Bacterial Antibiotic Resistance: on the Cusp of a Post-antibiotic World

  • Kameron Sprigg
  • Carolynn E. PietrangeliEmail author
Neglected Tropical Diseases (A Sanchez, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Neglected Tropical Diseases


Purpose of review

The specific aim of this article is to provide evidence that antibiotic resistance (AR) has become a human disease unto itself and to describe the current means of preventing, treating, and reversing AR in individuals and in affected populations.

Recent findings

An ever-increasing number of infections are being classified as multidrug resistant (MDR). Low and middle-income countries are most likely to increase the spread of AR due to limited healthcare infrastructure coupled with policies that promote unregulated access to antibiotics. The genetic basis for AR has become more thoroughly understood as efforts move toward a global big data approach to surveille and implement effective public health measures.


Antibiotic Stewardship (AS) programs are critical to prevent the spread of AR. As resistant pathogens reside in patients for many years after they are initially integrated into the microbiome, the potential for future infection increases substantially. This property contributes to the conclusion that AR is in and of itself a human disease that must be treated appropriately. While all bacteria are at risk to become AR, Staphylococcus, Klebsiella, Mycobacterium, Acinetobacter, and Pseudomonas represent the greatest challenges in infectious disease treatment as rapid AR acquisition leads to MDR infections.


Antibiotic resistance Antibiotic stewardship Multi-drug-resistance Extreme drug resistance Klebsiella pneumoniae carbapenemase Carbapenem-resistant Enterobacteriaceae 


Compliance with ethical standards

Conflict of interest

Kameron Sprigg declares that there are no competing interests.

Carolynn E. Pietrangeli declares that there are no competing interests.

Human and animal rights and informed consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Supplementary material

40506_2019_181_MOESM1_ESM.docx (66 kb)
ESM 1 (DOCX 45 kb)

