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1.  Increased Incidence of Tuberculosis in Zimbabwe, in Association with Food Insecurity, and Economic Collapse: An Ecological Analysis 
PLoS ONE  2014;9(2):e83387.
Zimbabwe underwent a socioeconomic crisis and resultant increase in food insecurity in 2008–9. The impact of the crisis on Tuberculosis (TB) incidence is unknown.
Prospective databases from two mission hospitals, which were geographically widely separated, and remained open during the crisis, were reviewed.
At the Howard Hospital (HH) in northern Zimbabwe, TB incidence increased 35% in 2008 from baseline rates in 2003–2007 (p<0.01) and remained at that level in 2009. Murambinda Hospital (MH) in Eastern Zimbabwe also demonstrated a 29% rise in TB incidence from 2007 to 2008 (p<0.01) and remained at that level in 2009. Data collected post-crisis at HH showed a decrease of 33% in TB incidence between 2009 to 2010 (p<0.001) and 2010/2011 TB incidence remained below that of the crisis years of 2008/2009 (p<0.01). Antenatal clinic HIV seroprevalence at HH decreased between 2001(23%) to 2011(11%) (p<0.001). Seasonality of TB incidence was analyzed at both MH and HH. There was a higher TB incidence in the dry season when food is least available (September-November) compared to post harvest (April-June) (p<0.001).
This study suggests that an epidemic of TB mirrored socioeconomic collapse and recovery in Zimbabwe. The seasonal data suggests that food security may have been associated with TB incidence both annually and during the crisis in this high HIV prevalence country.
PMCID: PMC3914787  PMID: 24505245
3.  Cost-Effectiveness and Efficacy of spa, SCCmec, and PVL Genotyping of Methicillin-Resistant Staphylococcus aureus as Compared to Pulsed-Field Gel Electrophoresis 
PLoS ONE  2013;8(11):e79149.
Pulsed-field gel electrophoresis (PFGE) is a valuable molecular typing assay used for methicillin-resistant Staphylococcus aureus (MRSA) surveillance and genotyping. However, there are several limitations associated with PFGE. In Alberta, Canada, the significant increase in the number of MRSA isolates submitted to the Provincial Laboratory for Public Health (ProvLab) for PFGE typing led to the need for an alternative genotyping method. In this study, we describe the transition from PFGE to Staphylococcus protein A (spa), Staphylococcal cassette chromosome (SCCmec), and Panton-Valentine leukocidin (PVL) typing. A total of 1915 clinical MRSA isolates collected from 2005 to 2009 were used to develop and validate an algorithm for assigning PFGE epidemic types using spa, SCCmec, and PVL typing and the resulting data was used to populate a new Alberta MRSA typing database. An additional 12620 clinical MRSA isolates collected from 2010 to 2012 as part of ongoing routine molecular testing at ProvLab were characterized using the new typing algorithm and the Alberta MRSA typing database. Switching to spa, SCCmec, and PVL from PFGE typing substantially reduced hands-on and turn-around times while maintaining historical PFGE epidemic type designations. This led to an approximate $77,000 reduction in costs from 2010 to 2012. PFGE typing is still required for a small subset of MRSA isolates that have spa types that are rare, novel, or associated with more than one PFGE epidemic type.
PMCID: PMC3828336  PMID: 24244440
4.  Surveillance Definitions of Infections in Long-Term Care Facilities: Revisiting the McGeer Criteria 
(See the commentary by Moro, on pages 978–980.)
Infection surveillance definitions for long-term care facilities (ie, the McGeer Criteria) have not been updated since 1991. An expert consensus panel modified these definitions on the basis of a structured review of the literature. Significant changes were made to the criteria defining urinary tract and respiratory tract infections. New definitions were added for norovirus gastroenteritis and Clostridum difficile infections.
PMCID: PMC3538836  PMID: 22961014
6.  Epidemiology and Outcome of Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus (MRSA) in Canadian Hospitals 
PLoS ONE  2013;8(9):e75171.
MRSA remains a leading cause of hospital-acquired (HAP) and healthcare-associated pneumonia (HCAP). We describe the epidemiology and outcome of MRSA pneumonia in Canadian hospitals, and identify factors contributing to mortality.
