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Bacterial Resistance to Fluoroquinolones: Mechanisms and Patterns

  • David C. Hooper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 390)

Abstract

Fluoroquinolones have been used increasingly in clinical medicine in the United States since the approval of norfloxacin, the first of these agents, by the U.S. Food and Drug Administration in 1986. Approvals of ciprofloxacin, ofloxacin, temafloxacin, lomefloxacin, and enoxacin followed, and other fluoroquinolones are under development. Although a nonfluorinated quinolone, nalidixic acid, has been available since the 1960s, its use was limited to treatment of urinary tract infections. Because of their greater potency and spectrum of activity and their extensive tissue distribution, many of the fluoroquinolones have been used to treat a broad range of infections at different body sites. Because of economic pressures, it is likely that oral antibiotics like the fluoroquinolones will be relied on increasingly in the future.

Keywords

Minimal Inhibitory Concentration Nalidixic Acid Antimicrob Agent Quinolone Resistance Multiple Antibiotic Resistance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    M. Gellert, DNA topoisomerases, Annu Rev Biochem. 50: 879 (1981).PubMedCrossRefGoogle Scholar
  2. 2.
    R.J. Reece and A. Maxwell, DNA gyrase: structure and function, Crit Rev Biochem Molec Biol. 26: 335 (1991).CrossRefGoogle Scholar
  3. 3.
    K.N. Kreuzer and N.R. Cozzarelli, Escherichia coli mutants thermosensitive for deoxyribonucleic acid gyrase subunit A: effects on deoxyribonucleic acid replication, transcription, and bacteriophage growth, J Bacteriol. 140: 424 (1979).PubMedGoogle Scholar
  4. 4.
    D.C. Hooper and J.S. Wolfson, Mechanisms of quinolone action and bacterial killing, in: “Quinolone Antimicrobial Agents,” Second Edition, D.C. Hooper and J.W. Wolfson, eds., American Society for Microbiology, Washington (1993).Google Scholar
  5. 5.
    H. Nikaido, Role of permeability barriers in resistance to J3-lactam antibiotics, Pharmacol Ther. 27: 197 (1985).PubMedCrossRefGoogle Scholar
  6. 6.
    J.S. Chapman and N.H. Georgopadakou, Routes of quinolonc permeatin in Escherichia coli, Antimicrob Agents Chemother. 32: 438 (1988).PubMedCrossRefGoogle Scholar
  7. 7.
    H. Nikaido and D.G. Thanassi, Penetration of lipophilic agents with multiple protonation sites into bacterial cells: tetracyclines and fluoroquinolones as examples, Antimicrob Agents Chemother. 37: 1393 (1993).PubMedCrossRefGoogle Scholar
  8. 8.
    H. H. Yoshida, M. Bogaki, S. Nakamura, K. Ubukata, and M. Konno, Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones, J Bacteriol. 172: 6942 (1990).PubMedGoogle Scholar
  9. 9.
    M.E. Cullen, A.W. Wyke, R. Kuroda, and L.M. Fisher, Cloning and characterization of a DNA gyrase A gene from Escherichia coli that confers clinical resistance to 4-quinolones. Antimicrob Agents Chemother. 33: 886 (1989).PubMedCrossRefGoogle Scholar
  10. 10.
    M. Oram and L.M. Fisher, 4-quinolone resistance mutations in the DNA gyrase of Escherichia coli clinical isolates identified by using the polymerase chain reaction, Antimicrob Agents Chemother. 35: 387 (1991).PubMedCrossRefGoogle Scholar
  11. 11.
    H. Yoshida, M. Bogaki, M. Nakamura, and S. Nakamura, Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli, Antimicrob Agents Chemother. 34: 1271 (1990).PubMedCrossRefGoogle Scholar
  12. 12.
    H. Yoshida, T. Kojima, J. Yamagishi, and S. Nakamura, Quinolone-resistant mutations of the gyrA gene of Escherichia coli, Mol Gen Genet. 211: 1 (1988).PubMedCrossRefGoogle Scholar
  13. 13.
