Biomedical subjects

Donald E Low

Publications and source records attributed to Donald E Low.

At least 19 recordsLinked to original sources

PubMed2007

High-level telithromycin resistance in a clinical isolate of Streptococcus pneumoniae.

A rare clinical isolate of Streptococcus pneumoniae, highly resistant to telithromycin, contained erm(B) with a truncated leader peptide and a mutant ribosomal protein L4. By transformation of susceptible strains, this study shows that high-level telithromycin resistance is conferred by erm(B), wild type or mutant, in combination with a (69)GTG(71)-to-TPS mutation in ribosomal protein L4.

Anti-Bacterial Agents↗

PubMed2006

Proton pump inhibitors and hospitalization for Clostridium difficile-associated disease: a population-based study.

BACKGROUND: Previous studies have examined the association between proton pump inhibitor (PPI) use and the risk of Clostridium difficile-associated disease (CDAD), with conflicting results. Whether outpatient PPI use influences the risk of hospital admission for CDAD among older patients who have recently been treated with antibiotics is unknown. METHODS: We conducted a population-based, nested case-control study of linked health care databases in Ontario, Canada, from 1 April 2002 through 31 March 2005. We identified patients aged > or = 66 years who were hospitalized for CDAD within 60 days of receiving outpatient antibiotic therapy. Each case patient with CDAD was matched with 10 control subjects on the basis of age, sex, and details of antibiotic use (antibiotic class, timing, and number of antibiotics used). PPI use by case patients and control subjects was categorized as current (within 90 days), recent (91-180 days), or remote (181-365 days). We used conditional logistic regression to estimate the odds ratio for the association between outpatient PPI use and risk of hospitalization for CDAD. RESULTS: We identified 1389 case patients and 12,303 matched control subjects. Case patients were no more likely than control subjects to have received a PPI in the preceding 90 days (adjusted odds ratio, 0.9; 95% confidence interval, 0.8-1.1). Similarly, we found no association between hospitalization for CDAD and more remote use of PPIs. CONCLUSIONS: Among community-dwelling older patients, PPI use is not a risk factor for hospitalization with CDAD.

Aged↗

PubMed2006

Outpatient gatifloxacin therapy and dysglycemia in older adults.

BACKGROUND: Gatifloxacin has been associated with both hypoglycemia and hyperglycemia. We examined dysglycemia-related health outcomes associated with various antibiotics in a population of approximately 1.4 million Ontario, Canada, residents 66 years of age or older. METHODS: We conducted two population-based, nested case-control studies. In the first, case patients were persons treated in the hospital for hypoglycemia after outpatient treatment with a macrolide, a second-generation cephalosporin, or a respiratory fluoroquinolone (gatifloxacin, levofloxacin, moxifloxacin, or ciprofloxacin). In the second, case patients were persons who received hospital care for hyperglycemia. For each case patient, we identified up to five controls matched according to age, sex, the presence or absence of diabetes, and the timing of antibiotic therapy. RESULTS: Between April 2002 and March 2004, we identified 788 patients treated for hypoglycemia within 30 days after antibiotic therapy. As compared with macrolide antibiotics, gatifloxacin was associated with an increased risk of hypoglycemia (adjusted odds ratio, 4.3; 95 percent confidence interval, 2.9 to 6.3). Levofloxacin was also associated with a slightly increased risk (adjusted odds ratio, 1.5; 95 percent confidence interval, 1.2 to 2.0), but no such risk was seen with moxifloxacin, ciprofloxacin, or cephalosporins. We then identified 470 patients treated for hyperglycemia within 30 days after antibiotic therapy. As compared with macrolides, gatifloxacin was associated with a considerably increased risk of hyperglycemia (adjusted odds ratio, 16.7; 95 percent confidence interval, 10.4 to 26.8), but no risk was noted with the other antibiotics. Risks were similar in the two studies regardless of the presence or absence of diabetes. CONCLUSIONS: As compared with the use of other broad-spectrum oral antibiotics, including other fluoroquinolones, the use of gatifloxacin among outpatients is associated with an increased risk of in-hospital treatment for both hypoglycemia and hyperglycemia.