Prospective surveillance for MRSA pneumonia in adults was done for one year (2011) in 11 Canadian hospitals. Standard criteria for MRSA HAP, HCAP, ventilator-associated pneumonia (VAP), and community-acquired pneumonia (CAP) were used to identify cases. MRSA isolates underwent antimicrobial susceptibility testing, and were characterized by pulsed-field gel electrophoresis (PFGE) and Panton-Valentine leukocidin (PVL) gene detection. The primary outcome was all-cause mortality at 30 days. A multivariable analysis was done to examine the association between various host and microbial factors and mortality.
A total of 161 patients with MRSA pneumonia were identified: 90 (56%) with HAP, 26 (16%) HCAP, and 45 (28%) CAP; 23 (14%) patients had VAP. The mean (± SD) incidence of MRSA HAP was 0.32 (± 0.26) per 10,000 patient-days, and of MRSA VAP was 0.30 (± 0.5) per 1,000 ventilator-days. The 30-day all-cause mortality was 28.0%. In multivariable analysis, variables associated with mortality were the presence of multiorgan failure (OR 8.1; 95% CI 2.5-26.0), and infection with an isolate with reduced susceptibility to vancomycin (OR 2.5, 95% CI 1.0-6.3).
MRSA pneumonia is associated with significant mortality. Severity of disease at presentation, and infection caused by an isolate with elevated MIC to vancomcyin are associated with increased mortality. Additional studies are required to better understand the impact of host and microbial variables on outcome.
PMCID: PMC3775759  PMID: 24069391
7.  A Caenorhabditis elegans host model correlates with invasive disease caused by Staphylococcus aureus recovered during an outbreak in neonatal intensive care 
Caenorhabditis elegans has previously been used as a host model to determine the virulence of clinical methicillin-resistant Staphylococcus aureus isolates. In the present study, methicillin-susceptible S aureus (MSSA) strains associated with an outbreak in a neonatal intensive care unit (NICU) were investigated using the C elegans model.
Two distinct outbreak clones, MSSA type-C and MSSA type-G, were identified by pulsed-field gel electrophoresis in a MSSA outbreak during a seven-month period in the NICU of the Sunnybrook Health Sciences Centre (Toronto, Ontario). MSSA type-C was associated with severe infection, while type-G was associated with less invasive disease. Four representative type-C isolates, three type-G and three infant-colonized isolates unrelated to the outbreak, were sent to Calgary (Alberta), for the double-blinded virulence tests in the C elegans host model and for further molecular characterization.
The invasive outbreak strains (type-C) demonstrated highly nematocidal activity, the noninvasive outbreak strains (type-G) an intermediate virulence, and the outbreak-unrelated colonization isolates demonstrated avirulence or low virulence in the C elegans model, with mean killing rates of 93.0%, 61.0% and 14.4% by day 9, respectively, for these three group strains. Different group MSSA strains had their own unique genetic profiles and virulence gene profiles, but all isolates within the same group (type-C or type-G) shared identical genetic characteristics and virulence gene patterns.
The present blinded evaluation demonstrated that the nematocidal activities of MSSA strains correlated well with the clinical manifestation in an MSSA outbreak in the NICU, supporting C elegans as a robust host model to study the pathogenesis of S aureus.
PMCID: PMC3476557  PMID: 23997780
Caenorhabditis elegans; Double-blinded test; Methicillin-suseptible Staphylococcus aureus outbreak; MSSA; Neonatal intensive care unit; NICU; Staphylococcus aureus; Virulence host model
8.  Risk Factors for Influenza among Health Care Workers during 2009 Pandemic, Toronto, Ontario, Canada 
Emerging Infectious Diseases  2013;19(4):606-615.
Influenza was associated with household exposure, aerosol-generating procedures, and lower adherence to hand hygiene recommendations.
