Resistance to Quinolones and Fluoroquinolones

  • L. J. V. Piddock
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 91)


The quinolone class of oral antimicrobial agents has enjoyed rapid expansion and development over recent years and a revival in interest in the earlier agents nalidixic and oxolinic acid. The quinolone class (which includes 4-pyridone antibacterials) share the 4-quinolone nucleus and also a carboxylic acid substituent at position 3 (Fig. 1). During the last twenty-five years many compounds have been synthesised with additional substituents upon the basic nucleus and have been evaluated for use in antimicrobial chemotherapy. The early agents, nalidixic and oxolinic acid, were only active against gram-negative bacteria and the achievable serum concentrations were below the concentration needed to inhibit most pathogens. Consequently, these agents were limited to the treatment of urinary tract infections. In recent years many compounds have been synthesised with a fluorine substituent at position 6 of the quinolone nucleus (Fig. 1). This was found to enhance the antibacterial activity and enable adequate serum concentrations to be achieved (Hooper and Wolfson 1985). Other substituents in addition to the fluorine have been added to the nucleus with the aim of increasing the anti-gram positive bacterial activity. There are now approximately one dozen significant quinolone and fluoro-quinolone compounds (referred to as “quinolone” for the rest of the chapter) which are active against a broad spectrum of pathogens, including those causing systemic infections. The spectrum of activity for the agents in Fig. 1 has been recently reviewed (Wolfson and Hooper 1985) as has the pharmacology, clinical uses and toxicities in humans (Hooper and Wolfson 1985).


Nalidixic Acid Antimicrob Agent Micrococcus Luteus Oxolinic Acid Pipemidic Acid 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anderson JD, Ingram LC, Richmond MH, Weidemann B (1973) Studies on the nature of plasmids arising from conjugation in the human gastro-intestinal tract. J Med Microbiol 6: 475–486PubMedGoogle Scholar
  2. Aoyama H, Sato K, Kato T, Hirai K, Mitsuhashi S (1987) Norfloxacin resistance in a clinical isolate of Escherichia coli. Antimicrob Agents Chemother 31: 1640–1641PubMedGoogle Scholar
  3. Aoyama H, Sato K, Fujii T, Fujimaka K, Inoue M, Mitsuhashi S (1988) Purification of Citrobacter freundii DNA gyrase and inhibition by quinolones. Antimicrob Agents Chemother 32: 104–109PubMedGoogle Scholar
  4. Azadian BS, Bendig JW, Samson DM (1986) Emergence of ciprofloxacin resistant Pseudomonas aeruginosa after combined therapy with ciprofloxacin and amikacin. J Antimicrob Chemother 18: 771PubMedGoogle Scholar
  5. Barry AL, Jones RN (1984) Cross-resistance among cinoxacin, ciprofloxacin, DJ-6783, enoxacin, nalidixic-acid, norfloxacin and oxolinic acid after in vitro selection of resistant populations. Antimicrob Agents Chemother 25: 775–777PubMedGoogle Scholar
  6. Bauer WR (1978) Structure and reactions of closed duplex DNA. Annu Rev Biophys Bioeng 7: 287–313PubMedGoogle Scholar
  7. Bounchchaud DH, Chabbert YA (1971) Practical effectiveness of agents curing R-factors and plasmids. Ann NY Acad Sci 182: 305–311Google Scholar
  8. Bourginon GJ, Levitt M, Sternglanz R (1973) Studies on the mechanism of action of nalidixic acid. Antimicrob Agents Chemother 4: 479Google Scholar
