA, Malani PN, May LS, Moran GJ, Neuhauser MM, Newland JG, Ohl CA, Samore MH, Seo SK, Trivedi KK. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2016 May 15:62(10):e51-77. doi: 10.1093/cid/ciw118. Epub 2016 Apr 13 [PubMed PMID: 27080992]
GBD 2021 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050. Lancet (London, England). 2024 Sep 28:404(10459):1199-1226. doi: 10.1016/S0140-6736(24)01867-1. Epub 2024 Sep 16 [PubMed PMID: 39299261]
Level 1 (high-level) evidenceHo CS, Wong CTH, Aung TT, Lakshminarayanan R, Mehta JS, Rauz S, McNally A, Kintses B, Peacock SJ, de la Fuente-Nunez C, Hancock REW, Ting DSJ. Antimicrobial resistance: a concise update. The Lancet. Microbe. 2025 Jan:6(1):100947. doi: 10.1016/j.lanmic.2024.07.010. Epub 2024 Sep 18 [PubMed PMID: 39305919]
Klein EY, Impalli I, Poleon S, Denoel P, Cipriano M, Van Boeckel TP, Pecetta S, Bloom DE, Nandi A. Global trends in antibiotic consumption during 2016-2023 and future projections through 2030. Proceedings of the National Academy of Sciences of the United States of America. 2024 Dec 3:121(49):e2411919121. doi: 10.1073/pnas.2411919121. Epub 2024 Nov 18 [PubMed PMID: 39556760]
Price R. O'Neill report on antimicrobial resistance: funding for antimicrobial specialists should be improved. European journal of hospital pharmacy : science and practice. 2016 Jul:23(4):245-247. doi: 10.1136/ejhpharm-2016-001013. Epub [PubMed PMID: 31156859]
Anderson M, Clift C, Schulze K, Sagan A, Nahrgang S, Ait Ouakrim D, Mossialos E. Averting the AMR crisis: What are the avenues for policy action for countries in Europe?. 2019:(): [PubMed PMID: 31287637]
Hardie KR. Antimicrobial resistance: the good, the bad, and the ugly. Emerging topics in life sciences. 2020 Sep 8:4(2):129-136. doi: 10.1042/ETLS20190194. Epub [PubMed PMID: 32463087]
Zhen X, Stålsby Lundborg C, Sun X, Zhu N, Gu S, Dong H. Economic burden of antibiotic resistance in China: a national level estimate for inpatients. Antimicrobial resistance and infection control. 2021 Jan 6:10(1):5. doi: 10.1186/s13756-020-00872-w. Epub 2021 Jan 6 [PubMed PMID: 33407856]
Yek C, Mancera AG, Diao G, Walker M, Neupane M, Chishti EA, Amirahmadi R, Richert ME, Rhee C, Klompas M, Swihart B, Warner SR, Kadri SS, National Institutes of Health Antimicrobial Resistance Outcomes Research Initiative. Impact of the COVID-19 Pandemic on Antibiotic Resistant Infection Burden in U.S. Hospitals : Retrospective Cohort Study of Trends and Risk Factors. Annals of internal medicine. 2025 Jun:178(6):796-807. doi: 10.7326/ANNALS-24-03078. Epub 2025 Apr 29 [PubMed PMID: 40294418]
Level 2 (mid-level) evidenceLuo Q, Lu P, Chen Y, Shen P, Zheng B, Ji J, Ying C, Liu Z, Xiao Y. ESKAPE in China: epidemiology and characteristics of antibiotic resistance. Emerging microbes & infections. 2024 Dec:13(1):2317915. doi: 10.1080/22221751.2024.2317915. Epub 2024 Feb 23 [PubMed PMID: 38356197]
Pulingam T, Parumasivam T, Gazzali AM, Sulaiman AM, Chee JY, Lakshmanan M, Chin CF, Sudesh K. Antimicrobial resistance: Prevalence, economic burden, mechanisms of resistance and strategies to overcome. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2022 Mar 1:170():106103. doi: 10.1016/j.ejps.2021.106103. Epub 2021 Dec 20 [PubMed PMID: 34936936]
Murray CJL, GBD 2021 Collaborators. Findings from the Global Burden of Disease Study 2021. Lancet (London, England). 2024 May 18:403(10440):2259-2262. doi: 10.1016/S0140-6736(24)00769-4. Epub [PubMed PMID: 38762327]
Hsu LY, Legido-Quigley H, Chua AQ. High-level political commitment to action against AMR: what is next? BMJ public health. 2025:3(1):e002351. doi: 10.1136/bmjph-2024-002351. Epub 2025 Apr 5 [PubMed PMID: 40196442]
Marston HD, Dixon DM, Knisely JM, Palmore TN, Fauci AS. Antimicrobial Resistance. JAMA. 2016 Sep 20:316(11):1193-1204. doi: 10.1001/jama.2016.11764. Epub [PubMed PMID: 27654605]
