Joseph M Blondeau

Saskatoon Health Region, Saskatoon, Saskatchewan, Canada

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Publications (94)265.83 Total impact

  • J.M. Blondeau, S.D. Shebelski, C.K. Hesje
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    ABSTRACT: Streptococcus pneumoniae continues to be a significant respiratory pathogen, and increasing antimicrobial resistance compromises the use of β-lactam and macrolide antibiotics. Bacterial eradication impacts clinical outcome, and bacterial loads at the site of infection may fluctuate. Killing of two macrolide- and quinolone-susceptible clinical S. pneumoniae isolates by azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin against varying bacterial densities was determined using the measured minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC). For kill experiments, 10(6)-10(9) CFU/mL were exposed to the drug and were sampled at 0, 0.5, 1, 2, 3, 4, 6, 12 and 24h following drug exposure. The log10 reduction and percent reduction (kill) of viable cells was recorded. MICs and MPCs (mg/L) for azithromycin, clarithromycin, erythromycin, telithromycin and gemifloxacin were 0.063-0.125/0.5-1, 0.031-0.063/0.25-0.5, 0.063/0.25-0.5, 0.008/0.016 and 0.031/0.25, respectively. Killing 10(6)-10(9) CFU/mL of bacteria by the drug MIC yielded incomplete killing, however log10 reductions occurred by 12h and 24h for all drugs. Exposure of 10(6)-10(9) CFU/mL to MPC drug concentrations resulted in the following log10 reduction by 6h of drug exposure: azithromycin, 1.3-3.9; clarithromycin, 1.9-5.8; erythromycin, 0.8-4.7; telithromycin, 0.3-1.7; and gemifloxacin, 1.8-4.2. Bacterial loads at the site of infection may range from 10(6) to 10(9), and kill experiments utilising a higher bacterial inoculum provided a more accurate measure of antibiotic performance in high biomass situations. Killing was slower with telithromycin. Kill was greater and fastest with MPC versus MIC drug concentrations. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
    International Journal of Antimicrobial Agents 02/2015; 45(6). DOI:10.1016/j.ijantimicag.2014.12.034 · 4.26 Impact Factor
  • C K Hesje, K Drlica, J M Blondeau
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    ABSTRACT: The mutant prevention concentration (MPC) reflects the antimicrobial susceptibility of the resistant mutant subpopulations present in large bacterial populations. In principle, combining the MPC with pharmacokinetic measurements can guide treatment to restrict the enrichment of resistant subpopulations, just as the MIC is used with pharmacokinetics to restrict the growth of bulk, susceptible populations. Little is known about the MPC of tigecycline, one of the more recently approved antimicrobials. Tigecycline is particularly interesting because it shows good activity against Gram-positive pathogens.
    Journal of Antimicrobial Chemotherapy 10/2014; 70(2). DOI:10.1093/jac/dku389 · 5.44 Impact Factor
  • Veterinary Dermatology 08/2014; DOI:10.1111/vde.12167 · 1.99 Impact Factor
  • Jane E. Sykes, Joseph M. Blondeau
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    ABSTRACT: Pradofloxacin is a novel third-generation oral veterinary fluoroquinolone with activity against Gram-positive aerobic bacteria and anaerobes (lower minimum inhibitory concentrations in vitro). It also has activity against other bacterial species, including Bartonella henselae, Pasteurella multocida, Bordetella bronchiseptica, extra-intestinal Escherichia coli, and some mycobacterial species. This review focuses on the current knowledge of the mechanism of action, adverse effects, clinical applications, and pharmacokinetic/pharmacodynamic properties of pradofloxacin in cats.
