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Biomedical subjects

D E Low

Publications and source records attributed to D E Low.

At least 19 recordsLinked to original sources
PubMed2002

Antibiotic therapy of community respiratory tract infections: strategies for optimal outcomes and minimized resistance emergence.

Widespread, increasing antibiotic resistance amongst the major respiratory pathogens has compromised traditional therapy of the major infective respiratory syndromes, including bacterial pneumonia and acute exacerbations of chronic bronchitis. Guidelines for antibiotic prescribing dating from the 1980s to 1990s, which attempted to address such problems, were commonly too prescriptive and difficult to apply, and took little account of end-user practice or locally prevalent resistance levels. Further confusion was caused by conflicting recommendations emanating from differing specialty groups. The evidence that such guidelines benefited either clinical outcomes or treatment costs has been disputed. They have probably had little effect on resistance emergence. We report the recommendations of an independent, multi-national, inter-disciplinary group, which met to identify principles underlying prescribing and guideline formulation in an age of increasing bacterial resistance. Unnecessary prescribing was recognized as the major factor in influencing resistance and costs. Antibiotic therapy must be limited to syndromes in which bacterial infection is the predominant cause and should attempt maximal reduction in bacterial load, with the ultimate aim of bacterial eradication. It should be appropriate in type and context of local resistance prevalence, and optimal in dosage for the pathogen(s) involved. Prescribing should be based on pharmacodynamic principles that predict efficacy, bacterial eradication and prevention of resistance emergence. Pharmacoeconomic analyses confirm that bacteriologically more effective antibiotics can reduce overall management costs, particularly with respect to consequential morbidity and hospital admission. Application of these principles should positively benefit therapeutic outcomes, resistance avoidance and management costs and will more accurately guide antibiotic choices by both individuals and formulary/guideline committees.

Community-Acquired Infections↗
PubMed2002

Genotypic characterization of macrolide-resistant strains of Streptococcus pneumoniae isolated in Quebec, Canada, and in vitro activity of ABT-773 and telithromycin.

Increasing resistance of Streptococcus pneumoniae to macrolides represents a challenge for clinicians. New ketolides have an enhanced activity against macrolide-resistant strains. Four hundred and seventy-four strains of S. pneumoniae were collected during the 2000-2001 season in Quebec through a surveillance network. Macrolide resistance was 20.2%, and significantly higher in non-invasive strains versus invasive ones (22.4% versus 14.8%), and in children (30%) versus adults (14.8%). For susceptible strains, MIC(90)s of ABT-773 and telithromycin were 0.008 and 0.015 mg/L. Among the 96 macrolide-resistant strains, 56 (58%) were erm(B), 35 (37%) carried the mef(A) gene, four were carrying both genes and one none. ABT-773 and telithromycin were very active against all these resistant strains irrespective of the resistance mechanism, with MIC(90)s of 0.25 and 0.5 mg/L, respectively.

Adolescent↗
PubMed2002

Activity of BMS-284756, a novel des-fluoro(6) quinolone, against Staphylococcus aureus, including contributions of mutations to quinolone resistance.

The in vitro activity of BMS-284756 against 602 Staphylococcus aureus isolates, including 152 that were both methicillin and ciprofloxacin resistant (MIC > or = 4 microg/ml), was determined. For ciprofloxacin-susceptible and nonsusceptible isolates, the MICs at which 50% of organisms were inhibited were 0.015 and 2 microg/ml and the MICs at which 90% of organisms were inhibited were 0.03 and 4 microg/ml, respectively.

Amino Acid Substitution↗
PubMed2002

Laboratory contamination of specimens with quality control strains of vancomycin-resistant enterococci in Ontario.

Cross-contamination with laboratory control strains of vancomycin-resistant Enterococcus faecalis was documented in 15 clinical specimens from nine clinical microbiology laboratories in Ontario, Canada. Laboratories should be alert to the possibility of contamination of specimens with vancomycin-resistant enterococci from the laboratory environment. Molecular typing of strains may assist in elucidating the source of such contamination.