Katz SE, Banerjee R, COMMITTEE ON INFECTIOUS DISEASES, COUNCIL ON ENVIRONMENTAL HEALTH AND CLIMATE CHANGE. Use of Antibiotics in Animal Agriculture: Implications for Pediatrics: Technical Report. Pediatrics. 2024 Oct 1:154(4):. pii: e2024068467. doi: 10.1542/peds.2024-068467. Epub [PubMed PMID: 39308322]
Level 3 (low-level) evidenceStanley D, Batacan R Jr, Bajagai YS. Rapid growth of antimicrobial resistance: the role of agriculture in the problem and the solutions. Applied microbiology and biotechnology. 2022 Nov:106(21):6953-6962. doi: 10.1007/s00253-022-12193-6. Epub 2022 Oct 5 [PubMed PMID: 36197458]
van Duijkeren E, Schink AK, Roberts MC, Wang Y, Schwarz S. Mechanisms of Bacterial Resistance to Antimicrobial Agents. Microbiology spectrum. 2018 Jan:6(1):. doi: 10.1128/microbiolspec.ARBA-0019-2017doi: 10.1128/microbiolspec.arba-0019-2017. Epub [PubMed PMID: 29327680]
Tenover FC. Mechanisms of antimicrobial resistance in bacteria. The American journal of medicine. 2006 Jun:119(6 Suppl 1):S3-10; discussion S62-70 [PubMed PMID: 16735149]
Nelson RR. Intrinsically vancomycin-resistant gram-positive organisms: clinical relevance and implications for infection control. The Journal of hospital infection. 1999 Aug:42(4):275-82 [PubMed PMID: 10467540]
Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ. Molecular mechanisms of antibiotic resistance. Nature reviews. Microbiology. 2015 Jan:13(1):42-51. doi: 10.1038/nrmicro3380. Epub 2014 Dec 1 [PubMed PMID: 25435309]
Abbas A, Barkhouse A, Hackenberger D, Wright GD. Antibiotic resistance: A key microbial survival mechanism that threatens public health. Cell host & microbe. 2024 Jun 12:32(6):837-851. doi: 10.1016/j.chom.2024.05.015. Epub [PubMed PMID: 38870900]
Sharma S, Chauhan A, Ranjan A, Mathkor DM, Haque S, Ramniwas S, Tuli HS, Jindal T, Yadav V. Emerging challenges in antimicrobial resistance: implications for pathogenic microorganisms, novel antibiotics, and their impact on sustainability. Frontiers in microbiology. 2024:15():1403168. doi: 10.3389/fmicb.2024.1403168. Epub 2024 Apr 29 [PubMed PMID: 38741745]
Hocquet D, Vogne C, El Garch F, Vejux A, Gotoh N, Lee A, Lomovskaya O, Plésiat P. MexXY-OprM efflux pump is necessary for a adaptive resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrobial agents and chemotherapy. 2003 Apr:47(4):1371-5 [PubMed PMID: 12654672]
Baran A, Kwiatkowska A, Potocki L. Antibiotics and Bacterial Resistance-A Short Story of an Endless Arms Race. International journal of molecular sciences. 2023 Mar 17:24(6):. doi: 10.3390/ijms24065777. Epub 2023 Mar 17 [PubMed PMID: 36982857]
Belay WY, Getachew M, Tegegne BA, Teffera ZH, Dagne A, Zeleke TK, Abebe RB, Gedif AA, Fenta A, Yirdaw G, Tilahun A, Aschale Y. Mechanism of antibacterial resistance, strategies and next-generation antimicrobials to contain antimicrobial resistance: a review. Frontiers in pharmacology. 2024:15():1444781. doi: 10.3389/fphar.2024.1444781. Epub 2024 Aug 16 [PubMed PMID: 39221153]
LESKOWITZ S, FOX CL Jr, RAYMOND S. The isolation and identification of para-aminobenzoic acid produced by staphylococci resistant to sulfonamide. The Journal of experimental medicine. 1952 Mar:95(3):247-50 [PubMed PMID: 14927789]
Shao K, Yang Y, Gong X, Chen K, Liao Z, Ojha SC. Staphylococcal Drug Resistance: Mechanisms, Therapies, and Nanoparticle Interventions. Infection and drug resistance. 2025:18():1007-1033. doi: 10.2147/IDR.S510024. Epub 2025 Feb 19 [PubMed PMID: 39990781]
Landy M, Larkum NW, Oswald EJ, Streightoff F. INCREASED SYNTHESIS OF p-AMINOBENZOIC ACID ASSOCIATED WITH THE DEVELOPMENT OF SULFONAMIDE RESISTANCE IN STAPHYLOCOCCUS AUREUS. Science (New York, N.Y.). 1943 Mar 19:97(2516):265-7 [PubMed PMID: 17744237]
Nasrollahian S, Graham JP, Halaji M. A review of the mechanisms that confer antibiotic resistance in pathotypes of E. coli. Frontiers in cellular and infection microbiology. 2024:14():1387497. doi: 10.3389/fcimb.2024.1387497. Epub 2024 Apr 4 [PubMed PMID: 38638826]