Aged↗

PubMed2006

Outcomes and health-related quality of life after esophagectomy for high-grade dysplasia and intramucosal cancer.

HYPOTHESIS: The reported morbidity and mortality associated with esophagectomy for high-grade dysplasia (HGD) and intramucosal cancer (IMC) have led asymptomatic patients to consider less invasive and possibly less effective treatments. This study provides a critical assessment of outcomes and health-related quality of life (HRQL) after esophagectomy for HGD and IMC. DESIGN: Cohort analytic study. SETTING: Section of thoracic surgery at a tertiary referral center. PATIENTS: All patients who presented between May 1991 and February 2003 with a biopsy-proven diagnosis of Barrett esophagus with HGD or IMC were assessed. MAIN OUTCOME MEASURES: Prospective analysis of postoperative morbidity, mortality, HRQL, and gastrointestinal symptoms. RESULTS: Follow-up was complete in 36 patients. Mean follow-up was 4.9 years (range, 0.5-12.0 years). The incidence of postoperative invasive cancer was 39%, with stages ranging from I to IIB. There were 4 major complications (11%) and no operative mortality. Twenty-eight patients were alive, with a cancer-free survival of 85%. The HRQL outcomes (Medical Outcomes Study 36-Item Short-Form Health Survey) were comparable with those of age- and sex-matched controls. Significant differences in postesophagectomy gastrointestinal symptoms were seen with a decreased incidence of heartburn (P < or = .001) and increased requirement for a slower speed of eating. Twenty-two (79%) of the 28 patients described their current eating pattern as "normal or insignificantly impacted." CONCLUSIONS: Esophagectomy for HGD and IMC can be accomplished with low morbidity and mortality. Furthermore, most patients are able to resume a normal eating pattern, and postoperative HRQL can be equivalent to that of the general population.

Adenocarcinoma↗

PubMed2006

Managing acute lower respiratory tract infections in an era of antibacterial resistance.

Respiratory tract infections account for more than 116 million office visits and an estimated 3 million visits to hospital EDs annually. Patients presenting at EDs with symptoms suggestive of lower respiratory tract infections of suspected bacterial etiology are often severely ill, thus requiring a rapid presumptive diagnosis and empiric antimicrobial treatment. Traditionally, clinicians have relied on beta-lactam or macrolide antibiotics to manage community-acquired lower respiratory tract infections. However, the emerging resistance of Streptococcus pneumoniae to beta-lactams and/or macrolides may affect the clinical efficacy of these agents. Inappropriate use of antibiotics and use of agents with an overly broad spectrum of antimicrobial activity have contributed to the emergence of antibiotic resistance. When treating respiratory infections, clinicians need to prescribe antimicrobial agents only for those individuals with infections of suspected bacterial etiology; to select agents with a targeted spectrum of activity that ensures coverage against typical S pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis strains, including antibiotic-resistant strains and atypical pathogens; and to consider agents with specific chemical properties that limit the development of antimicrobial resistance and that achieve concentrations at sites of infection that exceed those required for bactericidal activity. Newer classes of antimicrobial agents, such as the oxazolidinones and ketolides, will likely play a significant role in this era of antimicrobial resistance.

Acute Disease↗

PubMed2006

Viable group A streptococci in macrophages during acute soft tissue infection.

BACKGROUND: Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells. METHODS AND FINDINGS: We characterized in vivo interactions between group A streptococci (GAS) and cells involved in innate immune responses, using human biopsies (n = 70) collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria. CONCLUSIONS: This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis of streptococcal soft tissue infections highlights a need for alternative therapeutic strategies.

Bacterial Proteins↗

PubMed2006

Morbidity and mortality of patients with invasive group A streptococcal infections admitted to the ICU.

