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ABT-761 attenuates bronchoconstriction and pulmonary inflammation in rodents.

https://arctichealth.org/en/permalink/ahliterature15808
Source
J Pharmacol Exp Ther. 1997 Mar;280(3):1366-73
Publication Type
Article
Date
Mar-1997
Author
R L Bell
R R Harris
P E Malo
J B Bouska
T K Shaughnessy
K I Hulkower
C D Brooks
G W Carter
Author Affiliation
Immunosciences Research Area, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Source
J Pharmacol Exp Ther. 1997 Mar;280(3):1366-73
Date
Mar-1997
Language
English
Publication Type
Article
Keywords
Animals
Arachidonate 5-Lipoxygenase - antagonists & inhibitors
Bronchoconstriction - drug effects
Enzyme Inhibitors - pharmacology - therapeutic use
Eosinophils - pathology
Guinea Pigs
Humans
Hydroxyurea - analogs & derivatives - pharmacology - therapeutic use
In Vitro
Leukotriene E4 - antagonists & inhibitors
Macaca fascicularis
Male
Mice
Muscle Contraction - drug effects
Pneumonia - drug therapy - pathology
Rats
Abstract
Our primary goal has been to discover leukotriene biosynthesis inhibitors with characteristics that are appropriate for use as clinical agents. The success of the use of zileuton in the treatment of asthma led us to explore further the use of the N-hydroxyurea class of 5-lipoxygenase inhibitors as longer-acting compounds with good lung penetration. A variety of in vitro and in vivo methods were used to evaluate a large number of compounds, from which ABT-761 [(R)-N-(3-(5-(4-fluorophenylmethyl)thien-2-yl)-1-methyl-2-pr opynyl)-N-hydroxyurea] was selected for study. ABT-761 exhibited potent and selective inhibition of leukotriene formation both in vitro and in vivo. More importantly, the compound potently inhibited antigen-induced bronchospasm in guinea pigs when given either prophylactically or therapeutically. In addition, ABT-761 was a potent inhibitor of eosinophil influx into the lungs of Brown Norway rats. These data provide added support for the role of leukotrienes in both bronchospasm and eosinophilic inflammation and characterize ABT-761 as a particularly potent inhibitor of leukotrienes formed in pulmonary tissues. These data combined with the excellent pharmacokinetic characteristics of the compound indicate its potential use in the treatment of leukotriene-dependent human disease.
PubMed ID
9067325 View in PubMed
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Adherence to antibiotic guidelines for pneumonia in chronic-care facilities in Ontario.

https://arctichealth.org/en/permalink/ahliterature192097
Source
Clin Invest Med. 2001 Dec;24(6):304-10
Publication Type
Article
Date
Dec-2001
Author
M. Loeb
A E Simor
L. Landry
A. McGeer
Author Affiliation
Division of Medical Microbiology and Infectious Diseases, McMaster University and the Hamilton Regional Laboratory Program, Ont. loebm@mcmaster.ca
Source
Clin Invest Med. 2001 Dec;24(6):304-10
Date
Dec-2001
Language
English
Publication Type
Article
Keywords
Aged
Anti-Bacterial Agents - therapeutic use
Chronic Disease
Cohort Studies
Female
Humans
Long-Term Care
Male
Ontario - epidemiology
Pneumonia - drug therapy - mortality - radiography
Practice Guidelines as Topic
Prospective Studies
Treatment Outcome
Abstract
To evaluate adherence to antibiotic recommendations for the treatment of pneumonia in patients who receive long-term care and to assess outcomes associated with these recommendations.
A prospective cohort study.
Twenty-two facilities that provide long-term care in southern Ontario.
Older adults treated with antibiotics for a presumptive diagnosis of pneumonia and those with radiologically confirmed pneumonia
Over a 12-month period, older patients who were treated with antibiotics for presumptive pneumonia were prospectively identified. A random sample of these antibiotic courses (646 courses in 638 patients) was reviewed using a standardized data collection form, and demographic and clinical data were collected. Antibiotic courses were classified according to Canadian and American Thoracic Society antibiotic recommendations for pneumonia. In patients with radiologically confirmed pneumonia, the effect of adherence to these recommendations on mortality and persistence of symptoms was assessed.
Only 27.6% (178 of 646) of antibiotic prescriptions evaluated met antibiotic recommendations for nursing-home-acquired pneumonia, and the proportion meeting these varied greatly by facility, ranging from 0% to 53% (median 31%). For patients with radiologically confirmed pneumonia, age (adjusted odds ratio [OR] 1.6, 95% confidence interval [CI] 1.0-2.4, per increase in 10 yr, p = 0.02), sex (adjusted OR 3.0, 95% CI 1.1-8.0, p = 0.03), and adherence to recommended antibiotics (OR 3.0, 95% CI 1.3-7.2, p = 0.01) were associated with death. Adherence to the recommended antibiotics was also associated with adverse reactions, which occurred in 10% of prescriptions meeting the recommendations (OR 2.4, 95% CI 1.3-4.6, p = 0.01).
Adherence to recommended guidelines for antibiotic treatment was low and highly variable among study facilities. Use of recommended antibiotic regimens was associated with increased adverse events and worse outcomes in patients with radiologically confirmed pneumonia.
Notes
Comment In: Clin Invest Med. 2002 Jun;25(3):63-4; author reply 6412137250
PubMed ID
11767234 View in PubMed
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[Agreement between clinical practice guidelines for management of community-acquired pneumonia. A retrospective study of 101 hospitalized patients].