  9. Brooks K, Clark AJ (1967) Behaviour of lambda bacteriophage in a recombination deficient strain of Escherichia coli. J Virol 1: 283–293PubMedGoogle Scholar
  10. Brown PO, Cozzarelli NR (1979) A sign inversion mechanism for enzymatic supercoiling of DNA. Science 206: 1081–1083PubMedGoogle Scholar
  11. Brown PO, Reebles CI, Cozzarelli NR (1979) A topoisomerase from Escherichia coli related to DNA gyrase. Proc Natl Acad Sci USA 76: 6110PubMedGoogle Scholar
  12. Burman L (1977) R-plasmid transfer and its response to nalidixic acid. J Bacteriol 131: 76–81PubMedGoogle Scholar
  13. Cairns J (1963) The chromosome of Escherichia coli. Cold Spring Harbour. Symp Quant Biol 28: 43–45Google Scholar
  14. Champoux JJ (1978) Mechanism of the reaction catalysed by the DNA untwisting enzyme: attachment of the enzyme to 3’-terminus of the nicked DNA. J Mol Biol 118: 441–446PubMedGoogle Scholar
  15. Chapman ST, Speller DC, Reeves DS (1985) Resistance to ciprofloxacin. Lancet 2 (8445): 39PubMedGoogle Scholar
  16. Chin N-X, Neu H (1983) In vitro activity of enoxacin, a quinolone carboxylic acid, corn-pared with those of norfloxacin, new β-lactams, aminoglycosides, and trimethoprim. Antimicrob Agents Chemother 24: 754–763PubMedGoogle Scholar
  17. Cole ST (1983) Characterisation of the promoter for the Lex A regulated sul A gene of Escherichia coli. Mol Gen Genet 189: 400–404PubMedGoogle Scholar
  18. Cozzarelli NR (1980) DNA gyrase and the supercoiling of DNA. Science 207: 953–960PubMedGoogle Scholar
  19. Crook SM, Selkon JB, McLardy-Smith PD (1985) Clinical resistance to long-term oral ciprofloxacin. Lancet 1 (8440): 1275PubMedGoogle Scholar
  20. Crumplin GC (1985) Development and consequences of resistance to antimicrobial agents acting upon DNA gyrase. Annual Conference of the American Society of MicrobiologyGoogle Scholar
  21. Crumplin GC, Smith JT (1975) Nalidixic acid: an antibacterial paradox. Antimicrob Agents Chemother 8: 251–261PubMedGoogle Scholar
  22. Cullman W, Stieglitz M, Baars B, Opferkuch W (1985) Comparative evaluation of recently developed quinolone compounds–with a note on the frequency of resistant mutants. Chemotherapy 31: 19–28Google Scholar
  23. Diver JM, Piddock LJV, Wise R (1987) Investigations into the mechanism of cell death of E. coli K12 after exposure to quinolone antibacterials. 15th International Congress of Chemotherapy, IstanbulGoogle Scholar
  24. Domagala JM, Hanna LD, Heifetz CL, Hutt MP, Mich TF, Sanchez JP, Solomon M (1986) New structure-activity relationships of the quinolone antibacterials using the target enzyme. The development and application of a DNA gyrase assay. J Med Chem 29: 394–404PubMedGoogle Scholar
  25. Drlica K (1984) Biology of bacterial deoxyribonucleic acid topoisomerases. Microbiol Rev 48: 273–289PubMedGoogle Scholar
  26. Drlica K, Engle EC, Manes SH (1980) DNA gyrase on the bacterial chromosome: possibility of two levels of action. Proc Natl Acad Sci USA 77: 6879–6883PubMedGoogle Scholar
  27. Gellert M (1981) DNA topoisomerases. Annu Rev Biochem 50: 879–910PubMedGoogle Scholar
  28. Gellert M, Mizuuchi K, O’Dea MH, Nash HA (1976) DNA gyrase: an enzyme that introduces superhelical turns into DNA. Proc Natl Acad Sci USA 73: 3872–3876PubMedGoogle Scholar