STUDY OBJECTIVES: To describe the clinical features and outcome of patients with invasive group A streptococcal (GAS) infections admitted to the ICU. DESIGN: Prospective, population-based surveillance for invasive GAS infections was conducted in Ontario from January 1992 until June 2002. All 62 patients meeting clinical and/or histopathologic criteria for invasive GAS who were admitted to the ICUs of four university-affiliated hospitals in Toronto, Canada were included. Demographic and clinical information were obtained retrospectively by chart review. ICU morbidity data included the occurrence of organ dysfunction (renal, hepatic, coagulation, ARDS), treatment, and interventions such as hemodialysis and mechanical ventilation. MEASUREMENTS AND RESULTS: ARDS developed in 34%, renal dysfunction developed in 55%, hepatic dysfunction developed in 64%, and coagulopathy developed in 69% of patients. A total of 56% of patients were treated with IV polyspecific IgG (IVIG), 81% were intubated and placed on mechanical ventilation, and 21% required renal replacement therapy. The median durations of ICU and hospital stay were 5.3 days and 15.0 days, respectively. The overall mortality was 40%. Mortality correlated directly with acute physiology and chronic health evaluation II score and the number of dysfunctional organs. Survivors were younger, had lower severity of illness scores, fewer dysfunctional organs, and were less likely to have shock or to receive treatment with vasopressors, mechanical ventilation, or pulmonary artery catheters. There was no association between the use of IVIG, surgical intervention, or clindamycin, and survival. Variables independently associated with mortality on multivariable analysis were the presence of coagulopathy (p = 0.0005) and liver dysfunction (p = 0.0123). CONCLUSIONS: Patients with invasive GAS infection admitted to the ICU have a high mortality rate. In this group of patients, coagulopathy and liver failure were independently associated with mortality. We did not observe any association between the use of IVIG, surgical intervention, or clindamycin, and survival.

APACHE↗

PubMed2006

Triple reassortant H3N2 influenza A viruses, Canada, 2005.

Since January 2005, H3N2 influenza viruses have been isolated from pigs and turkeys throughout Canada and from a swine farmer and pigs on the same farm in Ontario. These are human/classical swine/avian reassortants similar to viruses that emerged in US pigs in 1998 but with a distinct human-lineage neuraminidase gene.

Animals↗

PubMed2005

Changing trends in antimicrobial-resistant pneumococci: it's not all bad news.

In the early 1990s, we witnessed a dramatic and relentless increase in multidrug-resistant pneumococci worldwide. However, there is now evidence of decreasing resistance to some antimicrobials in some regions of the world. This may well be a result of several initiatives to promote the judicious use of antimicrobials, as well as the introduction of the pneumococcal conjugate vaccine, suggesting that the fight against resistance is maybe not futile.

Anti-Bacterial Agents↗

PubMed2005

A review of Streptococcus pneumoniae infection treatment failures associated with fluoroquinolone resistance.

We reviewed all of the published reports of cases of fluoroquinolone treatment failures for respiratory tract infection due to fluoroquinolone-resistant Streptococcus pneumoniae. There were 20 ciprofloxacin and levofloxacin treatment failures reported. Physicians should be aware, when treating pneumococcal respiratory tract infections in older patients with a fluoroquinolone, that clinical failures might occur, especially for patients with comorbid illnesses and a history of recent fluoroquinolone use.

Aged↗

PubMed2005

Predicting antimicrobial resistance in invasive pneumococcal infections.