https://arctichealth.org/en/permalink/ahliterature181855
Source
Rev Mal Respir. 2003 Dec;20(6 Pt 1):858-70
Publication Type
Article
Date
Dec-2003
Author
J. Labarère
M. Fourny
P. Pavese
P. Bedouch
C. Brambilla
P. François
Author Affiliation
Unité d'Evaluation Médicale, Centre Hospitalier Universitaire de Grenoble, Grenoble, France. jlabarere@chu-grenoble.fr
Source
Rev Mal Respir. 2003 Dec;20(6 Pt 1):858-70
Date
Dec-2003
Language
French
Publication Type
Article
Keywords
Acute Disease
Aged
Anti-Bacterial Agents - therapeutic use
Canada
Community-Acquired Infections - drug therapy
Consensus
Europe
Female
Hospitalization
Humans
Male
Middle Aged
Pneumonia - drug therapy
Practice Guidelines as Topic
Retrospective Studies
United States
Abstract
Management guidelines for acute community acquired pneumonia vary considerably. The objective is to estimate by a retrospective study the uniformity of the recommendations for the management of patients and the choice of initial empirical antibiotic therapy.
Eight English and French language guidelines published between 1998 and 2001 were identified by a search of the literature. They were applied retrospectively to a sample of 101 patients admitted to a university hospital in 2000 with a diagnosis of pneumonia.
Hospital admission was advocated for between 61% and 95% and admission to intensive care for between 8% and 35% of the patients, depending on the guidelines under consideration. The actual management conformed to that advocated for between 34% and 94% of the patients (kappa=0.27 [0,19; 0,34]). Compliance of the empirical antibiotic therapy (drug, dose, mode of administration) with the recommendations varied from 0% to 68% of the patients depending on the guidelines considered (kappa=0.01 [-0,10; 0,12]).
The heterogeneity of the guidelines is manifest by important variations in the recommendations for management and initial empirical therapy. These differences are due, in part, to a paucity of evidence based data upon which to base the guidelines. It would appear essential to harmonise the guidelines in a way that is appropriate for the country of their intended use.
Notes
Comment In: Rev Mal Respir. 2003 Dec;20(6 Pt 1):841-314743083
PubMed ID
14743087 View in PubMed
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[Analysis of the efficiency of treatment and causes of death in nosocomial pneumonia in the Republic of Tatarstan].

https://arctichealth.org/en/permalink/ahliterature186845
Source
Probl Tuberk. 2002;(7):26-30
Publication Type
Article
Date
2002
Author
A A Gil'manov
A A Vizel'
I Iu Malysheva
M Sh Sorokina
R S Sadykova
A A Buniatian
Source
Probl Tuberk. 2002;(7):26-30
Date
2002
Language
Russian
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Anti-Bacterial Agents - therapeutic use
Cause of Death
Child
Cross Infection - drug therapy - epidemiology - mortality
Female
Hospitalization
Humans
Male
Middle Aged
Pneumonia - drug therapy - epidemiology - mortality
Russia - epidemiology
Socioeconomic Factors
Time Factors
Abstract
A comprehensive study was undertaken to examine morbidity due nosocomial pneumonia. An epidemiological survey demonstrated a growth in morbidity and mortality from this disease among the adult population of the Republic of Tatarstan. Pharmacological and epidemiological survey indicated that antibacterial therapy was in conformity with the federal protocols in 43.9% of cases, revealed the optimization of the use of antibacterial agents after introduction of the federal standards. At the same time the low social status of patients dying from pneumonia was accompanied by their appeal for medical aid, which leads to late hospitalization and untimely intensive therapy.
PubMed ID
12561638 View in PubMed
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An audit and feedback intervention study increased adherence to antibiotic prescribing guidelines at a Norwegian hospital.