PMCID: PMC3647716  PMID: 23631831
Influenza; virus; viruses; pandemic; health care worker; risk; hand hygiene; transmission; respiratory; ventilation; aerosol; Canada
9.  MupB, a New High-Level Mupirocin Resistance Mechanism in Staphylococcus aureus 
Mupirocin is a topical antibiotic used for the treatment of skin infections and the eradication of methicillin-resistant Staphylococcus aureus carriage. It inhibits bacterial protein synthesis by interfering with isoleucyl-tRNA synthetase activity. High-level mupirocin resistance (MIC of ≥512 μg/ml) is mediated by the expression of mupA (ileS2), which encodes an alternate isoleucyl-tRNA synthetase. In this study, we describe high-level mupirocin resistance mediated by a novel locus, mupB. The mupB gene (3,102 bp) shares 65.5% sequence identity with mupA but only 45.5% identity with ileS. The deduced MupB protein shares 58.1% identity (72.3% similarity) and 25.4% identity (41.8% similarity) with MupA and IleS, respectively. Despite this limited homology, MupB contains conserved motifs found in class I tRNA synthetases. Attempts to transfer high-level mupirocin resistance via conjugation or transformation (using plasmid extracts from an mupB-containing strain) were unsuccessful. However, by cloning the mupB gene into a shuttle vector, it was possible to transfer the resistance phenotype to susceptible S. aureus by electroporation, proving that mupB was responsible for the high-level mupirocin resistance. Further studies need to be done to determine the prevalence of mupB and to understand risk factors and outcomes associated with resistance mediated by this gene.
PMCID: PMC3318397  PMID: 22252810
12.  Risk of infection following a visit to the emergency department: a cohort study 
The risk of infection following a visit to the emergency department is unknown. We explored this risk among elderly residents of long-term care facilities.
We compared the rates of new respiratory and gastrointestinal infections among elderly residents aged 65 years and older of 22 long-term care facilities. We used standardized surveillance definitions. For each resident who visited the emergency department during the study period, we randomly selected two residents who did not visit the emergency department and matched them by facility unit, age and sex. We calculated the rates and proportions of new infections, and we used conditional logistic regression to adjust for potential confounding variables.
In total, we included 1269 residents of long-term care facilities, including 424 who visited the emergency department during the study. The baseline characteristics of residents who did or did not visit the emergency department were similar, except for underlying health status (visited the emergency department: mean Charlson Comorbidity Index 6.1, standard deviation [SD] 2.5; did not visit the emergency department: mean Charlson Comorbidity index 5.5, SD 2.7; p < 0.001) and the proportion who had visitors (visited the emergency department: 46.9%; did not visit the emergency department: 39.2%; p = 0.01). Overall, 21 (5.0%) residents who visited the emergency department and 17 (2.0%) who did not visit the emergency department acquired new infections. The incidence of new infections was 8.3/1000 patient-days among those who visited the emergency department and 3.4/1000 patient-days among those who did not visit the emergency department. The adjusted odds ratio for the risk of infection following a visit to the emergency department was 3.9 (95% confidence interval 1.4–10.8).
A visit to the emergency department was associated with more than a threefold increased risk of acute infection among elderly people. Additional precautions should be considered for residents following a visit to the emergency department.
PMCID: PMC3291696  PMID: 22271915
13.  Distribution of Antiseptic Resistance Genes qacA, qacB, and smr in Methicillin-Resistant Staphylococcus aureus Isolated in Toronto, Canada, from 2005 to 2009▿ 
Decreased susceptibility to chlorhexidine gluconate (CHDN) in methicillin-resistant Staphylococcus aureus (MRSA) is associated with the qacA, qacB, and smr genes, encoding efflux pumps. A total of 334 MRSA isolates were collected from two Canadian intensive care units between 2005 and 2009. We identified the qacAB genes in 7 strains (2%; 2 qacA genes and 5 qacB genes) and the smr gene in 23 (7%) strains. CHDN minimal bactericidal concentrations were slightly higher for strains harboring smr genes.
PMCID: PMC3101426  PMID: 21402848
14.  Genotypic and Phenotypic Characterization of Methicillin-Susceptible Staphylococcus aureus Isolates Misidentified as Methicillin-Resistant Staphylococcus aureus by the BD GeneOhm MRSA Assay▿ 
Journal of Clinical Microbiology  2011;49(4):1240-1244.