  29. Gellert M, Mizuuchi K, O’Dea MH, Itoh T, Tomizawa J (1977) Nalidixic acid resistance: a second genetic character involved in DNA gyrase activity. Proc Natl Acad Sci USA 74: 4767Google Scholar
  30. Gellert M, Mizuuchi K, O’Dea MH, Ohmori H, Tomizawa J (1978) DNA gyrase and DNA supercoiling. Cold Spring Harbour Symp Quant Biol 43: 35Google Scholar
  31. George A, Levy SB (1983) Gene in the major cotransduction map of the Escherichia coli K-12 linkage map required for the expression of chromosomal resistance to tetracycline and other antibiotics. J Bact 155: 531–540PubMedGoogle Scholar
  32. Glupczynski Y, Labbe M, Burette A, Delmee M, Avesari V, Bruck C (1987) Treatment failure of ofloxacin in Campylobacter pylori infection. Lancet 1 (8541): 1096PubMedGoogle Scholar
  33. Gudas LJ, Pardee AB (1976) DNA synthesis inhibition and the induction of protein X in Escherichia coli. J Mol Biol 101: 459–477PubMedGoogle Scholar
  34. Gutmann L, Williamson R, Moreau N, Kitzis MD, Collatz E, Acar JF, Goldstein FW (1985) Cross-resistance to nalidixic acid, trimethoprim and chloramphericol associated with alterations in outer membrane proteins of Klebsiella, Enterobacter and Serratia. J Infect Dis 151: 501–507PubMedGoogle Scholar
  35. Hahn FE, Ciak J (1976) Elimination of resistance determinants from R-factor R1 by intercalative compounds. Antimicrob Agents Chemother 9: 77–80PubMedGoogle Scholar
  36. Hane MW, Wood TH (1969) Escherichia coli K-12 mutants resistant to nalidixic acid: genetic mapping and dominance studies. J Bacteriol 99:238–241PubMedGoogle Scholar
  37. Hansen FG, von Meyenberg K (1979) Characterisation of the dnaA, gyr B and other genes in the dna A region of the Escherichia coli chromosome on specialised transducing phages lambda tna. Mol Gen Genet 175: 135PubMedGoogle Scholar
  38. Helling RB, Kukora JS (1971) Nalidixic acid-resistant mutants of Escherichia coli deficient in isocitrate dehydrogenase. J Bacteriol 105: 1224–1226PubMedGoogle Scholar
  39. Hertman I, Luria SE (1967) Transduction studies on the role of rec-gene in ultraviolet induction of prophage lambda. J Mol Biol 23: 117–133PubMedGoogle Scholar
  40. Higgins NP, Peebles CL, Sugino A, Cozzarelli NR (1978) Purification of subunits of Escherichia coli DNA gyrase and reconstitution of enzymatic activity. Proc Natl Acad Sci USA 75: 1773–1777PubMedGoogle Scholar
  41. Hirai K, Aoyama H, Irikura T, Iyobe S, Mitsuhashi S (1986a) Differences in susceptibilities to quinolones of outer membrane mutants of Salmonella typhimuruiri and Escherichia coli. Antimicrob Agents Chemother 29: 535–538PubMedGoogle Scholar
  42. Hirai K, Aoyama H, Suzue S, Irikura T, Iyobe S, Mitsuhashi S (1986b) Isolation and characterisation of norfloxacin-resistant mutants of Escherichia coli K-12. Antimicrob Agents Chemother 30: 248–253PubMedGoogle Scholar
  43. Hirai K, Suzue S, Irikura T, Iyobe S, Mitsuhashi S (1987) Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa. Antimicrob Agents Chemother 31: 582–586PubMedGoogle Scholar
  44. Hiruma R, Yamaguchi A, Sawai T (1984) The effect of LPS on lipid bilayer permeability of β-lactam antibiotics. FEBS Lett 170: 268PubMedGoogle Scholar
  45. Hogberg T, Khanna I, Drake SD, Mitscher LA, Shen LL (1984) Structure activity relationships among DNA gyrase inhibitions. Synthesis and evaluation of 1,2-dihydro-4-dimethyl-1 -oxo-2-napthalene carboxylic acids as 1 carba bioesters of oxolinic acid. J Med Chem 27: 306–310PubMedGoogle Scholar
