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Darren J Trott - One of the best experts on this subject based on the ideXlab platform.
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Phylogenetic grouping, antibiotic resistance profile, fluoroquinolone susceptibility and ST131 status of canine extraintestinal Escherichia coli isolated from submissions to a veterinary diagnostic laboratory 2005-08
Journal of Veterinary Science and Technology, 2011Co-Authors: Joanne L. Platell, Darren J Trott, Heinz-georg Wetzstein, Michael Leitner, Rowland N. CobboldAbstract:Fluoroquinolones (FQs) are a recommended treatment for Escherichia coli infections in companion animals, particularly in cases of resistance to other drug classes. In a retrospective study, 162 canine clinical E. coli isolates, obtained from veterinary diagnostic submissions (January 2005 - June 2008), were analyzed for phylogenetic group and antibiogram phenotype, using nine antimicrobials and enrofloxacin, ciprofloxacin, moxifloxacin and Pradofloxacin minimum inhibitory concentrations (MICs), either in the absence or presence of an efflux pump inhibitor. The isolate susceptibility distribution was bimodal; a high proportion (141/162;87%) showed a sensitivity equivalent to wildtype E. coli (enrofloxacin MIC 0.004 - 0.06 μg/mL), while a minority (4/162;2%) showed reduced susceptibility (enrofloxacin MICs of 0.125 - 0.5 μg/mL), and the remainder (17/162;10%) yielding enrofloxacin MICs in the highlevel resistance range of ≥16 μg/mL. All FQ-resistant isolates were also multidrug resistant. The majority of FQsensitive isolates belonged to phylogenetic group B2 (101/162;62%), and the majority of resistant isolates to group D (8/17;47%). A single resistant B2 isolate and three FQ-sensitive isolates were identified as ST131. Efflux pump activity contributed significantly to MICs for all FQs, except for ciprofloxacin, which may be attributable to its higher polarity compared to the other FQs. These findings confirm a low prevalence of FQ resistance in Australian canine E. coli isolates. Detection of a high moxifloxacin: low ciprofloxacin MIC efflux-associated phenotype (102/162;63%) amongst canine strains may indicate previous exposure to moxifloxacin selective pressure, providing more evidence of exchange of E. coli strains between humans and dogs. The presence of sensitive ST131 strains in the isolate collection does suggest, however, that resistant ST131 strains could potentially emerge under both human and veterinary antimicrobial selection pressure, a risk that could be mitigated by using the most active fluoroquinolone (i.e. Pradofloxacin in dogs) against wild-type E. coli at mutant prevention concentrations.
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susceptibility of rapidly growing mycobacteria and nocardia isolates from cats and dogs to Pradofloxacin
Veterinary Microbiology, 2011Co-Authors: Merran Govendir, Darren J Trott, Jacqueline M Norris, T Hansen, D I Wigney, G Muscatello, R MalikAbstract:Abstract Rapidly growing mycobacteria (RGM) and Nocardiae can cause severe or refractory infections in cats and dogs. Prolonged antibacterial therapy is required to cure these infections. As fluoroquinolones have been used in combination therapy for treating RGM infections, isolates from the Mycobacterium smegmatis cluster ( n = 64), Mycobacterium fortuitum cluster ( n = 17), and M. mageritense cluster ( n = 2), collected from feline and canine patients, underwent susceptibility testing to Pradofloxacin. The MIC 50 , MIC 90 and tentative epidemiological cut-off (ECOFF) values as determined by microbroth dilution susceptibility testing that inhibited growth of the M. smegmatis and M. fortuitum clusters were 0.063, 0.125 and ≤0.25; and 0.125, 0.250 and ≤1.0 μg/mL, respectively. E -Test results showed similar trends but MICs were lower than those for microbroth dilution. In summary, Pradofloxacin demonstrated effective in vitro activity against RGM isolates. Additionally, veterinary isolates of Nocardia nova ( n = 18), Nocardia farcinica ( n = 3) and Nocardia cyriacigeorgica ( n = 1) underwent microbroth dilution testing to ciprofloxacin, enrofloxacin and Pradofloxacin. The MIC 50 and MIC 90 of Pradofloxacin, ciprofloxacin and enrofloxacin that inhibited growth of Nocardia nova isolates were 2 (4), 8 (16), 16 (32) μg/mL, respectively. The tentative ECOFF values for Pradofloxacin and ciprofloxacin were 32 μg/mL and for enrofloxacin 64 μg/mL. The MIC or MIC range for the three N. farcinica isolates of Pradofloxacin, ciprofloxacin and enrofloxacin were 0.25–0.5, 2 and 2 μg/mL and for the single N. cyriacigeorgica isolate were 1, 4 and 4 μg/mL, respectively. On the basis on these results, fluoroquinolones appear to have limited therapeutic potential for most Nocardia infections.
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Fluoroquinolone resistance mechanisms in multidrug-resistant Escherichia coli isolated from extraintestinal infections in dogs.