https://arctichealth.org/en/permalink/ahliterature276521
Source
BMC Infect Dis. 2016;16:96
Publication Type
Article
Date
2016
Author
June Utnes Høgli
Beate Hennie Garcia
Frode Skjold
Vegard Skogen
Lars Småbrekke
Source
BMC Infect Dis. 2016;16:96
Date
2016
Language
English
Publication Type
Article
Keywords
Aged
Anti-Bacterial Agents - therapeutic use
Community-Acquired Infections - drug therapy
Disease Progression
Female
Formative Feedback
Guideline Adherence - statistics & numerical data
Hospitals, University - standards - statistics & numerical data
Humans
Inappropriate Prescribing - prevention & control - statistics & numerical data
Male
Medical Audit
Norway
Pneumonia - drug therapy
Practice Guidelines as Topic
Practice Patterns, Physicians' - statistics & numerical data
Pulmonary Disease, Chronic Obstructive - drug therapy
Retrospective Studies
Abstract
Appropriate antibiotic prescribing is associated with favourable levels of antimicrobial resistance (AMR) and clinical outcomes. Most intervention studies on antibiotic prescribing originate from settings with high level of AMR. In a Norwegian hospital setting with low level of AMR, the literature on interventions for promoting guideline-recommended antibiotic prescribing in hospital is scarce and requested. Preliminary studies have shown improvement potentials regarding antibiotic prescribing according to guidelines. We aimed to promote appropriate antibiotic prescribing in patients with community-acquired pneumonia (CAP) and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) at a respiratory medicine department in a Norwegian University hospital. Our specific objectives were to increase prescribing of appropriate empirical antibiotics, reduce high-dose benzylpenicillin and reduce total treatment duration.
We performed an audit and feedback intervention study, combined with distribution of a recently published pocket version of the national clinical practice guideline. We included patients discharged with CAP or AECOPD and prescribed antibiotics during hospital stay, and excluded those presenting with aspiration, nosocomial infection and co-infections. The pre- and post-intervention period was 9 and 6 months, respectively. Feedback was provided orally to the department physicians at an internal-educational meeting. To explore the effect of the intervention on appropriate empirical antibiotics and mean total treatment duration we applied before-after analysis (Student's t-test) and interrupted time series (ITS). We used Pearson's ?2 to compare dose changes.
In the pre-and post-intervention period we included 253 and 155 patients, respectively. Following the intervention, overall mean prescribing of appropriate empirical antibiotics increased from 61.7 to 83.8 % (P
Notes
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PubMed ID
26920549 View in PubMed
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Antibiotic management of pneumococcal infections in an era of increased resistance.

https://arctichealth.org/en/permalink/ahliterature207780
Source
J Paediatr Child Health. 1997 Aug;33(4):287-95
Publication Type
Article
Date
Aug-1997
Author
K. Grimwood
P J Collignon
B J Currie
M J Ferson
G L Gilbert
G G Hogg
D. Isaacs
P B McIntyre
Author Affiliation
Australasian Society for Infectious Diseases, Sydney, New South Wales, Australia.
Source
J Paediatr Child Health. 1997 Aug;33(4):287-95
Date
Aug-1997
Language
English
Publication Type
Article
Keywords
Anti-Bacterial Agents - pharmacology - therapeutic use
Child
Child, Preschool
Drug Resistance, Microbial
Drug Resistance, Multiple
Humans
Infant
Lactams
Meningitis - drug therapy
Microbial Sensitivity Tests
Otitis Media - drug therapy
Penicillin resistance
Penicillins - pharmacology - therapeutic use
Pneumococcal Infections - drug therapy - epidemiology
Pneumonia - drug therapy
Prevalence
Prognosis
Species Specificity
Streptococcus pneumoniae - drug effects
Abstract
Pneumococci are a leading cause of bacterial meningitis and bacteraemia, as well as pneumonia, otitis media and sinusitis in childhood. These organisms recently have shown a dramatic increase in antibiotic resistance. Penicillin-resistant pneumococci are of special concern as they are often resistant to other unrelated antibiotics. This is of particular significance to Aboriginal children who have among the highest rates of pneumococcal infection in the world. Laboratories should now test all invasive pneumococcal isolates for penicillin and third generation cephalosporin resistance. Local treatment guidelines are required for pneumococcal infections, especially for meningitis, taking into account the prevalence of resistant strains within the community. At present, penicillin and amoxycillin remain the drugs of choice for pneumococcal infections, with the exception of meningitis where initial empirical therapy must be with a third generation cephalosporin. Judicious antibiotic use, which avoids over-prescribing and unnecessary use of broad-spectrum agents, improved living standards in underprivileged communities and introduction of an effective conjugate vaccine, able to reduce the rates of pneumococcal infection and hopefully colonization, may limit the spread of resistant strains.
PubMed ID
9323614 View in PubMed
Less detail

Benzylpenicillin versus wide-spectrum beta-lactam antibiotics as empirical treatment of Haemophilus influenzae-associated lower respiratory tract infections in adults; a retrospective propensity score-matched study.

https://arctichealth.org/en/permalink/ahliterature297898
Source
Eur J Clin Microbiol Infect Dis. 2018 Sep; 37(9):1761-1775
Publication Type
Comparative Study
Journal Article
Date
Sep-2018
Author
John Thegerström
Viktor Månsson
Kristian Riesbeck
Fredrik Resman
Author Affiliation
Riesbeck laboratory, Clinical Microbiology, Department of Translational Medicine, Faculty of Medicine, Lund University, Jan Waldenströms gata 59, SE-205 02, Malmö, Sweden. john.thegerstrom@med.lu.se.
Source
Eur J Clin Microbiol Infect Dis. 2018 Sep; 37(9):1761-1775
Date
Sep-2018
Language
English
Publication Type
Comparative Study
Journal Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Anti-Bacterial Agents - administration & dosage - therapeutic use
Bacteremia - drug therapy - microbiology
Child
Child, Preschool
Community-Acquired Infections - drug therapy - epidemiology - microbiology - mortality
Female
Haemophilus Infections - drug therapy - epidemiology - microbiology - mortality
Haemophilus influenzae - drug effects
Hospitalization
Humans
Infant
Infant, Newborn
Male
Microbial Sensitivity Tests
Middle Aged
Penicillin G - administration & dosage - therapeutic use
Pneumonia - drug therapy - microbiology
Propensity Score
Respiratory Tract Infections - drug therapy - microbiology
Retrospective Studies
Sweden - epidemiology
Young Adult
beta-Lactams - administration & dosage - therapeutic use
Abstract
There is consensus that definitive therapy for infections with H. influenzae should include antimicrobial agents with clinical breakpoints against the bacterium. In Scandinavia, benzylpenicillin is the recommended empirical treatment for community-acquired pneumonia (CAP) except in very severe cases. However, the effect of benzylpenicillin on H. influenzae infections has been debated. The aim of this study was to compare the outcomes of patients given benzylpenicillin with patients given wide-spectrum beta-lactams (WSBL) as empirical treatment of lower respiratory tract H. influenzae infections requiring hospital care. We identified 481 adults hospitalized with lower respiratory tract infection by H. influenzae, bacteremic and non-bacteremic. Overall, 30-day mortality was 9% (42/481). Thirty-day mortality, 30-day readmission rates, and early clinical response rates were compared in patients receiving benzylpenicillin (n?=?199) and a WSBL (n?=?213) as empirical monotherapy. After adjusting for potential confounders, empirical benzylpenicillin treatment was not associated with higher 30-day mortality neither in a multivariate logistic regression (aOR 2.03 for WSBL compared to benzylpenicillin, 95% CI 0.91-4.50, p?=?0.082), nor in a propensity score-matched analysis (aOR 2.14, 95% CI 0.93-4.92, p?=?0.075). Readmission rates did not significantly differ between the study groups, but early clinical response rates were significantly higher in the WSBL group (aOR 2.28, 95% CI 1.21-4.31, p?=?0.011), albeit still high in both groups (84 vs 81%). In conclusion, despite early clinical response rates being slightly lower for benzylpenicillin compared to WSBL, we found no support for increased mortality or readmission rates in patients empirically treated with benzylpenicillin for lower respiratory tract infections by H. influenzae.
PubMed ID
29961165 View in PubMed
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68 records – page 1 of 7.