  46. Holloway BW, Morgan AP (1986) Genone organisation in Pseudomonas. Annu Ref Microbiol 40: 79–105Google Scholar
  47. Hooper D, Wolfson J (1985) The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans. Antimicrob Agents Chemother 28: 716–721PubMedGoogle Scholar
  48. Hooper D, Wolfson J, Souza KS, Tung C, McHugh G, Swartz M (1986) Genetic and biochemical characterisation of norfloxacin resistance in Escherichia coli. Antimicrob Agents Chemother 29: 639–644PubMedGoogle Scholar
  49. Hooper D, Wolfson J, Ng E, Swartz M (1987) Mechanisms of action of and resistance to ciprofloxacin. Am J Med 82 (4A): 12–20PubMedGoogle Scholar
  50. Hrebenda J, Heleszko H, Brzostek K, Bielecki H (1985) Mutation affecting resistance of Escherichia coli K12 to nalidixic acid. J Gen Microbiol 131: 2285–2292PubMedGoogle Scholar
  51. Huisman O, d’Ari R (1981) An inducible DNA replication-cell division coupling mechanism in E. coli. Nature 290: 797–799PubMedGoogle Scholar
  52. Humphreys H, Mulvihill E (1985) Ciprofloxacin-resistant Staphylococcus aureus. Lancet 2 (8451): 383PubMedGoogle Scholar
  53. Inoue Y, Sato K, Fujii T, Kirai K, Inoue M, Shizuko I, Mitsuhashi S (1987) Some properties of subunits of DNA gyrase from Pseudomonas aeruginosa PA01 and its nalidixic acid-resistant mutant. J Bacteriol 169: 2322–2325PubMedGoogle Scholar
  54. Inouye S, Ohne T, Yamagishi J, Nakamura S, Shimuzu M (1978) Mode of incomplete cross-resistance among pipemidic, piromidic and nalidixic acids. Antimicrob Agents Chemother 14: 240–245Google Scholar
  55. Jaffe A, Chabbert YA, Sernonin Q (1982) Role of porin proteins OMP F and OMP C in the permeation of β-lactams. Antimicrob Agents Chemother 22: 942–948PubMedGoogle Scholar
  56. Kaatz GW, Barriere SL, Schaberg DR, Fekety R (1987) The emergence of resistance to ciprofloxacin during treatment of experimental Staphylococcus aureus endocarditis. J Antimicrob Chemother 20: 753–758PubMedGoogle Scholar
  57. Kantor GJ, Deering RA (1968) Effect of nalidixic acid and hydroxy urea on division ability of Escherichia coli fil+ and /on-strains. J Bacteriol 95: 520–530PubMedGoogle Scholar
  58. Karu AE, Belk ED (1982) Induction of E. coli rec A protein via rec BC and alternate pathways: quantitation by enzyme-linked immunosorbent assay ( ELISA ). Mol Gen Genet 185: 275–282PubMedGoogle Scholar
  59. King A, Shannon K, Phillips I (1984) The in vitro activity of ciprofloxacin compared with that of norfloxacin and nalidixic acid. J Antimicrob Chemother 13: 325–331PubMedGoogle Scholar
  60. Kreuzer KN, Cozzarelli NR (1979) Escherichia coli mutants thermosensitive for deoxyribonucleic acid gyrase subunit A: effects on deoxyribonucleic acid replication, transcription and bacteriophage growth. J Bacteriol 140:424–435PubMedGoogle Scholar
  61. Kreuzer KN, Cozzarelli NR (1980) Formation and resolution of DNA catenates by DNA gyrase. Cell 20: 245–254PubMedGoogle Scholar
  62. Kubesch P, Wehsling M, Tummler B (1987) Membrane permeability of Pseudomonas aeru-ginosa to 4-quinolones. Zentralbl Bakteriol Mikrobiol Hyg (A) 265: 197–202Google Scholar
  63. Kumar S (1980) Types of spontaneous nalidixic acid resistant mutants of Escherichia coli. Indian J Exp Biol 18: 341–343PubMedGoogle Scholar