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Bushake L, A Brief History of antibiotic resistance [Internet]. Medical Daily. 2018 [cited 2 June 2018]. Available from: Accessed 2 Jun 2018.
  2. 2.
    Khan F, Arthur J, Maidment L, Blue D. Advancing antimicrobial stewardship: summary of the 2015 CIDSC report. Can Commun Dis Rep. 2016;42(11):238–41. Scholar
  3. 3.
    Antibiotic Stewardship | Antibiotic/antimicrobial resistance | CDC [Internet]. 2018 [cited 15 June 2018]. Available from: Accessed 15 Jun 2018.
  4. 4.
    Hughes D, Andersson D. Selection of resistance at lethal and non-lethal antibiotic concentrations. Curr Opin Microbiol. 2012;15(5):555–60. Scholar
  5. 5.
    Goossens H. Antibiotic consumption and link to resistance. Clin Microbiol Infect. 2009;15:12–5. Scholar
  6. 6.
    Balcazar J. Bacteriophages as vehicles for antibiotic resistance genes in the environment. PLoS Pathog. 2014;10(7):e1004219. Scholar
  7. 7.
    Karp G, Iwasa J, Marshall W. Cell and Molecular Biology. Hoboken, NJ: John Wiley & Sons, Inc.; 2015.Google Scholar
  8. 8.
    Toleman M, Bennett P, Walsh T. ISCR elements: novel gene-capturing systems of the 21st century? Microbiol Mol Biol Rev. 2006;70(2):296–316. Scholar
  9. 9.
    Das I, Lambert P, Hill D, Noy M, Bion J, Elliott T. Carbapenem-resistant Acinetobacter and role of curtains in an outbreak in intensive care units. J Hosp Infec. 2002;50(2):110–4. Scholar
  10. 10.
    Kumar A, Randhawa V, Nirupam N, Rai Y, Saili A. Risk factors for carbapenem-resistant Acinetobacter baumanii blood stream infections in a neonatal intensive care unit, Delhi, India. J Infec in Dev Ctries. 2014;8(08):1049–54. Scholar
  11. 11.
    Gozutok F, Mutlu Sariguzel F, Celik I, Berk E, Aydin B, Guzel D. Investigation of antimicrobial resistance rates of Acinetobacter baumannii strains from nosocomial infections. Ankem Derg. 2013;27(1):7–12. Scholar
  12. 12.
    Kireçcí E, Kireçcí M, Aksu M. Investigation of the antibiotic susceptibility of Acinetobacter baumannii strains isolated from clinical samples. Türk Mikrobiol Cemiy Derg. 2015;13(4):266–70.Google Scholar
  13. 13.
    Khajuria A. Molecular characterization of carbapenem resistant isolates of Acinetobacter baumannii in an intensive care unit of a tertiary care centre at Central India. J Clin Diagn Res. 2014;8(5):DC38–40. Scholar
  14. 14.
    Wang H, Wang J, Yu P, Ge P, Jiang Y, Xu R, et al. Identification of antibiotic resistance genes in the multidrug-resistant Acinetobacter baumannii strain, MDR-SHH02, using whole-genome sequencing. Int J Mol Med. 2016;39(2):364–72.CrossRefGoogle Scholar
  15. 15.
    Buyuk A, Yilmaz F, Gul Yurtsever S, Hosgor Limoncu M. Antibiotic resistance profiles and genotypes of Acinetobacter baumannii isolates and in vitro interactions of various antibiotics in combination with tigecycline and colistin. Turk J Pharma Sci. 2017;14(1):13–8. Scholar
  16. 16.
    Khyriem A, Lyngdoh W, Banik A, Choudhury B, Bhattacharyya P, Gurung J. Association of biofilm production with multidrug resistance among clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa from intensive care unit. Indian J of Crit Care Med. 2013;17(4):214–8. Scholar
  17. 17.
    Nunez M, Simarro E, Martinez-Campos L, Ruiz J, Gomez J, Perez J. Evolution of resistance among clinical isolates of Acinetobacter over a 6-year period. Eur J Clin Microbiol Infect Dis. 1999;18(4):292–5. Scholar
  18. 18.
    Luo Y, Wang Y, Ye L, Yang J. Molecular epidemiology and virulence factors of pyogenic liver abscess causing Klebsiella pneumoniae in China. Clin Microbiol Infect. 2014;20(11):O818–24. Scholar
  19. 19.
    Navon-Venezia S, Kondratyeva K, Carattoli A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol Revs. 2017;41(3):252–75.CrossRefGoogle Scholar
  20. 20.
    Kidd T, Mills G, Sá-Pessoa J, Dumigan A, Frank C, Insua J, et al. A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host defences and promotes virulence. EMBO Molecular Medicine. 2017;9:430–47. Scholar
  21. 21.
    Padmini N, Ajilda A, Sivakumar N, Selvakumar G. Extended spectrum β-lactamase producing Escherichia coli and Klebsiella pneumoniae: critical tools for antibiotic resistance pattern. J Basic Microbiol. 2017;57(6):460–70. Scholar
  22. 22.
    Sahu M, Siddharth B, Choudhury A, Vishnubhatla S, Singh S, Menon R, et al. Incidence, microbiological profile of nosocomial infections, and their antibiotic resistance patterns in a high volume cardiac surgical intensive care unit. Ann Card Anaesth. 2016;19(2):281–7. Scholar
  23. 23.