    J.S. Wolfson and D.C. Hooper, Fluoroquinolone antimicrobial agents, Clin Microbiol Rev. 2: 378 (1989).PubMedGoogle Scholar
  14. 14.
    C.J.R. Willmott and A. Maxwell, A single point mutation in the DNA gyrase A protein greatly reduces binding of fluoroquinolones to the gyrase-DNA complex, Antimicrob Agents Chemother. 37: 126 (1993).PubMedCrossRefGoogle Scholar
  15. 15.
    P. Heisig, H. Schedletsky, and H. Falkenstein-Paul, Mutations in the gyrA gene of a highly fluoroquinolone-resistant clinical isolate of Escherichia coli, Antimicrob Agents Chemother. 37: 696 (1993).PubMedCrossRefGoogle Scholar
  16. 16.
    E. Cambau, F. Bordon, E. Collatz, and L. Gutmann, Novel gyrA point mutation in a strain of Escherichia coli resistant to fluoroquinolones but not to nalidixic acid, Antimicrob Agents Chemother. 37: 1247 (1993).PubMedCrossRefGoogle Scholar
  17. 17.
    H. Yoshida, M. Bogaki, M. Nakamura, L.M. Yamanaka, and S. Nakamura. 1991. Quinolone resistance-determining region of the DNA gyrase gyrB gene of Escherichia coli, Antimicrob Agents Chemother. 35: 1647 (1991).Google Scholar
  18. 18.
    J. Yamagichi, H. Yoshida, M. Yamayoshi, and S. Nakamura, Nalidixic acid-resistant mutations of the gyrB gene of Escherichia coli, Mol. Gen. Genet. 204: 367 (1986).CrossRefGoogle Scholar
  19. 19.
    L.L. Shen, W.E. Kohlbrenner, D. Weigl, and J. Baranowski, Mechanism of quinolone inhibition of DNA gyrase. Appearance of unique norfloxacin binding sites in enzyme-DNA complexes J. Biol. Chem. 264: 2973 (1989).PubMedGoogle Scholar
  20. 20.
    L.L. Shen, L.A. Mitscher, P.N. Sharma, T.J. O’Donnell, D.W.T. Chu, C.S. Cooper, T. Rosen, and A.G. Pernet. Mechanism of inhibition of DNA gyrase by quinolone antibacterials: a cooperative drug-DNA binding model, Biochemistry 28: 3886 (1989).PubMedCrossRefGoogle Scholar
  21. 21.
    H. Yoshida, M. Nakamura, M. Bogaki, H. Ito, T. Kojima, H. Hattori, and S. Nakamura, Mechanism of action of quinolones against Escherichia coli DNA gyrase, Antimicrob Agents Chemother. 37: 839 (1993).PubMedCrossRefGoogle Scholar
  22. 22.
    T. Kirchhausen, J.C. Wang, and S.C. Harrison, DNA gyrase and its complexes with DNA: direct observations by electron microscopy, Cell 41: 933 (1985).PubMedCrossRefGoogle Scholar
  23. 23.
    S. Sreedharan, M. Oram, B. Jensen, L.R. Peterson, and L.M. Fisher, DNA gyrase gyrA mutations in ciprofloxacin-resistant strains of Staphylococcus aureus: close similarity with quinolone resistance mutations in Escherichia coli, J Bacteriol. 172: 7260 (1990).PubMedGoogle Scholar
  24. 24.
    Y. Wang, W.M. Huang, and D.E. Taylor, Cloning and nucleotide sequence of the Campylobacter jejuni gyrA gene and characterization of quinolone resistance mutations, Antimicrob Agents Chemother. 37: 457 (1993).PubMedCrossRefGoogle Scholar
  25. 25.
    H.E. Takiff, L. Salazar, C. Guerrero, W. Philipp, W.M. Huang, B. Kreiswirth, S.T. Cole, W.R. Jacobs, Jr., and A. Telenti. Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. Antimicrob Agents Chemother. 38: 773 (1994).PubMedCrossRefGoogle Scholar
  26. 26.
