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Papers by Dan Gregson

International Journal of Infectious Diseases, 2008

Objectives: The objective of the present study was to evaluate the etiology, risk factors, and pa... more Objectives: The objective of the present study was to evaluate the etiology, risk factors, and patterns of antimicrobial resistance of intensive care unit (ICU)-acquired urinary tract infections (UTIs) in patients admitted with sepsis. Methods: In this observational study, 100 septic patients hospitalized in a general ICU were selected. Demographic, clinical, and outcome data were obtained by chart review. Antibiotic resistance/susceptibility was determined using the minimal inhibitory concentration (MIC) technique. Results: A UTI was present in 28 (28%) patients; the male to female ratio was 19:9 and the mean age of the patients was 58.71 AE 19.45 years. From the total of 28 isolates, 27 were resistant to ciprofloxacin, 23 to amikacin, 27 to meropenem, 28 to cefepime, 26 to ceftazidime, and 27 to ceftriaxone. Conclusions: On the basis of our results, the rate of multidrug-resistant UTIs may be very high in some ICUs in patients admitted with sepsis. This antimicrobial susceptibility/resistance should be determined, and a special antimicrobial treatment protocol should be planned based

Clinical Infectious Diseases

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with... more Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%–30%. Despite this, <3000 people have been randomized into clinical trials of treatments for SAB infection. The limited evidence base partly results from clinical trials for SAB infections being difficult to complete at scale using traditional clinical trial methods. Here we provide the rationale and framework for an adaptive platform trial applied to SAB infections. We detail the design features of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial that will enable multiple questions to be answered as efficiently as possible. The SNAP trial commenced enrolling patients across multiple countries in 2022 with an estimated target sample size of 7000 participants. This approach may serve as an exemplar to increase efficiency of clinical trials for other infectious disease syndromes.

Official Journal of the Association of Medical Microbiology and Infectious Disease Canada, 2020

Background: Our laboratory uses matrix-assisted laser desorption/ionization time-of-flight mass s... more Background: Our laboratory uses matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI) and the VITEK 2 system (DV2) directly from positive blood cultures (BC) for organism identification (ID) and antimicrobial susceptibility testing (AST). Our objective was to compare direct MALDI–DV2 with a commercial BC ID–AST platform, the Accelerate Pheno system (AXDX), in the ID–AST of clinical and seeded BC positive for gram-negative bacilli (GNB). Methods: BC positive for GNB were collected over a 3-mo period and tested using AXDX and direct MALDI–DV2 and compared with conventional methods. A subset of sterile BC were seeded with multi-drug-resistant GNB. Results: Twenty-nine clinical samples and 35 seeded samples were analyzed. Direct MALDI had a higher ID failure rate (31.0%) than AXDX (3.4%; p < 0.001). Time to ID–AST was 1.5–6.9 h, 5.8–16.5 h, and 21.6–33.0 h for AXDX, direct MALDI–DV2, and conventional methods, respectively ( p < 0.001). For clinical s...

Official Journal of the Association of Medical Microbiology and Infectious Disease Canada, 2018

Background: Choosing Wisely Canada is a forum for health care professional societies to lead syst... more Background: Choosing Wisely Canada is a forum for health care professional societies to lead system change through identification and reduction of low-value practices. Microbiologic investigations are frequently overused and may contribute to unnecessary health care expenditures as well as patient harm. Methods: A Choosing Wisely Canada top five list in medical microbiology was developed by the Association of Medical Microbiology and Infectious Disease (AMMI) Canada through broad consultation of its members. Following an electronic survey of members, recommendations were developed and ranked by a working group, then further narrowed during a national open forum using the modified Delphi method. Feedback was solicited through an online forum prior to dissemination. Results: The top five declarative statements in medical microbiology are: ( 1 ) Don’t collect urine specimens for culture from adults who lack symptoms localizing to the urinary tract or fever, ( 2 ) Don’t routinely collec...