    The Veterinary Journal 08/2014; 201(2). DOI:10.1016/j.tvjl.2014.06.008 · 2.17 Impact Factor
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    ABSTRACT: Superficial bacterial folliculitis (SBF) is usually caused by Staphylococcus pseudintermedius and routinely treated with systemic antimicrobial agents. Infection is a consequence of reduced immunity associated with alterations of the skin barrier and underlying diseases that may be difficult to diagnose and resolve; thus, SBF is frequently recurrent and repeated treatment is necessary. The emergence of multiresistant bacteria, particularly meticillin-resistant S. pseudintermedius (MRSP), has focused attention on the need for optimal management of SBF. Provision of an internationally available resource guiding practitioners in the diagnosis, treatment and prevention of SBF. The guidelines were developed by the Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases, with consultation and advice from diplomates of the American and European Colleges of Veterinary Dermatology. They describe optimal methods for the diagnosis and management of SBF, including isolation of the causative organism, antimicrobial susceptibility testing, selection of antimicrobial drugs, therapeutic protocols and advice on infection control. Guidance is given for topical and systemic modalities, including approaches suitable for MRSP. Systemic drugs are classified in three tiers. Tier one drugs are used when diagnosis is clear cut and risk factors for antimicrobial drug resistance are not present. Otherwise, tier two drugs are used and antimicrobial susceptibility tests are mandatory. Tier three includes drugs reserved for highly resistant infections; their use is strongly discouraged and, when necessary, they should be used in consultation with specialists. Optimal management of SBF will improve antimicrobial use and reduce selection of MRSP and other multidrug-resistant bacteria affecting animal and human health.
    Veterinary Dermatology 04/2014; DOI:10.1111/vde.12118 · 1.99 Impact Factor
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    ABSTRACT: Antimicrobial resistance is a global challenge that impacts both human and veterinary health care. The resilience of microbes is reflected in their ability to adapt and survive in spite of our best efforts to constrain their infectious capabilities. As science advances, many of the mechanisms for microbial survival and resistance element transfer have been identified. During the 2012 meeting of Antimicrobial Agents in Veterinary Medicine (AAVM), experts provided insights on such issues as use vs. resistance, the available tools for supporting appropriate drug use, the importance of meeting the therapeutic needs within the domestic animal health care, and the requirements associated with food safety and food security. This report aims to provide a summary of the presentations and discussions occurring during the 2012 AAVM with the goal of stimulating future discussions and enhancing the opportunity to establish creative and sustainable solutions that will guarantee the availability of an effective therapeutic arsenal for veterinary species.
    Journal of Veterinary Pharmacology and Therapeutics 01/2014; 37(1). DOI:10.1111/jvp.12104 · 1.32 Impact Factor
  • Journal of Antimicrobial Chemotherapy 04/2013; 68(suppl 1):i23-i29. DOI:10.1093/jac/dkt023 · 5.44 Impact Factor
  • Kelli Metzler, Karl Drlica, Joseph M Blondeau
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    ABSTRACT: BACKGROUND: Previous work showed a higher prevalence of macrolide/azalide resistance in provinces of Canada where azithromycin was the major treatment for Streptococcus pneumoniae as compared with regions where clarithromycin was the dominant treatment. These data provided a way to test the mutant selection window hypothesis, which predicts that the serum drug concentration (AUC(24)) relative to the mutant prevention concentration (MPC) would be higher for clarithromycin than for azithromycin. METHODS: The MIC and MPC were determined for 191 penicillin/macrolide-susceptible clinical isolates of S. pneumoniae with azithromycin, clarithromycin and erythromycin using agar plate assays. RESULTS: The MIC(50/90) (mg/L) and MPC(50/90) (mg/L), respectively, were as follows: azithromycin 0.13/0.25 and 1/4; clarithromycin 0.031/0.063 and 0.13/0.5; erythromycin 0.063/0.13 and 0.25/2. We calculated from published pharmacokinetic values that the AUC(24)/MPC(90) for azithromycin was 0.85; for clarithromycin it was 96, and for erythromycin base and estolate it was 4 and 10, respectively. Thus the AUC(24)/MPC(90) was about 50 times higher for clarithromycin than for azithromycin. CONCLUSIONS: The elevated prevalence of azithromycin resistance may derive in part from a low value of AUC(24)/MPC(90) and/or time above MPC, since previous work indicates that the number of prescriptions per person was similar in the geographical regions examined.