DNA, Bacterial↗
PubMed2001

Antimicrobial drug use and resistance among respiratory pathogens in the community.

There is substantial evidence that the overuse of antibiotics is a major cause for the emergence of resistance in respiratory pathogens in the community. However, it is also recognized that the mechanisms of resistance, the cost of resistance to the fitness of the organism, and the ability of the resistant strain to disseminate are all important contributors to this problem. Therefore, when developing strategies to control and/or prevent the emergence of resistance, health care professionals must take each of these factors into consideration. As we enter a new era in the use of fluoroquinolones for the treatment of respiratory tract infections, we have an opportunity to apply such lessons learned in the past to minimize or prevent the development of resistance to this class of antimicrobial drugs in the future.

Anti-Bacterial Agents↗
PubMed2001

Evidence for superantigen involvement in severe group a streptococcal tissue infections.

Host-pathogen interactions were studied in tissue biopsy samples from patients with severe invasive group A streptococcus (GAS) infections. Skin, subcutaneous tissue, and fascia biopsy samples were divided into clinical grade 1 (no evidence of inflammation [n=7]) or clinical grade 2 (inflamed tissue--erythema and edema including cellulitis, fasciitis, and necrotizing fasciitis [n=24]). In situ imaging demonstrated significantly higher bacterial load in biopsy samples of higher clinical grade (P<.05), and the bacterial load correlated with the in vivo expression of the superantigen streptococcal pyrogenic exotoxin F (P<.02). Increased expression of the interleukin-1 cytokines and significantly higher expression of tumor necrosis factor-beta, interferon-gamma, and the homing receptors CC chemokine receptor 5, CD44, and cutaneous lymphocyte-associated antigen (P<.002-.05) were observed in biopsy samples of higher clinical grade. Thus, the cytokine profile at the local site of infection mimics that of a typical superantigen cytokine response. The findings of this study demonstrate a critical role for superantigens and Th1 cytokines in GAS tissue infections.

Bacterial Proteins↗
PubMed2001

A nosocomial outbreak of fluoroquinolone-resistant Streptococcus pneumoniae.

Over the course of a 20-month period, in a hospital respiratory ward in which ciprofloxacin was often used as empirical antimicrobial therapy for lower respiratory tract infections (LRTIs), 16 patients with chronic bronchitis developed nosocomial LRTIs caused by penicillin- and ciprofloxacin-resistant Streptococcus pneumoniae (serotype 23 F). The minimum inhibitory concentration (MIC) of ciprofloxacin for all isolates from the first 9 patients was 4 microg/mL, in association with a parC mutation. Isolates from the subsequent 7 patients all had a ciprofloxacin MIC of 16 microg/mL, in association with an additional mutation in gyrA. The MICs for this isolate were 8 microg/mL of levofloxacin (resistant), 2 microg/mL of moxifloxacin and gatifloxacin (intermediately resistant), and 0.12 microg/mL of gemifloxacin. This outbreak demonstrates the ability of S. pneumoniae to acquire multiple mutations that result in increasing levels of resistance to the fluoroquinolones and to be transmitted from person to person.

Aged↗
PubMed2001

Clinical prevalence, antimicrobial susceptibility, and geographic resistance patterns of enterococci: results from the SENTRY Antimicrobial Surveillance Program, 1997-1999.

As part of the SENTRY Antimicrobial Resistance Surveillance Program, a total of 4998 strains of enterococci isolated from 1997 to 1999 were processed. The occurrence of enterococcal infections by species and site of infection was analyzed, as were the occurrence of vancomycin-resistant enterococci (VRE) and their resistance phenotypes and genotypes. Trends in antimicrobial susceptibility to a variety of agents (including experimental compounds) were also reported. Enterococci accounted for >9% of isolates from all bloodstream infections (BSIs) in North America. Ampicillin was active against strains from Latin America and Europe but not against those from the United States and Canada. US isolates were considerably more resistant to vancomycin (17% resistant strains in 1999) than were those from patients in the rest of the world. The highest proportion of VRE was observed among BSI isolates (81.7%). Quinupristin-dalfopristin, chloramphenicol, and doxycycline were the most active agents tested against VRE. The results of this study confirm the worldwide trend in increasing occurrence of enterococci and the emerging pattern of antimicrobial resistance among such isolates.

