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author:("nonly, John M")
2.  Antimicrobial resistance programs in Canada 1995-2010: a critical evaluation 
In Canada, systematic efforts for controlling antibiotic resistance began in 1997 following a national Consensus Conference. The Canadian strategy produced 27 recommendations, one of which was the formation of the Canadian Committee on Antibiotic Resistance (CCAR). In addition several other organizations began working on a national or provincial basis over the ensuing years on one or more of the 3 identified core areas of the strategy. Critical evaluation of the major programs within Canada which focused on antimicrobial resistance and the identified core components has not been previously conducted.
Data was collected from multiple sources to determine the components of four major AMR programs that were considered national based on their scope or in the delivery of their mandates. Assessment of program components was adapted from the report from the International Forum on Antibiotic Resistance colloquium. Most of the programs used similar tools but only the Do Bugs Need Drugs Program (DBND) had components directed towards day cares and schools. Surveillance programs for antimicrobial resistant pathogens have limitations and/or significant sources of bias. Overall, there has been a 25.3% decrease in oral antimicrobial prescriptions in Canada since 1995, mainly due to decreases in β lactams, sulphonamides and tetracyclines in temporal association with multiple programs with the most comprehensive and sustained national programs being CCAR and DBND.
Although there has been a substantial decrease in oral antimicrobial prescriptions in Canada since 1995, there remains a lack of leadership and co-ordination of antimicrobial resistance activities.
PMCID: PMC3436608  PMID: 22958783
antimicrobial resistance; stewardship; antibiotic; scripts; prescribing; population; program components
7.  Novel Staphylococcal Cassette Chromosome mec Type, Tentatively Designated Type VIII, Harboring Class A mec and Type 4 ccr Gene Complexes in a Canadian Epidemic Strain of Methicillin-Resistant Staphylococcus aureus▿  
Staphylococcal cassette chromosome mec (SCCmec) is a mobile genetic element characterized by flanking terminal direct and, in most cases, inverted repeat sequences, the mec and ccr gene complexes, and their surrounding DNA regions. Unique combinations of the mec and ccr gene complexes generate various SCCmec types. Six SCCmec types have been reported to date. We describe here a novel SCCmec type identified in a Canadian methicillin-resistant Staphylococcus aureus (MRSA) epidemic strain. MRSA clinical isolates were screened for known SCCmec types by multiplex and conventional PCR methods. Three phenotypically and genotypically identical MRSA clinical isolates with a pulsotype identical to CMRSA9 were identified locally and found to be nontypeable by available SCCmec typing schemes. Complete sequencing of the SCCmec element revealed a nucleotide fragment of 32,168 bp integrated at an identical chromosomal integration site (attBscc) at the 3′ end of the orfX gene. The nucleotide sequences at the chromosome-SCCmec junction regions were typical of other SCCmec types, but the element harbored a unique combination of class A mec and type 4 ccr gene complexes. Sequence recombination analysis suggested that this unique SCCmec type may be derived from homologous recombination between the previously described SCCRP62A of S. epidermidis strain RP62A and SCC composite island of S. epidermidis ATCC 12228, respectively, or via recombination of other staphylococcal strains that carry the same or similar mobile cassettes. We identified a previously undescribed type of SCCmec from isolate C10682, tentatively designated type VIII, and we provide compelling evidence supporting the ability of SCC elements to transfer horizontally or undergo recombination to generate new SCCmec types.
PMCID: PMC2630601  PMID: 19064897
8.  Embracing ecology to limit antimicrobial resistance 
PMCID: PMC2638035  PMID: 19221342
9.  Novel Multiplex PCR Assay for Simultaneous Identification of Community-Associated Methicillin-Resistant Staphylococcus aureus Strains USA300 and USA400 and Detection of mecA and Panton-Valentine Leukocidin Genes, with Discrimination of Staphylococcus aureus from Coagulase-Negative Staphylococci▿  
Journal of Clinical Microbiology  2007;46(3):1118-1122.