    D.C. Hooper and J.S. Wolfson, Mechanisms of bacterial resistance to quinolones, in: “Quinolone Antimicrobial Agents,” Second Edition, D.C. Hooper and J.W. Wolfson, eds., American Society for Microbiology, Washington (1993).Google Scholar
  27. 27.
    D.C. Hooper, J.S. Wolfson, K.S. Souza, E.Y. Ng, G.L. McHugh, and M.N. Swartz, Mechanisms of quinolone resistance in Escherichia coli: characterization of nfxB and cfxB, two mutant resistance loci decreasing norfloxacin accumulation, Antimicrob Agents Chemother. 33: 283 (1989).PubMedCrossRefGoogle Scholar
  28. 28.
    K. Hirai, H. Aoyama, S. Suzue, T. Irikura, S. Iyobe, and S. Mitsuhashi, Isolation and characterization of norfloxacin-resistant mutants of Escherichia coli K12, Antimicrob Agents Chemother. 30: 248 (1986).PubMedCrossRefGoogle Scholar
  29. 29.
    A.M. George and S.B. Levy, Gene in the major cotransduction gap of the Escherichia coli K-12 linkage map required for the expression of chromosomal resistance to tetracycline and other antibiotics, J Bacteriol. 155: 541 (1983).PubMedGoogle Scholar
  30. 30.
    S.P. Cohen, L.M. McMurry, D.C. Hooper, J.S. Wolfson, and S.B. Levy, Cross-resistance to fluoroquinolones in multiple antibiotic resistant (Mar) Escherichia coli selected by tetracycline and chloramphenicol: decreased drug accumulation associated with membrane changes in addition to OmpF reduction, Antimicrob Agents Chemother. 33: 1318 (1989).PubMedCrossRefGoogle Scholar
  31. 31.
    H. Hächler, S.P. Cohen, and S.B. Levy, marA, a regulated locus which controls expression of chromosomal multiple antibiotic resistance in Escherichia coli, J Bacteriol. 163: 5532 (1991).Google Scholar
  32. 32.
    S.P. Cohen, H. Hächler, and S.B. Levy, Genetic and functional analysis of the multiple antibiotic resistance (mar) locus in Escherichia coli, J Bacteriol. 175: 1484 (1993).PubMedGoogle Scholar
  33. 33.
    R.R. Ariza, S.P. Cohen, N. Bachhawat, S.B. Levy, and 13. Demple, Repressor mutations in the marRAB operon that activate oxidative stress genes and multiple antibiotic resistance in Escherichia coli, J Bacteriol. 176: 143 (1994).PubMedGoogle Scholar
  34. 34.
    S.P. Cohen, L.M. McMurry, and S.B. Levy, marA locus causes decreased expression of OmpF porin in multiple-antibiotic-resistant (Mar) mutants of Escherichia coli, J Bacteriol. 170: 5416 (1988).PubMedGoogle Scholar
  35. 35.
    Hooper, D.C., J.S. Wolfson, M.A. Bozza, and E.Y. Ng, Genetics and regulation of outer membrane protein expression by quinolone resistance loci nfxB, nfxC, and cfxB, Antimicrob Agents Chemother. 36: 1151 (1992).PubMedCrossRefGoogle Scholar
  36. 36.
    S.P. Cohen, D.C. Hooper, J.S. Wolfson, K.S. Souza, L.M. McMurry, and S.B. Levy, An endogenous active efflux of norfloxacin in susceptible Escherichia coli, Antimicrob Agents Chemother. 32: 1187 (1988).PubMedCrossRefGoogle Scholar
  37. 37.
    V. Jarlier, L. Gutmann, and H. Nikaido, Interplay of cell wall barrier and ßlactamase activity determines high resistance to ß-lactam antibiotics in Mycobacterium chelonae, Antimicrob Agents Chemother. 35: 1937 (1991).PubMedCrossRefGoogle Scholar
  38. 38.
    D.M. Livermore, Interplay of impermeability and chromosomal ß-lactamase activity in imipenem-resistant Pseudomonas aeruginosa, Antimicrob Agents Chemother. 36: 2046 (1992).PubMedCrossRefGoogle Scholar
  39. 39.
