AIU – Faculty of Pharmacy
Published February 1, 2026 | Version v1
Journal article Restricted

Antimicrobial Armageddon: The Professional Guide to Conquering Antibiotic Resistance

Authors/Creators

Description

nan

Original Publication: https://doi.org/10.1007/s12602-026-10928-9

Note: This record is metadata-only as the original article may be subject to publisher restrictions.



This version is archived in the Arab International University (AIU) repository for open access and dissemination purposes. The content of this paper has not been modified from the original publication.
For more information, please visit the official repository of Arab International University (AIU):

https://aiu.edu.sy

Notes

Journal: Probiotics and Antimicrobial Proteins. Publisher: Springer Science and Business Media LLC

Files

Restricted

The record is publicly accessible, but files are restricted. <a href="https://zenodo.org/account/settings/login?next=https://zenodo.org/records/20050460">Log in</a> to check if you have access.

Additional details

Identifiers

DOI
10.1007/s12602-026-10928-9

References

  • Aslam B, Wang W, Arshad MI, Khurshid M, Muzammil S, Rasool MH, Nisar MA, Alvi RF, Aslam MA, Qamar MU, Salamat MKF, Baloch Z (2018) Antibiotic resistance: a rundown of a global crisis. Infect Drug Resist 11:1645–1658. https://doi.org/10.2147/IDR.S173867
  • Darby EM, Trampari E, Siasat P, Gaya MS, Alav I, Webber MA, Blair JMA (2023) Molecular mechanisms of antibiotic resistance revisited. Nat Rev Microbiol 21:280–295. https://doi.org/10.1038/s41579-022-00820-y
  • MacGowan A, Macnaughton E (2017) Antibiotic resistance. Med Baltim 45:622–628. https://doi.org/10.1016/j.mpmed.2017.07.006
  • Antimicrobial Resistance Collaborators (2022) Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399(10325):629–655. https://doi.org/10.1016/S0140-6736(21)02724-0
  • Brüssow H (2024) The antibiotic resistance crisis and the development of new antibiotics. Microb Biotechnol 17(7):e14510. https://doi.org/10.1111/1751-7915.14510
  • de Kraker ME, Stewardson AJ, Harbarth S (2016) Will 10 Million people die a year due to antimicrobial resistance by 2050? PLoS Med 13(11):e1002184. https://doi.org/10.1371/journal.pmed.1002184
  • Mickelsson M, Simbini T (2025) Health care integration for addressing antimicrobial resistance: traditional and conventional medical practices in AMR education. Glob Public Health 20(1):2579685. https://doi.org/10.1080/17441692.2025.2579685
  • Liu CSC, Pandey R (2024) Integrative genomics would strengthen AMR understanding through ONE health approach. Heliyon 10(14):e34719. https://doi.org/10.1016/j.heliyon.2024.e34719
  • Chen W, Li L, Dai X, Feng L, Yu X (2025) Health risk and benefit assessment methods for antibiotic resistance bacteria/genes in the environment: a critical review. J Environ Manage 396:128071. https://doi.org/10.1016/j.jenvman.2025.128071
  • Yan Y, Liu Z, Cao J, Fang J (2025) Mitigating antibiotic and antibiotic resistance gene contamination in animal manure compost by biochar: a review. Waste Management (New York, N.Y.) 210:115240. https://doi.org/10.1016/j.wasman.2025.115240
  • Li J, Song J, Wang X, Li W, Han M, Li M, Wang S, Xu J, Zhang Q, Chen J, Cui S, Yang B (2025) Food-associated stressors and their synergistic roles in bacterial antibiotic resistance across the food supply chain. J Agric Food Chem 73(46):29310–29327. https://doi.org/10.1021/acs.jafc.5c10696
  • Aslam B, Asghar R, Muzammil S, Shafique M, Siddique AB, Khurshid M, Ijaz M, Rasool MH, Chaudhry TH, Aamir A, Baloch Z (2024) AMR and sustainable development goals: at a crossroads. Global Health 20(1):73. https://doi.org/10.1186/s12992-024-01046-8
  • GBD 2023 Causes of Death Collaborators (2025) Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990–2023: a systematic analysis for the Global Burden of Disease Study 2023. Lancet 406(10513):1811–1872. https://doi.org/10.1016/S0140-6736(25)01917-8
  • Lee SJ, Yoon H, Shin JC, Cho SR (2026) Machine learning prediction of multidrug-resistant urinary tract infections in brain and spinal cord injury patients: a dual-center validation study. Int J Med Inform 206:106143. https://doi.org/10.1016/j.ijmedinf.2025.106143
  • Wang H, Ye C, Jiang H, Song R (2026) Application of next-generation sequencing in the detection of antimicrobial resistance. Clin Chim Acta 578:120520. https://doi.org/10.1016/j.cca.2025.120520
  • Elbehiry A, Abalkhail A (2025) Metagenomic next-generation sequencing in infectious diseases: clinical applications, translational challenges, and future directions. Diagnostics Basel 15(16):1991. https://doi.org/10.3390/diagnostics15161991
  • Abavisani M, Khoshrou A, Foroushan SK, Sahebkar A (2024) Chatting with artificial intelligence to combat antibiotic resistance: opportunities and challenges. Current Research in Biotechnology 7:100197
  • Lai H, Ge L, Sun M, Pan B, Huang J, Hou L, Estill J (2024) Assessing the risk of bias in randomized clinical trials with large language models. JAMA Netw Open 7(5):e2412687–e2412687
  • Prasad M (2024) Introduction to the GRADE tool for rating certainty in evidence and recommendations. Clin Epidemiol Glob Health 25:101484