Veterinary Microbiology, 2010Co-Authors: Justine S Gibson, Rowland N. Cobbold, Peter Heisig, M.t. Kyaw-tanner, Darren J TrottAbstract:Fluoroquinolone resistance is an emerging problem in companion animal practice. The present study aimed to determine comparative fluoroquinolone minimum inhibitory concentrations (MICs) for enrofloxacin, marbofloxacin and Pradofloxacin and identify plasmid-mediated quinolone resistance (PMQR) mechanisms in 41 multidrug-resistant (MDR) Escherichia coli isolates representing three main clonal groups (CGs) cultured from extraintestinal infections in dogs. All isolates were resistant to fluoroquinolones and the PMQR genes qnrA1, qnrB2, qnrS1 and qepA were identified in isolates from each CG. For a subset of 13 representative isolates, fluoroquinolone chromosomal resistance mechanisms were characterized. CG1 isolates had three mutations in the quinolone resistance determining region (QRDR), two in gyrA (Ser TCG-83 → Leu TTG and Asp GAC-87 → Asn AAC) and one in parC (Ser AGC-80 → Ile ATT), whilst CG2 and CG3 isolates also possessed an additional mutation in parC (Glu GAA-84 → Gly GGA) which was reflected in higher fluoroquinolone MICs compared to CG1. Organic solvent tolerance was demonstrated in 8 of the 13 isolates, and all 13 isolates demonstrated enhanced efflux on the basis of a 4-fold decrease or greater in the MIC of enrofloxacin when incubated with an efflux pump inhibitor. A mutation in acrR which can cause overexpression of the AcrAB multidrug efflux pump was detected in CG1 strains. These findings indicate that fluoroquinolone resistance in MDR E. coli isolated from extraintestinal infections in dogs is associated with a combination of target mutations in the QRDRs, transferable PMQR mechanisms and enhanced efflux. © 2010 Elsevier B.V.
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Identification of Qnr and AAC(6')-1b-cr plasmid-mediated fluoroquinolone resistance determinants in multidrug-resistant Enterobacter spp. isolated from extraintestinal infections in companion animals.
Veterinary Microbiology, 2010Co-Authors: Justine S Gibson, Rowland N. Cobbold, Peter Heisig, Hanna E. Sidjabat, M.t. Kyaw-tanner, Darren J TrottAbstract:Fluoroquinolone resistance is becoming more common in veterinary medicine. Resistance is due to a combination of chromosomal and plasmid-mediated fluoroquinolone resistance (PMQR) mechanisms. The aim of the present study was to screen 17 multidrug-resistant Enterobacter isolates obtained from opportunistic infections in companion animals for chromosomal and plasmid-mediated fluoroquinolone resistance determinants and to determine if they are co-located with other antimicrobial resistance genes including β-lactamases.Phenotypic tests (biochemical identification, organic solvent tolerance testing) were combined with genotypic analysis (PCR, pulsed field gel electrophoresis, sequencing, plasmid isolation and southern blot hybridization) to characterize the molecular basis for fluoroquinolone resistance. Antimicrobial susceptibility was determined by broth microdilution for fluoroquinolone antimicrobials (enrofloxacin, ciprofloxacin, moxifloxacin, marbofloxacin and Pradofloxacin) and by disk diffusion for other antimicrobials.Sixteen isolates were resistant to at least one of the five fluoroquinolones tested. Fourteen isolates possessed PMQR determinants which were identified as qnrA1 (n=3) or qnrB2 (n=11), often in combination with aac(6')-1b-cr (n=6). The PMQR genes were localized to large, transferable MDR plasmids often associated with an extended-spectrum β-lactamase and quinolone resistance was co-transferred with bla for 10 of the 14 qnr-positive strains. Three isolates had wild-type topoisomerases, 11 had a single point mutation in gyrA (Ser83Phe or Tyr), and three had two mutations; one in gyrA (Ser83Ile) and one in parC (Ser80Ile).PMQR genes in clinical veterinary Enterobacter isolates are co-located with β-lactamases and other resistance genes on large transferable plasmids. PMQR genes contribute to fluoroquinolone resistance when combined with topoisomerase mutations and efflux.
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Fluoroquinolone resistance mechanisms in multidrug-resistant Escherichia coli isolated from extraintestinal infections in dogs.
Veterinary microbiology, 2010Co-Authors: Justine S Gibson, Rowland N. Cobbold, Myat T Kyaw-tanner, Peter Heisig, Darren J TrottAbstract:Fluoroquinolone resistance is an emerging problem in companion animal practice. The present study aimed to determine comparative fluoroquinolone minimum inhibitory concentrations (MICs) for enrofloxacin, marbofloxacin and Pradofloxacin and identify plasmid-mediated quinolone resistance (PMQR) mechanisms in 41 multidrug-resistant (MDR) Escherichia coli isolates representing three main clonal groups (CGs) cultured from extraintestinal infections in dogs. All isolates were resistant to fluoroquinolones and the PMQR genes qnrA1, qnrB2, qnrS1 and qepA were identified in isolates from each CG. For a subset of 13 representative isolates, fluoroquinolone chromosomal resistance mechanisms were characterized. CG1 isolates had three mutations in the quinolone resistance determining region (QRDR), two in gyrA (Ser TCG-83→Leu TTG and Asp GAC-87→Asn AAC) and one in parC (Ser AGC-80→Ile ATT), whilst CG2 and CG3 isolates also possessed an additional mutation in parC (Glu GAA-84→Gly GGA) which was reflected in higher fluoroquinolone MICs compared to CG1. Organic solvent tolerance was demonstrated in 8 of the 13 isolates, and all 13 isolates demonstrated enhanced efflux on the basis of a 4-fold decrease or greater in the MIC of enrofloxacin when incubated with an efflux pump inhibitor. A mutation in acrR which can cause overexpression of the AcrAB multidrug efflux pump was detected in CG1 strains. These findings indicate that fluoroquinolone resistance in MDR E. coli isolated from extraintestinal infections in dogs is associated with a combination of target mutations in the QRDRs, transferable PMQR mechanisms and enhanced efflux.