    Summary of the latest data on antibiotic resistance in the European Union [Internet]. European Union; 2018 p. 1–8. Available from: Accessed 30 Jun 2018.
  24. 24.
    Ruh E, Gazi U, Güvenir M, Süer K, Çakır N. Antibiotic resistance rates of Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae isolated from a university-affiliated hospital in North Cyprus. Turk Bull Hyg Exper Biol. 2016;73(4):333–44. Scholar
  25. 25.
    Ullah W, Qasim M, Rahman H, Jie Y, Muhammad N. Beta-lactamase-producing Pseudomonas aeruginosa: phenotypic characteristics and molecular identification of virulence genes. J Chin Med Assoc. 2017;80(3):173–7. Scholar
  26. 26.
    Feng Y, Hodiamont C, van Hest R, Brul S, Schultsz C, ter Kuile B. Development of antibiotic resistance during simulated treatment of Pseudomonas aeruginosa in chemostats. PLoS One. 2016;11(2):e0149310. Scholar
  27. 27.
    Swetha C, Babu A, Rao K, Bharathy S, Supriya R, Rao T. A study on the antimicrobial resistant patterns of Pseudomonas Aeruginosa isolated from raw milk samples in and around Tirupati, Andhra Pradesh. Asian J Dairy and Food Res. 2017;36(02):100–5.
  28. 28.
    Antimicrobial resistance: global report on surveillance [internet]. WHO; 2014. Available from:;jsessionid=674CF15427C38E6822B8A0BAF121ED71?sequence=1. Accessed 30 Jun 2018.
  29. 29.
    Cheraghi S, Pourgholi L, Shafaati M, Fesharaki S, Jalali A, Nosrati R, et al. Analysis of virulence genes and accessory gene regulator (agr) types among methicillin-resistant Staphylococcus aureus strains in Iran. J of Glob Antimicrob Resist. 2017;10:315–20. Scholar
  30. 30.
    Gostev V, Kruglov A, Kalinogorskaya O, Dmitrenko O, Khokhlova O, Yamamoto T, et al. Molecular epidemiology and antibiotic resistance of methicillin-resistant Staphylococcus aureus circulating in the Russian Federation. Infect Genet Evol. 2017;53:189–94. Scholar
  31. 31.
    Ontario Agency for Health Protection and Promotion (Public Health Ontario), Provincial Infectious Diseases Advisory Committee. Infection prevention and control for clinical office practice. 1st revision ed. Toronto, ON: Queen’s Printer for Ontario; 2015.Google Scholar
  32. 32.
    Hawn T, Shah J, Kalman D. New tricks for old dogs: countering antibiotic resistance in tuberculosis with host-directed therapeutics. Immuno Revs. 2015;264(1):344–62.CrossRefGoogle Scholar
  33. 33.
    Fonseca J, Knight G, McHugh T. The complex evolution of antibiotic resistance in Mycobacterium tuberculosis. Intl J of Infec Dis. 2015;32:94–100.CrossRefGoogle Scholar
  34. 34.
    Liu F, Hu Y, Wang Q, Li H, Gao G, Liu C, et al. Comparative genomic analysis of Mycobacterium tuberculosis clinical isolates. BMC Genomics. 2014;15(1):469. Scholar
  35. 35.
    Nguyen L. Antibiotic resistance mechanisms in M. tuberculosis: an update. Arch Toxicol. 2016;90(7):1585–604. Scholar
  36. 36.
    Gandhi N, Moll A, Sturm A, Pawinski R, Govender T, Lalloo U, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006;368(9547):1575–80. Scholar
  37. 37.
    O’Donnell M, Padayatchi N, Kvasnovsky C, Werner L, Master I, Horsburgh C. Treatment outcomes for extensively drug-resistant tuberculosis and HIV co-infection. Emerg Infect Dis. 2013;19(3):416–24. Scholar
  38. 38.
    Iem V, Somphavong S, Buisson Y, Steenkeste N, Breysse F, Chomarat M, et al. Resistance of Mycobacterium tuberculosis to antibiotics in Lao PDR: first multicentric study conducted in 3 hospitals. BMC Infect Dis. 2013;13(1):275. Scholar
  39. 39.
    Shoji H, Maeda M, Shirakura T, Takuma T, Ugajin K, Fukuchi K, et al. More accurate measurement of vancomycin minimum inhibitory concentration indicates poor outcomes in meticillin-resistant Staphylococcus aureus bacteraemia. Int J Antimicrob Agents. 2015;46(5):532–7.CrossRefGoogle Scholar
  40. 40.
    Matar M, Moghnieh R, Alothman A, Althaqafi A, Alenazi T, Farahat F, et al. Treatment patterns, resource utilization, and outcomes among hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections in Lebanon and Saudi Arabia. Infec and Drug Resist. 2017;10:43–8. Scholar
  41. 41.
    Menzin J, Marton J, Meyers J, Carson R, Rothermel C, Friedman M. Inpatient treatment patterns, outcomes, and costs of skin and skin structure infections because of Staphylococcus aureus. Am J Infec Cntl. 2010;38:44–9.CrossRefGoogle Scholar
  42. 42.
    Blake D, Hillman K, Fenlon D, Low J. Transfer of antibiotic resistance between commensal and pathogenic members of the Enterobacteriaceae under ileal conditions. J Appl Microbiol. 2003;95:428–36. Scholar
  43. 43.