Niculescu AG, Mitache MM, Grumezescu AM, Chifiriuc MC, Mihai MM, Tantu MM, Tantu AC, Popa LG, Grigore GA, Cristian RE, Popa MI, Vrancianu CO. From Microbial Ecology to Clinical Challenges: The Respiratory Microbiome's Role in Antibiotic Resistance. Pathogens (Basel, Switzerland). 2025 Apr 5:14(4):. doi: 10.3390/pathogens14040355. Epub 2025 Apr 5 [PubMed PMID: 40333133]
Akram F, Imtiaz M, Haq IU. Emergent crisis of antibiotic resistance: A silent pandemic threat to 21(st) century. Microbial pathogenesis. 2023 Jan:174():105923. doi: 10.1016/j.micpath.2022.105923. Epub 2022 Dec 13 [PubMed PMID: 36526035]
Jernigan JA, Hatfield KM, Wolford H, Nelson RE, Olubajo B, Reddy SC, McCarthy N, Paul P, McDonald LC, Kallen A, Fiore A, Craig M, Baggs J. Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012-2017. The New England journal of medicine. 2020 Apr 2:382(14):1309-1319. doi: 10.1056/NEJMoa1914433. Epub [PubMed PMID: 32242356]
Mergoum AM. Amoxicillin Rash in Infectious Mononucleosis. The New England journal of medicine. 2021 Sep 9:385(11):1033. doi: 10.1056/NEJMicm2104358. Epub [PubMed PMID: 34496177]
Aslam B, Wang W, Arshad MI, Khurshid M, Muzammil S, Rasool MH, Nisar MA, Alvi RF, Aslam MA, Qamar MU, Salamat MKF, Baloch Z. Antibiotic resistance: a rundown of a global crisis. Infection and drug resistance. 2018:11():1645-1658. doi: 10.2147/IDR.S173867. Epub 2018 Oct 10 [PubMed PMID: 30349322]
Bertagnolio S, Dobreva Z, Centner CM, Olaru ID, Donà D, Burzo S, Huttner BD, Chaillon A, Gebreselassie N, Wi T, Hasso-Agopsowicz M, Allegranzi B, Sati H, Ivanovska V, Kothari KU, Balkhy HH, Cassini A, Hamers RL, Weezenbeek KV, WHO Research Agenda for AMR in Human Health Collaborators. WHO global research priorities for antimicrobial resistance in human health. The Lancet. Microbe. 2024 Nov:5(11):100902. doi: 10.1016/S2666-5247(24)00134-4. Epub 2024 Aug 13 [PubMed PMID: 39146948]
van Hecke O, Wang K, Lee JJ, Roberts NW, Butler CC. Implications of Antibiotic Resistance for Patients' Recovery From Common Infections in the Community: A Systematic Review and Meta-analysis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2017 Aug 1:65(3):371-382. doi: 10.1093/cid/cix233. Epub [PubMed PMID: 28369247]
Level 1 (high-level) evidenceJetté LP, Sinave C. Use of an oxacillin disk screening test for detection of penicillin- and ceftriaxone-resistant pneumococci. Journal of clinical microbiology. 1999 Apr:37(4):1178-81 [PubMed PMID: 10074547]
Fowler VG, Jezek A, Spivak ES, Talkington K. Urgent, Comprehensive Federal Action Needed To Stem Mortality and Medicare Costs Associated With Antimicrobial Resistance. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2022 Mar 23:74(6):1107-1111. doi: 10.1093/cid/ciab697. Epub [PubMed PMID: 34617117]
Gilchrist M, Wade P, Ashiru-Oredope D, Howard P, Sneddon J, Whitney L, Wickens H. Antimicrobial Stewardship from Policy to Practice: Experiences from UK Antimicrobial Pharmacists. Infectious diseases and therapy. 2015 Sep:4(Suppl 1):51-64. doi: 10.1007/s40121-015-0080-z. Epub 2015 Sep 11 [PubMed PMID: 26362295]
Doernberg SB, Abbo LM, Burdette SD, Fishman NO, Goodman EL, Kravitz GR, Leggett JE, Moehring RW, Newland JG, Robinson PA, Spivak ES, Tamma PD, Chambers HF. Essential Resources and Strategies for Antibiotic Stewardship Programs in the Acute Care Setting. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018 Sep 28:67(8):1168-1174. doi: 10.1093/cid/ciy255. Epub [PubMed PMID: 29590355]
Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023 Jul 18:():. pii: ciad428. doi: 10.1093/cid/ciad428. Epub 2023 Jul 18 [PubMed PMID: 37463564]
Tamma PD, Heil EL, Justo JA, Mathers AJ, Satlin MJ, Bonomo RA. Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2024 Aug 7:():. pii: ciae403. doi: 10.1093/cid/ciae403. Epub 2024 Aug 7 [PubMed PMID: 39108079]