Anti-Bacterial Agents↗
PubMed2001

Physicians' prevention practices and incidence of neonatal group B streptococcal disease in 2 Canadian regions.

BACKGROUND: The impact of expert guidelines on the prevention of neonatal group B streptococcal (GBS) disease has not been studied in Canada. Our aim was to determine physician practices with regard to this condition before and after publication of Canadian guidelines and to monitor concurrent trends in the incidence of neonatal GBS disease. METHODS: We used repeat cross-sectional surveys, distributed by mail to all family practitioners and obstetricians attending deliveries in Alberta and in the Metropolitan Toronto and Peel region, Ontario, in 1994, 1995 and 1997, to document prevention practices. Audits were conducted for a subset of respondents to confirm reported practices. Population-based surveillance involving all microbiology laboratories in both regions for 1995-1998 was used to document rates of neonatal disease. RESULTS: The overall survey response rates were as follows: for 1994, 1128/1458 (77%); for 1995, 1054/1450 (73%); and for 1997, 1030/1421 (72%). During 1995 and 1997, significantly more obstetric care providers were screening at least 75% of pregnant women in their practices than had been the case in 1994 (747/916 [82%] and 693/812 [85%] v. 754/981 [77%]; p < 0.001). The percentage of obstetric care providers who reported practice that conformed completely with any of 3 consensus prevention strategies increased from 10% in 1994 to 29% in 1997 (p < 0.001). There was a concurrent overall significant decrease in incidence of neonatal GBS disease during the same period. INTERPRETATION: The adoption by Canadian obstetric care providers of neonatal GBS prevention practices recommended by expert groups was slow but improved significantly over time. These findings highlight the difficulties associated with achieving compliance with diverse and frequently changing recommendations. However, the associated incidence of neonatal GBS disease, which was low or declining, suggests that efforts to disseminate current GBS prevention guidelines have been moderately successful.

Alberta↗
PubMed2001

A prospective evaluation of dietary status and symptoms after near-total esophagectomy without gastric emptying procedure.

BACKGROUND: After esophagectomy, the stomach is the most commonly utilized reconstructive conduit. There remains debate among surgeons regarding the requirements for pyloroplasty/pyloromyotomy following reconstruction. We present a series of patients having undergone near total esophagectomy and reconstruction with gastric tube without gastric emptying procedure to analyze critically these patients' ability to reestablish a subjectively acceptable and nutritionally adequate eating pattern without significant side effects of early satiety, dumping, or diarrhea. METHODS: Between 1991 and 1998, 48 patients underwent esophagectomy utilizing this technique and were available for long-term follow-up and nutritional assessment. Patient weights were recorded at 2 weeks, 6 months, and 1 year and a telephone interview conducted at a mean of 36 months postoperatively for the evaluation of eating patterns and symptoms. A subgroup of these patients (32 of 48) completed a 3-day dietary record that was assessed by a certified nutritionist. This patient group included 10 patients (21%) who had received perioperative chemoradiotherapy. RESULTS: Dietary intake was characterized as normal or minimally limited in 41 patients (85%). Those who had received perioperative chemoradiotherapy needed no significant increased time to return to a normal dietary baseline (6.1 versus 5.9 months). Mean weight loss prior to surgery was 3 kg. Weight loss continued for the first 6 months (mean 10 kg); however, 63% were able to gain weight from 6 months to 1 year following surgery (mean 3 kg). Most patients were overweight prior to operation (mean 115% of ideal body weight) and achieved a new postoperative baseline (mean 104% of ideal body weight) at 1 year. Patients demonstrated a mean daily caloric intake of 2,179 kilocalories per day, which was 98% of recommended according to their ideal body weight. Postoperative symptoms of short-term nausea (19%), occasional dysphagia with certain foods (38%), mild increased stool frequency (15%), and occasional regurgitation (25%) were noted. CONCLUSIONS: Near-total esophagectomy with verticalized gastric tube without a gastric emptying procedure is well tolerated and allows a return to subjectively acceptable and nutritionally appropriate dietary eating pattern without significant associated side effects.

