Resistance to moxifloxacin in toxigenic Clostridium difficile isolates is associated with mutations in gyrA

G. Ackermann, Y. J. Tang, R. Kueper, P. Heisig, A. C. Rodloff, Jr Silva J., Stuart H Cohen

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Clostridium difficile is the etiological agent of antibiotic-associated colitis and the most common cause of hospital-acquired infectious diarrhea. Fluoroquinolones such as ciprofloxacin are associated with lower risks of C. difficile-associated diarrhea. In this study, we have analyzed 72 C. difficile isolates obtained from patients with different clinical courses of disease, such as toxic megacolon and relapses; the hospital environment; public places; and horses. They were investigated for their susceptibilities to moxifloxacin (MXF), metronidazole (MEO), and vancomycin (VAN). Mutants highly resistant to fluoroquinolones were selected in vitro by stepwise exposure to increasing concentrations of MXF. The resulting mutants were analyzed for the presence of mutations in the quinolone resistance-determining regions of DNA gyrase (gyrA), the production of toxins A and B, and the epidemiological relationship of these isolates. These factors were also investigated using PCR-based methods. All strains tested were susceptible to MEO and VAN. Twenty-six percent of the clinical isolates (19 of 72) were highly resistant to MXF (MIC ≥ 16 μg/ml). Fourteen of these 19 strains contained nucleotide changes resulting in amino acid substitutions at position 83 in the gyrA protein. Resistant strains selected in vitro did not contain mutations at that position. These findings indicate that resistance to MXF in a majority of cases may be due to amino acid substitution in the gyrA gene.

Original languageEnglish (US)
Pages (from-to)2348-2353
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume45
Issue number8
DOIs
StatePublished - 2001

Fingerprint

Clostridium difficile
Mutation
Fluoroquinolones
Metronidazole
Amino Acid Substitution
Vancomycin
Diarrhea
Toxic Megacolon
DNA Gyrase
Pseudomembranous Enterocolitis
Quinolones
Ciprofloxacin
Horses
Nucleotides
Recurrence
Polymerase Chain Reaction
moxifloxacin
Genes
Proteins
In Vitro Techniques

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Resistance to moxifloxacin in toxigenic Clostridium difficile isolates is associated with mutations in gyrA. / Ackermann, G.; Tang, Y. J.; Kueper, R.; Heisig, P.; Rodloff, A. C.; Silva J., Jr; Cohen, Stuart H.

In: Antimicrobial Agents and Chemotherapy, Vol. 45, No. 8, 2001, p. 2348-2353.

Research output: Contribution to journalArticle

Ackermann, G. ; Tang, Y. J. ; Kueper, R. ; Heisig, P. ; Rodloff, A. C. ; Silva J., Jr ; Cohen, Stuart H. / Resistance to moxifloxacin in toxigenic Clostridium difficile isolates is associated with mutations in gyrA. In: Antimicrobial Agents and Chemotherapy. 2001 ; Vol. 45, No. 8. pp. 2348-2353.
@article{58730446a31844b9a85202f2f16fa2af,
title = "Resistance to moxifloxacin in toxigenic Clostridium difficile isolates is associated with mutations in gyrA",
abstract = "Clostridium difficile is the etiological agent of antibiotic-associated colitis and the most common cause of hospital-acquired infectious diarrhea. Fluoroquinolones such as ciprofloxacin are associated with lower risks of C. difficile-associated diarrhea. In this study, we have analyzed 72 C. difficile isolates obtained from patients with different clinical courses of disease, such as toxic megacolon and relapses; the hospital environment; public places; and horses. They were investigated for their susceptibilities to moxifloxacin (MXF), metronidazole (MEO), and vancomycin (VAN). Mutants highly resistant to fluoroquinolones were selected in vitro by stepwise exposure to increasing concentrations of MXF. The resulting mutants were analyzed for the presence of mutations in the quinolone resistance-determining regions of DNA gyrase (gyrA), the production of toxins A and B, and the epidemiological relationship of these isolates. These factors were also investigated using PCR-based methods. All strains tested were susceptible to MEO and VAN. Twenty-six percent of the clinical isolates (19 of 72) were highly resistant to MXF (MIC ≥ 16 μg/ml). Fourteen of these 19 strains contained nucleotide changes resulting in amino acid substitutions at position 83 in the gyrA protein. Resistant strains selected in vitro did not contain mutations at that position. These findings indicate that resistance to MXF in a majority of cases may be due to amino acid substitution in the gyrA gene.",
author = "G. Ackermann and Tang, {Y. J.} and R. Kueper and P. Heisig and Rodloff, {A. C.} and {Silva J.}, Jr and Cohen, {Stuart H}",
year = "2001",
doi = "10.1128/AAC.45.8.2348-2353.2001",
language = "English (US)",
volume = "45",
pages = "2348--2353",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "8",