    Austin DJ, Kristinsson KG, Anderson RM. The relationship between the volume of antimicrobial consumption in human communities and the frequency of resistance. PNAC. 1999;96:1152–6.CrossRefGoogle Scholar
  44. 44.
    Martinez JL, Baquero F. Mutation frequencies and antibiotic resistance. Antimicrob Agents Chemother. 2000;44:1771–7. Scholar
  45. 45.
    Bebell LM, Muiru AN. Antibiotic use and emerging resistance. Glob Heart. 2014;9:347–58. Scholar
  46. 46.
    Theuretzbacher U. Global antibacterial resistance: the never-ending story. J of Glob Antimicrob Resist. 2013;1:63–9. Scholar
  47. 47.
    Pugliese G, Favero MS. Airplane cabin air recirculation and risk of upper respiratory tract infection. Infect Control Hosp Epidemiol. 2002;23:554. Scholar
  48. 48.
    Leung E, Weil DE, Raviglione M, Nakatani H. The WHO policy package to combat antimicrobial resistance. Bull World Health Organ. 2011;89:390–2. Scholar
  49. 49.
    FACT SHEET. Obama administration releases National Action Plan to combat antibiotic- resistant bacteria. Washington D.C.: the white house; 2017.Google Scholar
  50. 50.
    Schürch AC, Schaik WV. Challenges and opportunities for whole-genome sequencing-based surveillance of antibiotic resistance. Ann N Y Acad Sci. 2017;1388:108–20. Scholar
  51. 51.
    Le T-T, Nadimpalli M, Wu J, Heaney CD, Stewart JR. Challenges in estimating characteristics of Staphylococcus aureus nasal carriage among humans enrolled in surveillance studies. Front Public Health. 2018;6:163.CrossRefGoogle Scholar
  52. 52.
    Kimura T, Uda A, Sakaue T, Yamashita K, Nishioka T, Nishimura S, et al. Long-term efficacy of comprehensive multidisciplinary antibiotic stewardship programs centered on weekly prospective audit and feedback. Infection. 2017;46:215–24.CrossRefGoogle Scholar
  53. 53.
    Liu L, Liu B, Li Y, Zhang W. Successful control of resistance in Pseudomonas aeruginosa using antibiotic stewardship and infection control programs at a Chinese university hospital: a 6-year prospective study. Infec & Drug Resist. 2018;Volume 11:637–46. Scholar
  54. 54.
    Murni IK, Duke T, Kinney S, Daley AJ, Soenarto Y. Reducing hospital-acquired infections and improving the rational use of antibiotics in a developing country: an effectiveness study. Arch Dis Child. 2014;100:454–9.CrossRefGoogle Scholar
  55. 55.
    Lawes T, Lopez-Lozano J-M, Nebot CA, Macartney G, Subbarao-Sharma R, Dare CR, et al. Effects of national antibiotic stewardship and infection control strategies on hospital-associated and community-associated meticillin-resistant Staphylococcus aureus infections across a region of Scotland: a non-linear time-series study. Lancet Infect Dis. 2015;15:1438–49. Scholar
  56. 56.
    Boyles TH, Naicker V, Rawoot N, Raubenheimer PJ, Eick B, Mendelson M. Sustained reduction in antibiotic consumption in a South African public sector hospital; four year outcomes from the Groote Schuur Hospital antibiotic stewardship program. South African Med J. 2017;107:115–8. Scholar
  57. 57.
    Inácio J, Barnes L-M, Jeffs S, Castanheira P, Wiseman M, Inácio S, et al. Master of pharmacy students’ knowledge and awareness of antibiotic use, resistance and stewardship. Curr in Pharm Teach & Learn. 2017;9:551–9. Scholar
  58. 58.
    Minen MT, Duquaine D, Marx MA, Weiss D. A survey of knowledge, attitudes, and beliefs of medical students concerning antimicrobial use and resistance. Microb Drug Resist. 2010;16:285–9. Scholar
  59. 59.
    Garau J, Nicolau DP, Wullt B, Bassetti M. Antibiotic stewardship challenges in the management of community-acquired infections for prevention of escalating antibiotic resistance. J of Glob Antimicrob Resist. 2014;2:245–53. Scholar
  60. 60.
    Butt AA, Navasero CS, Thomas B, Marri SA, Katheeri HA, Thani AA, et al. Antibiotic prescription patterns for upper respiratory tract infections in the outpatient Qatari population in the private sector. Intl J Infec Dis. 2017;55:20–3.CrossRefGoogle Scholar
  61. 61.
    • Pitiriga V, Vrioni G, Saroglou G, Tsakris A. The impact of antibiotic stewardship programs in combating quinolone resistance: a systematic review and recommendations for more efficient interventions. Adv Ther. 2017;34:854–65. This study demonstrates the health and economic benefits seen by hospitals implementing antibiotic stewardship programs in a thorough systematic review, as well as offering ideas to improve on techniques being used today.CrossRefPubMedGoogle Scholar
  62. 62.
    Tartari E, Pires D, Pittet D. Clean your hands 5th May 2017: fight antibiotic resistance - its in your hands. Antimicrob Resist Infec Cntrl. 2017;45(4):342.Google Scholar
  63. 63.
