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Antimicrobial Agents and Chemotherapy, January 2009, p. 229-234, Vol. 53, No. 1
0066-4804/09/$08.00+0     doi:10.1128/AAC.00722-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Relationships among Ciprofloxacin, Gatifloxacin, Levofloxacin, and Norfloxacin MICs for Fluoroquinolone-Resistant Escherichia coli Clinical Isolates{triangledown}

Lauren Becnel Boyd,1 Merry J. Maynard,1 Sonia K. Morgan-Linnell,1 Lori Banks Horton,1 Richard Sucgang,2 Richard J. Hamill,1,5,7 Javier Rojo Jimenez,8 James Versalovic,1,6 David Steffen,4 and Lynn Zechiedrich1,2,3*

Department of Molecular Virology and Microbiology,1 Verna and Marrs McLean Department of Biochemistry and Molecular Biology,2 Department of Pharmacology,3 Bioinformatics Research Center,4 Department of Medicine,5 Department of Pathology, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas,6 Michael E. DeBakey Veterans Administration Medical Center, Houston, Texas 77030,7 Department of Statistics, Rice University, Houston, Texas 770058

Received 2 June 2008/ Returned for modification 25 July 2008/ Accepted 28 September 2008

Fluoroquinolones are some of the most prescribed antibiotics in the United States. Previously, we and others showed that the fluoroquinolones exhibit a class effect with regard to the CLSI-established breakpoints for resistance, such that decreased susceptibility (i.e., an increased MIC) to one fluoroquinolone means a simultaneously decreased susceptibility to all. For defined strains, however, clear differences exist in the pharmacodynamic properties of each fluoroquinolone and the extent to which resistance-associated genotypes affect the MICs of each fluoroquinolone. In a pilot study of 920 clinical Escherichia coli isolates, we uncovered tremendous variation in norfloxacin MICs. The MICs for all of the fluoroquinolone-resistant isolates exceeded the resistance breakpoint, reaching 1,000 µg/ml. Approximately 25% of the isolates (n = 214), representing the full range of resistant norfloxacin MICs, were selected for the simultaneous determinations of ciprofloxacin, gatifloxacin, levofloxacin, and norfloxacin MICs. We found that (i) great MIC variation existed for all four fluoroquinolones, (ii) the ciprofloxacin and levofloxacin MICs of >90% of the fluoroquinolone-resistant isolates were higher than the resistance breakpoints, (iii) ciprofloxacin and levofloxacin MICs were distributed into two distinct groups, (iv) the MICs of two drug pairs (ciprofloxacin and norfloxacin by Kendall's Tau-b test and gatifloxacin and levofloxacin by paired t test) were similar with statistical significance but were different from each other, and (v) ~2% of isolates had unprecedented fluoroquinolone MIC relationships. Thus, although the fluoroquinolones can be considered equivalent with regard to clinical susceptibility or resistance, fluoroquinolone MICs differ dramatically for fluoroquinolone-resistant clinical isolates, likely because of differences in drug structure.

* Corresponding author. Mailing address: Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, mail stop BCM-280, Houston, TX 77030-3411. Phone: (713) 798-5126. Fax: (713) 798-7375. E-mail: elz{at}bcm.edu

{triangledown} Published ahead of print on 6 October 2008.

Antimicrobial Agents and Chemotherapy, January 2009, p. 229-234, Vol. 53, No. 1
0066-4804/09/$08.00+0     doi:10.1128/AAC.00722-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cavaco, L. M., Aarestrup, F. M. (2009). Evaluation of Quinolones for Use in Detection of Determinants of Acquired Quinolone Resistance, Including the New Transmissible Resistance Mechanisms qnrA, qnrB, qnrS, and aac(6')Ib-cr, in Escherichia coli and Salmonella enterica and Determinations of Wild-Type Distributions. J. Clin. Microbiol. 47: 2751-2758 [Abstract] [Full Text]  
  • Morgan-Linnell, S. K., Becnel Boyd, L., Steffen, D., Zechiedrich, L. (2009). Mechanisms Accounting for Fluoroquinolone Resistance in Escherichia coli Clinical Isolates. Antimicrob. Agents Chemother. 53: 235-241 [Abstract] [Full Text]  


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