Twenty-three nasal swab samples that tested positive for methicillin-resistant Staphylococcus aureus (MRSA) on initial testing by the BD GeneOhm MRSA assay (BD-MRSA PCR; BD GeneOhm, San Diego, CA) were culture positive only for methicillin-susceptible S. aureus (MSSA) from an enrichment broth. The 23 recovered isolates were confirmed as MSSA by a variety of phenotypic methods, including the BD Phoenix automated microbiology system (BD Diagnostics, Sparks, MD), oxacillin screening agar (BD Diagnostics), BBL CHROMagar MRSA (BD Diagnostics), and a PBP2′ assay (Denka Seiken Co., Tokyo, Japan); susceptibilities were determined by using Mueller-Hinton agar with oxacillin. All were positive by nuc PCR, specific for S. aureus, but negative for mecA with one exception. Isolates were characterized by using multiplex PCR methodology to determine structural types and variants (SCCmec typing); additional PCRs were performed for the detection of the ccr and mec complexes, the junkyard regions as well as the Panton-Valentine leukocidin. Pulsed-field gel electrophoresis was used to determine clonality. One phenotypic MSSA isolate contained an intact SCCmec. Twelve MSSA isolates tested positive for MRSA by the BD-MRSA PCR because of amplification of the mec priming site flanking the SCC insertion point, although these isolates lacked mecA. The 10 remaining isolates were not MRSA and tested as MSSA by phenotypic and genotypic assays. In our patient population, diagnostic and surveillance testing and subsequent infection control practices may be impacted by the frequency of these excision events when using the BD-MRSA PCR for MRSA detection.
PMCID: PMC3122879  PMID: 21307210
15.  New Delhi metallo-β-lactamase-1: local acquisition in Ontario, Canada, and challenges in detection 
New Delhi metallo-β-lactamase-1 (NDM-1) is a recently identified metallo-β-lactamase that confers resistance to carbapenems and all other β-lactam antibiotics, with the exception of aztreonam. NDM-1 is also associated with resistance to many other classes of antibiotics. The enzyme was first identified in organisms isolated from a patient in Sweden who had previously received medical treatment in India, but it is now recognized as endemic throughout India and Pakistan and has spread worldwide. The gene encoding NDM-1 has been found predominantly in Escherichia coli and Klebsiella pneumoniae. We describe the isolation NDM-1–producing organisms from two patients in Toronto, Ontario. To the best of our knowledge, this is the first report of an organism producing NDM-1 that was locally acquired in Canada. We also discuss the evidence that NDM-1 can affect bacterial species other than E. coli and K. pneumoniae, the limited options for treatment and the difficulty laboratories face in detecting organisms that produce NDM-1.
PMCID: PMC3153514  PMID: 21624908
16.  When should a diagnosis of influenza be considered in adults requiring intensive care unit admission? Results of population-based active surveillance in Toronto 
Critical Care  2011;15(4):R182.
There is a paucity of data about the clinical characteristics that help identify patients at high risk of influenza infection upon ICU admission. We aimed to identify predictors of influenza infection in patients admitted to ICUs during the 2007/2008 and 2008/2009 influenza seasons and the second wave of the 2009 H1N1 influenza pandemic as well as to identify populations with increased likelihood of seasonal and pandemic 2009 influenza (pH1N1) infection.
Six Toronto acute care hospitals participated in active surveillance for laboratory-confirmed influenza requiring ICU admission during periods of influenza activity from 2007 to 2009. Nasopharyngeal swabs were obtained from patients who presented to our hospitals with acute respiratory or cardiac illness or febrile illness without a clear nonrespiratory aetiology. Predictors of influenza were assessed by multivariable logistic regression analysis and the likelihood of influenza in different populations was calculated.