Bernd Stephan - One of the best experts on this subject based on the ideXlab platform.
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susceptibility of canine and feline bacterial pathogens to Pradofloxacin and comparison with other fluoroquinolones approved for companion animals
Veterinary Microbiology, 2013Co-Authors: Annekathrin Schink, Bernd Stephan, Kristina Kadlec, Tomasz Hauschild, Geovana Brenner Michael, Julia Charlotte Dorner, Carolin Ludwig, Christiane Susanne Werckenthin, Hansrobert Hehnen, Stefan SchwarzAbstract:Abstract In this study, 908 bacterial pathogens from defined infections of dogs and cats were tested for their susceptibility to the novel fluoroquinolone Pradofloxacin, which was approved in 2011 for use in cats and dogs. Most of the bacteria tested (Staphylococcus aureus, Staphylococcus pseudintermedius, Escherichia coli, β-haemolytic streptococci, Pasteurella multocida and Bordetella bronchiseptica) exhibited low Pradofloxacin MIC90 values of ≤0.25 μg/ml. Solely Proteus spp. and Pseudomonas aeruginosa had higher MIC90 values of ≥4 μg/ml. Only six (3.4%) of 177 S. pseudintermedius and 12 (5.3%) of 227 E. coli isolates showed Pradofloxacin MICs of ≥2 μg/ml. Analysis of the quinolone resistance determining regions of the target genes identified double mutations in GyrA that resulted in amino acid exchanges S83L + D87N or S83L + D87Y and single or double mutations in ParC that resulted in amino acid exchanges S80I or S80I + E84G in all 12 E. coli isolates. The six S. pseudintermedius isolates exhibited amino acid exchanges S84L or E88K in GyrA and S80I in GrlA. Comparative analysis of the MICs of Pradofloxacin and the MICs determined for enrofloxacin and its main metabolite ciprofloxacin, but also marbofloxacin, orbifloxacin, difloxacin and ibafloxacin was conducted for the target pathogens S. pseudintermedius, E. coli and P. multocida. This comparison confirmed that Pradofloxacin MICs were significantly lower than those of the other tested fluoroquinolones.
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bactericidal properties of Pradofloxacin against veterinary pathogens
Veterinary Microbiology, 2012Co-Authors: Peter Silley, Bernd Stephan, Heinrich A Greife, Andrew PridmoreAbstract:Abstract Pradofloxacin is a new veterinary 8-cyano-fluoroquinolone developed for use against bacterial infections in dogs and cats involving both aerobic and anaerobic bacteria. The minimal bactericidal concentrations have been determined against clinical isolates of Staphylococcus pseudintermedius , Staphylococcus aureus , Escherichia coli , Pasteurella multocida , Streptococcus canis , Proteus spp., Fusobacterium spp., Porphyromonas gingivalis and Prevotella species. A subset of these species was selected, and the in vitro rate of kill by Pradofloxacin was determined. For 27 of the 30 tested aerobic strains the Pradofloxacin MBC was within two doubling dilutions of the MIC. For the remaining strains, the MIC and MBC were within three to four doubling dilutions. Pradofloxacin also demonstrated bactericidal activity against all anaerobic strains, and the MBC was equal to the MIC for four of the strains, within 1 doubling dilution for three strains, within 2 dilutions for a further 3 strains and within 3 dilutions for the remaining five strains. As Pradofloxacin concentration was increased, a faster rate of killing was observed; bactericidal effects were seen in all cases at concentrations ≤0.25 μg/mL. The bactericidal activity against the anaerobic strains was marked, of particular relevance was the complete absence of regrowth even at 48 h at concentrations as low as 0.125 μg/mL. In conclusion, Pradofloxacin exhibits clear bactericidal activity in terms of MBC and kill kinetics against aerobic and anaerobic clinical isolates from dogs and cats at concentrations that are greatly exceeded within the systemic circulation after administration of the recommended therapeutic doses to the target animals. It is expected that such a rapid rate of kill will play a significant role in clinical efficacy. These data demonstrate the complete and rapid killing of anaerobic bacteria by a veterinary 8-cyano-fluoroquinolone.