  64. Little JW, Mount DW (1982) The SOS regulatory system of Escherichia coli. Cell 29: 11–22PubMedGoogle Scholar
  65. Liu LF, Wang JC (1978) Micrococcus luteus DNA gyrase: active components and a model for its supercoiling of DNA. Proc Natl Acad Sci USA 75: 2098PubMedGoogle Scholar
  66. Liu LF, Liu C-C, Alberts BM (1980) Type II DNA topoisomerases: enzymes that can un-knot a topologically knotted DNA molecule via a reversible double-strand break. Cell 19: 697–708PubMedGoogle Scholar
  67. Manes SH, Pruss GJ, Drlica K (1983) Inhibition of RNA synthesis by oxolinic acid is unrelated to average DNA supercoiling. J Bacteriol 155: 420–423PubMedGoogle Scholar
  68. McDaniel LS, Rogers LH, Hill WE (1978) Survival of recombination-deficient mutants of Escherichia coli during incubation with nalidixic acid. J Bacteriol 134: 1195–1198PubMedGoogle Scholar
  69. Mizuuchi K, Gellert M, Nash HA (1978) Involvement of supertwisted DNA in integrative recombination of bacteriophage lambda. J Mol Biol 212: 375–392Google Scholar
  70. Mizuuchi K, Fischer LM, O’Dea M, Gellert M (1980) DNA gyrase B action involves the introduction of transient double stranded breaks into DNA. Proc Natl Acad Sci USA 77: 1847–1851PubMedGoogle Scholar
  71. Munshi MH, Haider K, Rahaman M, Sack D, Ahmed Z, Morshed M (1987) Plasmid-me- diated resistance to nalidixic acid in Shigella dysenteriae type I. Lancet 2: 419–421PubMedGoogle Scholar
  72. Murphy PG, Ferguson WP (1987) Corynebacterium jeikeium (group JK) resistance to ciprofloxacin emerging during therapy. J Antimicrob Chemother 20:922–923PubMedGoogle Scholar
  73. Olsson-Llilequist B, Gezelius L, Svensson SB (1985) Selection of multiple antibiotic resistance by norfloxacin and nalidixic acid in Klebsiella and Enterobacter: correlation with outer membrane protein profiles. 25th ICAAC, MinneapolisGoogle Scholar
  74. Panhotra BR, Desai B (1983) Resistant Shigella dysenteriae. Lancet 2 (8364): 1420PubMedGoogle Scholar
  75. Panhotra BR, Desai B, Sharma PL (1985) Nalidixic-acid-resistant Shigella dysenteriae I. Lancet 1 (8431): 763PubMedGoogle Scholar
  76. Peebles CL, Higgins NP, Krenzer KN, Morrison A, Brown PO, Sugino A, Cozzarelli NR (1978) Structure and activities of Escherichia coli DNA gyrase. Cold Spring Harbour Symp Quant Biol 43: 41–52Google Scholar
  77. Piddock LJV, Wise R (1986) The effect of altered porin expression in Escherichia coli upon susceptibility to 4-quinolones. J Antimicrob Chemother 18: 547–552PubMedGoogle Scholar
  78. Piddock LJV, Wise R (1987) Induction of the SOS response by 4-quinolones. FEMS Microbiol Letts 41: 289–294Google Scholar
  79. Piddock LJV, Diver JM, Wise R (1986) Cross-resistance of nalidixic acid resistant enterobacteriaceae to new quinolones and other antimicrobials. Eur J Clin Microbiol 5: 411–415PubMedGoogle Scholar
  80. Piddock LJV, Wijnands WJA, van Klingeran B, Wise R (1987a) Characterisation of the mechanism of decreased susceptibility to enoxacin in a strain of Pseudomonas aeruginosa isolated from a patient after enoxacin therapy. 5th International congress of chemotherapy, IstanbulGoogle Scholar
  81. Piddock LN, Wijnands WJA, Wise R (1987b) Quinolone ureidopenicillin cross resistance. Lancet 17: 907Google Scholar
  82. Piddock LN, Diver JM, Wise R (1988a) Correlation of the biochemical responses with the bactericidal action of quinolone antimicrobial agents in E. coli K-12 (submitted)Google Scholar