  • Serwecińska L (2020) Antimicrobials and antibiotic-resistant bacteria: a risk to the environment and to public health. Water 12:3313. https://doi.org/10.3390/w12123313
  • Ahmad M, Khan AU (2019) Global economic impact of antibiotic resistance: a review. J Glob Antimicrob Resist 19:313–316. https://doi.org/10.1016/j.jgar.2019.05.024
  • Bhattacharya R, Bose D, Gulia K, Jaiswal A (2024) Impact of antimicrobial resistance on sustainable development goals and the integrated strategies for meeting environmental and socio-economic targets. Environ Prog Sustain Energy 43(1):e14320
  • Karnwal A, Jassim AY, Mohammed AA, Al-Tawaha ARMS, Selvaraj M, Malik T (2025) Addressing the global challenge of bacterial drug resistance: insights, strategies, and future directions. Front Microbiol 16:1517772
  • Ali T, Habib A, Nazir Z, Ali M, Haque MA (2024) Healthcare challenges in lmics: addressing antibiotic resistance threats, a call for comprehensive global solutions: an editorial. Int J Surg 110(5):3085–3087
  • Killai SN (2024) Antibiotic resistance: strategies for combating the global threat. Medalion Journal: Med Res Nurs Health Midwife Participation 5(4):268–277
  • Pitiot A, Rolin C, Seguin-Devaux C, Zimmer J (2025) Fighting Antibiotic Resistance: insights into human barriers and new opportunities: Antibiotic Resistance constantly rises with the development of human activities. We discuss barriers and opportunities to get it under control. Bioessays 47(6):e70001
  • Chamas C (2025) Global commitment to combat antimicrobial resistance. Cad Saude Publica 41:e00190924
  • Nazir A, Nazir A, Zuhair V, Aman S, Sadiq SUR, Hasan AH, Bulimbe DB (2025) The global challenge of antimicrobial resistance: mechanisms, case studies, and mitigation approaches. Health Sci Rep 8(7):e71077
  • Nwakoby IP, Iheukwumere IH, Iheukwumere CM, Nwakoby NE, Idigo MA, Ike VE (2025) Antimicrobial resistance: a legal and public health perspective. IPS J Appl Microbiol Biotechnol 4(4):230–236
  • Ehsan H (2025) Antibiotic resistance in developing countries: emerging threats and policy responses. Public Health Challenges 4(1):e70034
  • Navidifar T, Zare Banadkouki A, Parvizi E, Mofid M, Golab N, Beig M, Sholeh M (2025) Global prevalence of macrolide-resistant Staphylococcus spp.: a comprehensive systematic review and meta-analysis. Front Microbiol 16:1524452
  • Li J, Cheng F, Wei X, Bai Y, Wang Q, Li B, Zhang J (2025) Methicillin-resistant staphylococcus aureus (MRSA): resistance, prevalence, and coping strategies. Antibiotics 14(8):771
  • Abavisani M, Fazeli E, Ebadpour N, Karav S, Kesharwani P, Sahebkar A (2025) The road less traveled: unexplored targets in the quest for antibiotics against Pseudomonas aeruginosa. Biotechnol Adv 83:108621. https://doi.org/10.1016/j.biotechadv.2025.108621
  • Abavisani M, Khoshrou A, Khayami R, Kesharwani P, Sahebkar A (2025) Preclinical evaluation of repositioned non-antibiotic agents against Staphylococcus aureus: a network meta-analysis of survival outcomes. World Journal of Microbiology & Biotechnology 41(12):480. https://doi.org/10.1007/s11274-025-04705-z
  • ECDC (2022) European Centre for Disease Prevention and Control (ECDC), Surveillance report, Antimicrobial consumption in the EU/EEA (ESAC-Net). https://www.ecdc.europa.eu/sites/default/files/documents/AER-antimicrobial-consumption.pdf; accessed on 30 March 2024
  • Mestrovic T, Aguilar GR, Swetschinski LR, Ikuta KS, Gray AP, Weaver ND, Han C, Wool EE, Hayoon AG, Hay SI, Dolecek C (2022) The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis. Lancet Public Health 7(11):e897–e913. https://doi.org/10.1016/S2468-2667(22)00225-0
  • Chatterjee A, Modarai M, Naylor NR, Boyd SE, Atun R, Barlow J, Holmes AH, Johnson A, Robtham JV (2018) Quantifying drivers of antibiotic resistance in humans: a systematic review. Lancet Infect Dis 18:e368–e378. https://doi.org/10.1016/S1473-3099(18)30296-2
  • Mao X, Yin X, Yang Y, Che Y, Xu X, Deng Y, Zhang T (2024) Standardization in global environmental antibiotic resistance genes (ARGs) surveillance. Crit Rev Environ Sci Technol 54(22):1633–1650
  • Schwartz KL, Morris SK (2018) Travel and the spread of drug-resistant bacteria. Curr Infect Dis Rep 20(9):29. https://doi.org/10.1007/s11908-018-0634-9
  • Adebisi YA (2023) Balancing the risks and benefits of antibiotic use in a globalized world: the ethics of antimicrobial resistance. Glob Health Action 19:27. https://doi.org/10.1186/s12992-023-00930-z
  • Majumder MAA, Rahman S, Cohall D, Bharatha A, Singh K, Haque M et al (2020) Antimicrobial stewardship: fighting antimicrobial resistance and protecting global public health. Infect Drug Resist 13:4713–4738. https://doi.org/10.2147/IDR.S290835
  • Tacconelli E, Sifakis F, Harbarth S, Schrijver R, Mourik M, Voss A et al (2018) Surveillance for control of antimicrobial resistance. Lancet Infect Dis 18:e99–e106. https://doi.org/10.1016/S1473-3099(17)30485-1
  • Iskandar K, Molinier L, Hallit S, Sartelli M, Hardcastle TC, Haque M et al (2021) Surveillance of antimicrobial resistance in low- and middle-income countries: a scattered picture. Antimicrob Resist Infect Control 10:63. https://doi.org/10.1186/s13756-021-00931-w
