Molecular mechanisms of fluoroquinolone resistance

Journal of Microbiology, Immunology and Infection

Volumn 36, Issue 1, 2003, Pages 1-9

  Chen, Feng Jui ^a   Lo, Hsiu Jung ^a  

^a NATIONAL HEALTH RESEARCH INSTITUTES   (Taiwan)

Author keywords

Efflux pump; Fluoroquinolone resistance; Gyrase; Topoisomerase IV

Indexed keywords

CARRIER PROTEIN; CIPROFLOXACIN; DNA TOPOISOMERASE (ATP HYDROLYSING); DNA TOPOISOMERASE IV; ENROFLOXACIN; OFLOXACIN; PORIN; QUINOLINE DERIVED ANTIINFECTIVE AGENT;

AMINO ACID SUBSTITUTION; ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; CHRONIC OSTEOMYELITIS; DRUG ACCUMULATION; DRUG MECHANISM; DRUG TARGETING; GASTROINTESTINAL INFECTION; GENE MUTATION; HUMAN; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; RESPIRATORY TRACT INFECTION; REVIEW; SEXUALLY TRANSMITTED DISEASE; URINARY TRACT INFECTION;

ANIMALS; ANTI-INFECTIVE AGENTS; BACTERIA; BACTERIAL INFECTIONS; BACTERIAL PROTEINS; DNA GYRASE; DNA TOPOISOMERASE IV; DRUG RESISTANCE, BACTERIAL; FLUOROQUINOLONES; HUMANS; MICROBIAL SENSITIVITY TESTS;

EID: 0037355248     PISSN: 02532662     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (99)