BACKGROUND: The prevalence of multiantimicrobial resistance among Streptococcus pneumoniae continues to increase worldwide. In patients presenting with infection possibly due to pneumococci, recognition of risk factors that would identify those likely to have an antibiotic-resistant isolate might assist clinicians in choosing the most appropriate empirical therapy. METHODS: A prospective cohort study of invasive pneumococcal infection was conducted in Toronto, Canada. Risk factors for antimicrobial resistance were evaluated by means of univariate and multivariate modeling. RESULTS: A total of 3339 patients with invasive pneumococcal infection were identified between 1995 and 2002. Multivariate modeling revealed that risk factors for infection with penicillin-resistant as opposed to penicillin-susceptible pneumococci were year of infection (odds ratio [OR], 1.28; P < .001), absence of chronic organ system disease (OR, 1.72; P = .03), and previous use of penicillin (OR, 2.47; P = .006), trimethoprim-sulfamethoxazole (TMP-SMX; OR, 5.97; P < .001), and azithromycin (OR, 2.78; P = .05). Infection with TMP-SMX-resistant pneumococci was associated with absence of chronic organ system disease (OR, 1.64; P = .001) and with previous use of penicillin (OR, 1.71; P = .03), TMP-SMX (OR, 4.73; P < .001), and azithromycin (OR, 3.49; P = .001). Infection with macrolide-resistant isolates was associated with previous use of penicillin (OR, 1.77; P = .03), TMP-SMX (OR, 2.07; P = .04), clarithromycin (OR, 3.93; P < .001), and azithromycin (OR, 9.93; P < .001). Infection with fluoroquinolone-resistant pneumococci was associated with previous use of fluoroquinolones (OR, 12.1; P < .001), current residence in a nursing home (OR, 12.9; P < .001), and nosocomial acquisition of pneumococcal infection (OR, 9.94; P = .003). CONCLUSIONS: Knowledge of antimicrobial use during the 3 months before infection is crucial for determining appropriate therapy for a patient presenting to the hospital with an illness for which S. pneumoniae is a possible cause. Nosocomial acquisition and nursing home acquisition are significant risk factors for infection with fluoroquinolone-resistant pneumococci.

Adolescent↗

PubMed2005

Detection of airborne severe acute respiratory syndrome (SARS) coronavirus and environmental contamination in SARS outbreak units.

Severe acute respiratory syndrome (SARS) is characterized by a risk of nosocomial transmission; however, the risk of airborne transmission of SARS is unknown. During the Toronto outbreaks of SARS, we investigated environmental contamination in SARS units, by employing novel air sampling and conventional surface swabbing. Two polymerase chain reaction (PCR)-positive air samples were obtained from a room occupied by a patient with SARS, indicating the presence of the virus in the air of the room. In addition, several PCR-positive swab samples were recovered from frequently touched surfaces in rooms occupied by patients with SARS (a bed table and a television remote control) and in a nurses' station used by staff (a medication refrigerator door). These data provide the first experimental confirmation of viral aerosol generation by a patient with SARS, indicating the possibility of airborne droplet transmission, which emphasizes the need for adequate respiratory protection, as well as for strict surface hygiene practices.

Air Microbiology↗

PubMed2005

Can routine laboratory tests discriminate between severe acute respiratory syndrome and other causes of community-acquired pneumonia?

BACKGROUND: The clinical presentation of severe acute respiratory syndrome (SARS) resembles that of other etiologies of community-acquired pneumonia, making diagnosis difficult. Hematological and biochemical abnormalities, particularly lymphopenia, are common in patients with SARS. METHODS: With the use of 2 databases, we compared the ability of the absolute lymphocyte count, absolute neutrophil count, lactate dehydrogenase level, creatine kinase level, alanine aminotransferase level, and serum calcium level at hospital admission to discriminate between cases of SARS and cases of community-acquired pneumonia. The SARS database contained data for 144 patients with SARS from the 2003 Toronto SARS outbreak. The community-acquired pneumonia database contained data for 8044 patients with community-acquired pneumonia from Edmonton, Canada. Patients from the SARS database were matched to patients from the community-acquired pneumonia database according to age, and receiver operating characteristic curves were constructed for each laboratory variable. RESULTS: The areas under the receiver operating characteristic curves (AUCs) demonstrated fair to poor discriminatory ability for all laboratory variables tested except absolute neutrophil count, which had an AUC of 0.80, indicating good discriminatory ability (although there was no cutoff value of the absolute neutrophil count at which reasonable sensitivity or specificity could be obtained). Combinations of any 2 tests did not perform significantly better than did the absolute neutrophil count alone. CONCLUSIONS: Routine laboratory tests, including determination of absolute lymphocyte count, should not be used in the diagnosis of SARS or incorporated into current case definitions of SARS. The role of the absolute neutrophil count in SARS diagnosis is likely limited, but it should be assessed further.