  • Aiesh BM, Nazzal MA, Abdelhaq AI, Abutaha SA, Zyoud SH, Sabateen A (2023) Impact of an antibiotic stewardship program on antibiotic utilization, bacterial susceptibilities, and cost of antibiotics. Sci Rep 13:5040. https://doi.org/10.1038/s41598-023-32329-6
  • Lee CF, Cowling BJ, Feng S, Aso H, Wu P, Fukuda K et al (2018) Impact of antibiotic stewardship programmes in Asia: a systematic review and meta-analysis. J Antimicrob Chemother 73:844–851. https://doi.org/10.1093/jac/dkx492
  • Feldstein D, Sloane PD, Feltner C (2018) Antibiotic stewardship programs in nursing homes: a systematic review. J Am Med Dir Assoc 19:110–116. https://doi.org/10.1016/j.jamda.2017.06.019
  • Lin DM, Koskella B, Lin HC (2017) Phage therapy: an alternative to antibiotics in the age of multi-drug resistance. World J Gastrointest Pharmacol Ther 8:162–173. https://doi.org/10.4292/wjgpt.v8.i3.162
  • Romero-Calle D, Guimarães Benevides R, Góes-Neto A, Billington C (2019) Bacteriophages as alternatives to antibiotics in clinical care. Antibiotics 8:138. https://doi.org/10.3390/antibiotics8030138
  • Murugaiyan J, Kumar PA, Rao GS, Iskandar K, Hawser S, Hays JP et al (2022) Progress in alternative strategies to combat antimicrobial resistance: focus on antibiotics. Antibiotics 11:200. https://doi.org/10.3390/antibiotics11020200
  • Pradipta IS, Forsman LD, Bruchfeld J, Hak E, Alffenaar J-W (2018) Risk factors of multidrug-resistant tuberculosis: a global systematic review and meta-analysis. J Infect 77:469–478. https://doi.org/10.1016/j.jinf.2018.10.004
  • Xi Y, Zhang W, Qiao R-J, Tang J (2022) Risk factors for multidrug-resistant tuberculosis: a worldwide systematic review and meta-analysis. PLoS One 17:e0270003. https://doi.org/10.1371/journal.pone.0270003
  • Zhang Y, Yu Y, Fong PSW, Shen J (2023) Addressing unforeseen public health risks via the use of sustainable system and process management. Front Public Health 11:1249277. https://doi.org/10.3389/fpubh.2023.1249277
  • Wu C, Ye H, Xu M, Zhao X, Zhao X, Li L, Li M, Wei Y, Li Y, Hu B (2025) Occurrence of antibiotics and antibiotic resistance genes at various stages of different aquaculture modes surrounding Tai Lake, China. Front Microbiol 16:1543387. https://doi.org/10.3389/fmicb.2025.1543387
  • Dadgostar P (2019) Antimicrobial resistance: implications and costs. Infect Drug Resist 12:3903–3910. https://doi.org/10.2147/IDR.S234610
  • Huemer M, Mairpady Shambat S, Brugger SD, Zinkernagel AS (2020) Antibiotic resistance and persistence—implications for human health and treatment perspectives. EMBO Rep 21:e51034. https://doi.org/10.15252/embr.202051034
  • Xie W-Y, Shen Q, Zhao FJ (2018) Antibiotics and antibiotic resistance from animal manures to soil: a review. Eur J Soil Sci 69:181–195. https://doi.org/10.1111/ejss.12494
  • Manyi-Loh C, Mamphweli S, Meyer E, Okoh A (2018) Antibiotic use in agriculture and its consequential resistance in environmental sources: potential public health implications. Molecules 23:795. https://doi.org/10.3390/molecules23040795
  • Van TTH, Yidana Z, Smooker PM, Coloe PJ (2020) Antibiotic use in food animals worldwide, with a focus on Africa: pluses and minuses. J Glob Antimicrob Resist 20:170–177. https://doi.org/10.1016/j.jgar.2019.07.031
  • de Kraker MEA, Stewardson AJ, Harbarth S (2016) Will 10 Million People Die a Year due to Antimicrobial Resistance by 2050? PLoS Med 13:e1002184. https://doi.org/10.1371/journal.pmed.1002184
  • Hernando-Amado S, Coque TM, Baquero F, Martínez JL (2019) Defining and combating antibiotic resistance from one health and global health perspectives. Nat Microbiol 4:1432–1442. https://doi.org/10.1038/s41564-019-0503-9
  • Malik B, Bhattacharyya S (2019) Antibiotic drug-resistance as a complex system driven by socio-economic growth and antibiotic misuse. Sci Rep 9:9788. https://doi.org/10.1038/s41598-019-46078-y
  • Charani E, Holmes A (2019) Antibiotic stewardship—twenty years in the making. Antibiotics 8:7. https://doi.org/10.3390/antibiotics8010007
  • Zhang C, Fu X, Liu Y, Zhao H, Wang G (2023) Burden of infectious diseases and bacterial antimicrobial resistance in China: a systematic analysis for the global burden of disease study 2019. Lancet Reg Health West Pac 43:100972. https://doi.org/10.1016/j.lanwpc.2023.100972
  • Renwick M, Mossialos E (2018) What are the economic barriers of antibiotic R&D and how can we overcome them? Expert Opin Drug Discov 13:889–892. https://doi.org/10.1080/17460441.2018.1515908
  • Årdal C, Balasegaram M, Laxminarayan R, McAdams D, Outterson K, Rex JH et al (2020) Antibiotic development — economic, regulatory and societal challenges. Nat Rev Microbiol 18:267–274. https://doi.org/10.1038/s41579-019-0293-3
  • Ghosh C, Sarkar P, Issa R, Haldar J (2019) Alternatives to conventional antibiotics in the era of antimicrobial resistance. Trends Microbiol 27:323–338. https://doi.org/10.1016/j.tim.2018.12.010
  • Coates ARM, Hu Y, Holt J, Yeh P (2020) Antibiotic combination therapy against resistant bacterial infections: synergy, rejuvenation and resistance reduction. Expert Rev Anti Infect Ther 18:5–15. https://doi.org/10.1080/14787210.2020.1705155