Introduction: Our laboratory uses MALDI-TOF MS (MALDI) and the VITEK®2 system (DV2) directly from... more Introduction: Our laboratory uses MALDI-TOF MS (MALDI) and the VITEK®2 system (DV2) directly from positive blood cultures (BC) for organism identification (ID) and antimicrobial susceptibility testing (AST). Our objective was to compare direct MALDI/DV2 to a commercial BC ID/AST platform, the Accelerate Pheno™ system, in the ID/AST of clinical and seeded BC positive for Gram-negative bacilli (GNB). Methods: BC positive for GNB were collected over a three month period and tested using AXDX, direct MALDI/DV2, and compared to conventional methods. A subset of sterile BC were seeded with multi-drug resistant GNB. Discrepancies in very major errors (VME) and major errors (ME) were confirmed with broth microdilution. Results: A total of 29 clinical samples and 35 seeded samples were analyzed. Direct MALDI had a higher ID failure rate (31.0%) compared to AXDX (3.4%) [p<0.001]. Time to ID/AST was 1.5/6.9 hours, 5.8/16.5 hours and 21.6/33.0 hours for AXDX, direct MALDI/DV2 and conventiona...

Open Forum Infectious Diseases, 2019

Background Pyogenic liver abscess (PLA) is a significant cause of morbidity and mortality. Epidem... more Background Pyogenic liver abscess (PLA) is a significant cause of morbidity and mortality. Epidemiological data regarding risk factors and outcome determinants are often ascertained from referral population bases. We utilized a population-based study design to better understand PLA. Methods Calgary Health Zone (CHZ) residents ≥18 years of age (population ~1.3 million) who were hospitalized with PLA in 2017 were included. Charts were manually reviewed to determine demographics and clinical outcomes. Univariate and multivariate logistic regression were used to assess for factors associated with 30-day mortality using STATA 15.1 (College Stn., TX). Results Forty-four patients with PLA were identified (39% female, median age 61 [IQR 56–68] years) corresponding to an incidence rate of 3.7 cases per 100,000 population. Prevalent co-morbidities with PLA included; hemodialysis dependence (4.5%), cancer (25%), diabetes (23%), and cirrhosis (6.8%), each of which was significantly more common ...

The Journal of infectious diseases, Jan 9, 2016

During 2013, ST278 Klebsiella pneumoniae with blaNDM-7 was isolated from the urine (KpN01) and re... more During 2013, ST278 Klebsiella pneumoniae with blaNDM-7 was isolated from the urine (KpN01) and rectum (KpN02) of a patient in Calgary, Canada. The same strain (KpN04) was subsequently isolated from another patient in the same unit. Interestingly, a carbapenem-susceptible K. pneumoniae ST278 (KpN06) was obtained 1 month later from the blood of the second patient. Next-generation sequencing (NGS) revealed that the loss of carbapenem-resistance in KpN06 was due to a 5-kb deletion on the blaNDM-7-harboring IncX3 plasmid. In addition, an IncFIB plasmid in KpN06 had a 27-kb deletion that removed genes encoding for heavy metal resistance. Phylogenetic analysis showed that the K. pneumoniae ST278 from patient 2 was likely a descendant of KpN02 and that KpN06 was a close progenitor of an environmental ST278. It is unclear whether KpN06 lost the blaNDM-7 gene in vivo. This study detailed the remarkable plasticity and speed of evolutionary changes in multidrug-resistant K. pneumoniae, demonstr...

Canadian Journal of Infectious Diseases, 1994

Classically, a swollen, painful joint in a patient with hemophilia has been considered to be due ... more Classically, a swollen, painful joint in a patient with hemophilia has been considered to be due to a hemarthrosis until otherwise proven, and treated immediately with appropriate coagulation factor replacement. Two cases of human immunodeficiency virus (hiv)-infected hemophiliacs presenting with an initial apparent hemarthrosis, complicated subsequently by numerous pyarthroses and sepsis are described. In light of the prevalence ofhivinfection in the adult hemophiliac population with arthropathy, a reappraisal of the clinical caveat of immediate infusion without joint aspiration is required.

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, Jan 31, 2015

Transplantation, 1999

Your tda Votre rsUlsnce Our fi& Notre reHrence The author has granted a nonexclusive licence ailo... more Your tda Votre rsUlsnce Our fi& Notre reHrence The author has granted a nonexclusive licence ailowing the National Library of Canada to reproduce, loan, distribute or sel1 copies of this thesis in microfortn, paper or electronic formats. L'auteur a accordé une licence non exclusive permettant à la Bibliothèque nationale du Canada de reproduire, prêter, distribuer ou vendre des copies de cette thèse sous la forme de microfiche/fiim, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fiom it Ni la thèse ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation.