Alanine Transaminase↗

PubMed2005

Community-associated methicillin-resistant Staphylococcus aureus in horses and humans who work with horses.

OBJECTIVE: To evaluate the prevalence of nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) in horses and horse personnel. DESIGN: Prospective prevalence study. SAMPLE POPULATION: 972 horses and 107 personnel from equine farms in Ontario, Canada and New York state. PROCEDURE: Nasal swab specimens were collected from horses and humans on farms with (targeted surveillance) and without (nontargeted surveillance) a history of MRSA colonization or infection in horses during the preceding year. Selective culture for MRSA was performed. Isolates were typed via pulsed-field gel electrophoresis, and antibiograms were determined. RESULTS: MRSA was isolated from 46 of 972 (4.7%) horses (0/581 via nontargeted surveillance and 46/391 [12%] via targeted surveillance). Similarly, MRSA was isolated from 14 of 107 (13%) humans (2/41 [5%] from nontargeted surveillance and 12/66 [18%] from targeted surveillance). All isolates were subtypes of Canadian epidemic MRSA-5, an uncommon strain in humans. All isolates were resistant to at least 1 antimicrobial class in addition to beta-lactams. On all farms with colonized horses, at least 1 human was colonized with an indistinguishable subtype. For horses, residing on a farm that housed > 20 horses was the only factor significantly associated with MRSA colonization. For humans, regular contact with > 20 horses was the only identified risk factor. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirm a reservoir of colonized horses on a variety of farms in Ontario and New York and provide evidence that 1 MRSA strain is predominantly involved in MRSA colonization in horses and humans that work with horses.

Animals↗

PubMed2005

Open repair of paraesophageal hernia: reassessment of subjective and objective outcomes.

BACKGROUND: Surgical repair of paraesophageal hernias (PEH) remains a challenging operation. Increasing numbers of patients are undergoing laparoscopic repair. This series provides an up-to-date benchmark of the results of open repair of PEH to compare with current laparoscopic series. METHODS: All patients undergoing surgical repair of PEH by a single surgeon between April 1996 and November 2001 were included. Follow-up included postoperative SF-36 survey and objective reassessment (barium swallow or endoscopy) at a mean of 29.8 months. RESULTS: Seventy-two consecutive patients (mean age, 68.7 years) presented with large PEH. Presenting symptoms included heartburn (60%), dysphagia (43%), chest pain (42%), anemia (39%), and dyspnea (32%). Surgical treatment involved transabdominal open repair including sac excision, crural closure (primary closure 98.6%), and antireflux procedure (Hill procedure, 96%; Nissen fundoplication, 4%). No patient required a Collis procedure. Postoperative assessment (subjective, 97%; objective, 88%) was prospective. Median operative length was 155 minutes. Median length of stay was 4.5 days (range, 3 to 12 days). Postoperative complications occurred in 17 of 72 patients (23.6%), but no patient sustained intraoperative or postoperative visceral injuries. In-hospital and 30-day mortality was zero. Heartburn and dysphagia symptom scores demonstrated significant improvement (p < 0.001). Postoperative SF-36 scores demonstrated levels better than the general population (six of eight categories) and better than the age-matched population (eight of eight categories). Objective follow-up demonstrated recurrent hernias in 11 patients (18%). Most of these recurrences (73%) were less than 2-cm sliding hernias, and no patients required revisional surgery. CONCLUSIONS: The results of open repair of PEH have continued to evolve in the same time that has seen the introduction of laparoscopic PEH repairs. Results with the open approach in the modern era can provide excellent outcomes, which are comparable to and in some measures exceed those obtained with the laparoscopic approach.

Aged↗

PubMed2005

Treatment and vaccines for severe acute respiratory syndrome.