  • McInnes RS, McCallum GE, Lamberte LE, van Schaik W (2020) Horizontal transfer of antibiotic resistance genes in the human gut microbiome. Curr Opin Microbiol 53:35–43. https://doi.org/10.1016/j.mib.2020.02.002
  • Lerminiaux NA, Cameron ADS (2019) Horizontal transfer of antibiotic resistance genes in clinical environments. Can J Microbiol 65:34–44. https://doi.org/10.1139/cjm-2018-0275
  • Orlek A, Anjum MF, Mather AE, Stoesser N, Walker AS (2023) Factors associated with plasmid antibiotic resistance gene carriage revealed using large-scale multivariable analysis. Sci Rep 13(1):2500
  • McMillan EA, Jackson CR, Frye JG (2020) Transferable plasmids of Salmonella enterica associated with antibiotic resistance genes. Front Microbiol 11:562181. https://doi.org/10.3389/fmicb.2020.562181
  • Li L-G, Zhang T (2023) Plasmid-mediated antibiotic resistance gene transfer under environmental stresses: insights from laboratory-based studies. Sci Total Environ 887:163870. https://doi.org/10.1016/j.scitotenv.2023.163870
  • Botts RT, Apffel BA, Walters CJ, Davidson KE, Echols RS, Geiger MR et al (2017) Characterization of four multidrug resistance plasmids captured from the sediments of an urban coastal wetland. Front Microbiol. https://doi.org/10.3389/fmicb.2017.01922
  • Kakoullis L, Papachristodoulou E, Chra P, Panos G (2021) Mechanisms of antibiotic resistance in important Gram-positive and Gram-negative pathogens and novel antibiotic solutions. Antibiotics 10:415. https://doi.org/10.3390/antibiotics10040415
  • Durão P, Balbontín R, Gordo I (2018) Evolutionary mechanisms shaping the maintenance of antibiotic resistance. Trends Microbiol 26:677–691. https://doi.org/10.1016/j.tim.2018.01.005
  • Liu W-T, Chen E-Z, Yang L, Peng C, Wang Q, Xu Z et al (2021) Emerging resistance mechanisms for 4 types of common anti-MRSA antibiotics in Staphylococcus aureus: a comprehensive review. Microb Pathog 156:104915. https://doi.org/10.1016/j.micpath.2021.104915
  • Vestergaard M, Frees D, Ingmer H (2019) Antibiotic Resistance and the MRSA Problem. Microbiol Spectr 7:10.1128/microbiolspec.gpp3-0057–2018. https://doi.org/10.1128/microbiolspec.gpp3-0057-2018
  • Thakur V, Uniyal A, Tiwari V (2021) A comprehensive review on pharmacology of efflux pumps and their inhibitors in antibiotic resistance. Eur J Pharmacol 903:174151. https://doi.org/10.1016/j.ejphar.2021.174151
  • Ebbensgaard AE, Løbner-Olesen A, Frimodt-Møller J (2020) The role of efflux pumps in the transition from low-level to clinical antibiotic resistance. Antibiotics 9:855. https://doi.org/10.3390/antibiotics9120855
  • Nishino K, Yamasaki S, Nakashima R, Zwama M, Hayashi-Nishino M (2021) Function and inhibitory mechanisms of multidrug efflux pumps. Front Microbiol. https://doi.org/10.3389/fmicb.2021.737288
  • Du D, Wang-Kan X, Neuberger A, van Veen HW, Pos KM, Piddock LJV et al (2018) Multidrug efflux pumps: structure, function and regulation. Nat Rev Microbiol 16:523–539. https://doi.org/10.1038/s41579-018-0048-6
  • Reis AC, Kolvenbach BA, Nunes OC, Corvini PFX (2020) Biodegradation of antibiotics: the new resistance determinants – part I. New Biotechnol 54:34–51. https://doi.org/10.1016/j.nbt.2019.08.002
  • Yang QE, Walsh TR (2017) Toxin-antitoxin systems and their role in disseminating and maintaining antimicrobial resistance. FEMS Microbiol Rev 41(3):343–353. https://doi.org/10.1093/femsre/fux006
  • Sonika S, Singh S, Mishra S, Verma S (2025) Toxin-antitoxin systems in bacterial pathogenesis. Heliyon 11(4):e42945. https://doi.org/10.1016/j.heliyon.2025.e42945
  • Kunnath AP, Suodha Suoodh M, Chellappan DK, Chellian J, Palaniveloo K (2024) Bacterial persister cells and development of antibiotic resistance in chronic infections: an update. Br J Biomed Sci 81:12958. https://doi.org/10.3389/bjbs.2024.12958
  • den Van Bergh B, Fauvart M, Michiels J (2017) Formation, physiology, ecology, evolution and clinical importance of bacterial persisters. FEMS Microbiol Rev 41(3):219–251. https://doi.org/10.1093/femsre/fux001
  • Church NA, McKillip JL (2021) Antibiotic resistance crisis: challenges and imperatives. Biol 76:1535–1550. https://doi.org/10.1007/s11756-021-00697-x
  • Brauner A, Fridman O, Gefen O, Balaban NQ (2016) Distinguishing between resistance, tolerance and persistence to antibiotic treatment. Nat Rev Microbiol 14:320–330. https://doi.org/10.1038/nrmicro.2016.34
  • Valcourt JR, Lemons JM, Haley EM, Kojima M, Demuren OO, Coller HA (2012) Staying alive: metabolic adaptations to quiescence. Cell Cycle 11(9):1680–1696. https://doi.org/10.4161/cc.19879
  • Harms A, Maisonneuve E, Gerdes K (2016) Mechanisms of bacterial persistence during stress and antibiotic exposure. Science 354(6318):aaf4268. https://doi.org/10.1126/science.aaf4268
  • Salcedo-Sora JE, Kell DB (2020) A quantitative survey of bacterial persistence in the presence of antibiotics: towards antipersister antimicrobial discovery. Antibiotics 9(8):508. https://doi.org/10.3390/antibiotics9080508
  • Rahman KMT, Amaratunga R, Butzin XY, Singh A, Hossain T, Butzin NC (2025) Rethinking dormancy: antibiotic persisters are metabolically active, non-growing cells. Int J Antimicrob Agents 65(1):107386. https://doi.org/10.1016/j.ijantimicag.2024.107386
