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Donald E Low

Publications and source records attributed to Donald E Low.

At least 55 records · Page 3Linked to original sources
PubMed2004

Invasive M1T1 group A Streptococcus undergoes a phase-shift in vivo to prevent proteolytic degradation of multiple virulence factors by SpeB.

A globally disseminated strain of M1T1 group A Streptococcus (GAS) has been associated with severe infections in humans including necrotizing fasciitis and toxic shock syndrome. Recent clinicoepidemiologic data showed a striking inverse relationship between disease severity and the degree to which M1T1 GAS express the streptococcal cysteine protease, SpeB. Electrophoretic 2-D gel analysis of the secreted M1T1 proteome, coupled with MALDI-TOF mass spectroscopy, revealed that expression of active SpeB caused the degradation of the vast majority of secreted GAS proteins, including several known virulence factors. Injection of a SpeB+/SpeA- M1T1 GAS strain into a murine subcutanous chamber model of infection selected for a stable phase-shift to a SpeB-/SpeA+ phenotype that expressed a full repertoire of secreted proteins and possessed enhanced lymphocyte-stimulating capacity. The proteome of the SpeB-in vivo phase-shift form closely matched the proteome of an isogenic speB gene deletion mutant of the original M1T1 isolate. The absence or the inactivation of SpeB allowed proteomic identification of proteins in this M1T1 clone that are not present in the previously sequenced M1 genome including SpeA and another bacteriophage-encoded novel streptodornase allele. Further proteomic analysis of the M1T1 SpeB+ and SpeB- phase-shift forms in the presence of a cysteine protease inhibitor demonstrated differences in the expression of several proteins, including the in vivo upregulation of SpeA, which occurred independently of SpeB inactivation.

Animals↗
PubMed2004

Clinical significance of untreated Candida species isolated from ascites in cirrhotic patients.

The clinical significance of Candida species isolated from cirrhotic ascites is still unknown. We reviewed the clinical and laboratory features of all cirrhotic patients whose ascites samples were positive for Candida species. A total of 21 cirrhotic patients was identified. Patients were regarded as having peritonitis if they had 1 or more clinical symptom(s) or sign(s) in the absence of any other possible explanation. 10 patients (47.6%) were classified into the spontaneous Candida peritonitis (SCP) group, and the remaining 11 patients (52.4%) were classified into asymptomatic candidascites. Mortalities were higher in the SCP group at discharge (50.0% vs 27.3%), 6-month (90% vs 45.5%) and 1-y (100% vs 54.5%) (p=0.007). Receiver-operating characteristic curve analysis revealed that the cut-off value of ascitic fluid polymorphonuclear cell count of 315/mm(3) (0.315 x 10(9)/l) had the highest diagnostic accuracy with both sensitivity and specificity of 1.0. In conclusion, Candida species are associated with a grave outcome when manifested with peritonitis.

Adult↗
PubMed2004

Facility-level correlates of antimicrobial use in nursing homes.

We assessed the contribution of facility-level variables to antimicrobial use in a cohort of 50 nursing homes and found that antimicrobial use was significantly correlated with the percentage of nursing home residents with feeding tubes, the number of healthcare aides, and the country of origin of the facility.

Anti-Infective Agents↗
PubMed2004

Severe acute respiratory syndrome: an update.