Journal of Medical Microbiology, 2010

The ‘Streptococcus milleri’ group (SMG) has recently been recognized as a contributor to bronchop... more The ‘Streptococcus milleri’ group (SMG) has recently been recognized as a contributor to bronchopulmonary disease in cystic fibrosis (CF). Routine detection and quantification is limited by current CF microbiology protocols. McKay agar was developed previously for the semi-selective isolation of this group. Here, McKay agar was validated against a panel of clinical SMG isolates, which revealed improved SMG recovery compared with Columbia blood agar. The effectiveness of this medium was evaluated by appending it to the standard CF sputum microbiology protocols in a clinical laboratory for a 6-month period. All unique colony types were isolated and identified by 16S rRNA gene sequencing. Whilst a wide variety of organisms were isolated, members of the SMG were the most prevalent bacteria cultured, and McKay agar allowed routine quantification of the SMG from 103 to >108 c.f.u. ml−1 directly from sputum. All members of the SMG were detected [Streptococcus anginosus (40.7 %), Strepto...

Journal of Clinical Microbiology, 2006

The prevalence and characteristics of PCR ribotype 027 strains of Clostridium difficile have come... more The prevalence and characteristics of PCR ribotype 027 strains of Clostridium difficile have come into question following recent outbreaks in Eastern Canada and elsewhere. In order to determine the distribution of this strain in other regions in Canada, we screened a bank of 1,419 isolates recovered from three different Canadian health regions between 2000 and 2004. Among isolates from a Montreal area hospital, PCR ribotype 027 strains represented 115/153 strains (75.2%) from 2003 to 2004, but ribotype 027 strains were absent in 2000 and 2001. In Calgary, by contrast, ribotype 027 rates have remained relatively stable over 4 years of surveillance, representing 51/685 (7.4%) hospital isolates and 62/373 (16.6%) strains from the community ( P < 0.001). PCR ribotype 027 accounted for 8/135 (5.9%) hospital isolates in the Fraser Health Region in 2004. repetitive extragenic palindromic PCR was used to subtype a random selection of 027 isolates from each region. All 10 of the isolates ...

Journal of Clinical Microbiology, 2005

Organisms belonging to the “ Streptococcus milleri ” group are important invasive human pathogens... more Organisms belonging to the “ Streptococcus milleri ” group are important invasive human pathogens. A detailed understanding of their pathogenesis in human infection has only recently been facilitated by the use of molecular methods to study this group of organisms.

Journal of Clinical Microbiology, 2007

Legionella infection causes 2 to 14% of community-acquired pneumonia (CAP). Legionella micdadei c... more Legionella infection causes 2 to 14% of community-acquired pneumonia (CAP). Legionella micdadei constitutes <1% of these infections. We describe a case of cavitary L. micdadei CAP in a myeloma patient receiving thalidomide treatment. The importance of considering pneumonia and problems in diagnosing pneumonia caused by L. micdadei in this patient population are reviewed.

Journal of Clinical Microbiology, 2009

A study was designed to evaluate the ability of the DiversiLab fingerprinting kit, a type of repe... more A study was designed to evaluate the ability of the DiversiLab fingerprinting kit, a type of repetitive element PCR (rep-PCR), to identify Escherichia coli clone ST131 producing β-lactamase CTX-M-15. A set of 53 nonduplicate isolates of extended-spectrum β-lactamase-producing E. coli underwent rep-PCR, pulsed-field gel electrophoresis, and multilocus sequence typing. The DiversiLab system successfully identified E. coli clone ST131 producing CTX-M-15 and provides a simple standardized typing protocol for monitoring the spread of this clone.