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activity of Pradofloxacin against porphyromonas and prevotella spp implicated in periodontal disease in dogs susceptibility test data from a european multicenter study
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: Bernd Stephan, Heinrich A Greife, Andrew Pridmore, Peter SilleyAbstract:Collaborating veterinarians from five European countries collected subgingival bacterial samples from dogs exhibiting clinical periodontal disease. Sterile endodontic paper points were used for collection of the samples, which were transported to a central laboratory for susceptibility testing. Anaerobic bacteria were isolated and Porphyromonas and Prevotella isolates identified to the species level; susceptibility to Pradofloxacin and metronidazole was determined using the CLSI agar dilution methodology. A total of 630 isolates, 310 of Porphyromonas spp. and 320 of Prevotella spp., were isolated. Pradofloxacin MIC data for all isolates were in the range of ≤0.016 to 1 μg/ml, the overall MIC50 was 0.062, and the overall MIC90 was 0.25 μg/ml. There were no differences in activity against Porphyromonas and Prevotella isolates or in the Pradofloxacin susceptibility distributions from the different European countries. All isolates were within the wild-type distribution and were fully susceptible to Pradofloxacin. Metronidazole was also highly active against these strains: 316 of 320 Prevotella strains (98.8%) and 309 of 310 Porphyromonas strains (99.7%) were susceptible (MICs of ≤8 μg/ml). However, three Prevotella strains had intermediate metronidazole susceptibility (MICs of 16 μg/ml), while one Prevotella and one Porphyromonas strain were metronidazole resistant (MICs of 128 and 256 μg/ml, respectively). Pradofloxacin, a novel broad-spectrum fluoroquinolone, demonstrates a high degree of antianaerobic activity against strains isolated from clinical cases of periodontal disease and shows activity against metronidazole-resistant isolates. The broad-spectrum activity of Pradofloxacin makes it a suitable candidate for the treatment of periodontal disease in dogs.
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comparative activity of Pradofloxacin against anaerobic bacteria isolated from dogs and cats
Journal of Antimicrobial Chemotherapy, 2007Co-Authors: Peter Silley, Bernd Stephan, Heinrich A Greife, Andrew PridmoreAbstract:Objectives: To compare the intrinsic activity of Pradofloxacin, a new fluoroquinolone developed for use in veterinary medicine, with other fluoroquinolones, against anaerobic bacteria isolated from dogs and cats. Methods: One hundred and forty-one anaerobes were isolated from dogs and cats and comparative MICs of Pradofloxacin, marbofloxacin, enrofloxacin, difloxacin and ibafloxacin were determined according to standardized agar dilution methodology. Results: Pradofloxacin exerted the greatest antibacterial activity followed by marbofloxacin, enrofloxacin, difloxacin and ibafloxacin. Based on the distinctly lower MIC 50 , MIC 90 and mode MIC values, Pradofloxacin exhibited a higher in vitro activity than any of the comparator fluoroquinolones. Conclusions: Pradofloxacin, a novel third-generation fluoroquinolone, has broad-spectrum anti-anaerobe activity and offers utility as single-drug therapy for mixed aerobic/anaerobic infections.
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Pradofloxacin in the treatment of canine deep pyoderma a multicentred blinded randomized parallel trial
Veterinary Dermatology, 2007Co-Authors: Ralf S Mueller, Bernd StephanAbstract:A multicentre, randomized, blinded study compared the efficacy of Pradofloxacin with that of a combination of amoxycillin/clavulanic acid in the treatment of deep pyoderma in dogs. Dogs with clinical lesions of deep pyoderma and a positive bacterial culture were included in the study. At each visit, they were evaluated with lesion, pruritus and general condition scores. Dogs were treated either with Pradofloxacin at 3 mg kg − 1 once daily or with amoxycillin at 10 mg kg − 1 and clavulanic acid at 2.5 mg kg − 1 twice daily and evaluated weekly for 3 weeks and every 2 weeks thereafter until 2 weeks past clinical remission. Maximal treatment duration was 9 weeks, and maximal evaluation period was 11 weeks. Of the 56 dogs treated with Pradofloxacin (group 1), 48 dogs (86%) achieved clinical remission, four dogs improved, four dogs did not respond and a recurrence of clinical signs was not seen in any patient after 11 weeks. Of the 51 dogs treated with amoxycillin/clavulanic acid (group 2), 37 dogs achieved clinical remission (73%), three dogs showed improvement, five dogs showed no response and in six dogs, clinical signs recurred within 2 weeks of cessation of therapy. These results indicate that Pradofloxacin is an efficacious therapy comparable to amoxycillin/ clavulanic acid for deep bacterial pyoderma in dogs.
Peter Silley - One of the best experts on this subject based on the ideXlab platform.