    H. Yoshida, M. Bogaki, S. Nakamura, K. Ubukata, and M. Konno, Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones, J Bacteriol. 172: 6942 (1990).PubMedGoogle Scholar
  40. 40.
    G.W. Kaatz, S.M. Seo, and C.A. Ruble, Efflux-mediated fluoroquinolone resistance in Staphylococcus aureus, Antimicrob Agents Chemother. 37: 1086 (1993).PubMedCrossRefGoogle Scholar
  41. 41.
    A.A. Neyfakh, V.E. Bidnenko, and L.B. Chen, Efflux-mediated multidrug-resistance in Bacillus subtilis: similarities and dissimilarities with the mammalian system, Proc Natl Acad Sci USA. 88: 4781 (1991).PubMedCrossRefGoogle Scholar
  42. 42.
    I.T.,Paulsen and R.A. Skurray, Topology, structure and evolution of two families of proteins involved in antibiotic and antiseptic resistance in eukaryotes and prokaryotes - an analysis, Gene 124: 1 (1993).Google Scholar
  43. 43.
    E.Y. Ng, M. Trucksis, and D.C. Hooper, Quinolone resistance mediated by norA: physiologic characterization and relationship to flqB, a quinolone resistance locus on the Staphylococcus aureus chromosome, submitted (1994).Google Scholar
  44. 44.
    C.J. Soussy, J.S. Wolfson, E.Y. Ng, and D.C. Hooper, Limitations of plasmid complementation test for determination of quinolone resistance due to changes in the gyrase A protein and identification of conditional quinolone resistance locus, Antimicrob Agents Chemother. 37: 2588 (1993).PubMedCrossRefGoogle Scholar
  45. 45.
    J.-I. Kato, Y. Nishimura, R. Imamura, H. Niki, S. Hiraga, and H. Suzuki, New topoisomerase essential for chromosome segregation in E. coli. Cell 63: 393 (1990).Google Scholar
  46. 46.
    J.-I. Kato, H. Suzuki, and H. Ikeda, Purification and characterization of DNA topoisomerase IV in Escherichia coli, J Biol Chem. 267: 25676 (1992).PubMedGoogle Scholar
  47. 47.
    H. Peng and K.J. Marians, Escherichia coli topoisomerase IV. Purification, characterization, subunit structure, and subunit interactions, J Biol Chem. 268: 24481 (1993).PubMedGoogle Scholar
  48. 48.
    M. Trucksis, J.S. Wolfson, and D.C. Hooper., A novel locus conferring fluoroquinolone resistance in Staphylococcus aureus, J Bacteriol. 173: 5854 (1991).PubMedGoogle Scholar
  49. 49.
    S. Hori, Y. Ohshita, Y. Utsui, and K. Hiramatsu, Sequential acquisition of norfloxacin and ofloxacin resistance by methicillin-resistant and -susceptible Staphylococcus aureus, Antimicrob Agents Chemother. 37: 2278 (1993).PubMedCrossRefGoogle Scholar
  50. 50.
    M.F. Parry, K.B. Panzer, and M.E. Yukna, Quinolone resistance: susceptibility data from a 300-bed community hospital, Am J Med. 87 (Suppl 5A): 125 (1989).CrossRefGoogle Scholar
  51. 51.
    L.R. Peterson, Quinolone resistance in clinical practice: occurrence and importance, in: “Quinolone Antimicrobial Agents,” Second Edition, D.C. Hooper and J.W. Wolfson, eds., American Society for Microbiology, Washington (1993).Google Scholar
  52. 52.
    D.R. Schaberg, W.I. Dillon, M.S. Terpenning, K.A. Robinson, S.F. Bradley, and C.A. Kauffman, Increasing resistance of enterococci to ciprofloxacin, Antimicrob Agents Chemother. 36: 2533 (1992).PubMedCrossRefGoogle Scholar
  53. 53.
    J. Blaser, B.B. Stone, M.C. Groner, and S.H. Zinner, Comparative study with enoxacin and netilmicin in a pharmacodynamie model to determined importance of ratio of antibiotic peak concentration to MIC for bactericidal activity and emergence of resistance, Antimicrob Agents Chemother. 31: 1054 (1987).PubMedCrossRefGoogle Scholar
  54. 54.