1. Neu HC. Major advances in antibacterial quinolone therapy. Adv Pharmacol 1994;29A:227-62.
2. Lesher GY, Froelich EJ, Gruett MD, Bailey JH, Brundage RP. 1,8-Naphthyridine derivatives: a new class of chemotherapeutic agents. J Med Chem 1962;5:1063-5.
3. Wolfson JS, Hooper DC. The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob Agents Chemother 1985;28:581-6.
4. Monk JP, Campoli-Richards DM. Ofloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 1987;33:346-91.
5. Piddock LJ. Mechanisms of fluoroquinolone resistance: an update 1994-1998. Drugs 1999;58:11-8.
6. Gellert M, Mizuuchi K, O'Dea MH, Itoh T, Tomizawa JI. Nalidixic acid resistance: a second genetic character involved in DNA gyrase activity. Proc Natl Acad Sci USA 1977;74:4772-6.
7. Sugino A, Peebles CL, Kreuzer KN, Cozzarelli NR. 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 Natl Acad Sci USA 1977;74:4767-71.
8. Kato J, Nishimura Y, Imamura R, Niki H, Hiraga S, Suzuki H. New topoisomerase essential for chromosome segregation in Escherichia coli. Cell 1990;63:393-404.
9. Huang WM. Bacterial diversity based on type II DNA topoisomerase genes. Annu Rev Genet 1996;30:79-107.
10. Peng H, Marians KJ. Escherichia coli topoisomerase IV: purification, characterization, subunit structure, and subunit interactions. J Biol Chem 1993;268:24481-90.
11. Gellert M. DNA topoisomerases. Annu Rev Biochem 1981;50:879-910.
12. Shen LL, Chu DTW. Type II DNA topoisomerases as antibacterial targets. Curr Pharm Des 1996;2:195-208.
13. Peng H, Marians KJ. Decatenation activity of topoisomerase IV during oriC and pBR322 DNA replication in vitro. Proc Natl Acad Sci USA 1993;90:8571-5.
14. Zechiedrich EL, Cozzarelli NR. Roles of topoisomerase IV and DNA gyrase in DNA unlinking during replication in Escherichia coli. Genes Dev 1995;9:2859-69.
15. Peng H, Marians KJ. The interaction of Escherichia coli topoisomerase IV with DNA. J Biol Chem 1995;70:25286-90.
16. Gales AC, Gordon KA, Wilke WW, Pfaller MA, Jones RN. Occurrence of single-point gyrA mutations among ciprofloxacin-susceptible Escherichia coli isolates causing urinary tract infections in Latin America. Diagn Microbiol Infect Dis 2000;36:61-4.
17. McDonald LC, Chen FJ, Lo HJ, Yin HC, Lu PL, Huang CH, Chen P, Lauderdale TL, Ho M. Emergence of reduced susceptibility and resistance to fluoroquinolones in Escherichia coli in Taiwan and contributions of distinct selective pressures. Antimicrob Agents Chemother 2001;45:3084-91.
18. Chen FJ, McDonald LC, Ho M, Lo HJ. Identification of fluoroquinolone reduced-susceptibility in Escherichia coli: a herald for emerging resistance. J Antimicrob Chemother 2001;48:936-8.
19. Martinez-Martinez L, Pascual A, Jacoby GA. Quinolone resistance from a transferable plasmid. Lancet 1998;351:797-9.
20. Rella M, Haas D. Resistance of Pseudomonas aeruginosa PAO to nalidixic acid and low levels of β-lactam antibiotics: mapping of chromosomal genes. Antimicrob Agents Chemother 1982;22:242-9.
21. Poole K, Gotoh N, Tsujimoto H, Zhao Q, Wada A, Yamasaki T, Neshat S, Yamagishi J, Li XZ, Nishino T. Overexpression of the mexC-mexD-oprJ efflux operon in nfxB-type multidrug-resistant strains of Pseudomonas aeruginosa. Mol Microbiol 1996;21:713-24.
22. Jakics EB, Iyobe S, Hirai K, Fukuda H, Hashimoto H. Occurrence of the nfxB type mutation in clinical isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother 1992;36:2562-5.
23. Martinez-Martinez L, Hernandez-Alles S, Alberti S, Tomas JM, Benedi VJ, Jacoby GA. In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and expanded-spectrum-cephalosporins. Antimicrob Agents Chemother 1996;40:342-8.