}

TY - JOUR

T1 - Resistance to moxifloxacin in toxigenic Clostridium difficile isolates is associated with mutations in gyrA

AU - Ackermann, G.

AU - Tang, Y. J.

AU - Kueper, R.

AU - Heisig, P.

AU - Rodloff, A. C.

AU - Silva J., Jr

AU - Cohen, Stuart H

PY - 2001

Y1 - 2001

N2 - Clostridium difficile is the etiological agent of antibiotic-associated colitis and the most common cause of hospital-acquired infectious diarrhea. Fluoroquinolones such as ciprofloxacin are associated with lower risks of C. difficile-associated diarrhea. In this study, we have analyzed 72 C. difficile isolates obtained from patients with different clinical courses of disease, such as toxic megacolon and relapses; the hospital environment; public places; and horses. They were investigated for their susceptibilities to moxifloxacin (MXF), metronidazole (MEO), and vancomycin (VAN). Mutants highly resistant to fluoroquinolones were selected in vitro by stepwise exposure to increasing concentrations of MXF. The resulting mutants were analyzed for the presence of mutations in the quinolone resistance-determining regions of DNA gyrase (gyrA), the production of toxins A and B, and the epidemiological relationship of these isolates. These factors were also investigated using PCR-based methods. All strains tested were susceptible to MEO and VAN. Twenty-six percent of the clinical isolates (19 of 72) were highly resistant to MXF (MIC ≥ 16 μg/ml). Fourteen of these 19 strains contained nucleotide changes resulting in amino acid substitutions at position 83 in the gyrA protein. Resistant strains selected in vitro did not contain mutations at that position. These findings indicate that resistance to MXF in a majority of cases may be due to amino acid substitution in the gyrA gene.

AB - Clostridium difficile is the etiological agent of antibiotic-associated colitis and the most common cause of hospital-acquired infectious diarrhea. Fluoroquinolones such as ciprofloxacin are associated with lower risks of C. difficile-associated diarrhea. In this study, we have analyzed 72 C. difficile isolates obtained from patients with different clinical courses of disease, such as toxic megacolon and relapses; the hospital environment; public places; and horses. They were investigated for their susceptibilities to moxifloxacin (MXF), metronidazole (MEO), and vancomycin (VAN). Mutants highly resistant to fluoroquinolones were selected in vitro by stepwise exposure to increasing concentrations of MXF. The resulting mutants were analyzed for the presence of mutations in the quinolone resistance-determining regions of DNA gyrase (gyrA), the production of toxins A and B, and the epidemiological relationship of these isolates. These factors were also investigated using PCR-based methods. All strains tested were susceptible to MEO and VAN. Twenty-six percent of the clinical isolates (19 of 72) were highly resistant to MXF (MIC ≥ 16 μg/ml). Fourteen of these 19 strains contained nucleotide changes resulting in amino acid substitutions at position 83 in the gyrA protein. Resistant strains selected in vitro did not contain mutations at that position. These findings indicate that resistance to MXF in a majority of cases may be due to amino acid substitution in the gyrA gene.

UR - http://www.scopus.com/inward/record.url?scp=0034924147&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034924147&partnerID=8YFLogxK

U2 - 10.1128/AAC.45.8.2348-2353.2001

DO - 10.1128/AAC.45.8.2348-2353.2001

M3 - Article

C2 - 11451695

AN - SCOPUS:0034924147

VL - 45

SP - 2348

EP - 2353

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 8

ER -