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bactericidal properties of Pradofloxacin against veterinary pathogens
Veterinary Microbiology, 2012Co-Authors: Peter Silley, Bernd Stephan, Heinrich A Greife, Andrew PridmoreAbstract:Abstract Pradofloxacin is a new veterinary 8-cyano-fluoroquinolone developed for use against bacterial infections in dogs and cats involving both aerobic and anaerobic bacteria. The minimal bactericidal concentrations have been determined against clinical isolates of Staphylococcus pseudintermedius , Staphylococcus aureus , Escherichia coli , Pasteurella multocida , Streptococcus canis , Proteus spp., Fusobacterium spp., Porphyromonas gingivalis and Prevotella species. A subset of these species was selected, and the in vitro rate of kill by Pradofloxacin was determined. For 27 of the 30 tested aerobic strains the Pradofloxacin MBC was within two doubling dilutions of the MIC. For the remaining strains, the MIC and MBC were within three to four doubling dilutions. Pradofloxacin also demonstrated bactericidal activity against all anaerobic strains, and the MBC was equal to the MIC for four of the strains, within 1 doubling dilution for three strains, within 2 dilutions for a further 3 strains and within 3 dilutions for the remaining five strains. As Pradofloxacin concentration was increased, a faster rate of killing was observed; bactericidal effects were seen in all cases at concentrations ≤0.25 μg/mL. The bactericidal activity against the anaerobic strains was marked, of particular relevance was the complete absence of regrowth even at 48 h at concentrations as low as 0.125 μg/mL. In conclusion, Pradofloxacin exhibits clear bactericidal activity in terms of MBC and kill kinetics against aerobic and anaerobic clinical isolates from dogs and cats at concentrations that are greatly exceeded within the systemic circulation after administration of the recommended therapeutic doses to the target animals. It is expected that such a rapid rate of kill will play a significant role in clinical efficacy. These data demonstrate the complete and rapid killing of anaerobic bacteria by a veterinary 8-cyano-fluoroquinolone.
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activity of Pradofloxacin against porphyromonas and prevotella spp implicated in periodontal disease in dogs susceptibility test data from a european multicenter study
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: Bernd Stephan, Heinrich A Greife, Andrew Pridmore, Peter SilleyAbstract:Collaborating veterinarians from five European countries collected subgingival bacterial samples from dogs exhibiting clinical periodontal disease. Sterile endodontic paper points were used for collection of the samples, which were transported to a central laboratory for susceptibility testing. Anaerobic bacteria were isolated and Porphyromonas and Prevotella isolates identified to the species level; susceptibility to Pradofloxacin and metronidazole was determined using the CLSI agar dilution methodology. A total of 630 isolates, 310 of Porphyromonas spp. and 320 of Prevotella spp., were isolated. Pradofloxacin MIC data for all isolates were in the range of ≤0.016 to 1 μg/ml, the overall MIC50 was 0.062, and the overall MIC90 was 0.25 μg/ml. There were no differences in activity against Porphyromonas and Prevotella isolates or in the Pradofloxacin susceptibility distributions from the different European countries. All isolates were within the wild-type distribution and were fully susceptible to Pradofloxacin. Metronidazole was also highly active against these strains: 316 of 320 Prevotella strains (98.8%) and 309 of 310 Porphyromonas strains (99.7%) were susceptible (MICs of ≤8 μg/ml). However, three Prevotella strains had intermediate metronidazole susceptibility (MICs of 16 μg/ml), while one Prevotella and one Porphyromonas strain were metronidazole resistant (MICs of 128 and 256 μg/ml, respectively). Pradofloxacin, a novel broad-spectrum fluoroquinolone, demonstrates a high degree of antianaerobic activity against strains isolated from clinical cases of periodontal disease and shows activity against metronidazole-resistant isolates. The broad-spectrum activity of Pradofloxacin makes it a suitable candidate for the treatment of periodontal disease in dogs.
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comparative activity of Pradofloxacin against anaerobic bacteria isolated from dogs and cats
Journal of Antimicrobial Chemotherapy, 2007Co-Authors: Peter Silley, Bernd Stephan, Heinrich A Greife, Andrew PridmoreAbstract:Objectives: To compare the intrinsic activity of Pradofloxacin, a new fluoroquinolone developed for use in veterinary medicine, with other fluoroquinolones, against anaerobic bacteria isolated from dogs and cats. Methods: One hundred and forty-one anaerobes were isolated from dogs and cats and comparative MICs of Pradofloxacin, marbofloxacin, enrofloxacin, difloxacin and ibafloxacin were determined according to standardized agar dilution methodology. Results: Pradofloxacin exerted the greatest antibacterial activity followed by marbofloxacin, enrofloxacin, difloxacin and ibafloxacin. Based on the distinctly lower MIC 50 , MIC 90 and mode MIC values, Pradofloxacin exhibited a higher in vitro activity than any of the comparator fluoroquinolones. Conclusions: Pradofloxacin, a novel third-generation fluoroquinolone, has broad-spectrum anti-anaerobe activity and offers utility as single-drug therapy for mixed aerobic/anaerobic infections.
Joseph M Blondeau - One of the best experts on this subject based on the ideXlab platform.
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In vitro killing of canine strains of Staphylococcus pseudintermedius and Escherichia coli by cefazolin, cefovecin, doxycycline and Pradofloxacin over a range of bacterial densities.