In 5,482 patients, 126 (2.3%) were found to have influenza. Admission temperature ≥38°C (odds ratio (OR) 4.7 for pH1N1, 2.3 for seasonal influenza) and admission diagnosis of pneumonia or respiratory infection (OR 7.3 for pH1N1, 4.2 for seasonal influenza) were independent predictors for influenza. During the peak weeks of influenza seasons, 17% of afebrile patients and 27% of febrile patients with pneumonia or respiratory infection had influenza. During the second wave of the 2009 pandemic, 26% of afebrile patients and 70% of febrile patients with pneumonia or respiratory infection had influenza.
The findings of our study may assist clinicians in decision making regarding optimal management of adult patients admitted to ICUs during future influenza seasons. Influenza testing, empiric antiviral therapy and empiric infection control precautions should be considered in those patients who are admitted during influenza season with a diagnosis of pneumonia or respiratory infection and are either febrile or admitted during weeks of peak influenza activity.
PMCID: PMC3387625  PMID: 21798012
17.  Efficacy and Safety of CVT-E002, a Proprietary Extract of Panax quinquefolius in the Prevention of Respiratory Infections in Influenza-Vaccinated Community-Dwelling Adults: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Trial 
CVT-E002 (a proprietary extract) was found to be effective in the prevention of upper respiratory infections (URIs) in healthy adults, and institutionalized and community-dwelling seniors. A multicenter, randomized, double-blind, placebo-controlled trial was carried out to determine effects of CVT-E002 in the prevention of URIs in influenza-vaccinated community-dwelling adults. 783 community-dwelling adults were randomized to receive placebo, 400 mg or 800 mg treatment/d (1 : 1 : 1) for 6 months. Primary analysis on the incidence of laboratory-confirmed-clinical URIs (LCCUs), including influenza A and B, was performed on those receiving at least one dose. Secondary analysis was performed on study completers and included incidence, severity, and duration of URIs meeting a Jackson-based criteria and safety of CVT-E002. The incidence of LCCUs in the ITT group was 5.5%, 5.2%, and 4.6% in the placebo, 400 mg and 800 mg groups, respectively (P = 0.89). Jackson-confirmed URIs were significantly lower in the treated groups (P < 0.04). CVT-E002 supplementation reduced the severity and duration of Jackson-confirmed URIs. The results indicate that CVT-E002 can be safely used by similar groups and may prevent symptoms of URIs; larger sample size is warranted.
PMCID: PMC3447298  PMID: 23074661
18.  Impact of accessory gene regulator (agr) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant Staphylococcus aureus 
The accessory gene regulator (agr) is a quorum sensing cluster of genes which control colonization and virulence in Staphylococcus aureus. We evaluated agr function in community- (CA) and healthcare-associated (HA) MRSA, to compare the pharmacodynamics and bactericidal activity of vancomycin against agr functional and dysfunctional HA-MRSA and CA-MRSA.
40 clinical isolates of MRSA from the Canadian Nosocomial Infection Surveillance Program were evaluated for delta-haemolysin production, as a surrogate marker of agr function. Time kill experiments were performed for vancomycin at 0 to 64 times the MIC against an initial inoculum of 106 and 108 cfu/ml of agr functional and dysfunctional CA-MRSA and HA-MRSA and these data were fit to a hill-type pharmacodynamic model.
15% isolates were agr dysfunctional, which was higher among HA-MRSA (26.3%) versus CA-MRSA (4.76%). Against a low initial inoculum of 106 cfu/ml of CA-MRSA, vancomycin pharmacodynamics were similar among agr functional and dysfunctional strains. However, against a high initial inoculum of 108 cfu/ml, killing activity was notably attenuated against agr dysfunctional CA-MRSA (USA400) and HA-MRSA (USA100). CA-MRSA displayed a 20.0 fold decrease in the maximal reduction in bacterial counts (Emax) which was 3.71 log10 CFU/ml for agr functional vs. 2.41 log10 CFU/ml for agr dysfunctional MRSA (p = 0.0007).
Dysfunction in agr was less common among CA-MRSA vs. HA-MRSA. agr dysfunction demonstrated an impact on vancomycin bactericidal activity and pharmacodynamics against a high initial inoculum of CA-MRSA and HA-MRSA, which may have implications for optimal antimicrobial therapy against persistent, difficult to treat MRSA infections.