24. Ferrero L, Cameron B, Manse B, Lagneaux D, Crouzet J, Famechon A, Blanche F. Cloning and primary structure of Staphylococcus aureus DNA topoisomerase IV: a primary target of fluoroquinolones. Mol Microbiol 1994;13:641-53.
25. Kaatz GW, Seo SM. Inducible NorA-mediated multidrug resistance in Staphylococcus aureus. Antimicrob Agents Chemother 1995;39:2650-5.
26. Heisig P. High-level fluoroquinolone resistance in a Salmonella typhimurium isolate due to alterations in both gyrA and gyrB genes. J Antimicrob Chemother 1993;32:367-77.
27. Yoshida H, Bogaki M, Nakamura M, Nakamura S. Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli. Antimicrob Agents Chemother 1990;34:1271-2.
28. Heisig P, Tschorny R. Characterization of fluoroquinolone-resistant mutants of Escherichia coli selected in vitro. Antimicrob Agents Chemother 1994;38:1284-91.
29. Martinez-Martinez L, Garcia I, Ballesta S, Benedi VJ, Hernandez-Alles S, Pascual A. Energy-dependent accumulation of fluoroquinolones in quinolone-resistant Klebsiella pneumoniae strains. Antimicrob Agents Chemother 1998;42:1850-2.
30. Dimri GP, Das HK. Cloning and sequence analysis of gyrA gene of Klebsiella pneumoniae. Nucleic Acids Res 1990;18:151-6.
31. Weigel LM, Steward CD, Tenover FC. gyrA mutations associated with fluoroquinolone resistance in eight species of Enterobacteriaceae. Antimicrob Agents Chemother 1998;42:2661-7.
32. Deguchi T, Fukuoka A, Yasuda M, Nakano M, Ozeki S, Kanematsu E, Nishino Y, Ishihara S, Ban Y, Kawada Y. Alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV in quinolone-resistant clinical isolates of Klebsiella pneumoniae. Antimicrob Agents Chemother 1997;41:699-701.
33. Une T, Fujimoto T, Sato K, Osada Y. In vitro activity of DR-3355, an optically active ofloxacin. Antimicrob Agents Chemother 1988;32:1336-40.
34. Truong QC, Ouabdesselam S, Hooper DC, Moreau NJ, Soussy CJ. Sequential mutations of gyrA in Escherichia coli associated with quinolone therapy. J Antimicrob Chemother 1995;36:1055-9.
35. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing: 9th informational supplement. Wayne, PA: National Committee for Clinical Laboratory Standards; 1999.
36. Ho M, McDonald LC, Lauderdale TL, Yeh LL, Chen PC, Shiau YR. Surveillance of antibiotic resistance in Taiwan, 1998. J Microbiol Immunol Infect 1999;32:239-49.
37. Ferrero L, Cameron B, Crouzet J. Analysis of gyrA and grlA mutations in stepwise-selected ciprofloxacin-resistant mutants of Staphylococcus aureus. Antimicrob Agents Chemother 1995;39:1554-8.
38. Pan XS, Ambler J, Mehtar S, Fisher LM. Involvement of topoisomerase IV and DNA gyrase as ciprofloxacin targets in Streptococcus pneumoniae. Antimicrob Agents Chemother 1996;40:2321-6.
39. Gootz TD, Zaniewski R, Haskell S, Schmieder B, Tankovic J, Girard D, Courvalin P, Polzer RJ. Activity of the new fluoroquinolone trovafloxacin (CP-99,219) against DNA gyrase and topoisomerase IV mutants of Streptococcus pneumoniae selected in vitro. Antimicrob Agents Chemother 1996;40:2691-7.
40. Cohen SP, McMurry LM, Hooper DC, Wolfson JS, Levy SB. 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 1989;33:1318-25.
41. Maneewannakul K, Levy SB. Identification for mar mutants among quinolone-resistant clinical isolates of Escherichia coli. Antimicrob Agents Chemother 1996;40:1695-8.
42. Okusu H, Ma D, Nikaido H. AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants. J Bacteriol 1996;178:306-8.
43. Fukuda H, Hosaka M, Hirai K, Iyobe S. New norfloxacin resistance gene in Pseudomonas aeruginosa PAO. Antimicrob Agents Chemother 1990;34:1757-61.
44. Hirai K, Suzue S, Irikura T, Iyobe S, Mitsuhashi S. Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa. Antimicrob Agents Chemother 1987;31:582-6.
45. Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother 1995;39:1948-53.
46. Kohler T, Michea-Hamzehpour M, Henze U, Gotoh N, Curty LK, Pechere JC. Characterization of MexE-MexF-OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa. Mol Microbiol 1997;23:345-54.
47. Ziha-Zarifi I, Llanes C, Kohler T, Pechere JC, Plesiat P. In vivo emergence of multidrug-resistant mutants of Pseudomonas aeruginosa overexpressing the active efflux system MexA-MexB-OprM. Antimicrob Agents Chemother 1999;43:287-91.
48. Michea-Hamzehpour M, Auckenthaler R, Regamey P, Pechere JC. Resistance occurring after fluoroquinolone therapy of experimental Pseudomonas aeruginosa peritonitis. Antimicrob Agents Chemother 1987;31:1803-8.
49. Yoshida H, Bogaki M, Nakamura S, Ubukata K, Konno M. Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones. J Bacteriol 1990;172:6942-9.
50. Neyfakh AA, Borsch CM, Kaatz GW. Fluoroquinolone resistance protein NorA of Staphylococcus aureus is a multidrug efflux transporter. Antimicrob Agents Chemother 1993;37:128-9.
51. Lynch C, Courvalin P, Nikaido H. Active efflux of antimicrobial agents in wild-type strains of enterococci. Antimicrob Agents Chemother 1997;41:869-71.
52. Baranova NN, Neyfakh AA. Apparent involvement of a multidrug transporter in the fluoroquinolone resistance of Streptococcus pneumoniae. Antimicrob Agents Chemother 1997;41:1396-8.
53. Liu J, Takiff HE, Nikaido H. Active efflux of fluoroquinolones in Mycobacterium smegmatis mediated by LfrA, a multidrug efflux pump. J Bacteriol 1996;178:3791-5.
54. Chapman JS, Georgopapadakou NH. Routes of quinolone permeation in Escherichia coli. Antimicrob Agents Chemother 1988;32:438-42.
55. Aoyama H, Sato K, Kato T, Hirai K, Mitsuhashi S. Norfloxacin resistance in a clinical isolate of Escherichia coli. Antimicrob Agents Chemother 1987;31:1640-1.
56. Piddock LJ, Griggs DJ, Hall MC, Jin YF. Ciprofloxacin resistance in clinical isolates of Salmonella typhimurium obtained from two patients. Antimicrob Agents Chemother 1993;37:662-6.
57. Nakamura S. Veterinary use of new quinolones in Japan. Drugs 1995;49(Suppl 2):S152-8.
58. Frost JA, Kelleher A, Rowe B. Increasing ciprofloxacin resistance in salmonellas in England and Wales 1991-1994. J Antimicrob Chemother 1996;37:85-91.
59. Chiu CH, Wu TL, Su LH, Chu C, Chia JH, Kuo AJ, Chien MS, Lin TY. The emergence in Taiwan of fluoroquinolone resistance in Salmonella enterica serotype choleraesuis. N Engl J Med 2002;346:413-9.
60. Molbak K, Baggesen DL, Aarestrup FM, Ebbesen JM, Engberg J, Frydendahl K, Gerner-Smidt P, Petersen AM, Wegener HC. An outbreak of multidrug-resistant, quinolone-resistant Salmonella enterica serotype Typhimurium DT104. N Engl J Med 1999;341:1420-5.
61. Smith KE, Besser JM, Hedberg CW, Leano FT, Bender JB, Wicklund JH, Johnson BP, Moore KA, Osterholm MT, Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992-1998. N Engl J Med 1999;340:1525-32.
62. Webber M, Piddock LJ. Quinolone resistance in Escherichia coli. Vet Res 2001;32:275-84.
63. Aarestrup FM, Seyfarth AM, Emborg HD, Pedersen K, Hendriksen RS, Bager F. Effect of abolishment of the use of antimicrobial agents for growth promotion on occurrence of antimicrobial resistance in fecal enterococci from food animals in Denmark. Antimicrob Agents Chemother 2001;45:2054-9.
64. Daum TE, Schaberg DR, Terpenning MS, Sottile WS, Kauffman CA. Increasing resistance of Staphylococcus aureus to ciprofloxacin. Antimicrob Agents Chemother 1990;34:1862-3.
65. Schaefler S. Methicillin-resistant strains of Staphylococcus aureus resistant to quinolones. J Clin Microbiol 1989;27:335-6.
