Relationships between Mutant Prevention Concentrations and Mutation Frequencies against Enrofloxacin for Avian Pathogenic &lt;i&gt;Escherichia coli&lt;/i&gt; Isolates

Ozawa, Manao; Asai, Tetsuo

doi:10.1292/jvms.12-0131

Cited by 6 publications

(6 citation statements)

References 22 publications

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“…This corresponded with MPC/MIC ratios of 4 (MIC 0.032 μg/mL) or 8 (MIC 0.016 μg/mL). These results dovetail with other reports of MPC measurements in E. coli and APEC strains [ 14 , 49 ].…”

Section: Discussionsupporting

confidence: 92%

Evaluation of Fluoroquinolone Resistance in Clinical Avian Pathogenic Escherichia coli Isolates from Flanders (Belgium)

et al. 2020

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Fluoroquinolones are frequently used antimicrobials for the treatment of avian pathogenic Escherichia coli (APEC) infections. However, rapid development and selection of resistance to this class of antimicrobial drugs is a significant problem. The aim of this study was to investigate the occurrence and mechanisms of antimicrobial resistance against enrofloxacin (ENRO) in APEC strains in Flanders, Belgium. One hundred and twenty-five APEC strains from broilers with clinical colibacillosis were collected in Flanders from November 2017 to June 2018. The minimum inhibitory concentration (MIC) of all strains and the mutant prevention concentration (MPC) of a sample of sensitive isolates were determined using a commercial gradient strip test and via the agar dilution method, respectively. Non-wild type (NWT) isolates were further characterized using polymerase chain reaction (PCR), gel electrophoresis and gene sequencing. Forty percent of the APEC strains were NWT according to the epidemiological cut-off (ECOFF) measure (MIC > 0.125 μg/mL). With respect to clinical breakpoints, 21% were clinically intermediate (0.5 ≤ MIC ≤ 1 μg/mL) and 10% were clinically resistant (MIC ≥ 2). The MPC values of the tested strains ranged from 0.064 to 1 μg/mL, resulting in MPC/MIC ratios varying from 4 to 32. The majority (92%) of the NWT strains carried one or two mutations in gyrA. Less than a quarter (22%) manifested amino acid substitutions in the topoisomerase IV parC subunit. Only three of the NWT strains carried a mutation in parE. Plasmid mediated quinolone resistance (PMQR) associated genes were detected in 18% of the NWT strains. In contrast to the relatively large number of NWT strains, only a small percentage of APEC isolates was considered clinically resistant. The most common MPC value for sensitive strains was 0.125 μg/mL. Some isolates showed higher values, producing wide mutant selection windows (MSW). Chromosomal mutations in DNA gyrase and topoisomerase IV were confirmed as the main source of decreased antimicrobial fluoroquinolone susceptibility, de-emphasizing the role of PMQR mechanisms.

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Section: Discussionsupporting

confidence: 92%

Evaluation of Fluoroquinolone Resistance in Clinical Avian Pathogenic Escherichia coli Isolates from Flanders (Belgium)

et al. 2020

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“…These results indicate that tva (A) raises the MPC and widens the MSW. Mutants were only recovered from isolates harbouring tva(A) and the geometric mean of mutation frequency was 1.88 × 10 −8 , similar to mutation rates reported for E. coli and S. enterica exposed to quinolones (Randall et al, 2004 ; Ozawa and Asai, 2013 ).…”

Section: Resultssupporting

confidence: 80%

“…We applied the principles of the mutation prevention concentration (MPC) hypothesis, which defines the antibiotic concentration at which mutations giving rise to resistance do not occur (Drlica and Zhao, 2007 ), when exposing isolates to inhibitory tiamulin concentrations. The MPC has been applied to assess the development of resistance to various antibiotics including quinolones, macrolides, tetracyclines, and pleuromutilins in many bacterial species including Escherichia coli, Salmonella enterica, Mycoplasma gallisepticum , and Staphylococcus aureus (Randall et al, 2004 ; Drlica and Zhao, 2007 ; Ozawa and Asai, 2013 ; Zhang et al, 2017 ). Maintaining antibiotic concentrations above the MPC during therapy is thought to help reduce the development of resistance (Drlica and Zhao, 2007 ) and we related our findings to published tiamulin pharmacokinetic and pharmacodynamic parameters in pigs to help inform veterinary options for the treatment of SD.…”

Section: Introductionmentioning

confidence: 99%

Identification of a New Antimicrobial Resistance Gene Provides Fresh Insights Into Pleuromutilin Resistance in Brachyspira hyodysenteriae, Aetiological Agent of Swine Dysentery

Card

Stubberfield²,

Rogers³

et al. 2018

Front. Microbiol.