PURPOSE OF REVIEW: An international outbreak of severe acute respiratory syndrome, a recently recognized syndrome caused by the newly identified severe acute respiratory syndrome-associated coronavirus, began in November 2002 and ended in July 2003. Since then, a large body of research on the syndrome has been published; the most updated developments are summarized here. RECENT FINDINGS: Recent findings suggest that animal severe acute respiratory syndrome-like coronaviruses may have been transmitted to humans without detection for years before the recent outbreak, and that such transmission may be continuing today. The 2002-2003 outbreak probably originated from similar animal-to-human transmission, but selection and purification of the animal severe acute respiratory syndrome-like virus appears to have occurred, creating the more virulent severe acute respiratory syndrome-associated coronavirus. Recent studies have documented that severe acute respiratory syndrome-associated coronavirus is primarily transmitted via contact and/or respiratory droplets and that the combination of standard, contact, and droplet precautions is generally effective for its control. It has been shown that severe acute respiratory syndrome-associated coronavirus is typically relatively inefficiently transmitted, with the notable exception of transmission during superspreading events. Insights into the pathogenesis of severe acute respiratory syndrome have been made: one study suggests that human leukocyte antigen HLA-B*4601 is a possible risk factor for more severe disease, while another identifies angiotensin-converting enzyme 2 as a cellular receptor for severe acute respiratory syndrome-associated coronavirus. Promising treatments have been identified, including interferons, an anti-spike monoclonal antibody, and fusion inhibitors. In addition, many promising vaccines are currently in development. SUMMARY: New findings regarding severe acute respiratory syndrome are continuing to be discovered at an unprecedented pace, permitting a better understanding of the disease and enabling better preparation for its possible return.

China↗
PubMed2004

In vitro antimicrobial susceptibilities of Streptococcus pneumoniae clinical isolates obtained in Canada in 2002.

Empirical treatment is best guided by current surveillance of local resistance patterns. The goal of this study is to characterize the prevalence of antimicrobial nonsusceptibility within pneumococcal isolates from Canada. The Canadian Bacterial Surveillance Network is comprised of laboratories from across Canada. Laboratories collected a defined number of consecutive clinical and all sterile site isolates of S. pneumoniae in 2002. In vitro susceptibility testing was performed by broth microdilution with NCCLS guidelines. Rates of nonsusceptibility were compared to previously published reports from the same network. A total of 2,539 isolates were tested. Penicillin nonsusceptibility increased to 15% (8.5% intermediate, 6.5% resistant) compared to 12.4% in 2000 (P < or = 0.025, chi(2)). Only 32 (1.3%) isolates had an amoxicillin MIC of > or = 4 microg/ml and only 2 of 32 cerebrospinal fluid isolates had an intermediate susceptibility to ceftriaxone by meningeal interpretive criteria (MIC = 1 microg/ml). A total of 354 (13.9%) isolates were macrolide nonsusceptible (46.3% MLS(B), 56.7% M phenotype), increasing from 11.4% in 2000 (P < or = 0.0075, chi(2)). Only 13 (<1%) isolates had a telithromycin MIC of >1 microg/ml. Ciprofloxacin nonsusceptibility (defined as an MIC of > or = 4 microg/ml) increased to 2.7% compared to 1.4% in 2000 (P < or = 0.0025, chi(2)) and was primarily found in persons > or =18 years old (98.5%). Nonsusceptibility to penicillin, macrolides, and fluoroquinolones is increasing in Canada. Nonsusceptibility to amoxicillin and ceftriaxone remains uncommon. Newer antimicrobials such as telithromycin and respiratory fluoroquinolones have excellent in vitro activity.

Adolescent↗
PubMed2004

Use of the Vitek-1 and Vitek-2 systems for detection of constitutive and inducible macrolide resistance in group B streptococci.

A prospective study of erythromycin and clindamycin resistance was performed with 304 consecutive group B streptococci (GBS) isolates. According to two automated susceptibility testing systems, Vitek-1 and Vitek-2, and double-disk agar diffusion, 79.9% were susceptible to both erythromycin and clindamycin. However, for macrolide-lincosamide-streptogramin B-inducible isolates, the accuracies of the Vitek-1 and Vitek-2 systems were 5.6 and 94.4%. In light of these results, we recommend that GBS be routinely tested using the double-disk diffusion method.

Clindamycin↗
PubMed2004

Optimizing antibacterial therapy for community-acquired respiratory tract infections in children in an era of bacterial resistance.