66. Shalit I, Berger SA, Gorea A, Frimerman H. Widespread quinolone resistance among methicillin-resistant Staphylococcus aureus isolates in a general hospital. Antimicrob Agents Chemother 1989;33:593-4.
67. Paterson DL, Mulazimoglu L, Casellas JM, Ko WC, Goossens H, Von Gottberg A, Mohapatra S, Trenholme GM, Klugman KP, McCormack JG, Yu VL. Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum β-lactamase production in Klebsiella pneumoniae isolates causing bacteremia. Clin Infect Dis 2000;30:473-8.
68. National Committe for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing: 11th informational supplement M100-S11. Villanova, PA: National Committee for Clinical Laboratory Standards; 2001.
69. Vasallo FJ, Martin-Rabadan P, Alcala L, Garcia-Lechuz JM, Rodriguez-Creixems M, Bouza E. Failure of ciprofloxacin therapy for invasive nontyphoidal salmonellosis. Clin Infect Dis 1998;26:535-6.
70. Hooper DC. Mechanisms of fluoroquinolone resistance. Drug Resist Updat 1999;2:38-55.
71. Heisig P. Genetic evidence for a role of parC mutations in development of high-level fluoroquinolone resistance in Escherichia coli. Antimicrob Agents Chemother 1996;40:879-85.
72. Kumagai Y, Kato JI, Hoshino K, Akasaka T, Sato K, Ikeda H. Quinolone-resistant mutants of Escherichia coli DNA topoisomerase IV parC gene. Antimicrob Agents Chemother 1996;40:710-4.
73. Yamagishi J, Kojima T, Oyamada Y, Fujimoto K, Hattori H, Nakamura S, Inoue M. Alterations in the DNA topoisomerase IV grlA gene responsible for quinolone resistance in Staphylococcus aureus. Antimicrob Agents Chemother 1996;40:1157-63.
74. Vila J, Ruiz J, Goni P, De Anta MT. Detection of mutations in parC in quinolone-resistant clinical isolates of Escherichia coli. Antimicrob Agents Chemother 1996;40:491-3.
75. Piddock LJ. Fluoroquinolone resistance in Salmonella serovars isolated from humans and food animals. FEMS Microbiol Rev 2002;26:3-16.
76. Griggs DJ, Gensberg K, Piddock LJ. Mutations in gyrA gene of quinolone-resistant Salmonella serotypes isolated from humans and animals. Antimicrob Agents Chemother 1996;40:1009-13.
77. Deguchi T, Kawamura T, Yasuda M, Nakano M, Fukuda H, Kato H, Kato N, Okano Y, Kawada Y. In vivo selection of Klebsiella pneumoniae strains with enhanced quinolone resistance during fluoroquinolone treatment of urinary tract infections. Antimicrob Agents Chemother 1997;41:1609-11.
78. George AM, Hall RM, Stokes HW. Multidrug resistance in Klebsiella pneumoniae: a novel gene, ramA, confers a multidrug resistance phenotype in Escherichia coli. Microbiology 1995;141:1909-20.
79. Cambau E, Perani E, Dib C, Petinon C, Trias J, Jarlier V. Role of mutations in DNA gyrase genes in ciprofloxacin resistance of Pseudomonas aeruginosa susceptible or resistant to imipenem. Antimicrob Agents Chemother 1995;39:2248-52.
80. Poole K, Tetro K, Zhao Q, Neshat S, Heinrichs DE, Bianco N. Expression of the multidrug resistance operon mexA-mexB-oprM in Pseudomonas aeruginosa: mexR encodes a regulator of operon expression. Antimicrob Agents Chemother 1996;40:2021-8.
81. Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol 1993;175:7363-72.
82. Poole K, Gotoh N, Tsujimoto H, Zhao Q, Wada A, Yamasaki T, Neshat S, Yamagishi J, Li XZ, Nishino T. Overexpression of the mexC-mexD-oprJ efflux operon in nfxB-type multidrug-resistant strains of Pseudomonas aeruginosa. Mol Microbiol 1996;21:713-24.
83. Okazaki T, Hirai K. Cloning and nucleotide sequence of the Pseudomonas aeruginosa nfxB gene, conferring resistance to new quinolones. FEMS Microbiol Lett 1992;76:197-202.
84. Kohler T, Michea-Hamzehpour M, Henze U, Gotoh N, Curty LK, Pechere JC. Characterization of MexE-MexF-OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa. Mol Microbiol 1997;23:345-54.