We developed a novel multiplex PCR assay for rapid identification and discrimination of the USA300 and USA400 strains and concomitant detection of Panton-Valentine leukocidin genes, with simultaneous discrimination of methicillin-resistant Staphylococcus aureus strains from methicillin-susceptible S. aureus strains, S. aureus strains from coagulase-negative staphylococci, and staphylococci from other bacteria.
PMCID: PMC2268379  PMID: 18160447
12.  Novel Multiplex PCR Assay for Detection of the Staphylococcal Virulence Marker Panton-Valentine Leukocidin Genes and Simultaneous Discrimination of Methicillin-Susceptible from -Resistant Staphylococci 
Journal of Clinical Microbiology  2006;44(3):1141-1144.
We developed a new multiplex PCR assay for detection of Panton-Valentine leukocidin virulence genes and simultaneous discrimination of methicillin-susceptible from -resistant staphylococci. This assay is simple, rapid, and accurate and offers the potential for prompt detection of newly emerging community-associated methicillin-resistant Staphylococcus aureus.
PMCID: PMC1393128  PMID: 16517915
14.  Novel Multiplex PCR Assay for Characterization and Concomitant Subtyping of Staphylococcal Cassette Chromosome mec Types I to V in Methicillin-Resistant Staphylococcus aureus 
Journal of Clinical Microbiology  2005;43(10):5026-5033.
Staphylococcal cassette chromosome mec (SCCmec) typing is essential for understanding the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). SCCmec elements are currently classified into types I to V based on the nature of the mec and ccr gene complexes, and are further classified into subtypes according to their junkyard region DNA segments. Previously described traditional SCCmec PCR typing schemes require multiple primer sets and PCR experiments, while a previously published multiplex PCR assay is limited in its ability to detect recently discovered types and subtypes such as SCCmec type V and subtypes IVa, b, c, and d. We designed new sets of SCCmec type- and subtype-unique and specific primers and developed a novel multiplex PCR assay allowing for concomitant detection of the methicillin resistance (mecA gene) (also serving as an internal control) to facilitate detection and classification of all currently described SCCmec types and subtypes I, II, III, IVa, b, c, d, and V. Our assay demonstrated 100% sensitivity and specificity in accurately characterizing 54 MRSA strains belonging to the various known SCCmec types and subtypes, when compared with previously described typing methods. Further application of our assay in 453 randomly selected local clinical isolates confirmed its feasibility and practicality. This novel assay offers a rapid, simple, and feasible method for SCCmec typing of MRSA, and may serve as a useful tool for clinicians and epidemiologists in their efforts to prevent and control infections caused by this organism.
PMCID: PMC1248471  PMID: 16207957
18.  The costs and consequences of methicillin-resistant Staphylococcus aureus infection treatments in Canada 
A multinational randomized controlled trial has shown a trend toward early discharge of patients taking oral linezolid versus intravenous vancomycin (IV) in the treatment of methicillinresistant Staphylococcus aureus (MRSA) infections. Infection treatments resulting in shorter hospitalization durations are associated with cost savings from the hospital perspective.
To determine whether similar economic advantages are associated with oral linezolid, the costs and consequences of linezolid use following vancomycin IV versus the existing practice in the treatment of infections caused by MRSA were compared.
The charts of all patients admitted to one of three tertiary care teaching hospitals between January 1, 1997 and August 31, 2000 and treated with vancomycin IV for an active MRSA infection (skin and soft tissue only) were reviewed. Based on the vancomycin IV chart review data set and a simulated linezolid data set, the clinical consequences and the associated costs of MRSA treatment with vancomycin IV, and oral and IV forms of linezolid were quantified and compared within the framework of a cost-consequence analysis.
Patients treated with oral and IV forms of linezolid compared with the existing practice had a shorter length of stay and required fewer home IV care services, which resulted in a cost savings of $750 (2001 values) to the Canadian health care perspective.