  • Balaban NQ, Liu J (2019) Evolution under Antibiotic Treatments: Interplay between Antibiotic Persistence, Tolerance, and Resistance. In: Lewis K (ed) Persister Cells and Infectious Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-25241-0_1
  • Römling U, Balsalobre C (2012) Biofilm infections, their resilience to therapy and innovative treatment strategies. J Intern Med 272(6):541–561. https://doi.org/10.1111/joim.12004
  • La Rosa R, Johansen HK, Molin S (2022) Persistent bacterial infections, antibiotic treatment failure, and microbial adaptive evolution. Antibiotics (Basel) 11(3):419. https://doi.org/10.3390/antibiotics11030419
  • Almatroudi A (2025) Biofilm resilience: molecular mechanisms driving antibiotic resistance in clinical contexts. Biology 14(2):165. https://doi.org/10.3390/biology14020165
  • Baquero F, Martínez JL, F Lanza V, Rodríguez-Beltrán J, Galán JC, San Millán A, Cantón R, Coque TM (2021) Evolutionary pathways and trajectories in antibiotic resistance. Clin Microbiol Rev 34(4):e0005019. https://doi.org/10.1128/CMR.00050-19
  • Marine JC, Dawson SJ, Dawson MA (2020) Non-genetic mechanisms of therapeutic resistance in cancer. Nat Rev Cancer 20:743–756. https://doi.org/10.1038/s41568-020-00302-4
  • Balaban NQ (2011) Persistence: mechanisms for triggering and enhancing phenotypic variability. Curr Opin Genet Dev 21(6):768–775. https://doi.org/10.1016/j.gde.2011.10.001
  • Lewis K (2012) Persister cells: molecular mechanisms related to antibiotic tolerance. Handb Exp Pharmacol 211:121–133. https://doi.org/10.1007/978-3-642-28951-4_8
  • Mahto KU, Kumari S, Das S (2022) Unraveling the complex regulatory networks in biofilm formation in bacteria and relevance of biofilms in environmental remediation. Crit Rev Biochem Mol Biol 57(3):305–332. https://doi.org/10.1080/10409238.2021.2015747
  • Ramamurthy T, Ghosh A, Chowdhury G, Mukhopadhyay AK, Dutta S, Miyoshi SI (2022) Deciphering the genetic network and programmed regulation of antimicrobial resistance in bacterial pathogens. Front Cell Infect Microbiol 12:952491. https://doi.org/10.3389/fcimb.2022.952491
  • Kirthika P, Lloren KKS, Jawalagatti V, Lee JH (2023) Structure, substrate specificity and role of Lon protease in bacterial pathogenesis and survival. Int J Mol Sci 24(4):3422. https://doi.org/10.3390/ijms24043422
  • Kumar A, Alam A, Bharadwaj P, Tapadar S, Rani M, Hasnain SE (2019) Toxin-Antitoxin (TA) Systems in Stress Survival and Pathogenesis. In: Hasnain S, Ehtesham N, Grover S (eds) Mycobacterium Tuberculosis: Molecular Infection Biology, Pathogenesis, Diagnostics and New Interventions. Springer, Singapore. https://doi.org/10.1007/978-981-32-9413-4_15
  • Hayes F (2003) Toxins-antitoxins: plasmid maintenance, programmed cell death, and cell cycle arrest. Science 301(5639):1496–14969. https://doi.org/10.1126/science.1088157
  • Unterholzner SJ, Poppenberger B, Rozhon W (2013) Toxin-antitoxin systems: biology, identification, and application. Mob Genet Elem 3(5):e26219. https://doi.org/10.4161/mge.26219
  • Schumacher MA, Piro KM, Xu W, Hansen S, Lewis K, Brennan RG (2009) Molecular mechanisms of HipA-mediated multidrug tolerance and its neutralization by HipB. Science 323(5912):396–401. https://doi.org/10.1126/science.1163806
  • Edelmann D, Berghoff BA (2022) A shift in perspective: a role for the type I toxin TisB as persistence-stabilizing factor. Front Microbiol 13:871699. https://doi.org/10.3389/fmicb.2022.871699
  • Bahassi EM, O'Dea MH, Allali N, Messens J, Gellert M, Couturier M (1999) Interactions of CcdB with DNA gyrase. Inactivation of Gyra, poisoning of the gyrase-DNA complex, and the antidote action of CcdA. J Biol Chem 274(16):10936–10944. https://doi.org/10.1074/jbc.274.16.10936
  • Jolivet-Gougeon A, Bonnaure-Mallet M (2019) Bacterial Persistence in Biofilms and Antibiotics. Antibiotic Drug Resistance. John Wiley & Sons, Ltd, pp 181–210. https://doi.org/10.1002/9781119282549.ch9
  • Uruén C, Chopo-Escuin G, Tommassen J, Mainar-Jaime RC, Arenas J (2021) Biofilms as promoters of bacterial antibiotic resistance and tolerance. Antibiotics 10:3. https://doi.org/10.3390/antibiotics10010003
  • Yousefi L, Kadkhoda H, Shirmohammadi M, Moaddab SY, Ghotaslou R, Sadeghi J, Somi MH, Rezaee MA, Ganbarov K (2024) Kafil, HS. CRISPR-like sequences association with antibiotic resistance and biofilm formation in Helicobacter pylori clinical isolates. Heliyon
  • Pulcini C, Clerc-Urmes I, Attinsounon CA, Fougnot S, Thilly N (2019) Antibiotic resistance of Enterobacteriaceae causing urinary tract infections in elderly patients living in the community and in the nursing home: a retrospective observational study. J Antimicrob Chemother 74:775–781. https://doi.org/10.1093/jac/dky488
  • Chambers HF, DeLeo FR (2009) Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol 7:629–641. https://doi.org/10.1038/nrmicro2200
  • Dellit TH, Owens RC, McGowan JE, Gerding DN, Weinstein RA, Burke JP et al (2007) Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 44:159–177. https://doi.org/10.1086/510393
  • Sikkens JJ, van Agtmael MA, Peters EJG, Vandenbroucke-Grauls CMJE, Kramer MHH, de Vet HCW (2016) Assessment of appropriate antimicrobial prescribing: do experts agree? J Antimicrob Chemother 71:2980–2987. https://doi.org/10.1093/jac/dkw207