The spread of antibacterial resistance in bacteria that commonly cause childhood community-acquired respiratory tract infections (RTIs), such as acute otitis media, community-acquired pneumonia, and acute pharyngitis, is a major healthcare problem. One of the foremost concerns is the rapid increase in penicillin, macrolide, and multidrug resistance in Streptococcus pneumoniae. There is also a rising prevalence of macrolide resistance in Streptococcus pyogenes in pockets of the United States, and beta-lactamase production in Haemophilus influenzae is widespread. Although data are limited, some evidence suggests that resistance to antibacterials can impair bacteriologic and clinical outcomes in childhood RTIs. Optimizing antibacterial use is important both in the care of individual patients and within strategies to address the wider problem of antibacterial resistance. This involves encouraging judicious antibacterial use (i.e., reducing overuse for viral infection and prophylaxis), and preventing misuse through the wrong choice, dosage, and duration of therapy. Given that initial therapy is usually empiric, antibacterials used to treat community-acquired RTIs in children should ideally have the following properties: an optimal targeted spectrum of activity; high clinical and bacteriologic efficacy against respiratory pathogens, including resistant strains; simple, short-course therapy; and good tolerability and palatability. New antibacterials will continue to have a role in the treatment of RTIs in children, especially where resistance compromises existing therapies.

Acute Disease↗
PubMed2004

Chest radiographic manifestations of severe acute respiratory syndrome in health care workers: the Toronto experience.

OBJECTIVE: The purpose of this article is to describe the chest radiographic manifestations of severe acute respiratory syndrome (SARS) in previously uninfected health care workers during the early stages of an outbreak in Toronto, Canada. CONCLUSION: The study group was composed of 13 patients from a single institution. Three distinct chest radiographic patterns were observed: focal peripheral air-space disease at presentation with gradual resolution (most common pattern, 10/13 patients), normal findings on chest radiography at presentation followed by focal air-space disease (2/13 patients), and normal findings on chest radiography at presentation followed by a "round" pneumonia pattern (1/13 patients). There was no evidence of pleural reaction, lymphadenopathy, or interstitial changes.

Adult↗
PubMed2004

Severe acute respiratory syndrome-associated coronavirus in lung tissue.

Efforts to contain severe acute respiratory syndrome (SARS) have been limited by the lack of a standardized, sensitive, and specific test for SARS-associated coronavirus (CoV). We used a standardized reverse transcription-polymerase chain reaction assay to detect SARS-CoV in lung samples obtained from well-characterized patients who died of SARS and from those who died of other reasons. SARS-CoV was detected in all 22 postmortem lung tissues (to 10(9) viral copies/g) from 11 patients with probable SARS but was not detected in any of the 23 lung control samples (sample analysis was blinded). The sensitivity and specificity (95% confidence interval) were 100% (84.6% to 100%) and 100% (85.1% to 100%), respectively. Viral loads were significantly associated with a shorter course of illness but not with the use of ribavirin or steroids. CoV was consistently identified in the lungs of all patients who died of SARS but not in control patients, supporting a primary role for CoV in deaths.

Adult↗
PubMed2004

Possible SARS coronavirus transmission during cardiopulmonary resuscitation.

Infection of healthcare workers with the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is thought to occur primarily by either contact or large respiratory droplet transmission. However, infrequent healthcare worker infections occurred despite the use of contact and droplet precautions, particularly during certain aerosol-generating medical procedures. We investigated a possible cluster of SARS-CoV infections in healthcare workers who used contact and droplet precautions during attempted cardiopulmonary resuscitation of a SARS patient. Unlike previously reported instances of transmission during aerosol-generating procedures, the index case-patient was unresponsive, and the intubation procedure was performed quickly and without difficulty. However, before intubation, the patient was ventilated with a bag-valve-mask that may have contributed to aerosolization of SARS-CoV. On the basis of the results of this investigation and previous reports of SARS transmission during aerosol-generating procedures, a systematic approach to the problem is outlined, including the use of the following: 1) administrative controls, 2) environmental engineering controls, 3) personal protective equipment, and 4) quality control.

