PubMed Health⌕ Search

Biomedical subjects

Karl Weiss

Publications and source records attributed to Karl Weiss.

17 recordsLinked to original sources
PubMed2006

Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile-associated diarrhea.

BACKGROUND: Current antibiotic therapies for Clostridium difficile-associated diarrhea have limitations, including progression to severe disease, recurrent C. difficile-associated diarrhea, and selection for nosocomial pathogens. Tolevamer, a soluble, high-molecular weight, anionic polymer that binds C. difficile toxins A and B is a unique nonantibiotic treatment option. METHODS: In this 3-arm, multicenter, randomized, double-blind, active-controlled, parallel-design phase II study, patients with mild to moderately severe C. difficile-associated diarrhea were randomized to receive 3 g of tolevamer per day (n = 97), 6 g of tolevamer per day (n = 95), or 500 mg of vancomycin per day (n = 97). The primary efficacy parameter was time to resolution of diarrhea, defined as the first day of 2 consecutive days when the patient had hard or formed stools (any number) or < or = 2 stools of loose or watery consistency. RESULTS: In the per-protocol study population, resolution of diarrhea was achieved in 48 (67%) of 72 patients receiving 3 g of tolevamer per day (median time to resolution of diarrhea, 4.0 days; 95% confidence interval, 2.0-6.0 days), in 58 (83%) of 70 patients receiving 6 g of tolevamer per day (median time to resolution of diarrhea, 2.5 days; 95% confidence interval, 2.0-3.0 days), and in 73 (91%) of 80 patients receiving vancomycin (median time to resolution of diarrhea, 2.0 days; 95% confidence interval, 1.0-3.0 days). Tolevamer administered at a dosage of 6 g per day was found to be noninferior to vancomycin administered at a dosage of 500 mg per day with regard to time to resolution of diarrhea (P = .02) and was associated with a trend toward a lower recurrence rate. Tolevamer was well tolerated but was associated with an increased risk of hypokalemia. CONCLUSIONS: Tolevamer, a novel polystyrene binder of C. difficile toxins A and B, effectively treats mild to moderate C. difficile diarrhea and merits further clinical development.

Adult↗
PubMed2006

VanG-type vancomycin-resistant Enterococcus faecalis strains isolated in Canada.

Enterococcus faecalis G1-0247 (vancomycin MIC, 16 microg/ml) was found to harbor a vanG operon 99% identical to the vanG operon in E. faecalis BM4518. E. faecalis N03-0233 (vancomycin MIC, 16 microg/ml) was found to harbor a novel vanG operon, vanG2, on an element in a different chromosomal location than the vanG-harboring elements in G1-0247 and BM4518.

Anti-Bacterial Agents↗
PubMed2005

Molecular characteristics of pbp1a and pbp2b in clinical Streptococcus pneumoniae isolates in Quebec, Canada.

OBJECTIVES: To investigate the nature of the amino acid motifs found in penicillin-binding protein (PBP) 2b and PBP1a of penicillin-resistant Streptococcus pneumoniae isolates across Quebec (Canada), and to obtain preliminary information regarding the prevalence of these alterations. METHODS: DNA sequences of pbp2b (codons 210-675) and pbp1a (codons 310-682) transpeptidase domains were determined and compared in 48 clinical isolates comprising 17 penicillin-susceptible (PSSP), 19 penicillin-intermediate (PISP) and 12 penicillin-resistant (PRSP) pneumococci. RESULTS: The degree of diversity within PBP1a and PBP2b correlated with increased resistance to beta-lactam antibiotics. There were an average of 0.6 +/- 0.4 and 2.9 +/- 0.2 mutations in PSSP, 16.8 +/- 1.4 and 36.3 +/- 5.2 in PISP, and 18.7 +/- 2.5 and 51.4 +/- 1.3 in PRSP isolates compared with control penicillin-susceptible R6-PBP2b and R6-PBP1a sequences, respectively. At least seven PBP2b and six PBP1a distinct amino acid profiles were identified among intermediate or resistant strains isolated in Quebec. The pattern of distribution of the PBPs' altered amino acids differs from that of other countries, with pneumococci isolates from Quebec showing a unique genetic signature. CONCLUSION: This study will serve as a basis for future monitoring of genetic changes associated with the emergence and spread of beta-lactam resistance in Quebec, Canada.

Adolescent↗
PubMed2005

Genetic analysis of pbp2x in clinical Streptococcus pneumoniae isolates in Quebec, Canada.

