Introduction to Antibiotic Resistance

Part of the Handbook of Experimental Pharmacology book series (HEP, volume 211)


The inexorable rise in multidrug-resistant Gram-negative bacteria has been widely reported. Multiple modes of resistance often present in a single strain of bacteria, and this may also be combined with an increase in virulence, both of which are leading to a significant increase in morbidity and mortality in patients. Against this background, the absolute number of new antibiotics licensed has declined especially for Gram-negative multidrug-resistant pathogens. The reasons for this failure are presented here: market issues, big pharma changes, regulatory constraints, difficulties in finding drugable targets and, lastly, suitable compounds worthy of full development.


Antibiotic resistance Gram-positive bacteria Gram-negative bacteria Regulatory 


  1. Arias CA, Murray BE (2012) Antibiotic-resistant bugs in the 21st century – a clinical super challenge. N Engl J Med 360(5):439–43CrossRefGoogle Scholar
  2. Bax RP, Anderson R, Crew J et al (1998) Antibiotic resistance—What can we do? Nat Med 4(5):545–6PubMedCrossRefGoogle Scholar
  3. Bax RP, Gabbay F, Phillips I (1999) The Witley Park Study Group. Clin Microbiol Infect 5(12):774–778Google Scholar
  4. Boucher HW, Talbot GH, Bradey JS, Edwards JE, Gilbert D, Rise LB et al (2009) Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infectious Dis 48:1–12CrossRefGoogle Scholar
  5. Bouchett W, Talbot GH, Bradley JS (2009) Bad bugs, no drugs: no ESCAPE. Clin Infect Dis 48:1–12CrossRefGoogle Scholar
  6. Cuny C, Friedrich A, Kozytska S, Layer F, Nübel U, Ohlsen K, Strommenger B, Walther B, Wieler L, Witte W (2010) Emergence of methicillin-resistant Staphylococcus aureus (MRSA) in different animal species. Int J Med Microbiol 300(2–3):109–17PubMedCrossRefGoogle Scholar
  7. Dufour P, Gillet Y, Bes M, Lina G, Vandenesch F, Floret D, Etienne J, Richet H (2002) Community-acquired methicillin-resistant Staphylococcus aureus infections in France: emergence of a single clone that produces Panton-Valentine leukocidin. Clin Infect Dis 35(7):819–24PubMedCrossRefGoogle Scholar
  8. Falagas ME, Rizos M, Bliziotis A (2005) Toxicity after prolonged administration of intravenous colistin. BML Infect Dis 5(1):1–8CrossRefGoogle Scholar
  9. Finch R (2011) J Antimicrob Chemother 66:1945–1947PubMedCrossRefGoogle Scholar
  10. Giamarellou H (2009) Multi-drug resistant Gram-negative infections. Drugs 69(14):1879–1901PubMedCrossRefGoogle Scholar
  11. Gopalakrishnan R, Sureshkumar D (2010) Changing trends in antimicrobial susceptibility and hospital acquired infections over an 8 year period in a tertiary care hospital in relation to introduction of an infection control programme. J Assoc Physicians India 58(Suppl):25–31PubMedGoogle Scholar
  12. Infectious Disease Society of America (2004) Bad bugs, no drugs. As antibiotic discovery stagnates… A Public Health Crisis BrewsGoogle Scholar
  13. Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, Chaudhary U, Doumith M, Giske CG, Irfan S, Krishnan P, Kumar AV, Maharjan S, Mushtaq S, Noorie T, Paterson DL, Pearson A, Perry C, Pike R, Rao B, Ray U, Sarma JB, Sharma M, Sheridan E, Thirunarayan MA, Turton J, Upadhyay S, Warner M, Welfare W, Livermore DM, Woodford N (2010) Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. The Lancet Infectious Diseases 10(9):597–602Google Scholar
  14. Livermore DM (2004) The need for new antibiotics. Clin Microbiol Infect 10(suppl 4):1–9PubMedCrossRefGoogle Scholar