    Journal of Antimicrobial Chemotherapy 11/2012; 68(3). DOI:10.1093/jac/dks461 · 5.44 Impact Factor
  • Joseph M Blondeau, Shohreh Farshad
    Expert Review of Clinical Pharmacology 11/2012; 5(6):609-11. DOI:10.1586/ecp.12.61
  • J M Blondeau
    10/2012; 17(8). DOI:10.1111/j.2044-3862.2012.00240.x
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    ABSTRACT: Mannheimia haemolytica is the most prevalent cause of bovine respiratory disease (BRD) and this disease accounts for 75% of morbidity, 50-70% of feedlot deaths and is estimated to cost up to $1 billion dollars annually in the USA. Antimicrobial therapy is essential for reducing morbidity, mortality and impacting on the financial burden of this disease. Due to the concern of increasing antimicrobial resistance, investigation of antibacterial agents for their potential for selecting for resistance is of paramount importance. A novel in vitro measurement called the mutant prevention concentration (MPC) defines the antimicrobial drug concentration necessary to block the growth of the least susceptible cells present in high density (≥10(7) colony forming units/ml) bacterial populations such as those seen in acute infection. We compared the minimum inhibitory concentration (MIC) and MPC values for 5 antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tilmicosin, tulathromycin) against 285 M. haemolytica clinical isolates. The MIC(90)/MPC(90) values for each agent respectively were as follows: 0.016/2, 0.125/1, 2/≥16, 8/≥32, 2/8. Dosing to achieve MPC concentrations (where possible) may serve to reduce the selection of bacterial subpopulations with reduced antimicrobial susceptibility. The rank order of potency based on MIC(90) values was ceftiofur>enrofloxacin>florfenicol=tulathromycin>tilmicosin. The rank order of potency based on MPC(90) values was enrofloxacin>ceftiofur>tulathromycin>florfenicol≥tilmicosin.
    Veterinary Microbiology 05/2012; 160(1-2):85-90. DOI:10.1016/j.vetmic.2012.05.006 · 2.73 Impact Factor
  • Joseph M Blondeau
    Expert Review of Clinical Pharmacology 01/2012; 5(1):9-11. DOI:10.1586/ecp.11.71
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    ABSTRACT: Background: CD is the most common nosocomial infectious cause of diarrhea. SHR is the largest health region in the province, serving approximately 300,000 residents. The objective of this trial was to assess if MB tests BD GeneOhm™ (BG) and Meridian Illumigene™ (MI) were more sensitive and specific than the TechLab Tox A/B II™ (TT) EIA-based test. Methods: SHR stool samples submitted by a physician for CD testing between Nov '10 to Feb '11 and that met the screening criteria for processing were tested simultaneously with BG, MI and TT. Results for all samples were recorded as positive or negative for each testing platform. If all 3 results were concordant, then the true result was recorded as such. If any of the 3 results were discordant for a sample, then further testing was performed using cytotoxicity assay testing and this was used as the true result. Results: A total of 301 stool samples were tested during the study period. Eleven (3.7%) samples required cytotoxicity testing for discordant results. The prevalence of disease was 10.6% and 55% of samples were from female patients. The median age of patients with positive samples was 77.5 vs. 63.0 years for those with negative results (p=0.02). TT displayed a sensitivity (SN) of 90.6% (95% CI: 73.8-97.5%), specificity (SP) 100% (95% CI: 98.2-100%), positive predictive value (PPV) 100% (95% CI: 85.4-100%) and negative predictive value (NPV) 98.9% (95% CI: 96.5-99.7%). BG and MI testing had SN 100% (95% CI: 86.7-100%), SP 97.4% (95% CI: 94.5-98.9%), PPV 82.1% (95% CI: 65.9-91.9%) and NPV 100% (95% CI: 98.2-100%). The agreement of results between the two MB tests was very strong (kappa=0.97) but weaker between the MB and EIA tests (kappa=0.84). Cytotoxicity testing had higher agreement with EIA (kappa=0.95) vs. MB testing (kappa=0.89). Conclusion: Sensitivity of MB testing was higher than EIA testing, but the reverse was true of specificity. Agreement between testing methodologies and the historical gold standard for CD was higher with EIA rather than MB testing. While unexpected, these results challenge the idea of cytotoxicity testing being the gold standard, as the two MB test results had high levels of correlation. More studies are needed to assess if MB testing should become the new gold standard for CD.