PMCID: PMC3120648  PMID: 21599878
19.  Characterization of Staphylococcus aureus Isolates with a Partial or Complete Absence of Staphylococcal Cassette Chromosome Elements▿  
Journal of Clinical Microbiology  2010;48(10):3525-3531.
Detection of methicillin-resistant Staphylococcus aureus (MRSA) by single-locus PCR assays that target the extremity of the staphylococcal cassette chromosome-mec (SCCmec) and part of the adjacent S. aureus-specific open reading frame gene (orfX) is a significant diagnostic advancement, since it provides real-time detection directly from screening specimens. However, isolates harboring mecA deletions within SCCmec may result in false-positive identification of MRSA in these assays. We characterized 24 methicillin-susceptible S. aureus (MSSA) isolates that tested positive in one such assay to investigate this phenomenon. Seven isolates resembled USA100 and carried SCCmec II elements with mecA deletions that spanned 20 to 46 kbp. The mecA excisions in USA100-resembling isolates appeared to be linked with IS431 transposable elements present in SCCmec II. For 17 isolates that resembled USA400 and/or MSSA476, the identity and possible excision of SCC elements could not be confirmed. The downstream common sequence (dcs) shared by SCCmec I, II, and IV elements was detected in these isolates. Sequence analysis of the chromosomal regions flanking the missing SCC element revealed an intact SCC integration site, a duplicate dcs, and the enterotoxin gene cluster downstream of orfX. An annealing sequence for one of the SCCmec-specific primers (mecii574) in the single-locus PCR assay was identified in the duplicate dcs. In the absence of SCC, a 176-bp amplicon can be generated from this mecii574 annealing sequence to yield a false-positive result. In conclusion, partial SCCmec II excisions via IS431 elements in strains that resembled USA100 and the presence of a duplicate mecii574 annealing sequence in strains that resembled USA400/MSSA476 were identified as causes for false-positive results in a single-locus PCR assay that targets the SCCmec/orfX junction.
PMCID: PMC2953136  PMID: 20668131
20.  Multicenter Study To Determine Disk Diffusion and Broth Microdilution Criteria for Prediction of High- and Low-Level Mupirocin Resistance in Staphylococcus aureus▿  
Journal of Clinical Microbiology  2010;48(7):2469-2475.
Mupirocin susceptibility testing of Staphylococcus aureus has become more important as mupirocin is used more widely to suppress or eliminate S. aureus colonization and prevent subsequent health care- and community-associated infections. The present multicenter study evaluated two susceptibility testing screening methods to detect mupirocin high-level resistance (HLR), broth microdilution (BMD) MICs of ≥512 μg/ml, and a 6-mm zone diameter for a disk diffusion (DD) test with a 200-μg disk. Initial testing indicated that with Clinical and Laboratory Standards Institute methods for BMD and DD testing, the optimal conditions for the detection of mupirocin HLR were 24 h of incubation and reading of the DD zone diameters with transmitted light. Using the presence or absence of mupA as the “gold standard” for HLR, the sensitivity and specificity of a single-well 256 μg/ml BMD test were 97 and 99%, respectively, and those for the 200-μg disk test were 98 and 99%, respectively. Testing with two disks, 200 μg and 5 μg, was evaluated for its ability to distinguish HLR isolates (MICs ≥ 512 μg/ml), low-level-resistant (LLR) isolates (MICs = 8 to 256 μg/ml), and susceptible isolates (MICs ≤ 4 μg/ml). Using no zone with both disks as an indication of HLR and no zone with the 5-μg disk plus any zone with the 200-μg disk as LLR, only 3 of the 340 isolates were misclassified, with 3 susceptible isolates being classified as LLR. Use of standardized MIC or disk tests could enable the detection of emerging high- and low-level mupirocin resistance in S. aureus.
PMCID: PMC2897470  PMID: 20444971
21.  Mortality in a heterogeneous population of low-risk febrile neutropenic patients treated initially with cefazolin and tobramycin 
At Sunnybrook Health Sciences Centre in Toronto, Ontario, the recommended empiric regimen for febrile neutropenia has been cefazolin and tobramycin for at least 25 years. However, we had no objective data to reassure us that patient mortality had not increased over the past five years.