  15. Livermore DM (2009) Has the era of unbeatable infections arrived? J Antimicrob Chemother 64(suppl 1):i29–i36PubMedCrossRefGoogle Scholar
  16. Livermore DM, Sefton AM, Scott GM (2003) Properties and potential of ertapenem. J Antimicrob Chemother 52(3):331–44PubMedCrossRefGoogle Scholar
  17. Livermore DM, Mushtag S, Warner M et al (2011) Activities of NXL 104 combination with ceftazidime and azthreonam against carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother 55:390–4PubMedCrossRefGoogle Scholar
  18. Meyer E, Schwab F, Schroeren-Boersch B, Gastmeier P (2010) Dramatic increase of third-generation cephalosporin-resistant E. coli in German intensive care units: secular trends in antibiotic drug use and bacterial resistance, 2001 to 2008. Crit Care 14(3):113CrossRefGoogle Scholar
  19. Page MGP, Clothilde D, Eric D (2012) In vitro properties of BAL30072, a novel siderophore sulfactin with activity against multiresistant Gram-negative Bacilli. Antimicrob Agents Chemother 6:2291–2302Google Scholar
  20. Peleg AY, Hooper DC (2010) Hospital-acquired infections due to Gram-negative bacteria. N Engl J Med 362(19):1804–1813PubMedCrossRefGoogle Scholar
  21. Pitout JDD, Laupland KB (2008) Extended B-lactamase producing Enterobacteriaceae: an emerging problem. Lancet Infect Dis 8:159–66PubMedCrossRefGoogle Scholar
  22. Poirel L, Pitout JD, Nordmann P (2007) Carbapenemases: molecular diversity and clinical consequences. Fut Microbiol 2:501–12CrossRefGoogle Scholar
  23. Potron A, Poirel L, Nordmann P (2011) Plasmid-mediated transfer of the bla(NDM-1) gene in Gram-negative rods. FEMS Microbiol Lett 324(2):111–6PubMedCrossRefGoogle Scholar
  24. Sader HS, Streit JM, Fritsche TR, Jones RN (2006) Antimicrobial susceptibility of gram-positive bacteria isolated from European medical centres: results of the Daptomycin Surveillance Programme (2002–2004). Clin Microbiol Infect 12(9):844–52PubMedCrossRefGoogle Scholar
  25. Silver LL (2011) Challenges of antibacterial discovery. Clin Microbiol Rev 24:71–109PubMedCrossRefGoogle Scholar
  26. So AD, Gupta N, Cars O (2012) Tackling antibiotic resistance. BMJ 340:1091–96Google Scholar
  27. Taubes G (2008) The bacteria fight back. Science 321(5887):356–61PubMedCrossRefGoogle Scholar
  28. van Duijn PJ, Dautzenberg MJ, Oostdijk EA (2011) Recent trends in antibiotic resistance in European ICUs. Curr Opin Crit Care 17(6):658–65PubMedCrossRefGoogle Scholar
  29. Vincent JL, Rello J, Marshall J (2009) International Study of the prevalence and outcomes of infection in intensive care Units 2009. JAMA 302(21):2323–29PubMedCrossRefGoogle Scholar
  30. Walsh TR, Weeks J, Livermore DM, Toleman MA (2011) Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study. The Lancet Infectious Diseases 11(5):355–362Google Scholar
  31. Williams KJ, Bax RP (2009) Challenges in developing new antibacterial drugs. Curr Opin Invest Drugs 10(2):157–163Google Scholar
  32. Woodford N (2008) Successful, multiresistant clones. J Antimicrob Chemother 61(2):233–4PubMedCrossRefGoogle Scholar
  33. Woodford N, Turton JF, Livermore DM (2011) Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance. FEMS Microbiol Rev 35(5):736–55PubMedCrossRefGoogle Scholar
  34. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, Walsh TR (December 2009) Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 53(12):5046–5054Google Scholar

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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.TranScrip Partners LLPReadingUK

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