Aerosols↗
PubMed2004

Combining clinical and epidemiologic features for early recognition of SARS.

Early recognition and rapid initiation of infection control precautions are currently the most important strategies for controlling severe acute respiratory syndrome (SARS). No rapid diagnostic tests currently exist that can rule out SARS among patients with febrile respiratory illnesses. Clinical features alone cannot with certainty distinguish SARS from other respiratory illnesses rapidly enough to inform early management decisions. A balanced approach to screening that allows early recognition of SARS without unnecessary isolation of patients with other respiratory illnesses will require clinicians not only to look for suggestive clinical features but also to routinely seek epidemiologic clues suggestive of SARS coronavirus exposure. Key epidemiologic risk factors include 1) exposure to settings where SARS activity is suspected or documented, or 2) in the absence of such exposure, epidemiologic linkage to other persons with pneumonia (i.e., pneumonia clusters), or 3) exposure to healthcare settings. When combined with clinical findings, these epidemiologic features provide a possible strategic framework for early recognition of SARS.

Cluster Analysis↗
PubMed2004

Resistance to antibiotics: administrative response to the challenge.

The authors discuss antibiotic resistance within a conceptual framework that illustrates the dynamic relationships among antibiotic, patient, and population factors. The complexity of these interactions makes it unlikely that any single intervention or approach will adequately address the problem of increasing rates of antibiotic resistance. A case study focused on Streptococcus pneumoniae in the context of community-acquired pneumonia provides a detailed examination of the manner in which antibiotic use, expenditures, and microbial resistance are affected by an administrative reimbursement restriction implemented by a single government payer.

Drug Costs↗
PubMed2003

Modulation of bacterial growth by tumor necrosis factor-alpha in vitro and in vivo.

Tumor necrosis factor-alpha (TNF-alpha) plays an important role in innate immunity. Recent in vitro studies have shown that TNF-alpha may also serve as a growth factor for some bacteria. We examined the physiologic relevance of this phenomenon both in vitro and in vivo. Recombinant mouse TNF-alpha increased in vitro proliferation of Escherichia coli but not Pseudomonas aeruginosa in a concentration-dependent manner, and this effect was attenuated by anti-TNF-alpha antibodies. However, in vivo, TNF-alpha gene-deficient (TNF-alpha-/-) mice showed higher mortality than wild-type (TNF-alpha+/+) mice after inoculation of intranasal bacteria. An impaired bacterial clearance in TNF-alpha-/- mice was associated with decreased systemic concentrations of chemokine macrophage inflammatory protein-2, reduced pulmonary neutrophil recruitment, and depressed expression of neutrophil CD11b and CD16/CD32, suggesting that the effect of TNF-alpha on E. coli growth was outweighed by the recruited neutrophils. We also demonstrated that neutropenic TNF-alpha+/+ mice had approximately 100-fold higher E. coli counts in their lungs than TNF-alpha-/- mice, although survival rates in both groups were similar. We conclude that TNF-alpha augments E. coli growth in vitro and in vivo. However, in vivo, this effect becomes only apparent in neutropenic animals. The relevance of these findings for immune compromised patients remains to be investigated.

Animals↗
PubMed2003

Emergence of levofloxacin-resistant pneumococci in immunocompromised adults after therapy for community-acquired pneumonia.

We describe 4 patients infected with levofloxacin-resistant pneumococci after therapy for community-acquired pneumonia (CAP). The 4 patients had 15 episodes of CAP; Streptococcus pneumoniae was isolated from blood or sputum samples obtained during 14 of the episodes. The underlying medical condition was Bruton agammaglobulinemia in 3 patients and chronic lymphoid leukemia in the other. The initial episode of CAP in each patient was due to a levofloxacin-susceptible strain. One of 4 reinfections and 5 of 6 relapses were due to levofloxacin-resistant strains. All of these strains had amino acid substitutions in the quinolone-resistance-determining region of the genes parC and gyrA. The time between episodes of pneumonia varied from 1 to 4 months. In immunocompromised patients with suspected or proven pneumococcal infection, it may be prudent not to use fluoroquinolone monotherapy empirically when the patient has a history of fluoroquinolone therapy in at least the past 4 months.