A retrospective chart review of 48 episodes occurring in 44 patients admitted for the treatment of febrile neutropenia secondary to chemotherapy in 2002, and initially managed with cefazolin and tobramycin was conducted. Prospective data from 48 episodes in 2007 had previously been collected. Patients who developed febrile neutropenia while in hospital were excluded. The primary objective of the present study was to compare the all-cause mortality in 2007 with that from 2002.
There were no statistically significant differences between the groups (P>0.05). All-cause mortality in 2007 was 8.3% (four of 48) compared with 10.4% (five of 48) in 2002 (P=1). All deaths occurred in patients considered to be at high risk according to the Talcott score.
Mortality has not increased in the past five years with the use of empiric cefazolin and tobramycin for the treatment of patients admitted with febrile neutropenia at Sunnybrook Health Sciences Centre. Rates are comparable with those reported in the literature for similar patients. The results of the present study provide reassurance that the regimen continues to be effective for lower-risk febrile neutropenic patients.
PMCID: PMC2807246  PMID: 21119792
Cefazolin; Fever; Mortality; Neutropenia; Tobramycin
22.  Positive urine cultures: A major cause of inappropriate antimicrobial use in hospitals? 
Urine specimens are among the most common samples submitted for culture to microbiology laboratories. The objectives of the present study were to describe the indications for obtaining urine cultures in a cohort of hospitalized patients, and to determine the appropriateness of antimicrobial therapy in response to urine culture results.
The study was performed at a teaching hospital with an adjoining long-term care facility from June 1 to July 31, 2006. The medical records of nonpregnant adult patients with and without bacteriuria were reviewed. A symptomatic urinary tract infection was defined as the presence of bacteriuria in a patient with fever or urinary symptoms; asymptomatic bacteriuria was defined as bacteriuria without urinary symptoms and no infection evident at another site.
Medical records of 335 eligible patients (64% male; mean age 68 years) were reviewed, including all 137 with bacteriuria, and 198 with negative urine cultures. In total, 51% of the urine specimens were obtained from an indwelling urinary catheter, and 28% were voided urine samples. Confusion (57%) and fever (36%) were the most common indications noted for obtaining the urine cultures. Only 34 patients (25% of those with positive urine cultures) met the criteria for a symptomatic urinary tract infection; 67 (49%) had asymptomatic bacteriuria and 36 (26%) had infection at a nonurinary site. Of those with asymptomatic bacteriuria, 64% received antimicrobial therapy for a total of 347 days. Confused patients with asymptomatic bacteriuria were more likely to be treated than were bacteriuric patients without altered mental status (OR 1.8, 95% CI 1.2 to 4.1; P=0.03).
Urine cultures are frequently obtained from hospitalizedpatients,evenintheabsenceofurinarysymptoms.Asymptomatic bacteriuria is often treated in these patients, and accounts for a substantial burden of inappropriate antimicrobial use in hospitals. Effective strategies to improve urine culture ordering and antimicrobial utilization in hospitals need to be implemented.
PMCID: PMC2807252  PMID: 21119801
Antimicrobial treatment; Asymptomatic bacteriuria; Laboratory utilization; Urinary tract infection
23.  Antimicrobial Susceptibilities of Health Care-Associated and Community-Associated Strains of Methicillin-Resistant Staphylococcus aureus from Hospitalized Patients in Canada, 1995 to 2008▿  
We determined the in vitro antimicrobial susceptibilities of 7,942 methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained from patients hospitalized in 48 Canadian hospitals from 1995 to 2008. Regional variations in susceptibilities were identified. The dissemination of community-associated strains in Canada appears to have contributed to increased susceptibility of MRSA to several non-β-lactam antimicrobial agents in the past decade. Reduced susceptibility to glycopeptides was not identified.