OBJECTIVES: To investigate the nature of the amino acid motifs found in penicillin-binding protein (PBP) 2x of penicillin-resistant Streptococcus pneumoniae isolates across the province of Quebec (Canada), and to obtain preliminary information regarding the prevalence of these alterations. METHODS: The pbp2x genomic region encompassing codons 178-703, which includes the entire region of the transpeptidase domain, was sequenced and compared for 52 clinical isolates comprising 20 penicillin-susceptible (PSSP), 20 penicillin-intermediate (PISP) and 12 penicillin-resistant (PRSP) pneumococci. RESULTS: The degree of diversity within PBP2x correlated with increased resistance to beta-lactam antibiotics. There were an average of 5.0 +/- 1.8 mutations in PSSP, 37.9 +/- 4.4 in PISP, and 63.0 +/- 2.0 in PRSP isolates when compared with the control penicillin-susceptible strain R6. At least six distinct amino acid profiles were identified among PISP strains isolated in Quebec. In contrast, all PRSP isolates shared a similar pattern of altered amino acids compared with the sequence from susceptible strains. CONCLUSIONS: These data will be useful in future studies to monitor the genetic changes associated with the emergence and spread of beta-lactam resistance in Quebec.

Amino Acid Sequence↗
PubMed2005

A proteomic analysis of penicillin resistance in Streptococcus pneumoniae reveals a novel role for PstS, a subunit of the phosphate ABC transporter.

Resistance to penicillin is widespread in the Gram-positive bacterium Streptococcus pneumoniae, and while several mutations are known to be implicated in resistance other mechanisms are likely to occur. We used a proteomic screen of two independent mutants in which resistance was selected in vitro. We found a number of differentially expressed proteins including PstS, a subunit of the phosphate ABC transporter of S. pneumoniae. This protein was increased in both mutants, a phenotype correlated to increased RNA expression of the entire phosphate ABC transporter operon. Inactivation of the pstS gene led to increased susceptibility to penicillin in the wild-type strain. To further link the expression of the ABC phosphate transporter with penicillin resistance, we looked at pstS mRNA levels in 12 independent clinical isolates sensitive and resistant to penicillin and found an excellent correlation between resistance and increased expression of pstS. Inactivation of pstS in one of the clinical isolates significantly reduced penicillin resistance. Global approaches are ideally suited for the discovery of novel factors in the biology of resistance.

ATP-Binding Cassette Transporters↗
PubMed2005

The controversy of combination vs monotherapy in the treatment of hospitalized community-acquired pneumonia.

BACKGROUND: The majority of community-acquired pneumonia (CAP) patients (about 80%) will be treated as outpatients, because therapy with a single agent will work. For the remaining 20% of patients requiring hospitalization, there is some growing debate regarding the efficacy of different management approaches. For hospitalized patients, monotherapy with a respiratory fluoroquinolone agent seems to be gaining popularity, but dual therapy combining a beta-lactam and an advanced macrolide still represents a good choice. Indeed, this regimen was recommended for all of the inpatient categories in the latest Infectious Disease Society of America CAP guidelines in 2003. AIM: The purpose of this review was to examine the current clinical evidence to support one option or the other by gathering all of the available published literature. We will review the existing controversies in terms of microbiology, immunology, and clinical outcomes comparing dual therapy (ie, with any combination of beta-lactams, macrolides, or fluoroquinolones) with monotherapy in the treatment of CAP. RESULTS: For the vast majority of patients with CAP (ie, outpatients and inpatients on medical wards), the type of antibiotic regimen prescribed does not have any significant impact. For patients with severe pneumonia, for which there is no accepted definition so far, the controversy remains alive. Mortality from pneumococcal pneumonia has been reduced over the last decades, but despite improved medical care, bacteremic pneumococcal pneumonia is still as lethal as ever, probably because of the aging population, the greater number of immunocompromised patients, and the number of patients with frequent comorbid conditions. Worldwide, the increasing rates of resistance of Streptococcus pneumoniae to antibiotics are also a serious concern, and the clinical implications are not always obvious. Although limited in number, the four studies showing the importance of adding a macrolide to a beta-lactam regimen for the treatment of bacteremic S pneumoniae pneumonia are retrospective and nonblinded, the findings are consistent, and they point to a trend that has to be explored more thoroughly. Studies published in the last few years suggest that combination therapy may be superior for bacteremic S pneumoniae pneumonia. CONCLUSION: In the meantime, for practical purposes, patients hospitalized with a diagnosis of severe CAP may benefit from a dual antibiotic therapy combining a third-generation cephalosporin and a macrolide. For the majority of hospitalized patients with CAP who are not severely ill, fluoroquinolone monotherapy remains an approved, tested, and reliable option. Indeed, the time for more aggressive outpatient fluoroquinolone therapy may reduce the number of patients who are hospitalized with CAP. Independent prospective studies comparing combination therapy with standard monotherapy are urgently required for hospitalized patients with severe CAP.

Anti-Bacterial Agents↗
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↗
PubMed2002

An open-label, randomized, multicenter, comparative study of the efficacy and safety of 7 days of treatment with clarithromycin extended-release tablets versus clarithromycin immediate-release tablets for the treatment of patients with acute bacterial exacerbation of chronic bronchitis.