  • Baur D, Gladstone BP, Burkert F, Carrara E, Foschi F, Döbele S et al (2017) Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect Dis 17:990–1001. https://doi.org/10.1016/S1473-3099(17)30325-0
  • Abavisani M, Foroushan SK, Kesharwani P, Sahebkar A (2025) The frontier of health: exploring therapeutic potentials of the microbiome. PharmaNutrition 31:100435. https://doi.org/10.1016/j.phanu.2025.100435
  • Pontali E, Raviglione MC, Migliori GB (2019) Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives. Eur Respir Rev. https://doi.org/10.1183/16000617.0035-2019
  • Abavisani M, Khoshrou A, Eshaghian S, Karav S, Sahebkar A (2024) Overcoming antibiotic resistance: the potential and pitfalls of drug repurposing. J Drug Target 33(3):341–367. https://doi.org/10.1080/1061186X.2024.2424895
  • Khawbung JL, Nath D, Chakraborty S (2021) Drug resistant Tuberculosis: a review. Comp Immunol Microbiol Infect Dis 74:101574. https://doi.org/10.1016/j.cimid.2020.101574
  • Khawcharoenporn T, Chuncharunee A, Maluangnon C, Taweesakulvashra T, Tiamsak P (2018) Active monotherapy and combination therapy for extensively drug-resistant Pseudomonas aeruginosa pneumonia. Int J Antimicrob Agents 52:828–834. https://doi.org/10.1016/j.ijantimicag.2018.09.008
  • Tyers M, Wright GD (2019) Drug combinations: a strategy to extend the life of antibiotics in the 21st century. Nat Rev Microbiol 17:141–155. https://doi.org/10.1038/s41579-018-0141-x
  • Brill MJE, Kristoffersson AN, Zhao C, Nielsen EI, Friberg LE (2018) Semi-mechanistic pharmacokinetic–pharmacodynamic modelling of antibiotic drug combinations. Clin Microbiol Infect 24:697–706. https://doi.org/10.1016/j.cmi.2017.11.023
  • Laws M, Shaaban A, Rahman KM (2019) Antibiotic resistance breakers: current approaches and future directions. FEMS Microbiol Rev 43:490–516. https://doi.org/10.1093/femsre/fuz014
  • García-Beltrán JM, Arizcun M, Chaves-Pozo E (2023) Antimicrobial peptides from photosynthetic marine organisms with potential application in aquaculture. Mar Drugs 21:290. https://doi.org/10.3390/md21050290
  • Malaekeh-Nikouei B, Fazly Bazzaz BS, Mirhadi E, Tajani AS, Khameneh B (2020) The role of nanotechnology in combating biofilm-based antibiotic resistance. J Drug Deliv Sci Technol 60:101880. https://doi.org/10.1016/j.jddst.2020.101880
  • Hetta HF, Ramadan YN, Al-Harbi AI, Ahmed A, Battah E, Abd Ellah B (2023) Nanotechnology as a promising approach to combat multidrug resistant bacteria: a comprehensive review and future perspectives. Biomedicines 11:413. https://doi.org/10.3390/biomedicines11020413
  • Rabetafika HN, Razafindralambo A, Ebenso B, Razafindralambo HL (2023) Probiotics as antibiotic alternatives for human and animal applications. Encyclopedia 3:561–581. https://doi.org/10.3390/encyclopedia3020040
  • Ranjan A (2022) The use of Probiotics, Prebiotics, and synbiotics as an alternative to antibiotics. In: Saha T, Deb Adhikari M, Tiwary BK (eds) Alternatives to antibiotics: recent trends and future prospects. Springer Nature, Singapore, pp 449–465. https://doi.org/10.1007/978-981-19-1854-4_18
  • Ouwehand AC, Forssten S, Hibberd AA, Lyra A, Stahl B (2016) Probiotic approach to prevent antibiotic resistance. Ann Med 48:246–255. https://doi.org/10.3109/07853890.2016.1161232
  • Maldonado Galdeano C, Cazorla SI, Lemme Dumit JM, Vélez E, Perdigón G (2019) Beneficial effects of probiotic consumption on the immune system. Ann Nutr Metab 74:115–124. https://doi.org/10.1159/000496426
  • Gaspar C, Donders GG, Palmeira-de-Oliveira R, Queiroz JA, Tomaz C, Martinez-de-Oliveira J et al (2018) Bacteriocin production of the probiotic Lactobacillus acidophilus KS400. AMB Express 8:153. https://doi.org/10.1186/s13568-018-0679-z
  • Ozma MA, Moaddab SR, Hosseini H, Khodadadi E, Ghotaslou R, Asgharzadeh M et al (2023) A critical review of novel antibiotic resistance prevention approaches with a focus on postbiotics. Crit Rev Food Sci Nutr 0:1–19. https://doi.org/10.1080/10408398.2023.2214818
  • McCulloch TR, Wells TJ, Souza-Fonseca-Guimaraes F (2022) Towards efficient immunotherapy for bacterial infection. Trends Microbiol 30:158–169. https://doi.org/10.1016/j.tim.2021.05.005
  • Ramamurthy D, Nundalall T, Cingo S, Mungra N, Karaan M, Naran K et al (2021) Recent advances in immunotherapies against infectious diseases. Immunother Adv 1:ltaa007. https://doi.org/10.1093/immadv/ltaa007
  • Motley MP, Banerjee K, Fries BC (2019) Monoclonal antibody-based therapies for bacterial infections. Curr Opin Infect Dis 32:210. https://doi.org/10.1097/QCO.0000000000000539
  • Domenech M, Sempere J, de Miguel S, Yuste J (2018) Combination of antibodies and antibiotics as a promising strategy against multidrug-resistant pathogens of the respiratory tract. Front Immunol. https://doi.org/10.3389/fimmu.2018.02700
  • Rosini R, Nicchi S, Pizza M, Rappuoli R (2020) Vaccines against antimicrobial resistance. Front Immunol. https://doi.org/10.3389/fimmu.2020.01048
  • Abavisani M, Khayami R, Hoseinzadeh M, Kodori M, Kesharwani P, Sahebkar A (2023) CRISPR-Cas system as a promising player against bacterial infection and antibiotic resistance. Drug Resist Updat 68:100948. https://doi.org/10.1016/j.drup.2023.100948