Journal of Antimicrobial Chemotherapy, 2008

of Escherichia coli, Klebsiella spp., Proteus mirabilis and Morganella morganii resistant to cipr... more of Escherichia coli, Klebsiella spp., Proteus mirabilis and Morganella morganii resistant to ciprofloxacin and/or tobramycin were screened for PMQR determinants using a multiplex PCR for qnrA, qnrS and qnrB and aac(6 0)-Ib genes; aac(6 0)-Ib-cr was further identified by digestion with BstF5I. Results: In 2004, 6/139 (4%) of the resistant E. coli were positive for aac(6 0)-Ib-cr. In 2007, 53/398 (13%) were positive for aac(6 0)-Ib-cr, 3/398 (0.8%) were positive for qnrS, and one isolate was positive for both. All the isolates were present in urines and the majority [40/63 (63%)] were submitted from community collection sites; 8 (13%) isolates co-produced AmpC b-lactamases and 34 (54%) co-produced CTX-M-15. aac(6 0)-Ib-cr was present in one Klebsiella pneumoniae and one P. mirabilis, whereas one isolate of K. pneumoniae was positive for both aac(6 0)-Ib-cr and qnrB. Conclusions: Our results showed that isolates with aac(6 0)-Ib-cr, often associated with CTX-M-15, are emerging among fluoroquinolone-resistant E. coli in the CHR. Our study suggests that surveillance for PMQR determinants should be undertaken on a regular basis.

Diagnostic Microbiology and Infectious Disease, 2011

Automated repetitive PCR (rep-PCR; DiversiLab) was compared to PCR ribotyping of the 16S-23S RNA ... more Automated repetitive PCR (rep-PCR; DiversiLab) was compared to PCR ribotyping of the 16S-23S RNA intergenic spacer of Clostridium difficile (CD) as the "gold standard" method for CD typing. PCR products were separated on DiversiLab LabChips (bioMérieux, St. Laurent, Quebec, Canada) utilizing a 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA) operating the DiversiLab v1.4 assay. Bioanalyzer data were exported to a secure DiversiLab website and analyzed with DiversiLab v3.4 software. Replicability of each method was verified by confirming that the 5 CD reference strains (RS) formed distinct clusters (CD4, CD6, VL0047, VL0013 [ribotype 027], VL0018 [ribotype 001]) by both typing methods. Ninety randomly selected clinical isolates (CS) were analyzed by both methods: 49 from community-acquired and 41 from hospital-acquired cases. A similarity index (SI) of ≥90% was used to define clusters when comparing the known RS cluster to the PCR ribotyping and rep-PCR patterns of CS. Fourteen different PCR-ribotype clusters were identified, but most CS formed 4 major clusters (i.e., CD4 [15/90; 17%], CD6 [17%], 027 [12%], and 001 [9%]). A total of 7 rep-PCR types were identified, but most CS formed 2 major rep-PCR clusters (i.e., CD4 [29/90; 32%] and CD6 [23%]); several PCR ribotypes occurred within a single rep-PCR cluster. Rep-PCR did not distinguish 027 or 001 isolates; i) 027 RS strain did not cluster, ii) eleven 027 CS strains clustered as CD4, iii) no 027 CS strains clustered with the 027 RS, and iv) only 2 001 CS clustered with the RS. Agreement between the PCR-ribotype and rep-PCR clusters only occurred for 35/90 (39%) of the CS using a rep-PCR SI of ≥90%. Rep-PCR time to results was similar, but the annual costs of routinely using this method are 32% higher than PCR ribotyping. Routine use of rep-PCR for CD typing is limited by its lack of definitive separation of the hypertoxigenic 027 or 001 outbreak CD strains.

Canadian Medical Association Journal, 2006

Clinical Infectious Diseases, 2002

A prospective, population-based, surveillance study of invasive soft-tissue infections due to gro... more A prospective, population-based, surveillance study of invasive soft-tissue infections due to group A streptococci was conducted in Ontario, Canada, from 1992 through 1996. Demographic and clinical information was obtained by patient interview and chart review. Isolates were characterized by M protein and T agglutination typing. The incidence of necrotizing fasciitis (NF) increased from 0.08 cases per 100,000 population in 1992 to 0.49 cases per 100,000 population in 1995. The case-fatality rate was 13% (68 of 520 patients died). Hypotension and multiorgan dysfunction complicated 64 cases (12%), and NF complicated 119 cases (23%). Underlying diabetes, alcohol abuse, cancer, and cardiac and pulmonary disease increased the risk of disease. Prior use of nonsteroidal anti-inflammatory agents did not influence disease severity. All 197 patients without NF, underlying illness, and hypotension at presentation survived, as did 95 (99%) of 96 normotensive patients who were !65 years old but who had underlying chronic illness. Previously healthy patients without hypotension or NF may be considered for outpatient treatment.