OBJECTIVE: The aim of this study was to compare the efficacy and safety of clarithromycin extended-release (ER) tablets and immediate-release (IR) tablets. METHODS: This was a Phase III, open-label, randomized, multicenter, comparative study in ambulatory patients with a diagnosis of acute exacerbation of chronic bronchitis (AECB). Eligible patients were randomized 1:1 to receive either 1 clarithromycin ER 500-mg tablet QD for 7 days or 1 clarithromycin IR 250-mg tablet BID for 7 days. Clinical and bacteriologic responses were assessed within 48 hours after the last dose of study drug and at a test-of-cure visit 21 +/- 2 days posttreatment. RESULTS: Of 233 patients randomized, 162 (86/117 [73.5%] in the ER group and 76/115 [66.1%] in the IR group) completed the study protocol. Compliance did not differ significantly between the treatment groups; however, significantly fewer patients in the ER group reported missing doses of study medication than in the IR group (7/118 [5.9%] vs 16/115 [13.9%]; P = 0.04). The clinical cure rates for the clarithromycin ER and IR groups were 81.0% (68/84) and 82.1% (64/78) and the clinical success (clinical cure plus clinical improvement) rates were 94.0% [79/84] and 89.7% [70/78], respectively. There were insufficient data for analysis of bacteriologic efficacy. However, bacteria were eradicated or presumed eradicated in 71.4% (10/14) and 79.2% (19/24) of patients in the ER and IR groups, respectively. The number of adverse events (AEs) considered to be possibly or probably related to study drug (23.4% [52/222] of patients receiving clarithromycin ER and 24.4% [43/176] of patients receiving clarithromycin IR) was similar between groups, as was the severity of these events (94.2% [49/52] in the ER group classified as mild or moderate vs 93.0% [40/43] in the IR group). Overall, the most commonly reported AEs were diarrhea, nausea, abdominal pain, headache, and taste disturbance. CONCLUSION: Clarithromycin ER 500-mg tablets QD for 7 days were as effective and well tolerated as clarithromycin IR 250-mg tablets BID for 7 days in treating adults with AECB.

Adult↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

Acute bacterial sinusitis in adults: management in the primary care setting.

Sinus disease is inherently associated with viral upper respiratory tract infections and occurs in 90% of individuals with the common cold. Acute bacterial sinusitis occurs in 0.5 to 2% of these individuals. Although the diagnosis of acute bacterial sinusitis is usually based on physical findings, no one sign or symptom is either sensitive or specific for sinusitis. The predictive power can be significantly improved when all signs and symptoms are combined into a clinical impression. Imaging studies have not been shown to be cost effective in the initial assessment and treatment of patients in the primary care setting. Simple plain films may be indicated to resolve the diagnosis in patients with an equivocal history or to follow patients admitted to hospital with severe sinus disease. The initial management of acute sinusitis should be directed toward the relief of symptoms with a 7-day course of decongestants and mucoevacuents. For patients who fail to improve with symptomatic treatment, a 10-day course of amoxicillin is recommended. Second line antibiotics should be initiated if improvement is not seen within 72 to 96 hours.

Adult↗
PubMedDate not supplied

State of the Art Compendium: Canadian Thoracic Society recommendations for the management of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common cause of disability and death in Canada. Moreover, morbidity and mortality from COPD continue to rise, and the economic burden is enormous. The main goal of the Canadian Thoracic Society's evidence-based guidelines is to optimize early diagnosis, prevention and management of COPD in Canada. The main message of the guidelines is that COPD is a preventable and treatable disease. Targeted spirometry is strongly recommended to expedite early diagnosis in smokers and former smokers who develop respiratory symptoms, and who are at risk for COPD. Smoking cessation remains the single most effective intervention to reduce the risk of COPD and to slow its progression. Education, especially self-management plans, are key interventions in COPD. Therapy should be escalated on an individual basis in accordance with the increasing severity of symptoms and disability. Long-acting anticholinergics and beta-2-agonist inhalers should be prescribed for patients who remain symptomatic despite short-acting bronchodilator therapy. Inhaled steroids should not be used as first line therapy in COPD, but have a role in preventing exacerbations in patients with more advanced disease who suffer recurrent exacerbations. Acute exacerbations of COPD cause significant morbidity and mortality and should be treated promptly with bronchodilators and a short course of oral steroids; antibiotics should be prescribed for purulent exacerbations. Patients with advanced COPD and respiratory failure require a comprehensive management plan that incorporates structured end-of-life care. Management strategies, consisting of combined modern pharmacotherapy and nonpharmacotherapeutic interventions (eg, pulmonary rehabilitation and exercise training) can effectively improve symptoms, activity levels and quality of life, even in patients with severe COPD.

Canada↗