  • Coates ARM, Hu Y (2007) Novel approaches to developing new antibiotics for bacterial infections. Br J Pharmacol 152:1147–1154. https://doi.org/10.1038/sj.bjp.0707432
  • Clatworthy AE, Pierson E, Hung DT (2007) Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol 3:541–548. https://doi.org/10.1038/nchembio.2007.24
  • Talat A, Bashir Y, Khan AU (2022) Repurposing of antibiotics: sense or non-sense. Front Pharmacol 13:833005. https://doi.org/10.3389/fphar.2022.833005
  • Zheng W, Sun W, Simeonov A (2018) Drug repurposing screens and synergistic drug-combinations for infectious diseases. Br J Pharmacol 175:181–191. https://doi.org/10.1111/bph.13895
  • Rácz B, Spengler G (2023) Repurposing antidepressants and phenothiazine antipsychotics as efflux pump inhibitors in cancer and infectious diseases. Antibiotics 12:137. https://doi.org/10.3390/antibiotics12010137
  • Miró-Canturri A, Ayerbe-Algaba R, Smani Y (2019) Drug repurposing for the treatment of bacterial and fungal infections. Front Microbiol 10:41. https://doi.org/10.3389/fmicb.2019.00041
  • Farha MA, Brown ED (2019) Drug repurposing for antimicrobial discovery. Nat Microbiol 4:565–577. https://doi.org/10.1038/s41564-019-0357-1
  • Ahmed A, Azim A, Gurjar M, Baronia AK (2014) Current concepts in combination antibiotic therapy for critically ill patients. Indian J Crit Care Med Peer-Rev Off Publ Indian Soc Crit Care Med 18:310–314. https://doi.org/10.4103/0972-5229.132495
  • Yeh Y-C, Huang T-H, Yang S-C, Chen C-C, Fang J-Y (2020) Nano-based drug delivery or targeting to eradicate bacteria for infection mitigation: a review of recent advances. Front Chem 8:286. https://doi.org/10.3389/fchem.2020.00286
  • Siraj EA, Yayehrad AT, Belete A (2023) How combined macrolide nanomaterials are effective against resistant pathogens? A comprehensive review of the literature. Int J Nanomed 18:5289–5307. https://doi.org/10.2147/IJN.S418588
  • Tang J, Ouyang Q, Li Y, Zhang P, Jin W, Qu S et al (2022) Nanomaterials for delivering antibiotics in the therapy of pneumonia. Int J Mol Sci 23:15738. https://doi.org/10.3390/ijms232415738
  • Munir MU, Ahmed A, Usman M, Salman S (2020) Recent advances in nanotechnology-aided materials in combating microbial resistance and functioning as antibiotics substitutes. Int J Nanomed 15:7329–7358. https://doi.org/10.2147/IJN.S265934
  • Yang X, Ye W, Qi Y, Ying Y, Xia Z (2021) Overcoming multidrug resistance in bacteria through antibiotics delivery in surface-engineered nano-cargos: recent developments for future nano-antibiotics. Front Bioeng Biotechnol. https://doi.org/10.3389/fbioe.2021.696514
  • Hochvaldová L, Večeřová R, Kolář M, Prucek R, Kvítek L, Lapčík L et al (2022) Antibacterial nanomaterials: upcoming hope to overcome antibiotic resistance crisis. Nanotechnol Rev 11:1115–1142. https://doi.org/10.1515/ntrev-2022-0059
  • Biswaro LS, da Costa Sousa MG, Rezende TMB, Dias SC, Franco OL (2018) Antimicrobial peptides and nanotechnology, recent advances and challenges. Front Microbiol. https://doi.org/10.3389/fmicb.2018.00855
  • Tan P, Fu H, Ma X (2021) Design, optimization, and nanotechnology of antimicrobial peptides: from exploration to applications. Nano Today 39:101229. https://doi.org/10.1016/j.nantod.2021.101229
  • Masimen MAA, Harun NA, Maulidiani M, Ismail WIW (2022) Overcoming methicillin-resistance Staphylococcus aureus (MRSA) using antimicrobial peptides-silver nanoparticles. Antibiotics 11:951. https://doi.org/10.3390/antibiotics11070951
  • Surwade P, Ghildyal C, Weikel C, Luxton T, Peloquin D, Fan X et al (2019) Augmented antibacterial activity of ampicillin with silver nanoparticles against methicillin-resistant Staphylococcus aureus (MRSA). J Antibiot (Tokyo) 72:50–53. https://doi.org/10.1038/s41420111-6
  • Liao S, Zhang Y, Pan X, Zhu F, Jiang C, Liu Q et al (2019) Antibacterial activity and mechanism of silver nanoparticles against multidrug-resistant Pseudomonas aeruginosa. Int J Nanomedicine 14:1469–1487. https://doi.org/10.2147/IJN.S191340
  • Ha Gan B, Gaynord J, Rowe M, Deingruber S, Spring TR (2021) The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions. Chem Soc Rev 50:7820–7880. https://doi.org/10.1039/D0CS00729C
  • Lima PG, Oliveira JTA, Amaral JL, Freitas CDT, Souza PFN (2021) Synthetic antimicrobial peptides: characteristics, design, and potential as alternative molecules to overcome microbial resistance. Life Sci 278:119647. https://doi.org/10.1016/j.lfs.2021.119647
  • Bibens L, Becker J-P, Dassonville-Klimpt A, Sonnet P (2023) A review of fatty acid biosynthesis enzyme inhibitors as promising antimicrobial drugs. Pharmaceuticals 16:425. https://doi.org/10.3390/ph16030425
  • Idrees M, Mohammad AR, Karodia N, Rahman A (2020) Multimodal role of amino acids in microbial control and drug development. Antibiotics 9:330. https://doi.org/10.3390/antibiotics9060330
  • Sharma D, Garg A, Kumar M, Rashid F, Khan AU (2019) Down-regulation of flagellar, fimbriae, and pili proteins in carbapenem-resistant Klebsiella pneumoniae (NDM-4) clinical isolates: a novel linkage to drug resistance. Front Microbiol. https://doi.org/10.3389/fmicb.2019.02865