    Infectious Diseases Society of America 2011 Annual Meeting; 10/2011
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    ABSTRACT: Enrofloxacin is a fluoroquinolone antibacterial agent used to treat infections in companion animals. Enrofloxacin's antimicrobial spectrum includes Gram positive and Gram-negative bacteria and demonstrates concentration-dependent bacteriocidal activity. In dogs and cats, enrofloxacin is partially metabolized to ciprofloxacin and both active agents circulate simultaneously in treated animals at ratios of approximately 60-70% enrofloxacin to 30-40% ciprofloxacin. We were interested in determining the killing of companion animal isolates of Escherichia coli, Staphylococcus pseudintermedius and Pseudomonas aeruginosa by enrofloxacin and ciprofloxacin combined using clinically relevant drug concentrations and ratios. For E. coli isolates exposed to 2.1 and 4.1μg/ml of enrofloxacin/ciprofloxacin at 50:50, 60:40 and 70:30 ratios, a 1.7-2.5log(10) reduction (94-99% kill) was seen following 20min of drug exposure; 0.89-1.7log(10) (92-99% kill) of S. pseudintermedius following 180min of drug exposure; 0.85-3.4log(10) (98-99% kill) of P. aeruginosa following 15min of drug exposure. Killing of S. pseudintermedius was enhanced in the presence of enrofloxacin whereas killing of P. aeruginosa was enhanced in the presence of ciprofloxacin. Antagonism was not seen when enrofloxacin and ciprofloxacin were used in kill assays. The unique feature of partial metabolism of enrofloxacin to ciprofloxacin expands the spectrum of enhanced killing of common companion animal pathogens.
    Veterinary Microbiology 08/2011; 155(2-4):284-90. DOI:10.1016/j.vetmic.2011.08.015 · 2.73 Impact Factor
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    ABSTRACT: Urinary tract disease is a common reason for use (and likely misuse, improper use, and overuse) of antimicrobials in dogs and cats. There is a lack of comprehensive treatment guidelines such as those that are available for human medicine. Accordingly, guidelines for diagnosis and management of urinary tract infections were created by a Working Group of the International Society for Companion Animal Infectious Diseases. While objective data are currently limited, these guidelines provide information to assist in the diagnosis and management of upper and lower urinary tract infections in dogs and cats.
    06/2011; 2011:263768. DOI:10.4061/2011/263768
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    ABSTRACT: The CANWARD study (Canadian Ward Surveillance Study) assessed the antimicrobial susceptibility of a variety of available agents against 15 644 pathogens isolated from patients in Canadian hospitals between 2007 and 2009. The most active (based on MIC data) agents against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci were daptomycin, linezolid, tigecycline, and vancomycin (MRSA only) with MIC(90)'s (μg/mL) of 0.25 and 2, 2 and 2, 0.5 and 0.12, and 1, respectively. The most active agents against extended-spectrum β-lactamase-producing Escherichia coli were colistin (polymyxin E), doripenem, ertapenem, meropenem, and tigecycline with MIC(90)'s (μg/mL) of 1, ≤ 0.12, 0.25, ≤ 0.12, and 1, respectively. The most active agents against Pseudomonas aeruginosa were amikacin, cefepime, ceftazidime, colistin, doripenem, meropenem, and piperacillin-tazobactam with MIC(90)'s (μg/mL) of 32, 16, 32, 2, 4, 8, and 64, respectively. Overall, the most active agents versus Gram-positive cocci from Canadian hospitals were vancomycin, linezolid, daptomycin, and tigecycline and versus Gram-negative bacilli were amikacin, cefepime, doripenem, ertapenem (excluding Pseudomonas aeruginosa), meropenem, piperacillin-tazobactam, and tigecycline (excluding Pseudomonas aeruginosa).