Adult↗
PubMed2001

The spectrum of electrophysiological abnormalities in Bell's palsy.

BACKGROUND: As part of an investigation of a suspected "outbreak" of Bell's palsy in the Greater Toronto Area, a population-based sample of patients with Bell's palsy was investigated electrophysiologically to help understand the spectrum of abnormalities that can be seen in this setting. METHODS: Two hundred and twenty-four patients were surveyed, of whom 91 underwent formal neurological assessment. Of the latter, 44 were studied electrophysiologically using standard techniques. Thirty-two of the 44 patients fulfilled clinical criteria for Bell's palsy. RESULTS: A wide range of electrophysiological changes was observed. Blink responses were the most useful test showing diagnostic sensitivity of 81% and specificity of 94% compared to the contralateral control side. Needle electromyography was additionally helpful in only one patient of six with normal conduction studies. CONCLUSIONS: There is a wide spectrum of electrophysiological abnormalities in Bell's palsy. Blink reflex latencies may be under-utilized in the assessment of the facial nerve in Bell's palsy. Facial EMG is not generally useful in routine assessment.

Adolescent↗
PubMed2001

Evasion of human innate and acquired immunity by a bacterial homolog of CD11b that inhibits opsonophagocytosis.

Microbial pathogens must evade the human immune system to survive, disseminate and cause disease. By proteome analysis of the bacterium Group A Streptococcus (GAS), we identified a secreted protein with homology to the alpha-subunit of Mac-1, a leukocyte beta2 integrin required for innate immunity to invading microbes. The GAS Mac-1-like protein (Mac) was secreted by most pathogenic strains, produced in log-phase and controlled by the covR-covS two-component gene regulatory system, which also regulates transcription of other GAS virulence factors. Patients with GAS infection had titers of antibody specific to Mac that correlated with the course of disease, demonstrating that Mac was produced in vivo. Mac bound to CD16 (FcgammaRIIIB) on the surface of human polymorphonuclear leukocytes and inhibited opsonophagocytosis and production of reactive oxygen species, which resulted in significantly decreased pathogen killing. Thus, by mimicking a host-cell receptor required for an innate immune response, the GAS Mac protein inhibits professional phagocyte function by a novel strategy that enhances pathogen survival, establishment of infection and dissemination.

Acute Disease↗
PubMed2001

Direct esophageal metastasis from a distant primary tumor is a submucosal process: a review of six cases.

Malignant esophageal stricture secondary to invasion from a tumor arising in a contiguous organ is a relatively rare finding; even more uncommon is a direct metastasis to the esophagus from a distant primary carcinoma. We present six cases, the largest current series, of esophageal strictures secondary to metastases from a separate primary cancer. We reviewed the records of 20 patients treated at Virginia Mason Medical Center between 1972 and 2000 with a diagnosis of malignant esophageal stricture secondary to an extraesophageal primary carcinoma. Patients whose stricture appeared to be secondary to esophageal invasion or compression from a contiguous tumor or lymph nodes were excluded. The remaining six patients who had metastases to the esophagus itself were reviewed with respect to the nature of the primary tumor, presentation, radiologic and endoscopic findings, and treatment. Among the 20 patients reviewed, 14 were excluded owing to either contiguous involvement from a nearby primary malignancy, regional nodal involvement, or complications of external beam radiation treatment. Six patients were considered to have direct metastasis to the esophagus from distant primary malignancies. The mean age of these patients was 72 years (range 68-74). Two of the primary lesions were lung carcinoma, while four primaries were breast cancers. The average time interval from the diagnosis of a primary tumor to esophageal involvement was 7 years in patients with breast cancer and 5 months in patients with lung cancer. Three patients were palliated with endoscopic dilation and stent placement. The other three patients have died secondary to upper gastrointestinal bleeding. Metastatic cancer to the esophagus is a rare occurrence. The process is usually submucosal and can be difficult to diagnose. The diagnosis should be considered when a patient presents with malignant dysphagia and has a background of distant carcinoma.