PMCID: PMC2863599  PMID: 20231402
24.  Initial Vancomycin Dosing Recommendations for Critically Ill Patients Undergoing Continuous Venovenous Hemodialysis 
Delaying appropriate antimicrobial therapy for critically ill patients increases the risk of death. Currently, there are insufficient data to guide initial vancomycin dosing for patients undergoing continuous venovenous hemodialysis (CVVHD).
To develop practical recommendations for initial dosing of vancomycin, based on the pharmacokinetics of this drug in critically ill patients undergoing CVVHD.
A chart review was conducted for 24 critically ill adult patients who had undergone concurrent CVVHD and vancomycin therapy. Mean pharmacokinetic parameters were determined, along with practical recommendations for initial vancomycin dosing that targeted steady-state trough concentrations for patients receiving intermittent infusions and steady-state levels for those receiving continuous infusions between 15 and 20 mg/L. Monte Carlo simulation was used to develop the initial vancomycin dosing recommendations.
The mean (95% confidence interval) pharmacokinetic parameters for vancomycin (elimination rate constant 0.0315 [0.0254–0.0391], half-life 22.0 h [17.72–27.24 h], volume of distribution 0.96 L/kg [0.77–1.20 L/kg], and clearance 2.4 L/h [1.97–2.92 L/h]) indicated that initial intermittent IV dosing of 1.25–1.5 g q24h or 15 mg/kg q24h would be suitable. For continuous infusion, a 1.5-g IV loading dose followed by continuous infusion of 1–1.5 g IV over 24 h (42–62 mg/h) would be recommended. However, Monte Carlo simulation revealed that the probability of achieving desired concentrations between 15 and 20 mg/L with any of these initial regimens is low.
There was considerable variation in vancomycin pharmacokinetics in this patient population. The observations reported here raise concerns about the reliability of numerous empiric dosing recommendations derived from small pharmacokinetic studies in heterogeneous populations. Follow-up therapeutic drug monitoring is essential to ensure that concentrations remain within the target range.
PMCID: PMC2901779  PMID: 22478979
vancomycin; pharmacokinetics; continuous venovenous hemodialysis; vancomycine; pharmacocinétique; hémodialyse veinoveineuse continue
25.  Risk factors for and outcomes associated with clinical isolates of Escherichia coli and Klebsiella species resistant to extended-spectrum cephalosporins among patients admitted to Canadian hospitals 
Clinical features associated with Gram-negative bacterial isolates with extended-spectrum beta-lactamase (ESBL)- and AmpC-mediated resistance identified in Canadian hospitals is largely unknown. The objective of the present study was to determine the demographics, risk factors and outcomes of patients with ESBL- or AmpC-mediated resistant organisms in Canadian hospitals.
Patients with clinical cultures of Escherichia coli or Klebsiella species were matched with patients with a similar organism but susceptible to third-generation cephalosporins. Molecular identification of the AmpC or ESBL was determined using a combination of polymerase chain reaction and sequence analysis. Univariate and multivariate logistic regression analysis was performed to identify variables associated with becoming a case.
Eight Canadian hospitals identified 106 cases (ESBL/AmpC) and 106 controls. All risk factors identified in the univariate analysis as a predictor of being an ESBL/AmpC cases at the 0.20 P-value were included in the multivariate analysis. No significant differences in outcomes were observed (unfavourable responses 17% versus 15% and mortality rates 13% versus 7%, P not significant). Multivariate logistic regression found an association of becoming an ESBL/AmpC case with: previous admission to a nursing home (OR 8.28, P=0.01) or acute care facility (OR 1.96, P=0.03), length of stay before infection (OR 3.05, P=0.004), and previous use of first-generation cephalosporins (OR 2.38, P=0.02) or third-generation cephalosporins (OR 4.52, P=0.01). Appropriate antibiotics were more likely to be given to controls (27.0% versus 13.3%, P=0.05) and number of days to appropriate antibiotics was longer for cases (median 2.8 days versus 1.2 days, P=0.05).
The importance of patient medical history, present admission and antibiotic use should be considered for all E coli or Klebsiella species patients pending susceptibility testing results.
PMCID: PMC2770301  PMID: 20808455
AmpC resistance; Case-control; Extended-spectrum beta-lactamases; Outcomes; Risk factors

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