    Diagnostic microbiology and infectious disease 03/2011; 69(3):291-306. DOI:10.1016/j.diagmicrobio.2010.10.025 · 2.57 Impact Factor
  • Marguerite McDonald, Joseph M Blondeau
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    ABSTRACT: Resistance to antibiotic agents is becoming increasingly prevalent among ocular infections. Between 19% and 60% of Streptococcus pneumoniae and Staphylococcus aureus isolates have been shown to be resistant to macrolide antibiotic agents, penicillin, and older fluoroquinolones. Although topical fluoroquinolones are considered first-line treatment of ocular infections, as much as 85% of methicillin-resistant S aureus isolates are resistant to ophthalmic fluoroquinolones, including the newer 8-methoxy fluoroquinolones, gatifloxacin and moxifloxacin. Besifloxacin, an 8-chlorofluoroquinolone, has a lower minimum inhibitory concentration against multidrug-resistant staphylococcal strains than other fluoroquinolones and less selective pressure for resistance development because of the lack of a systemic counterpart. In addition to the development of new antibacterial agents, antibiotic resistance in ocular infections may be reduced by following the same strategies used to minimize antimicrobial resistance in systemic infections.
    Journal of Cataract and Refractive Surgery 09/2010; 36(9):1588-98. DOI:10.1016/j.jcrs.2010.06.028 · 2.55 Impact Factor
  • Joseph M Blondeau, Glenn S Tillotson
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    ABSTRACT: Uncomplicated urinary infections are a significant and growing cause of morbidity amongst young women. Commonly these infections are caused by Escherichia coil or Staphylococcus saprophyticus. Escherichia coil is resistant to several empirical antibiotics: amoxicilin, trimetoprima-sulfametozaxol and, more recently, to some more old flouroquinolons. Gemifloxacin is a flouroquinolon with an excellent in vitro activity against many community acquired bacteria which cause respiratory or urinary infections. This antibiotic has a very unique and dual action mechanism directed against girasa and topoisomerasa II DNA, which grants minimum low inhibitory concentrations against Escherichia coil, Klebsiella and S. saprophyticus species and others attacking respiratory system. Young women with uncomplicated urinary infections were evaluated in two random clinical studies; they were treated with 320 mg gemifloxacin once a day for three days. Gemifloxacin was compared to ofloxacin or ciprofloxacin in approved doses and durations and it proved to be useful with clinical success rates of 95% or more in both studies. Gemifloxacin showed to be safe and well tolerated. A dose a day is a safe and useful alternative amongst current empirical options to treat patients with uncomplicated urinary infections.
    Ginecología y obstetricia de México 12/2009; 77(12):573-82.
  • Joseph M Blondeau
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    ABSTRACT: Current measurements of antimicrobial susceptibility or resistance utilize a standardized bacterial inoculum (10(5) cfu/mL) exposed to varying drug concentrations in a test tube. Following incubation under ideal conditions, the lowest drug concentration inhibiting growth is the minimum inhibitory concentration (MIC). When the MIC exceeds the amount of drug that can be safely achieved in the body, we call these microorganisms resistant; established breakpoints for various 'bug-drug' combinations are used to categorize microorganisms as susceptible, intermediate or resistant. MIC testing has been used for decades to guide antimicrobial therapy and remains an important measurement for infectious diseases. More recently, the mutant prevention concentration (MPC) has been described as a novel measurement of in vitro susceptibility or resistance and is based on the testing of larger bacterial inocula, i.e. > or =10(9) cfu/mL - such as those associated with some infections in humans and animals. MPC defines the lowest drug concentration required to block the growth of the least susceptible cell present in high density bacterial populations. MPC testing applies to microorganisms considered susceptible to the drug by MIC testing. The mutant selection window (MSW) defines the 'danger zone' for therapeutic drug concentrations. Minimizing the length of time the drug concentration remains in the MSW may reduce the likelihood for resistance selection during therapy. The MSW is bordered by the MIC and MPC values and the drug concentration range between the measured MIC and MPC values defines the MSW. MPC values, when considered with drug pharmacology, may allow prediction on the probability of resistance selection when bacteria are exposed to antimicrobial agents during therapy for infectious diseases. In today's environment, resistance prevention should be a goal of antimicrobial therapy.