    Lushniak BD. Antibiotic resistance: a public health crisis. Public Health Rep. 2014;129:314–6. Scholar
  64. 64.
    Perez KK, Olsen RJ, Musick WL, Cernoch PL, Davis JR, Peterson LE, et al. Integrating rapid diagnostics and antimicrobial stewardship improves outcomes in patients with antibiotic-resistant Gram-negative bacteremia. J of Infec. 2014;69:216–25. Scholar
  65. 65.
    Okeke IN, Peeling RW, Goossens H, Auckenthaler R, Olmsted SS, de Lavison JF, et al. Diagnostics as essential tools for containing antibacterial resistance. Drug Resist Updat. 2011;14:95–106. Scholar
  66. 66.
    Niwa T, Watanabe T, Suzuki K, Hayashi H, Ohta H, Nakayama A, et al. Early optimization of antimicrobial therapy improves clinical outcomes of patients administered agents targeting methicillin-resistant Staphylococcus aureus. J Clin Pharm Ther. 2015;41:19–25.CrossRefGoogle Scholar
  67. 67.
    Köser CU, Ellington MJ, Peacock SJ. Whole-genome sequencing to control antimicrobial resistance. Trends Genet. 2014;30:401–7. Scholar
  68. 68.
    Reddy PN, Srirama K, Dirisala VR. An update on clinical burden, diagnostic tools, and therapeutic options of Staphylococcus aureus. Infec Dis: Res and Treat. 2017;10:117991611770399.Google Scholar
  69. 69.
    Peeling RW, Boeras DI, Nkengasong J. Re-imagining the future of diagnosis of neglected tropical diseases. Compu and Struct Biotech J. 2017;15:271–4. Scholar
  70. 70.
    Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010;54:969–76. Scholar
  71. 71.
    Liu B, Pop M. ARDB—antibiotic resistance genes database. Nucleic Acids Res. 2009;37:D443–7. Scholar
  72. 72.
    •• Mcarthur AG, Wright GD. Bioinformatics of antimicrobial resistance in the age of molecular epidemiology. Curr Op Microbiol. 2015;27:45–50. This study outlines a feasible framework for implementing global data collection as a tool for surveillance and diagnostic capacity of antibiotic resistance in new infections. Scholar
  73. 73.
    Mourad R, Sinoquet C, Leray P. Probabilistic graphical models for genetic association studies. Briefings in Bioinf. 2011;13:20–33.CrossRefGoogle Scholar
  74. 74.
    Morar M, Wright GD. The genomic enzymology of antibiotic resistance. Annu Rev Genet. 2010;44:25–51. Scholar
  75. 75.
    Illumina. Personal correspondence - MiniSeq sequencer small affordable benchtop sequencer. 2017. Accessed 16 Jan 2019.
  76. 76.
    Farrar JS, Wittwer CT. Extreme PCR: efficient and specific DNA amplification in 15-60 seconds. Clin Chem. 2014;61:145–53.CrossRefGoogle Scholar
  77. 77.
    Tanner NA, Zhang Y, Evans TC. Visual detection of isothermal nucleic acid amplification using pH-sensitive dyes. BioTechniques. 2015;58:59–68. Scholar
  78. 78.
    Hu C, Kalsi S, Zeimpekis I, Sun K, Ashburn P, Turner C, et al. Ultra-fast electronic detection of antimicrobial resistance genes using isothermal amplification and thin film transistor sensors. Biosens Bioelectron. 2017;96:281–7. Scholar
  79. 79.
    Credo GM, Su X, Wu K, Elibol OH, Liu DJ, Reddy B, et al. Label-free electrical detection of pyrophosphate generated from DNA polymerase reactions on field-effect devices. Analyst. 2012;137:1351–62. Scholar
  80. 80.
    Górski A, Międzybrodzki R, Weber-Dąbrowska B, Fortuna W, Letkiewicz S, Rogóż P, et al. Phage therapy: combating infections with potential for evolving from merely a treatment for complications to targeting diseases. Front Microbiol. 2016;7:1515. Scholar
  81. 81.
    Atterbury RJ, Hobley L, Till R, Lambert C, Capeness MJ, Lerner TR, et al. Effects of orally administered Bdellovibrio bacteriovorus on the well-being and Salmonella colonization of young chicks. Appl Environ Microbiol. 2011;77:5794–803. Scholar
  82. 82.
    O’Neill J. Antimicrobial resistance: tackling a crisis for the health and wealth of nations. Antimicrob Resist. 2014;1:1–14.Google Scholar
  83. 83.
    Gomes ALC, Galagan JE, Segrè D. Resource competition may lead to effective treatment of antibiotic resistant infections. PLoS One. 2013;8:e80775. Scholar
  84. 84.
    Palmer AC, Angelino E, Kishony R. Erratum: corrigendum: chemical decay of an antibiotic inverts selection for resistance. Nat Chem Biol. 2010;6:244–9. Scholar
  85. 85.
    Ahuja SD, Ashkin D, Avendano M, Banerjee R, Bauer M, et al. Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: An Individual patient data meta-analysis of 9,153 patients. PLoS Med. 2012;9(8):e10001300.

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Authors and Affiliations

  1. 1.Department of Health SciencesBrock UniversitySt. CatharinesCanada

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