Adult↗
PubMed2003

West Nile virus infection in 2002: morbidity and mortality among patients admitted to hospital in southcentral Ontario.

BACKGROUND: In August and September 2002 an outbreak of West Nile virus (WNV) infection occurred in southern Ontario. We encountered a number of seriously ill patients at our hospitals. In this article we document the clinical characteristics of these cases. METHODS: We conducted a retrospective chart review of patients who came to the attention of infectious disease or neurology consultants or the microbiology laboratories at 7 hospitals in the municipalities of Toronto, Peel and Halton, Ont. Patients were included if they had been admitted to hospital or stayed overnight in the emergency department, had serological evidence of WNV infection and had clinical evidence of WNV fever, aseptic meningitis, encephalomyelitis or motor neuronopathy. RESULTS: In all, 64 patients met the inclusion criteria; 57 had encephalitis or neuromuscular weakness or both, 5 had aseptic meningitis, and 2 had WNV fever. The mean age was 61 years (range 26-87). The patients were predominantly active, middle-aged or elderly people living independently in the community. Seven patients were immunocompromised A febrile prodromal illness preceded the neurological symptoms in almost all cases. The most common neurological abnormality was decreased level of consciousness; this frequently evolved to severe lower motor neuron neuromuscular weakness. Ataxia and swallowing disorders were frequent and important problems. Sixteen patients (25%) required intubation and mechanical ventilation because of a decreased level of consciousness, inability to clear secretions or respiratory muscle weakness; 9 others had disabling muscle weakness of one or more limbs. Ten patients died. The study patients were in hospital a total of 1856 patient-days, including 532 patient-days in an intensive care unit. Only 28% (13/47) of the patients who survived encephalitis or neuromuscular weakness, or both, were discharged home without additional support. Slow turnaround time for serological test results resulted in delayed diagnosis. INTERPRETATION: The 2002 WNV infection outbreak in Ontario caused serious morbidity and mortality in the subset of patients who had encephalitis or neuromuscular weakness severe enough to require hospital admission.

Adult↗
PubMed2003

Identification of severe acute respiratory syndrome in Canada.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a condition of unknown cause that has recently been recognized in patients in Asia, North America, and Europe. This report summarizes the initial epidemiologic findings, clinical description, and diagnostic findings that followed the identification of SARS in Canada. METHODS: SARS was first identified in Canada in early March 2003. We collected epidemiologic, clinical, and diagnostic data from each of the first 10 cases prospectively as they were identified. Specimens from all cases were sent to local, provincial, national, and international laboratories for studies to identify an etiologic agent. RESULTS: The patients ranged from 24 to 78 years old; 60 percent were men. Transmission occurred only after close contact. The most common presenting symptoms were fever (in 100 percent of cases) and malaise (in 70 percent), followed by nonproductive cough (in 100 percent) and dyspnea (in 80 percent) associated with infiltrates on chest radiography (in 100 percent). Lymphopenia (in 89 percent of those for whom data were available), elevated lactate dehydrogenase levels (in 80 percent), elevated aspartate aminotransferase levels (in 78 percent), and elevated creatinine kinase levels (in 56 percent) were common. Empirical therapy most commonly included antibiotics, oseltamivir, and intravenous ribavirin. Mechanical ventilation was required in five patients. Three patients died, and five have had clinical improvement. The results of laboratory investigations were negative or not clinically significant except for the amplification of human metapneumovirus from respiratory specimens from five of nine patients and the isolation and amplification of a novel coronavirus from five of nine patients. In four cases both pathogens were isolated. CONCLUSIONS: SARS is a condition associated with substantial morbidity and mortality. It appears to be of viral origin, with patterns suggesting droplet or contact transmission. The role of human metapneumovirus, a novel coronavirus, or both requires further investigation.

Adult↗