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Donald E Low

Publications and source records attributed to Donald E Low.

83 records · Page 5Linked to original sources

Clinical aspects and cost of invasive Streptococcus pneumoniae infections in children: resistant vs. susceptible strains.

Invasive Streptococcus pneumoniae infections in children are associated with serious consequences in terms of morbidity and mortality. The main objective of the study was to determine if invasive infections caused by penicillin-resistant Streptococcus pneumoniae (PRSP) differed in clinical presentation, outcome, risk factors, or cost from those caused by penicillin-susceptible strains (PSSP) in children. All patients aged 18 or less with invasive Streptococcus pneumoniae infections admitted to two teaching hospitals in Montreal between 1989 and 1998 were included in the study. We present a case-control study in which for each index case of PRSP, 3 controls with PSSP infections were matched for age, sex, and site of infection. One hundred and forty-four patients were included in the analysis (36 cases, 108 controls). There was no difference between the two groups in terms of initial clinical presentation (vital signs, laboratory results) or total length of stay. Mortality was 2.7% in both groups. Hospital antibiotic cost was higher in the PRSP group (211 Canadian dollars (CAD) vs. 74 CAD; P=0.02). Antibiotic consumption in the preceding month was significantly associated with PRSP infection. Underlying diseases or day-care attendance were not shown to be significant risk factors for acquiring invasive PRSP infection. There were no differences between invasive infections caused by PRSP and PSSP in terms of clinical presentation, morbidity or mortality in a paediatric population.

Adolescent↗

Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in Canada during 2000.

A total of 2,245 clinical isolates of Streptococcus pneumoniae were collected from 63 microbiology laboratories from across Canada during 2000 and characterized at a central laboratory. Of these isolates, 12.4% were not susceptible to penicillin (penicillin MIC, >or=0.12 microg/ml) and 5.8% were resistant (MIC, >or=2 microg/ml). Resistance rates among non-beta-lactam agents were the following: macrolides, 11.1%; clindamycin, 5.7%; chloramphenicol, 2.2%; levofloxacin, 0.9%; gatifloxacin, 0.8%; moxifloxacin, 0.4%; and trimethoprim-sulfamethoxazole, 11.3%. The MICs at which 90% of the isolates were inhibited (MIC90s) of the fluoroquinolones were the following: gemifloxacin, 0.03 microg/ml; BMS-284756, 0.06 microg/ml; moxifloxacin, 0.12 microg/ml; gatifloxacin, 0.25 microg/ml; levofloxacin, 1 microg/ml; and ciprofloxacin, 1 microg/ml. Of 578 isolates from the lower respiratory tract, 21 (3.6%) were inhibited at ciprofloxacin MICs of >or=4 microg/ml. None of the 768 isolates from children were inhibited at ciprofloxacin MICs of >or=4 microg/ml, compared to 3 of 731 (0.6%) from those ages 15 to 64 (all of these >60 years old), and 27 of 707 (3.8%) from those over 65. The MIC90s for ABT-773 and telithromycin were 0.015 microg/ml for macrolide-susceptible isolates and 0.12 and 0.5 microg/ml, respectively, for macrolide-resistant isolates. The MIC of linezolid was <or=2 microg/ml for all isolates. Many of the new antimicrobial agents tested in this study appear to have potential for the treatment of multidrug-resistant strains of pneumococci.

Adolescent↗

Activities of new fluoroquinolones, ketolides, and other antimicrobials against blood culture isolates of viridans group streptococci from across Canada, 2000.

The rates of nonsusceptibility to penicillin, erythromycin, and clindamycin of 191 blood culture isolates of viridans group streptococci collected from across Canada in 2000 were 36, 42, and 10%, respectively. Although 8% of the strains were resistant to ciprofloxacin (MIC >or= 4 microg/ml), the MICs of gemifloxacin, BMS 284756, telithromycin, and ABT 773 at which 90% of the strains were inhibited were 0.06, 0.06, 0.12, and 0.03 microg/ml, respectively.

Anti-Bacterial Agents↗

Identification of a streptolysin S-associated gene cluster and its role in the pathogenesis of Streptococcus iniae disease.

Streptococcus iniae causes meningoencephalitis and death in cultured fish species and soft-tissue infection in humans. We recently reported that S. iniae is responsible for local tissue necrosis and bacteremia in a murine subcutaneous infection model. The ability to cause bacteremia in this model is associated with a genetic profile unique to strains responsible for disease in fish and humans (J. D. Fuller, D. J. Bast, V. Nizet, D. E. Low, and J. C. S. de Azavedo, Infect. Immun. 69:1994-2000, 2001). S. iniae produces a cytolysin that confers a hemolytic phenotype on blood agar media. In this study, we characterized the genomic region responsible for S. iniae cytolysin production and assessed its contribution to virulence. Transposon (Tn917) mutant libraries of commensal and disease-associated S. iniae strains were generated and screened for loss of hemolytic activity. Analysis of two nonhemolytic mutants identified a chromosomal locus comprising 9 genes with 73% homology to the group A streptococcus (GAS) sag operon for streptolysin S (SLS) biosynthesis. Confirmation that the S. iniae cytolysin is a functional homologue of SLS was achieved by PCR ligation mutagenesis, complementation of an SLS-negative GAS mutant, and use of the SLS inhibitor trypan blue. SLS-negative sagB mutants were compared to their wild-type S. iniae parent strains in the murine model and in human whole-blood killing assays. These studies demonstrated that S. iniae SLS expression is required for local tissue necrosis but does not contribute to the establishment of bacteremia or to resistance to phagocytic clearance.