    Veterinary Dermatology 10/2009; 20(5-6):383-96. DOI:10.1111/j.1365-3164.2009.00856.x · 1.99 Impact Factor
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    ABSTRACT: To assess the impact of benzalkonium chloride (BAK) on the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of gatifloxacin against Gram-positive pathogens in comparison to gatifloxacin and moxifloxacin alone, moxifloxacin plus BAK, and/or levofloxacin. The MIC was measured following incubation of 10(5) colony-forming units (CFU)/mL of coagulase-negative staphylococci (CNS; n = 20), methicillin-susceptible Staphylococcus aureus (MSSA; n = 20), and methicillin-resistant S. aureus (MRSA; n = 20) with gatifloxacin, levofloxacin, or moxifloxacin. When present, BAK was added from 3.125 microg/mL to 6.25 microg/mL. The MPC was measured following incubation of 10(10) CFU/mL of MRSA (n = 9) and a commercially available MSSA strain with gatifloxacin or moxifloxacin in the absence and presence of BAK at concentrations from 7 microg/mL to 10 microg/mL. CNS was more susceptible to gatifloxacin (MIC(90) = 2 microg/mL) than levofloxacin (MIC(90) = 8 microg/mL) or moxifloxacin (MIC(90) = 4 microg/mL). MSSA was more susceptible to moxifloxacin (MIC(90) = 1 microg/mL) than gatifloxacin (MIC(90) = 4 microg/mL) or levofloxacin (MIC(90) = 4 microg/mL). MRSA were resistant to gatifloxacin, levofloxacin, and moxifloxacin. In the presence of BAK, however, the MIC(90) of gatifloxacin and moxifloxacin against CNS, MSSA, and MRSA was < or =0.008 microg/mL. Gatifloxacin and moxifloxacin had similar MPCs against MRSA (> or =4 microg/mL). In the presence of BAK, the MPC of gatifloxacin and moxifloxacin against MRSA ranged from < or =0.004 microg/mL to 0.125 microg/mL. Conclusions: BAK substantially lowered the MIC and MPC of gatifloxacin and moxifloxacin against Gram-positive staphylococci compared to gatifloxacin alone, moxifloxacin alone, and/or levofloxacin. These findings suggest that the presence of BAK in the ophthalmic formulation of gatifloxacin (Zymar) may serve to enhance the potency of gatifloxacin and decrease its propensity to select for fluoroquinolone-resistant S. aureus strains.
    Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 09/2009; 25(4):329-34. DOI:10.1089/jop.2009.0031 · 1.42 Impact Factor

Publication Stats

2k Citations
265.83 Total Impact Points

Institutions

  • 2007–2014
    • Saskatoon Health Region
      Saskatoon, Saskatchewan, Canada
  • 1995–2014
    • University of Saskatchewan
      • Department of Microbiology and Immunology
      Saskatoon, Saskatchewan, Canada
  • 2000–2012
    • Royal University Hospital
      Saskatoon, Saskatchewan, Canada
  • 1994–2002
    • St. Paul's Hospital
      Saskatoon, Saskatchewan, Canada
  • 2001
    • Public Health research Institute, India
      Davis, California, United States