Veterinary Dermatology, 2020Co-Authors: Joseph M Blondeau, Shantelle D. FitchAbstract:BACKGROUND: Bacterial densities likely fluctuate during infection and may exceed the bacterial density used in susceptibility testing. As such, investigation of bacterial killing by antibiotics over a range of varying bacterial densities may provide important differences between compounds and could impact drug selection for therapy. HYPOTHESIS/OBJECTIVES: To measure killing of clinical isolates of Staphylococcus pseudintermedius and Escherichia coli by cefazolin, cefovecin, doxycycline and Pradofloxacin at clinically relevant (minimum inhibitory, mutant prevention, maximum serum and maximum tissue) drug concentrations against varying densities of bacteria. ANIMALS/MATERIALS: Bacterial strains collected from dogs with urinary tract infections were studied. METHODS AND MATERIALS: High bacterial densities ranging from 10⁶ to 10⁹ colony forming units (cfu)/mL were exposed to minimum inhibitory, mutant prevention, blood and tissue drug concentrations, and the percentages (log₁₀) of viable cells killed following 30 min, 1, 2, 4, 6, 12 and 24 h of drug exposure were quantified. RESULTS: Doxycycline exhibited bacteriostatic properties with less killing than the other three agents. For example, at a 10⁷ cfu/mL density of S. pseudintermedius, more cells were killed by Pradofloxacin (P
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in vitro killing of canine strains of staphylococcus pseudintermedius and escherichia coli by cefazolin cefovecin doxycycline and Pradofloxacin over a range of bacterial densities
Veterinary Dermatology, 2020Co-Authors: Joseph M Blondeau, Shantelle D. FitchAbstract:BACKGROUND: Bacterial densities likely fluctuate during infection and may exceed the bacterial density used in susceptibility testing. As such, investigation of bacterial killing by antibiotics over a range of varying bacterial densities may provide important differences between compounds and could impact drug selection for therapy. HYPOTHESIS/OBJECTIVES: To measure killing of clinical isolates of Staphylococcus pseudintermedius and Escherichia coli by cefazolin, cefovecin, doxycycline and Pradofloxacin at clinically relevant (minimum inhibitory, mutant prevention, maximum serum and maximum tissue) drug concentrations against varying densities of bacteria. ANIMALS/MATERIALS: Bacterial strains collected from dogs with urinary tract infections were studied. METHODS AND MATERIALS: High bacterial densities ranging from 10⁶ to 10⁹ colony forming units (cfu)/mL were exposed to minimum inhibitory, mutant prevention, blood and tissue drug concentrations, and the percentages (log₁₀) of viable cells killed following 30 min, 1, 2, 4, 6, 12 and 24 h of drug exposure were quantified. RESULTS: Doxycycline exhibited bacteriostatic properties with less killing than the other three agents. For example, at a 10⁷ cfu/mL density of S. pseudintermedius, more cells were killed by Pradofloxacin (P < 0.0001) and cefovecin (P = 0.0014) but not cefazolin when compared to doxycycline at the maximum serum drug concentration following 12 h of drug exposure. CONCLUSIONS AND CLINICAL IMPORTANCE: Differences were seen between some drugs in the speed and extent of bacterial killing; this could be clinically important and may impact drug selection and length of therapy.
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a pilot study on the comparative minimum inhibitory and mutant prevention concentration values for moxifloxacin and Pradofloxacin against canine and human isolates of staphylococcus pseudintermedius and s schleiferi
Veterinary Dermatology, 2019Co-Authors: Curtis Plowgian, Joseph M Blondeau, Matthew R Levinson, Wayne S RosenkrantzAbstract:BACKGROUND: Moxifloxacin is a fourth-generation fluoroquinolone (FQ) that is approved for use in people to treat a variety of infections. Some veterinary microbiology laboratories report moxifloxacin in culture and sensitivity profiles for Staphylococcus pseudintermedius and S. schleiferi albeit using Clinical & Laboratory Standards Institute (CLSI) breakpoints for S. aureus. Previous studies have shown that S. aureus breakpoints can mischaracterize S. pseudintermedius susceptibility to various drugs. Pradofloxacin is a third generation veterinary FQ with a similar mechanism of action and spectrum of activity to moxifloxacin; however, the dose format (25 mg/mL solution) available in the USA may limit its practical use in large dogs. OBJECTIF: Determiner la concentration minimale inhibitrice (MIC), la concentration de prevention de mutant (MPC) et la fenetre de selection de mutant (MSW) de la moxifloxacine et la Pradofloxacine pour les souches de S. pseudintermedius et S. schleiferi. MATERIELS ET METHODES: Une electrophorese sur gel en champ pulse a ete realisee pour etablir que chaque isolat bacterien selectionne pour l'essai representait une souche unique. Les MIC, MPC et MSW pour la moxifloxacine et la Pradofloxacine ont ete determinees pour 60 souches de S. pseudintermedius et sept souches de S. schleiferi. RESULTATS: Les MIC et MPC de moxifloxacine et Pradofloxacine pour S. pseudintermedius sensibles a la meticiline etaient semblables. Cependant, les MIC et MPC etaient plus larges et la resistance aux deux molecules etait plus frequente pour les souches de S. pseudintermedius et S. schleiferi resistantes a la meticiline. CONCLUSIONS ET IMPORTANCE CLINIQUE: L’etroitesse des MSW pour ces molecules peut reduire le risque de selection pour les sous-populations resistantes aux antibiotiques. Des etudes pharmacocinetiques, pharmacodynamiques et d'innocuite sont necessaires. RESULTS: The MIC and MPC ranges of moxifloxacin and Pradofloxacin for meticillin-susceptible S. pseudintermedius were similar. However, MIC and MPC ranges were much wider and resistance to both drugs was more common for meticillin-resistant strains of S. pseudintermedius and S. schleiferi. CONCLUSIONS AND CLINICAL IMPORTANCE: The narrow MSW of these drugs may reduce the risk of selecting for antibiotic-resistant subpopulations. Pharmacokinetic, pharmacodynamic and safety studies are needed.