  • Erhardt M (2016) Strategies to block bacterial pathogenesis by interference with motility and chemotaxis. Curr Top Microbiol Immunol 398:185–205. https://doi.org/10.1007/82_2016_493
  • Dickey SW, Cheung GYC, Otto M (2017) Different drugs for bad bugs: antivirulence strategies in the age of antibiotic resistance. Nat Rev Drug Discov 16:457–471. https://doi.org/10.1038/nrd.2017.23
  • Rezzoagli C, Archetti M, Mignot I, Baumgartner M, Kümmerli R (2020) Combining antibiotics with antivirulence compounds can have synergistic effects and reverse selection for antibiotic resistance in Pseudomonas aeruginosa. PLoS Biol 18:e3000805. https://doi.org/10.1371/journal.pbio.3000805
  • Dehbanipour R, Ghalavand Z (2022) Anti-virulence therapeutic strategies against bacterial infections: recent advances. Germs 12:262–275. https://doi.org/10.18683/germs.2022.1328
  • Gordillo Altamirano FL, Barr JJ (2019) Phage therapy in the postantibiotic era. Clin Microbiol Rev. https://doi.org/10.1128/cmr.00066-18
  • Górski A, Międzybrodzki R, Węgrzyn G, Jończyk-Matysiak E, Borysowski J, Weber-Dąbrowska B (2020) Phage therapy: current status and perspectives. Med Res Rev 40:459–463. https://doi.org/10.1002/med.21593
  • Hatfull GF, Dedrick RM, Schooley RT (2022) Phage therapy for antibiotic-resistant bacterial infections. Annu Rev Med 73:197–211. https://doi.org/10.1146/annurev-med-080219-122208
  • Schmelcher M, Donovan DM, Loessner MJ (2012) Bacteriophage endolysins as novel antimicrobials. Future Microbiol 7:1147. https://doi.org/10.2217/fmb.12.97
  • Abavisani M, Hoseinzadeh M, Khayami R, Kodori M, Soleimanpour S, Sahebkar A (2025) Statins, allies against antibiotic resistance? Curr Med Chem 32(4):729–752. https://doi.org/10.2174/0929867331666230829141301
  • Abavisani M, Keikha M (2023) Global analysis on the mutations associated with multidrug-resistant urogenital mycoplasmas and ureaplasmas infection: a systematic review and meta-analysis. Ann Clin Microbiol Antimicrob 22(1):70. https://doi.org/10.1186/s12941-023-00627-6
  • Gajic I, Kabic J, Kekic D, Jovicevic M, Milenkovic M, Mitic Culafic D et al (2022) Antimicrobial susceptibility testing: a comprehensive review of currently used methods. Antibiotics 11:427. https://doi.org/10.3390/antibiotics11040427
  • Van Norman GA (2021) Decentralized clinical trials. JACC: Basic to Translational Science 6:384–387. https://doi.org/10.1016/j.jacbts.2021.01.011
  • Shlaes DM, Sahm D, Opiela C, Spellberg B (2013) The FDA reboot of antibiotic development. Antimicrob Agents Chemother 57:4605–4607. https://doi.org/10.1128/AAC.01277-13
  • Krendyukov A, Singhvi S, Zabransky M (2021) Value of adaptive trials and surrogate endpoints for clinical decision-making in rare cancers. Front Oncol 11:636561. https://doi.org/10.3389/fonc.2021.636561
  • Bhatt DL, Mehta C (2016) Adaptive designs for clinical trials. N Engl J Med 375:65–74. https://doi.org/10.1056/NEJMra1510061
  • Dartois VA, Rubin EJ (2022) Anti-tuberculosis treatment strategies and drug development: challenges and priorities. Nat Rev Microbiol 20:685–701. https://doi.org/10.1038/s41579-022-00731-y
  • Kerantzas CA, Jacobs WR (2017) Origins of combination therapy for tuberculosis: lessons for future antimicrobial development and application. mBio 8:e01586-16. https://doi.org/10.1128/mBio.01586-16
  • Yamin D, Uskoković V, Wakil AM, Goni MD, Shamsuddin SH, Mustafa FH et al (2023) Current and future technologies for the detection of Antibiotic-Resistant bacteria. Diagnostics 13:3246. https://doi.org/10.3390/diagnostics13203246
  • Kaprou GD, Bergšpica I, Alexa EA, Alvarez-Ordóñez A, Prieto M (2021) Rapid methods for antimicrobial resistance diagnostics. Antibiotics 10:209. https://doi.org/10.3390/antibiotics10020209
  • Wang H, Jia C, Li H, Yin R, Chen J, Li Y et al (2022) Paving the way for precise diagnostics of antimicrobial resistant bacteria. Front Mol Biosci. https://doi.org/10.3389/fmolb.2022.976705
  • Bordier M, Binot A, Pauchard Q, Nguyen DT, Trung TN, Fortané N et al (2018) Antibiotic resistance in Vietnam: moving towards a one health surveillance system. BMC Public Health 18:1136. https://doi.org/10.1186/s12889-018-6022-4
  • Wu D, Walsh TR, Wu Y (2021) World Antimicrobial Awareness Week 2021 — spread awareness, stop resistance. China CDC Wkly 3:987–993. https://doi.org/10.46234/ccdcw2021.241
  • Mathew P, Sivaraman S, Chandy S (2019) Communication strategies for improving public awareness on appropriate antibiotic use: bridging a vital gap for action on antibiotic resistance. J Fam Med Prim Care 8:1867. https://doi.org/10.4103/jfmpc.jfmpc_263_19
  • Suay-García B, Pérez-Gracia MT (2021) Present and Future of Carbapenem-Resistant Enterobacteriaceae Infections. Advances in Clinical Immunology, Medical Microbiology, COVID-19, and Big Data. Jenny Stanford Publishing
  • Tilahun M, Kassa Y, Gedefie A, Ashagire M (2021) Emerging carbapenem-resistant Enterobacteriaceae infection, its epidemiology and novel treatment options: a review. Infect Drug Resist 14:4363–4374. https://doi.org/10.2147/IDR.S337611
  • Aziz A-M (2013) The role of healthcare strategies in controlling antibiotic resistance. Br J Nurs Mark Allen Publ 22:1066–1074. https://doi.org/10.12968/bjon.2013.22.18.1066