Adenocarcinoma↗
PubMed2001

Phenotypic and genotypic characterization of macrolide-resistant group A Streptococcus strains in the province of Quebec, Canada.

Resistance to macrolides among group A streptococci is an increasing problem worldwide. We examined 496 strains phenotypically and genotypically for resistance to erythromycin and clindamycin. Strains were isolated in five different geographical areas representing about 45% of the total Quebec population. The overall resistance rate was 4.6% but varied from 0% in rural areas to 9.4% in Montreal. Of the 23 strains showing resistance to erythromycin, 15 (65%) had an identical pulsed-field gel electrophoresis pattern, were of serotype M28T28 and harboured the erm(TR) gene, suggesting the spread of a single clone. Of the remaining eight strains, two strains had the erm(B) gene, five had the mef gene and one with a different serotype also had the erm(TR) gene.

Anti-Bacterial Agents↗
PubMed2001

In vitro activity of a novel ketolide ABT-773 against invasive strains of Streptococcus pneumoniae.

New ketolides such as ABT-773 are a promising group of antibiotics in an era of increasing antibiotic resistance. We tested 704 invasive strains of Streptococcus pneumoniae collected from 1990 to 1998. Overall resistance was 8.3, 4.6, 4.5 and 3.6% for penicillin, cefuroxime, erythromycin and clarithromycin, respectively. By using a recommended breakpoint for susceptibility of <0.5 mg/L, no strains showed reduced susceptibility to ABT-773. ABT-773 was very active against all penicillin-resistant strains (MIC > 2 mg/L, with a mean geometric mean <0.06 mg/L), and against all 33 erythromycin-resistant strains, irrespective of the mode of resistance [mef- or erm(B)-mediated]. ABT-773 is a very active and promising agent against invasive strains of S. pneumoniae, including multiresistant strains.

Anti-Bacterial Agents↗
PubMed2001

Prevalence and mechanisms of macrolide resistance in invasive and noninvasive group B streptococcus isolates from Ontario, Canada.

Macrolide resistance has been demonstrated in group B streptococcus (GBS), but there is limited information regarding mechanisms of resistance and their prevalence. We determined these in GBS obtained from neonatal blood cultures and vaginal swabs from pregnant women. Of 178 isolates from cases of neonatal GBS sepsis collected from 1995 to 1998, 8 and 4.5% were resistant to erythromycin and clindamycin, respectively, and one isolate showed intermediate penicillin resistance (MIC, 0.25 microg/ml). Of 101 consecutive vaginal or rectal/vaginal isolates collected in 1999, 18 and 8% were resistant to erythromycin and clindamycin, respectively. Tetracycline resistance was high (>80%) among both groups of isolates. Of 32 erythromycin-resistant isolates, 28 possessed the erm methylase gene (7 ermB and 21 ermTR/ermA) and 4 harbored the mefA gene; one isolate harbored both genes. One isolate which was susceptible to erythromycin but resistant to clindamycin (MIC, 4 microg/ml) was found to have the linB gene, previously identified only in Enterococcus faecium. The mreA gene was found in all the erythromycin-resistant strains as well as in 10 erythromycin-susceptible strains. The rate of erythromycin resistance increased from 5% in 1995-96 to 13% in 1998-99, which coincided with an increase in macrolide usage during that time.

Adult↗