Amino Acid Sequence↗

Postgenomic analysis of four novel antigens of group a streptococcus: growth phase-dependent gene transcription and human serologic response.

Analysis of three group A Streptococcus genomes (serotypes M1, M3, and M18) recently identified four previously undescribed genes that encode extracellular proteins. Each of these genes encode proteins with an LPXTG amino acid motif that covalently links many virulence factors produced by gram-positive bacteria to the cell surface. Western immunoblot analysis of serum samples obtained from 80 patients with invasive infections, noninvasive soft tissue infections, pharyngitis, and rheumatic fever indicated that these four proteins are expressed in vivo. However, the level of gene transcript and the time of maximal gene transcription varied in representative serotype M1, M3, and M18 strains. Surface expression of two proteins was confirmed by flow cytometry. Studies using a mouse infection model suggest that antibodies specific for one of the proteins (Spy0843) may contribute to a protective host immune response against a serotype M1 infection. These results are additional evidence that postgenomic strategies provide new ways to identify and investigate novel bacterial proteins that may participate in host-pathogen interactions or serve as targets for therapeutics research.

Animals↗

Effect on antibiotic prescribing of repeated clinical prompts to use a sore throat score: lessons from a failed community intervention study.

OBJECTIVES: Infections with group A streptococcus (GAS) occur in 10% to 20% of patients with sore throats, whereas antibiotics are prescribed 50% of the time. Clinical scoring rules can more accurately predict the likelihood of GAS infection, but whether family physicians will adopt such approaches is unclear. This study sought to determine whether repeated clinical prompts to use a scoring approach could help family physicians lower antibiotic use in patients with a sore throat. STUDY DESIGN: Randomized trial in which physicians were assigned to use either (1) chart stickers that prompted them to calculate a score based on clinical findings and provided management recommendations linked to score totals or (2) a clinical checklist. POPULATION: Ninety-seven family physicians in Ontario, Canada, assessed 621 children and adults with sore throat and obtained a throat swab for culture. OUTCOMES MEASURED: (1) Unnecessary antibiotic prescriptions given to patients with a negative throat culture and (2) overall antibiotic use. RESULTS: There were no differences between the control and intervention group in unnecessary antibiotic prescriptions (16.1% vs 20.4%, respectively, P =.29) or overall antibiotic use (27.9% vs 28.1%, P =.97). However, a number of physicians dropped out of the study; as a result, the characteristics of the physicians in the 2 groups were dissimilar in factors related to prescribing. After adjusting for these differences and patient clustering by physician, the odds ratio for the effect of the intervention on unnecessary antibiotic prescriptions was 0.76 (95% confidence interval [CI] = 0.42, 1.40) and 0.57 for overall antibiotic use (95% CI = 0.27, 1.17). CONCLUSIONS: Chart prompts during clinical encounters to use a clinical score in the assessment of patients with a sore throat did not reduce unnecessary antibiotic prescribing by family physicians. The problems encountered in conducting this community-based intervention trial are discussed in relation to the negative result.

Adult↗

Near-total esophagectomy: the influence of standardized multimodal management and intraoperative fluid restriction.

BACKGROUND AND OBJECTIVES: Esophagectomy can be associated with high morbidity and mortality. We present our experience managing these patients using a standardized multimodal approach that emphasizes intraoperative fluid restriction and early extubation. METHODS: This case series includes 56 consecutive patients over a 2-year period (1999-2000) that underwent near-total esophagectomy at a high-volume center. Surgical approach was determined by patient and tumor characteristics; intraoperative fluid replacement was conservative; and patient-controlled epidural anesthesia/analgesia was used to promote early extubation, enteral feeding, and ambulation. RESULTS: Overall morbidity was 18%; in-hospital and 30-day mortality was zero. Intraoperative urinary volume averaged 0.57 mL/kg/h. No patient developed postoperative renal dysfunction or pulmonary complications. All patients were extubated in the operating room. First ambulation averaged 1.6 days after surgery. Median intensive care unit and hospital stays were 1 and 10 days, respectively. Side effects from thoracic epidural analgesia were minimal. CONCLUSIONS: Significant reduction in esophagectomy-related morbidity is possible using a standardized multimodal approach in routine clinical practice. Intraoperative fluid restriction may facilitate early extubation and reduce pulmonary complications without compromising renal function. This preliminary observation warrants further study in a randomized clinical trial.

Adolescent↗

Canadian guidelines for the management of acute exacerbations of chronic bronchitis.

Acute exacerbations of chronic bronchitis (AECB) account for over 1.5 million physician visits annually in Canada and are a cause of significant morbidity and mortality. This document represents a joint effort between respirologists, microbiologists, infectious disease specialists and family physicians to update the Canadian AECB guidelines published in 1994. Treatment recommendations are graded on the strength of evidence in the published literature where possible. The role for oral corticosteroid therapy in preventing treatment failures, speeding up recovery and delaying the time to next exacerbation is discussed. Risk factors for treatment failure were used to stratify patients into risk groups to help guide antibiotic treatment recommendations. The importance of emerging antimicrobial resistance to current antibiotics is reviewed and strategies to prevent future AECB episodes are suggested.

Adrenal Cortex Hormones↗