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A pilot study on the comparative minimum inhibitory and mutant prevention concentration values for moxifloxacin and Pradofloxacin against canine and human isolates of Staphylococcus pseudintermedius and S. schleiferi
Veterinary Dermatology, 2019Co-Authors: Curtis Plowgian, Joseph M Blondeau, Matthew R Levinson, Wayne S RosenkrantzAbstract:BACKGROUND: Moxifloxacin is a fourth-generation fluoroquinolone (FQ) that is approved for use in people to treat a variety of infections. Some veterinary microbiology laboratories report moxifloxacin in culture and sensitivity profiles for Staphylococcus pseudintermedius and S. schleiferi albeit using Clinical & Laboratory Standards Institute (CLSI) breakpoints for S. aureus. Previous studies have shown that S. aureus breakpoints can mischaracterize S. pseudintermedius susceptibility to various drugs. Pradofloxacin is a third generation veterinary FQ with a similar mechanism of action and spectrum of activity to moxifloxacin; however, the dose format (25 mg/mL solution) available in the USA may limit its practical use in large dogs. OBJETIVO: Determinar a concentracao inibitoria minima (MIC), concentracao de prevencao de mutantes (MPC) e a janela de selecao de mutantes (MSW) de moxifloxacina e Pradofloxacina para isolados de S. pseudintermedius e S. schleiferi. METODOS E MATERIAIS: Eletroforese em campo pulsante foi realizada para estabelecer que cada isolado bacteriano selecionado para o teste representasse uma cepa unica. MIC, MPC e MSW para moxifloxacina e Pradofloxacina foram determinadas com 60 cepas de S. pseudintermedius e sete cepas de S. schleiferi. RESULTADOS: As faixas de MIC e MPC de moxifloxacina e Pradofloxacina para S. pseudintermedius suscetivel a meticilina foram similares. Entretanto, as faixas de MIC e MPC foram muito mais amplas e resistencia aos dois farmacos foi comum nas cepas resistentes a meticilina de S. pseudintermedius e S. schleiferi. CONCLUSOES E IMPORTÂNCIA CLINICA: A MSW estreita destas drogas pode reduzir o risco de selecao de subpopulacoes resistentes a antibioticos. Estudos de farmacocinetica, farmacodinâmica e seguranca sao necessarios. RESULTS: The MIC and MPC ranges of moxifloxacin and Pradofloxacin for meticillin-susceptible S. pseudintermedius were similar. However, MIC and MPC ranges were much wider and resistance to both drugs was more common for meticillin-resistant strains of S. pseudintermedius and S. schleiferi. CONCLUSIONS AND CLINICAL IMPORTANCE: The narrow MSW of these drugs may reduce the risk of selecting for antibiotic-resistant subpopulations. Pharmacokinetic, pharmacodynamic and safety studies are needed.
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comparative in vitro killing of canine strains of staphylococcus pseudintermedius and escherichia coli by cefovecin cefazolin doxycycline and Pradofloxacin
Veterinary Dermatology, 2016Co-Authors: Joseph M Blondeau, Shantelle D ShebelskiAbstract:Background Bacterial eradication is necessary for clinical cure of infections and antimicrobial agents are important adjunctive therapies for inhibiting the growth of or killing bacteria. Pre-existing skin diseases predispose animals to infection by Staphylococcus pseudintermedius and, more rarely, by Gram-negative bacilli. The property of rapid killing of bacteria may influence drug selection and duration of therapy in the setting of infection. Objectives To test the killing of canine isolates of S. pseudintermedius and Escherichia coli by cefazolin, cefovecin, doxycycline and Pradofloxacin at the minimum inhibitory, mutant prevention, maximum serum and maximum tissue drug concentrations. Methods Under standard conditions, bacterial cells were exposed to clinically relevant drug concentrations in vitro and the log10 reduction (and % kill) of viable cells measured at 5, 10, 15, 20, 25, 30, 60, 120 and 180 min after drug exposure. Results Statistically significant differences were seen between killing efficiencies by Pradofloxacin versus the other agents, whereby Pradofloxacin killed cells more rapidly than the others. For example, against the S. pseudintermedius strains, significantly more cells were killed by Pradofloxacin following 15 min of maximum tissue drug concentration exposure than for cefazolin (P = 0.0002), cefovecin (P = 0.0007) and doxycycline (P ≤ 0.0001). Conclusion and clinical importance The rank order of potency based on these kill experiments was Pradofloxacin > cefazolin > cefovecin > doxycycline. Rapid killing of bacteria affects the speed of clinical resolution and may influence drug selection and duration of therapy for skin infections.