  83. Piddock LN, Griggs D, Wise R (1988b) The selection and phenotypic characterisation of the mechanism of resistance of selected Enterobacteriaceae to quinolones. Proceedings of the 2nd symposium of new quinolones, GenevaGoogle Scholar
  84. Piffaretti JC, Demarta A, Leidi-Bulla L, Peduzzi R (1983) In vitro emergence of Escherichia coli and Pseudomonas aeruginosa strains resistant to norfloxacin and nalidixic acid. Antimicrob Agents Chemother 23: 641–648Google Scholar
  85. Pugsley A, Schnaitman CC (1978) Outer membrane proteins of Escherichia coli VII. Evidence that bacteriophage-directed protein 2 functions as a pore. J Bact 133: 1181–1189PubMedGoogle Scholar
  86. Ratcliffe NT, Smith JT (1985) Norfloxacin has a bactericidal mechanism of action unrelated to that of other 4-quinolones. J Pharm Pharmacol 37: 92 PGoogle Scholar
  87. Ravizzola G, Pirali F, Paolucci A, Terlenghi L, Peroni L, Columbi A, Turano A (1987) Reduced virulence in ciprofloxacin-resistant variants of Pseudomonas aeruginosa strains. J Antimicrob Chemother 20: 825–829PubMedGoogle Scholar
  88. Reeve EC, Doherty P (1968) Linkage relationships of two genes causing partial resistance to chloramphenicol in Escherichia coli K-12. Genet Res II: 303–309Google Scholar
  89. Relia M, Haas D (1982) Resistance of Pseudomonas aeruginosa PAO to nalidixic acid and low levels of β-lactam antibiotics: mapping of chromosomal genes. Antimicrob Agents Chemother 22: 242–249Google Scholar
  90. Renzini GG, Ravagnan G, Piccolomini R, Nicoletti M, Oliva B (1982) Comparison of different chinolonic compounds as extra-chromosomal transfer inhibitors. Chemotherapia 1: 451–453Google Scholar
  91. Roberts CM, Batten J, Hodson ME (1985) Ciprofloxacin-resistant pseudomonas. Lancet 1 (8443): 1442PubMedGoogle Scholar
  92. Salles B, Paoletti C (1983) Control of uv induction of rec A protein. Proc Natl Acad Sci USA 80: 65–69PubMedGoogle Scholar
  93. Salles E, Defrais M (1984) Signal of induction of recA protein in E. coli. Mutat Res 131: 53–59PubMedGoogle Scholar
  94. Sanders CC, Watanakunakorn C (1986) Emergence of resistance to beta-lactams, amino-glycosides and quinolones during combination therapy for infection due to Serratia marcescens. J Infect Dis 153: 617–619PubMedGoogle Scholar
  95. Sanders CC, Sanders WE, Goering RV, Werner V (1984) Selection of multiple antibiotic resistance by quinolones, beta-lactams, and aminoglycosides with special reference to cross-resistance between unrelated drug classes. Antimicrob Agents Chemother 26: 797–801PubMedGoogle Scholar
  96. Sato K, Inoue Y, Fjuii T, Aoyama H, Inoue M, Mitsuhashi S (1987) Purification and properties of DNA gyrase from a fluoroquinolone resistant strain of Escherichia coli. Antimicrob Agents Chemother 30: 777–780Google Scholar
  97. Setlow JK, Cabrera-Juarez, Albritton NL, Spikes D, Mutschler A (1986) Mutations affecting gyrase in Haemophilus influenza. J Bact 164: 525–534Google Scholar
  98. Slack R (1984) Review of bacterial resistance — a challenge to the treatment of urinary infection. J Antimicrob Chemother [Suppl B] 13: 1–7Google Scholar
  99. Smith GM, Cashmore C, Leyland MJ (1985) Ciprofloxacin-resistant staphylococci. Lancet 2 (8461): 949PubMedGoogle Scholar
