Skip to main content
SpringerLink
Log in

Expanding and Preserving the Utility of Quinolone Antimicrobials

  • Conference paper
Antibacterial Therapy: Achievements, Problems and Future Perspectives

Abstract

It is a distinct honor for me to have the opportunity to participate in this symposium in honor of Dr. Karl Metzger, who was instrumental in the identification and development of ciprofloxacin, the fluoroquinolone that opened the door to the expanded therapeutic potential of the quinolone class of antimicrobials (Wolfson and Hooper 1989; Hooper and Wolfson 1991). The first member of the quinolone class, nalidixic acid, is a naphthyridine derivative that was developed in the mid-1960s. Nalidixic acid was, however, limited in its clinical application to the treatment of urinary tract infections, and it was not until the 1980s with the development of the newer members of this class, the fluoroquinolones, that it became possible to treat a broad range of Gram-negative and some Gram-positive bacterial infections at many body sites. Ciprofloxacin, with its novel cyclopropane ring substituent, was the first broad-spectrum fluoroquinolone to be used successfully to treat infections outside the genitourinary tract. The increasing problem of resistance to other classes of antimicrobial agents has contributed to the need for and value of current fluoroquinolones such as ciprofloxacin. In particular, the occurrence in some strains of Klebsiella pneumoniae of plasmid-mediated multidrug resistance that includes most β-lactams and aminoglycosides, has resulted in organisms that are susceptible only to imipenem and amikacin. In addition, increasing resistance to β-lactams in Enterobacter spp. and Pseudomonas aeruginosa has enhanced the need for other classes of agents with activity against these organisms.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Alarcon T, Pita J, Lopez-Brea M, Piddock LI (1993) High-level quinolone resistance amongst clinical isolates of Escherichia coli and Klebsiella pneumoniae from Spain. J Antimicrob Chemother 32: 605–609

    Article  PubMed  CAS  Google Scholar 

  • Ariza RR, Cohen SP, Bachhawat N, Levy SB, Demple B (1994) Repressor mutations in the marRAB operon that activate oxidative stress genes and multiple antibiotic resistance in Escherichia coli. J Bacteriol 176: 143–148

    PubMed  CAS  Google Scholar 

  • Beck WT (1990) Mechanisms of multidrug resistance in human tumor cells. The roles of P-glycoprotein, DNA topoisomerase II, and other factors. Cancer Treat Rev 17 Suppl A: 11–20

    Google Scholar 

  • Cohen SP, McMurry LM, Hooper DC, Wolfson JS, Levy SB (1989) Cross-resistance to fluoroquinolones in multiple-antibiotic-resistant (Mar) Escherichia coli selected by tetracycline or chloramphenicol: decreased drug accumulation associated with membrane changes in addition to OmpF reduction. Antimicrob Agents Chemother 33: 1318–1325

    PubMed  CAS  Google Scholar 

  • Crumplin GC, Kenwright M, Hirst T (1984) Investigations into the mechanism of action of the antibacterial agent norfloxacin. J Antimicrob Chemother 13 [Suppl B]: 9–23

    PubMed  CAS  Google Scholar 

  • 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: 6879–6883

    Article  PubMed  CAS  Google Scholar 

  • Drlica K, Kreiswirth B (1994) 4-quinolones and the physiology of DNA gyrase. Adv Pharmacol 29: 263–283

    Google Scholar 

  • Eliopoulos GM, Klimm K, Grayson ML (1990) In vitro activity of sparfloxacin (AT-4140, CI-978, PD 131501), a new quinolone antimicrobial agent. Diagn Microbiol Infect Dis 13: 345–348

    Article  PubMed  CAS  Google Scholar 

  • Endtz HP, Ruijs GJ, van Klingeren B, Jansen WH, van der Reyden T, Mouton RP (1991) Quinolone resistance in campylobacter isolated from man and poultry following the introduction of fluoroquinolones in veterinary medicine. J Antimicrob Chemother 27: 199–208

    Article  PubMed  CAS  Google Scholar 

  • Ferrero L, Cameron B, Manse B, Lagneaux D, Crouzet J, Famechon A, Blanche F (1994) Cloning and primary structure of Staphylococcus aureus DNA topoisomerase IV: a primary target of fluoroquinolones. Mol Microbiol 13: 641–653

    Article  PubMed  CAS  Google Scholar 

  • Ferrero L, Cameron B, Crouzet J (1995) Analysis of gyrA and grlA mutations in stepwise-selected ciprofloxacin-resistant mutants of Staphylococcus aureus. Antimicrob Agents Chemother 39: 1554–1558

    PubMed  CAS  Google Scholar 

  • Fink MP, Snydman DR, Niederman MS, Leeper KV Jr, Johnson RH, Heard SO, Wunderink RG, Caldwell JW, Schentag JJ, Siami GA, Zameck RL, Haverstock DC, Reinhart HH, Echols RM, Severe Pneumonia Study Group (1994) Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. Antimicrob Agents Chemother 38: 547–557