85. Kohler T, Michea-Hamzehpour M, Plesiat P, Kahr AL, Pechere JC. Differential selection of multidrug efflux systems by quinolones in Pseudomonas aeruginosa. Antimicrob Agents Chemother 1997;41:2540-3.
86. Belland RJ, Morrison SG, Ison C, Huang WM. Neisseria gonorrhoeae acquires mutations in analogous regions of gyrA and parC in fluoroquinolone-resistant isolates. Mol Microbiol 1994;14:371-80.
87. Deguchi T, Yasuda M, Nakano M, Kanematsu E, Ozeki S, Ishihara S, Saito I, Kawada Y. Antimicrobial activity of a new fluoroquinolone, DU-6859a, against quinolone-resistant clinical isolates of Neisseria gonorrhoeae with genetic alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV. J Antimicrob Chemother 1997;39:247-9.
88. Deguchi T, Yasuda M, Nakano M, Ozeki S, Kanematsu E, Fukuda H, Maeda S, Saito I, Kawada Y. Comparison of in vitro antimicrobial activity of AM-1155 with those of tosufloxacin and fleroxacin against clinical isolates of Neisseria gonorrhoeae harboring quinolone resistance alterations in GyrA and ParC. Chemotherapy 1997;43:239-44.
89. Taylor DE, Chau AS. Cloning and nucleotide sequence of the gyrA gene from Campylobacter fetus subsp. fetus ATCC 27374 and characterization of ciprofloxacin-resistant laboratory and clinical isolates. Antimicrob Agents Chemother 1997;41:665-71.
90. Charvalos E, Tselentis Y, Hamzehpour MM, Kohler T, Pechere JC. Evidence for an efflux pump in multidrug-resistant Campylobacter jejuni. Antimicrob Agents Chemother 1995;39:2019-22.
91. Moore RA, Beckthold B, Wong S, Kureishi A, Bryan LE. Nucleotide sequence of the gyrA gene and characterization of ciprofloxacin-resistant mutants of Helicobacter pylori. Antimicrob Agents Chemother 1995;39:107-11.
92. Pan XS, Fisher LM. Cloning and characterization of the parC and pare genes of Streptococcus pneumoniae encoding DNA topoisomerase IV: role in fluoroquinolone resistance. J Bacteriol 1996;178:4060-9.
93. Pan XS, Fisher LM. Targeting of DNA gyrase in Streptococcus pneumoniae by sparfloxacin: selective targeting of gyrase or topoisomerase IV by quinolones. Antimicrob Agents Chemother 1997;41:471-4.
94. Tankovic J, Perichon B, Duval J, Courvalin P. Contribution of mutations in gyrA and parC genes to fluoroquinolone resistance of mutants of Streptococcus pneumoniae obtained in vivo and in vitro. Antimicrob Agents Chemother 1996;40:2505-10.
95. Munoz R, De La Campa AG. ParC subunit of DNA topoisomerase IV of Streptococcus pneumoniae is a primary target of fluoroquinolones and cooperates with DNA gyrase A subunit in forming resistance phenotype. Antimicrob Agents Chemother 1996;40:2252-7.
96. Takiff HE, Cimino M, Musso MC, Weisbrod T, Martinez R, Delgado MB, Salazar L, Bloom BR, Jacobs WR, Jr. Efflux pump of the proton antiporter family confers low-level fluoroquinolone resistance in Mycobacterium smegmatis. Proc Natl Acad Sci USA 1996;93:362-6.
97. Everett MJ, Jin YF, Ricci V, Piddock LJ. Contributions of individual mechanisms to fluoroquinolone resistance in 36 Escherichia coli strains isolated from humans and animals. Antimicrob Agents Chemother 1996;40:2380-6.
98. Vila J, Ruiz J, Marco F, Barcelo A, Goni P, Giralt E, Jimenez dAT. Association between double mutation in gyrA gene of ciprofloxacin-resistant clinical isolates of Escherichia coli and MICs. Antimicrob Agents Chemother 1994;38:2477-9.
99. Vila J, Vargas M, Ruiz J, Corachan M, Jimenez De Anta MT, Gascon J. Quinolone resistance in enterotoxigenic Escherichia coli causing diarrhea in travelers to India in comparison with other geographical areas. Antimicrob Agents Chemother 2000;44:1731-3.