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Brachyspira hyodysenteriae is the aetiological agent of swine dysentery, a globally distributed disease that causes profound economic loss, impedes the free trade and movement of animals, and has significant impact on pig health. Infection is generally treated with antibiotics of which pleuromutilins, such as tiamulin, are widely used for this purpose, but reports of resistance worldwide threaten continued effective control. In Brachyspira hyodysenteriae pleuromutilin resistance has been associated with mutations in chromosomal genes encoding ribosome-associated functions, however the dynamics of resistance acquisition are poorly understood, compromising stewardship efforts to preserve pleuromutilin effectiveness. In this study we undertook whole genome sequencing (WGS) and phenotypic susceptibility testing of 34 UK field isolates and 3 control strains to investigate pleuromutilin resistance in Brachyspira hyodysenteriae. Genome-wide association studies identified a new pleuromutilin resistance gene, tva(A) (tiamulin valnemulin antibiotic resistance), encoding a predicted ABC-F transporter. In vitro culture of isolates in the presence of inhibitory or sub-inhibitory concentrations of tiamulin showed that tva(A) confers reduced pleuromutilin susceptibility that does not lead to clinical resistance but facilitates the development of higher-level resistance via mutations in genes encoding ribosome-associated functions. Genome sequencing of antibiotic-exposed isolates identified both new and previously described mutations in chromosomal genes associated with reduced pleuromutilin susceptibility, including the 23S rRNA gene and rplC, which encodes the L3 ribosomal protein. Interesting three antibiotic-exposed isolates harboured mutations in fusA, encoding Elongation Factor G, a gene not previously associated with pleuromutilin resistance. A longitudinal molecular epidemiological examination of two episodes of swine dysentery at the same farm indicated that tva(A) contributed to development of tiamulin resistance in vivo in a manner consistent with that seen experimentally in vitro. The in vitro studies further showed that tva(A) broadened the mutant selection window and raised the mutant prevention concentration above reported in vivo antibiotic concentrations obtained when administered at certain doses. We show how the identification and characterisation of tva(A), a new marker for pleuromutilin resistance, provides evidence to inform treatment regimes and reduce the development of resistance to this class of highly important antimicrobial agents.

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“…This is in agreement with Jurado et al 14 , who found no significant differences among different enrofloxacin dosage schemes that were administered orally to broiler chickens. Although various studies have showed that dosage can have an effect on the emergence of resistance, 34,35,60,61 the results of the present study suggest that it does not have an effect on the selection and spread of resistance. Grouping the referred studies with regards to commensal versus pathogenic E. coli isolates, the mutation frequencies of the strains were compared.…”

Section: Treatment Dosecontrasting

confidence: 78%

Studying the effect of administration route and treatment dose on the selection of enrofloxacin resistance in commensal Escherichia coli in broilers

Chantziaras¹,

Smet²,

Haesebrouck³

et al. 2017

Journal of Antimicrobial Chemotherapy

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Relationships between Mutant Prevention Concentrations and Mutation Frequencies against Enrofloxacin for Avian Pathogenic <i>Escherichia coli</i> Isolates

Cited by 6 publications

References 22 publications

Evaluation of Fluoroquinolone Resistance in Clinical Avian Pathogenic Escherichia coli Isolates from Flanders (Belgium)

Evaluation of Fluoroquinolone Resistance in Clinical Avian Pathogenic Escherichia coli Isolates from Flanders (Belgium)

Identification of a New Antimicrobial Resistance Gene Provides Fresh Insights Into Pleuromutilin Resistance in Brachyspira hyodysenteriae, Aetiological Agent of Swine Dysentery

Studying the effect of administration route and treatment dose on the selection of enrofloxacin resistance in commensal Escherichia coli in broilers

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