    R.R. Muder, C. Brennen, A.M. Goetz, M.M. Wagener, and J.D. Rihs, Association with prior fluoroquinolone therapy of widespread ciprofloxacin resistance among gram-negative isolates in a Veterans Affairs medical center, Antimicrob Agents Chemother. 35: 256 (1991).PubMedCrossRefGoogle Scholar
  55. 55.
    Y.C. Yee, R.R. Muder, M.H. Hsieh, and T.C. Lee, Molecular epidemiology of endemic ciprofloxacin-susceptilbe and -resitant Enterobacteriaceae, Infect Control Hosp Epidemiol. 13: 706 (1992).PubMedCrossRefGoogle Scholar
  56. 56.
    H.M. Blumberg, D. Rimland, D.J. Carroll, P. Terry, and I.K. Wachsmuth, Rapid development of ciprofloxacin resistance in methicillin-susceptible and -resistant Staphylococcus aureus, J Infect Dis. 163: 1279 (1991).PubMedCrossRefGoogle Scholar
  57. 57.
    T.E. Daum, D.R. Schaberg, M.S. Terpenning, W.W. Sottile, and C.A. Kauffman, Increasing resistance of Staphylococcus aureus to ciprofloxacin, Antimicrob Agents Chemother. 34: 1862 (1990).PubMedCrossRefGoogle Scholar
  58. 58.
    M.C. Raviglione, J.F. Boyle, P. mauriuz, A. Paublos-Mendez, H. Cortes, and A. Merlo, Ciprofloxacin-resistant methicillin-resistant Staphylococcus aureus in an acute-care hospital, Antimicrob Agents Chemother. 34: 2050 (1990).PubMedCrossRefGoogle Scholar
  59. 59.
    S.M. Smith, R.H.K. Eng, P. Bais, P. Fan-Havard, and F. Tecson-Tumang, Epidemiology of ciprofloxacin resistance among patients with methicillinresistant Staphylococcus aureus, J Antimicrob Chemother. 26: 567 (1990).PubMedCrossRefGoogle Scholar
  60. 60.
    H.M. Blumberg, D. Rimland, J.A. Kiehlbauch, P.M. Terry, and I.K. Wachsmuth, Epidemiologic typing of Staphylococcus aureus by DNA restriction fragment length polymorphisms of rRNA genes: elucidation of the clonal nature of a group of bacteriophage-nontypeable, ciprofloxacin-resistant, methicillin-susceptible S. aureus isolates, J Clin Microbiol. 30: 362 (1992).PubMedGoogle Scholar
  61. 61.
    G.L. McHugh, J.S. Wolfson, and D.C. Hooper, unpublished observations.Google Scholar
  62. 62.
    J.F. Acar, T.F. O’Brien, F.W. Goldstein, and R.N. Jones, The epidemiology of bacterial resistance to quinolones, Drugs 45 (Suppl 3): 24 (1993).PubMedCrossRefGoogle Scholar
  63. 63.
    H.P. Endtz, G.J. Ruijs, B. van Klingeren, W.H. Jansen, T. van der Reyden, and R.P. Mouton, Quinolone resistance in campylobacter isolated from man and poultry following the introduction of fluoroquinolones in veterinary medicine, J Antimicrob Chemother. 27: 199 (1991).PubMedCrossRefGoogle Scholar
  64. 64.
    J.M. Aguiar, J. Chacon, R. Canton, and F. Baquero, The emergence of highly fluoroquinolone-resistant Escherichia coli in community-acquired urinary tract infections, J Antimicrob Chemother. 29: 349 (1992).PubMedCrossRefGoogle Scholar
  65. 65.
    E. Pérez-Trallero, M. Urbieta, D. Jimenez, J.M. García-Arenzana, and G. Cilla, Ten-year survey of quinolone resistance in Escherichia coli causing urinary tract infections, Eur J Clin Microbiol Infect Dis. 12: 349 (1993).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • David C. Hooper
    • 1
  1. 1.Infectious Disease UnitMassachusetts General HospitalBostonUSA

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