    Google Scholar 

  • Franco RJ, Drlica K (1988) DNA gyrase on the bacterial chromosome. Oxolinic acid-induced DNA cleavage in the dnaA-gyrB region. J Mol Biol 201: 229–233

    Article  PubMed  CAS  Google Scholar 

  • Gellert M, Mizuuchi K, O’Dea MH, Nash HA (1976) DNA gyrase: an enzyme that in- troduces superhelical turns into DNA. Proc Natl Acad Sci USA 73: 3872–3876

    Article  PubMed  CAS  Google Scholar 

  • Gellert M, Mizuuchi K, O’Dea MH, Itoh T, Tomizawa JI (1977) Nalidixic acid resistance: a second genetic character involved in DNA gyrase activity. Proc Natl Acad Sci USA 74: 4772–4776

    Article  PubMed  CAS  Google Scholar 

  • Gellert M (1981) DNA topoisomerases. Annu Rev Biochem 50: 879–910

    Article  PubMed  CAS  Google Scholar 

  • Hachler H, Cohen SP, Levy SB (1991) marA, a regulated locus which controls expression of chromosomal multiple antibiotic resistance in Escherichia coli. J Bacteriol 173: 5532–5538

    Google Scholar 

  • Hooper DC, Wolfson JS (1991) Fluoroquinolone antimicrobial agents. N Engl J Med 324: 384–394

    Article  PubMed  CAS  Google Scholar 

  • Hooper DC, Wolfson JS ( 1993 a) Adverse effects. In: Hooper DC, Wolfson JS (eds) Quinolone antimicrobial agents. American Society for Microbiology, Washington, pp 489–512

    Google Scholar 

  • Hooper DC, Wolfson JS ( 1993 b) Mechanisms of bacterial resistance to quinolones. In: Hooper DC, Wolfson JS (eds) Quinolone antimicrobial agents. American Society for Microbiology, Washington, pp 97–118

    Google Scholar 

  • Hooper DC, Wolfson JS ( 1993 c) Mechanisms of quinolone action and bacterial killing. In: Hooper DC, Wolfson JS (eds) Quinolone antimicrobial agents. American Society for Microbiology, Washington, pp 53–75

    Google Scholar 

  • Horio T, Miyauchi H, Asada Y, Aoki Y, Harada M (1994) Phototoxicity and photoallergenicity of quinolones in guinea pigs. J Dermatol Sci 7: 130–135

    Article  PubMed  CAS  Google Scholar 

  • Hoshino K, Kitamura A, Morrissey I, Sato K, Kato J, Ikeda H (1994) Comparison of inhibition of Escherichia coli topoisomerase IV by quinolones with DNA gyrase inhibition. Antimicrob Agents Chemother 38: 2623–2627

    PubMed  CAS  Google Scholar 

  • Jolley A, Andrews JM, Brenwald N, Wise R (1993) The in vitro activity of a new highly active quinolone, DU-6859a. J Antimicrob Chemother 32: 757–763

    Article  PubMed  CAS  Google Scholar 

  • Kato J, Nishimura Y, Imamura R, Niki H, Hiraga S, Suzuki H (1990) New topoisomerase essential for chromosome segregation in Escherichia coli. Cell 63: 393–404 (erratum 65: 1289)

    Google Scholar 

  • Kato J, Suzuki H, Ikeda H (1992) Purification and characterization of DNA topoisomerase IV in Escherichia coli. J Biol Chem 267: 25676–25684

    PubMed  CAS  Google Scholar 

  • Khodursky AB, Zechiedrich EL, Cozzarelli NR (1995) Topoisomerase IV is a target of quinolones in Escherichia coli. Proc Natl Acad Sci USA 92: 11801–11805

    Article  PubMed  CAS  Google Scholar 

  • Korten V, Tomayko JF, Murray BE (1994) Comparative in vitro activity of DU-6859a, a new fluoroquinolone agent, against gram-positive cocci. Antimicrob Agents Chemother 38: 611–615

    PubMed  CAS  Google Scholar 

  • Levy SB (1992) Active efflux mechanisms for antimicrobiol resistance. Antimicrob Agents Chemother 36: 695–703

    PubMed  CAS  Google Scholar 

  • Marshall SA, Jones RN (1993) In vitro activity of DU-68S9a, a new fluorocyclopropyl quinolone. Antimicrob Agents Chemother 37: 2747–2753

    PubMed  CAS  Google Scholar 

  • Marutani K, Matsumoto M, Otabe Y, Nagamuta M, Tanaka K, Miyoshi A, Hasegawa T, Nagano H, Matsubara S, Kamide R (1993) Reduced phototoxicity of a fluoroquinolone antibacterial agent with a methoxy group at the 8 position in mice irradiated with long-wavelength UV light. Antimicrob Agents Chemother 37: 2217–2223

    PubMed  CAS  Google Scholar 

  • Nakashima M, Uematsu T, Kosuge K, Umemura K, Hakusui H, Tanaka M (1995) Pharmacokinetics and tolerance of DU-6859a, a new fluoroquinolone, after single and multiple oral doses in healthy volunteers. Antimicrob Agents Chemother 39: 170–174 (erratum 39: 1015)