  100. Smith JT (1984) Mutational resistance to 4 quinolone antibacterial agents. Eur J Clin Microbiol 3: 347–350PubMedGoogle Scholar
  101. Sugino A, Bott KF (1980) Bacillus subtilis deoxyribonucleic acid gyrase. J Bacteriol 141:1331–1339PubMedGoogle Scholar
  102. Sugino A, Cozzarelli NR (1980) The intrinsic ATPase of DNA gyrase. J Biol Chem 255: 6299–6306PubMedGoogle Scholar
  103. Sugino A, Peebles K, Krenzer K, Cozzarelli N (1977) Mechanism of action of nalidixic acid: purification of Escherichia coli nal A gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme. Proc Natl Acad Sci USA 74: 4767–4771PubMedGoogle Scholar
  104. Tenney JH, Maack RW, Chippendale GR (1983) Rapid selection of organisms with increasing resistance on subinhibitory concentrations of norfloxacin in agar. Antimicrob Agents Chemother 23: 188–189PubMedGoogle Scholar
  105. Traub WH, Kleber I (1973) Isolation of two strains of Klebsiella pneumonae with transferable determinants against ten antimicrobial drugs from clinical material. Zentralbi Bakteriol Mikrobiol Hyg [A] 229: 80–88Google Scholar
  106. Vasquez-Ramos JM, Mandelstram J (1981) Oxilinic acid-resistant mutants of Bacillus sub-tills. J Gen Microbiol 127: 1–9Google Scholar
  107. Wagenvoort JH, van-der-Willgen AH, van Vliet HJ, Michel MF, van Klingeren B (1986) Resistance of Neisseria gonorrhoeae to enoxacin. J Antimicrob Chemother 18: 429PubMedGoogle Scholar
  108. Walker GC (1984) Mutagenesis and inducible responses to deoxyribonucleic acid damage in Escherichia coli. Microbiol Rev 48: 60–93PubMedGoogle Scholar
  109. Wang JC (1985) DNA topoisomerases. Annu Rev Biochem 54: 665–697PubMedGoogle Scholar
  110. Wang JC, Gumport RI, Javaherian K, Kirkegaard K, Kievan L, Katewicz ML, Tse YC (1981) In: Alberts BM, Fox CF (eds) Mechanistic studies of DNA replication and genetic recombination. Academic, New YorkGoogle Scholar
  111. Weisser J, Weidemann B (1985) Elimination of plasmids by new 4-quinolones. Antimicrob Agents Chemother 28: 700–702PubMedGoogle Scholar
  112. Weisser J, Weidemann B (1987) Inhibition of R-plasmid transfer in Escherichia coli by 4-quinolones. Antimicrob Agents Chemother 31: 531–534PubMedGoogle Scholar
  113. Wise R, Baker SL, Misra M, Griggs D (1987) The pharmacokinetics of enoxacin in elderly patients. J Antimicrob Chemother 19: 343–350PubMedGoogle Scholar
  114. Witkin EM (1976) Ultraviolet mutagenesis and inducible DNA repair in Escherichia coli. Bacteriol Rev 40: 869–907PubMedGoogle Scholar
  115. Wolfson J, Hooper DC (1985) The fluoroquinolones: structures, mechanisms of action and resistance and spectra of activity in vitro. Antimicrob Agents Chemother 28: 581–586PubMedGoogle Scholar
  116. Yamagishi J, Furutani Y, Inoue S, Ohue T, Nakamura S, Shimizu M (1981) New nalidixic acid resistance mutations related to deoxynitonucleic acid gyrase activity. J Bacteriol 148: 450–458PubMedGoogle Scholar
  117. Yamagishi J, Yoshida H, Yamaycshi M, Nakamura S (1986) Nalidixic acid-resistant mutations of the gyr B gene of Escherichia coli. Mol Gen Genet 204: 367–373PubMedGoogle Scholar
  118. Yamashita S, Inone Y, Sato K, Inone M, Mitsuhashi S (1986) DNA gyrase from fluoroquinolone resistant E. cloacae. Proc 1st Int Symp New Quinolones:13Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • L. J. V. Piddock

There are no affiliations available

Personalised recommendations