The estimated cost savings associated with linezolid use not only offset the higher acquisition cost of the anti-infective, but may be substantial to health care systems across Canada, especially as the incidence of MRSA continues to rise.
PMCID: PMC2094976  PMID: 18159495
Consequences; Costs; Linezolid; Methicillin-resistant Staphylococcus aureus; MRSA; Vancomycin
21.  New Quadriplex PCR Assay for Detection of Methicillin and Mupirocin Resistance and Simultaneous Discrimination of Staphylococcus aureus from Coagulase-Negative Staphylococci 
Journal of Clinical Microbiology  2004;42(11):4947-4955.
Major challenges in diagnostic molecular microbiology are to develop a simple assay to distinguish Staphylococcus aureus from the less virulent but clinically important coagulase-negative staphylococci (CoNS) and to simultaneously determine their antibiotic resistance profiles. Multiplex PCR assays have been developed for the detection of methicillin- and mupirocin-resistant S. aureus and CoNS but not for the simultaneous discrimination of S. aureus from CoNS. We designed a new set of Staphylococcus genus-specific primers and developed a novel quadriplex PCR assay targeting the 16S rRNA (Staphylococcus genus specific), nuc (S. aureus species specific), mecA (a determinant of methicillin resistance), and mupA (a determinant of mupirocin resistance) genes to identify most staphylococci, to discriminate S. aureus from CoNS and other bacteria, and to simultaneously detect methicillin and mupirocin resistance. Validation of the assay with 96 ATCC control strains and 323 previously characterized clinical isolates, including methicillin- and mupirocin-sensitive and -resistant S. aureus and CoNS isolates and other bacteria, demonstrated 100% sensitivity, specificity, and accuracy. This assay represents a simple, rapid, accurate, and reliable approach for the detection of methicillin- and mupirocin-resistant staphylococci and offers the hope of preventing their widespread dissemination through early and reliable detection.
PMCID: PMC525205  PMID: 15528678
23.  A retrospective analysis of practice patterns in the treatment of methicillin-resistant Staphylococcus aureus skin and soft tissue infections at three Canadian tertiary care centres 
Methicillin-resistant Staphylococcus aureus (MRSA) infections are increasingly being encountered and pose an increasing burden to the health care system in Canada.
To elucidate and characterize the factors influencing the current MRSA treatment patterns in patients with skin and soft tissue infections (SSTIs) before linezolid became available on the Canadian market.
A retrospective study collected demographic, treatment and resource use data on patients hospitalized at one of three geographically distinct tertiary care facilities, where MRSA SSTI treatment was initiated with intravenous (IV) vancomycin. Analysis of opportunities for IV-to-oral switch therapy was based on eligibility criteria.
Of 89 patients identified over a 43-month period, the mean (±SD) durations of anti-infective treatment and hospitalization were 22.4±21 days and 28.9±20.8 days, respectively. An infected surgical wound was most common, representing 62.9% of infections. The mean duration of vancomycin treatment was 19.5 days and the mean number of 1 g doses received was 29.0±32.9. The majority of patients (55.1%) initiated vancomycin therapy a mean of 5.4±8.9 days after confirmation of MRSA. Of the 70% of patients meeting criteria for IV-to-oral switch therapy, only 10% received oral treatment. The most common reason cited for not switching was lack of an effective oral alternative. Analysis of switch therapy criteria found that IV treatment continued for a mean of 13 days despite the appropriateness of the oral route.
Considerable variation exists in treatment patterns for MRSA infections. Improvements in the initiation of therapy and the use of IV-to-oral switch therapy may improve care and reduce the duration of hospitalization for MRSA SSTIs.
PMCID: PMC2094957  PMID: 18159474
Methicillin-resistant Staphylococcus aureus; Switch therapy; Treatment patterns; Vancomycin

Results 1-25 (47)