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bactericidal properties of Pradofloxacin against veterinary pathogens
Veterinary Microbiology, 2012Co-Authors: Peter Silley, Bernd Stephan, Heinrich A Greife, Andrew PridmoreAbstract:Abstract Pradofloxacin is a new veterinary 8-cyano-fluoroquinolone developed for use against bacterial infections in dogs and cats involving both aerobic and anaerobic bacteria. The minimal bactericidal concentrations have been determined against clinical isolates of Staphylococcus pseudintermedius , Staphylococcus aureus , Escherichia coli , Pasteurella multocida , Streptococcus canis , Proteus spp., Fusobacterium spp., Porphyromonas gingivalis and Prevotella species. A subset of these species was selected, and the in vitro rate of kill by Pradofloxacin was determined. For 27 of the 30 tested aerobic strains the Pradofloxacin MBC was within two doubling dilutions of the MIC. For the remaining strains, the MIC and MBC were within three to four doubling dilutions. Pradofloxacin also demonstrated bactericidal activity against all anaerobic strains, and the MBC was equal to the MIC for four of the strains, within 1 doubling dilution for three strains, within 2 dilutions for a further 3 strains and within 3 dilutions for the remaining five strains. As Pradofloxacin concentration was increased, a faster rate of killing was observed; bactericidal effects were seen in all cases at concentrations ≤0.25 μg/mL. The bactericidal activity against the anaerobic strains was marked, of particular relevance was the complete absence of regrowth even at 48 h at concentrations as low as 0.125 μg/mL. In conclusion, Pradofloxacin exhibits clear bactericidal activity in terms of MBC and kill kinetics against aerobic and anaerobic clinical isolates from dogs and cats at concentrations that are greatly exceeded within the systemic circulation after administration of the recommended therapeutic doses to the target animals. It is expected that such a rapid rate of kill will play a significant role in clinical efficacy. These data demonstrate the complete and rapid killing of anaerobic bacteria by a veterinary 8-cyano-fluoroquinolone.
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activity of Pradofloxacin against porphyromonas and prevotella spp implicated in periodontal disease in dogs susceptibility test data from a european multicenter study
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: Bernd Stephan, Heinrich A Greife, Andrew Pridmore, Peter SilleyAbstract:Collaborating veterinarians from five European countries collected subgingival bacterial samples from dogs exhibiting clinical periodontal disease. Sterile endodontic paper points were used for collection of the samples, which were transported to a central laboratory for susceptibility testing. Anaerobic bacteria were isolated and Porphyromonas and Prevotella isolates identified to the species level; susceptibility to Pradofloxacin and metronidazole was determined using the CLSI agar dilution methodology. A total of 630 isolates, 310 of Porphyromonas spp. and 320 of Prevotella spp., were isolated. Pradofloxacin MIC data for all isolates were in the range of ≤0.016 to 1 μg/ml, the overall MIC50 was 0.062, and the overall MIC90 was 0.25 μg/ml. There were no differences in activity against Porphyromonas and Prevotella isolates or in the Pradofloxacin susceptibility distributions from the different European countries. All isolates were within the wild-type distribution and were fully susceptible to Pradofloxacin. Metronidazole was also highly active against these strains: 316 of 320 Prevotella strains (98.8%) and 309 of 310 Porphyromonas strains (99.7%) were susceptible (MICs of ≤8 μg/ml). However, three Prevotella strains had intermediate metronidazole susceptibility (MICs of 16 μg/ml), while one Prevotella and one Porphyromonas strain were metronidazole resistant (MICs of 128 and 256 μg/ml, respectively). Pradofloxacin, a novel broad-spectrum fluoroquinolone, demonstrates a high degree of antianaerobic activity against strains isolated from clinical cases of periodontal disease and shows activity against metronidazole-resistant isolates. The broad-spectrum activity of Pradofloxacin makes it a suitable candidate for the treatment of periodontal disease in dogs.
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comparative activity of Pradofloxacin against anaerobic bacteria isolated from dogs and cats
Journal of Antimicrobial Chemotherapy, 2007Co-Authors: Peter Silley, Bernd Stephan, Heinrich A Greife, Andrew PridmoreAbstract:Objectives: To compare the intrinsic activity of Pradofloxacin, a new fluoroquinolone developed for use in veterinary medicine, with other fluoroquinolones, against anaerobic bacteria isolated from dogs and cats. Methods: One hundred and forty-one anaerobes were isolated from dogs and cats and comparative MICs of Pradofloxacin, marbofloxacin, enrofloxacin, difloxacin and ibafloxacin were determined according to standardized agar dilution methodology. Results: Pradofloxacin exerted the greatest antibacterial activity followed by marbofloxacin, enrofloxacin, difloxacin and ibafloxacin. Based on the distinctly lower MIC 50 , MIC 90 and mode MIC values, Pradofloxacin exhibited a higher in vitro activity than any of the comparator fluoroquinolones. Conclusions: Pradofloxacin, a novel third-generation fluoroquinolone, has broad-spectrum anti-anaerobe activity and offers utility as single-drug therapy for mixed aerobic/anaerobic infections.