The causative agent of severe acute respiratory syndrome (SARS), which affected over 8000 individuals worldwide and was responsible for over 700 deaths in the 2002-2003 outbreak, is a coronavirus that was unknown before the outbreak. Although many different treatments were used during the outbreak, none were implemented in a controlled fashion. Thus, the optimal treatment for SARS is unknown. Since the outbreak, much work has been done testing new agents against SARS using in-vitro methods and animal models. In addition, global research efforts have focused on the development of vaccines against SARS. Efforts should be made to evaluate the most promising treatments and vaccines in controlled clinical trials, should another SARS outbreak occur.

Animals↗

PubMed2005

Screening for asymptomatic bacteriuria in pregnancy.

OBJECTIVE: To compare the following 4 screening strategies for detecting asymptomatic bacteriuria (ABU) in pregnancy: urine testing with leukocyte-esterase-nitrite (LEN) strips at each prenatal visit followed by a urine culture if positive; a single urine culture at fewer than 20 weeks' gestation; 2 urine cultures, at fewer than 20 weeks' gestation and at 28 weeks' gestation; or 3 urine cultures, at fewer than 20 weeks', at 28 weeks', and at 36 weeks' gestation. METHODS: Participants were pregnant women presenting to 2 obstetricians and 6 family physicians at outpatient family medicine and obstetrical clinics in a large Canadian urban teaching hospital. LEN dipstick urine testing was conducted at each prenatal visit. A midstream urine culture was obtained from all women before 20 weeks' gestation and at 28 weeks' and 36 weeks' gestation, as well as for positive LEN tests. Any positive urine culture in an asymptomatic woman was designated a case of ABU. The total number of ABU cases that would be detected by each of the 4 strategies (LEN dipstick testing only, a single urine culture, 2 cultures, and 3 cultures) was determined and compared. RESULTS: There were 49 cases of ABU among 1050 women (4.7%). LEN testing at each prenatal visit identified 7 cases (14.3%), compared with 20 cases (40.8%) with 1 urine culture, 31 (63.3%) with 2 urine cultures, and 43 (87.8%) with 3 urine cultures. CONCLUSION: A single urine culture before 20 weeks' gestation missed more than one-half the ABU cases. A culture in each trimester identified most ABU cases.

Adult↗

PubMed2005

Pulmonary pathology of severe acute respiratory syndrome in Toronto.

The severe acute respiratory syndrome (SARS) pandemic in Toronto resulted in a large number of autopsies on its victims. We describe the pulmonary pathology of patients who died in the 2003 Toronto outbreak. Autopsy material from the lungs of 20 patients who died between March and July 2003 were characterized by histology, molecular biology, and immunohistochemistry for cytokeratins, thyroid transcription factor-1, CD68, Epstein-Barr virus, cytomegalovirus, and human herpes simplex viruses. Matched controls were obtained from patients who died of other causes over the same interval. The mean duration of illness was 27 days (range 5-108 days). Post-mortem lung tissues from 19 of 20 patients with probable SARS were positive for SARS-associated coronavirus by RT-PCR. Histologically, all patients showed varying degrees of exudative and proliferative phase acute lung injury, evidenced in conventional and immunohistochemical stains by edema, inflammatory infiltrate, pneumocyte hyperplasia, fibrinous exudates, and organization. Eight of 20 patients showed predominantly a diffuse alveolar damage pattern of acute lung injury, six showed predominantly an acute fibrinous and organizing pneumonia pattern, and the remainder showed an admixture of the two patterns. Squamous metaplasia and scattered multinucleate giant cells were present in most cases. Vascular fibrin thrombi were a common finding and were often associated with pulmonary infarcts. Special stains demonstrated vascular endothelial damage of both small- and mid-sized pulmonary vessels. Two cases were complicated by invasive fungal disease consistent with Aspergillosis, and another by coinfection with cytomegalovirus. Our findings indicate that the lungs of patients who die of SARS are almost always positive for the SARS-associated coronavirus by RT-PCR, and may show features of both diffuse alveolar damage and acute fibrinous and organizing pneumonia patterns of acute injury. Cases of SARS may be complicated by coexistent infections and therapy-related lung injury.

Adult↗