    Google Scholar 

  • Ng EY, Trucksis M, Hooper DC (1994) Quinolone resistance mediated by norA: physiologic characterization and relationship to flqB, a quinolone resistance locus on the Staphylococcus aureus chromosome. Antimicrob Agents Chemother 38: 1345–1355

    PubMed  CAS  Google Scholar 

  • Ng EY, Trucksis M, Hooper DC (1996) Quindone resistance mutations in topoisomerase IV: relationship to the flgA locus and genetic evidence that topoisomerase IV is the primary target and DNA gyrase the secondary target of fluoroquinolones in Staphylococcus aureus. Antimicrob Agents Chemother 40: 1881–1888

    PubMed  CAS  Google Scholar 

  • Parry MF, Panzer KB, Yukna ME (1989) Quinolone resistance. Susceptibility data from a 300-bed community hospital. Am J Med 87: 12S - 16S

    Article  PubMed  CAS  Google Scholar 

  • Peng H, Marians KJ (1993) Escherichia coli topoisomerase IV. Purification, characterization, subunit structure, and subunit interactions. J Biol Chem 268: 24481–24490

    Google Scholar 

  • Perez-Trallero E, Urbieta M, Jimenez D, Garcia-Arenzana JM, Cilla G (1993) Ten-year survey of quinolone resistance in Escherichia coli causing urinary tract infections. Eur J Clin Microbiol Infect Dis 12: 349–351

    Article  PubMed  CAS  Google Scholar 

  • Peterson LR (1993) Quinolone Resistance in Clinical Practice: Occurrence and Importance. In: Hooper DC, Wolfson JS (eds) Quinolone Antimicrobial Agents. American Society for Microbiology, Washington, pp 119–137

    Google Scholar 

  • Richard P, Gutmann L (1992) Sparfloxacin and other new fluoroquinolones. J Antimicrob Chemother 30: 739–744

    Article  PubMed  CAS  Google Scholar 

  • Schaad UB, Wedgwood J (1992) Lack of quinolone-induced arthropathy in children. J Antimicrob Chemother 30: 414–416

    Article  PubMed  CAS  Google Scholar 

  • Shimada J, Nogita T, Ishibashi Y (1993) Clinical pharmacokinetics of sparfloxacin. Clin Pharmacokinet 25: 358–369

    Article  PubMed  CAS  Google Scholar 

  • Snyder M, Drlica K (1979) DNA gyrase on the bacterial chromosome: DNA cleavage induced by oxolinic acid. J Mol Biol 131: 287–302

    Google Scholar 

  • Sugino A, Peebles CL, Kreuzer KN, Cozzarelli NR (1977) Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme. Proc Nati Acad Sci USA 74: 4767–4771

    Article  CAS  Google Scholar 

  • Trucksis M, Wolfson JS, Hooper DC (1991) A novel locus conferring fluoroquinolone resistance in Staphylococcus aureus. J Bacteriol 173: 5854–5860

    PubMed  CAS  Google Scholar 

  • Visser MR, Rozenberg-Arska M, Beumer H, Hoepelman IM, Verhoef J (1991) Comparative in vitro antibacterial activity of sparfloxacin (AT-414o; RP 64206), a new quinolone. Antimicrob Agents Chemother 35: 858–868

    PubMed  CAS  Google Scholar 

  • Wang JC (1985) DNA topoisomerases. Annu Rev Biochem 54: 665–697

    Article  PubMed  CAS  Google Scholar 

  • Wang JC (1991) DNA topoisomerases: why so many? J Biol Chem 266: 6659–6662

    PubMed  CAS  Google Scholar 

  • Wiedemann B, Zuhlsdorf MT (1989) Resistance development to fluoroquinolones in Europe. Am J Med 87: 9S - 11S

    Article  PubMed  CAS  Google Scholar 

  • Wise R, Andrews JM, Brenwald N (1993) The in vitro activity of OPC-17116, a new 5-methyl substituted quinolone. J Antimicrob Chemother 31: 497–504

    Article  PubMed  CAS  Google Scholar 

  • Wolfson JS, Hooper DC (1989) Fluoroquinolone antimicrobial agents. Clin Microbiol Rev 2: 378–424

    PubMed  CAS  Google Scholar 

  • Yoshida H, Bogaki M, Nakamura S, Ubukata K, Konno M (1990) Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones. J Bacteriol 172: 6942–6949

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Infectious Disease Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA

    D. C. Hooper

Authors
  1. D. C. Hooper
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Bayer AG, Geschäftsbereich Pharma, D-42096, Wuppertal, Germany

    W.-D. Busse , H. Labischinski  & H.-J. Zeiler ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Hooper, D.C. (1997). Expanding and Preserving the Utility of Quinolone Antimicrobials. In: Busse, WD., Labischinski, H., Zeiler, HJ. (eds) Antibacterial Therapy: Achievements, Problems and Future Perspectives. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60803-2_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-60803-2_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-62896-5

  • Online ISBN: 978-3-642-60803-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation