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Antimicrobial Agents and Chemotherapy May 2014A systematic review and meta-analyses were performed to identify the risk factors associated with carbapenem-resistant Pseudomonas aeruginosa and to identify sources and... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analyses were performed to identify the risk factors associated with carbapenem-resistant Pseudomonas aeruginosa and to identify sources and reservoirs for the pathogen. A systematic search of PubMed and Embase databases from 1 January 1987 until 27 January 2012 identified 1,662 articles, 53 of which were included in a systematic review and 38 in a random-effects meta-analysis study. The use of carbapenem, use of fluoroquinolones, use of vancomycin, use of other antibiotics, having medical devices, intensive care unit (ICU) admission, having underlying diseases, patient characteristics, and length of hospital stay were significant risk factors in multivariate analyses. The meta-analyses showed that carbapenem use (odds ratio [OR] = 7.09; 95% confidence interval [CI] = 5.43 to 9.25) and medical devices (OR = 5.11; 95% CI = 3.55 to 7.37) generated the highest pooled estimates. Cumulative meta-analyses showed that the pooled estimate of carbapenem use was stable and that the pooled estimate of the risk factor "having medical devices" increased with time. We conclude that our results highlight the importance of antibiotic stewardship and the thoughtful use of medical devices in helping prevent outbreaks of carbapenem-resistant P. aeruginosa.
Topics: Anti-Bacterial Agents; Carbapenems; Drug Resistance, Bacterial; Pseudomonas aeruginosa; Risk Factors
PubMed: 24550343
DOI: 10.1128/AAC.01758-13 -
Journal of Cystic Fibrosis : Official... Sep 2014A systematic literature review of the last 40 years on the research of serum antibodies to Pseudomonas aeruginosa in cystic fibrosis and its utility as a diagnostic tool. (Review)
Review
BACKGROUND
A systematic literature review of the last 40 years on the research of serum antibodies to Pseudomonas aeruginosa in cystic fibrosis and its utility as a diagnostic tool.
METHODS
Research papers in English, Portuguese, and Spanish were accessed through electronic databases (PubMed, Medline, LILACS, and SciELO).
RESULTS
26 studies were assessed. ELISA technique was the most commonly used technique to detect serum P. aeruginosa antibodies. The most consistent results were those in which the response against the antigen St-Ag:1-17 was evaluated. The accuracy levels of the ELISA technique remain controversial, but most studies showed a good correlation between antibody titers and microbiological culture.
CONCLUSIONS
The detection of serum antibodies to P. aeruginosa shows capacity for early detection of this pathogen and potential utility and viability of incorporation in the diagnostic routine of patients with cystic fibrosis.
Topics: Antibodies, Bacterial; Cystic Fibrosis; Enzyme-Linked Immunosorbent Assay; Humans; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 24522086
DOI: 10.1016/j.jcf.2014.01.005 -
European Respiratory Review : An... Dec 2013This systematic review evaluated evidence for two dry powder formulations, colistimethate sodium and tobramycin, for the treatment of chronic Pseudomonas aeruginosa in... (Review)
Review
This systematic review evaluated evidence for two dry powder formulations, colistimethate sodium and tobramycin, for the treatment of chronic Pseudomonas aeruginosa in cystic fibrosis, as part of the UK national recommendation process for new technologies. Electronic bibliographic databases were searched in May 2012 (MEDLINE, MEDLINE in-Process, EMBASE, Cochrane Library databases, CINAHL, Web of Science, Conference Proceedings Citation Index and BIOSIS Previews). Relevant outcomes included rate and extent of microbial response (e.g. sputum density of P. aeruginosa), lung function (e.g. forced expiratory volume in 1 s (FEV1)), frequency, severity of acute exacerbations and adverse events. Three trials were included, and both dry powder formulations were reported to be non-inferior in the short term to nebulised tobramycin for FEV1. However, long-term follow-up data were missing and the effect on exacerbation rates was not always reported. Whilst short-term results showed that both dry powder drugs were non-inferior to nebulised tobramycin, there was no long-term follow-up and no phase 3 trials compared nebulised and dry powder colistimethate sodium. The use of FEV1 as the primary end-point may not accurately represent changes in lung health. This review illustrates the difficulty in assessing new technologies where the evidence base is poor.
Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Cystic Fibrosis; Disease Progression; Dry Powder Inhalers; Evidence-Based Medicine; Forced Expiratory Volume; Humans; Lung; Powders; Pseudomonas Infections; Pseudomonas aeruginosa; Research Design; Time Factors; Tobramycin; Treatment Outcome
PubMed: 24293463
DOI: 10.1183/09059180.00001513 -
Health Technology Assessment... Dec 2013Cystic fibrosis (CF) is an inherited condition characterised by the abnormal transport of chloride ions across transporting epithelia. This leads to the production of... (Review)
Review
Colistimethate sodium powder and tobramycin powder for inhalation for the treatment of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis: systematic review and economic model.
BACKGROUND
Cystic fibrosis (CF) is an inherited condition characterised by the abnormal transport of chloride ions across transporting epithelia. This leads to the production of thick sticky mucus in the lungs, pancreas, liver, intestine and reproductive tract, and an increase in the salt content in sweat. Among other problems, people with CF experience recurrent respiratory infections and have difficulties digesting food. CF affects over 9000 individuals in the UK. CF shortens life expectancy and adversely affects quality of life. In 2010, CF was recorded as the cause of 103 deaths in England and Wales.
OBJECTIVE
To evaluate the clinical effectiveness and cost-effectiveness of colistimethate sodium dry powder for inhalation (DPI) (Colobreathe(®), Forest Laboratories) and tobramycin DPI (TOBI Podhaler(®), Novartis Pharmaceuticals) for the treatment of Pseudomonas aeruginosa lung infection in CF.
DATA SOURCES
Electronic databases were searched in February and March 2011 [MEDLINE, MEDLINE In-Process & Other Non-Indexed citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Conference Proceedings Citation Index (CPCI) and Bioscience Information Service (BIOSIS) Previews]. Relevant databases were searched for ongoing and unpublished studies, and bibliographies of relevant systematic reviews and the manufacturers' submissions were also hand-searched.
REVIEW METHODS
A systematic review of the clinical effectiveness and cost-effectiveness of colistimethate sodium DPI and tobramycin DPI for the treatment of chronic P. aeruginosa lung infection in CF was conducted. Existing economic evidence within the literature was reviewed and a de novo health economic model was also developed.
RESULTS
Three randomised controlled trials (RCTs) were included in the clinical effectiveness review. Both colistimethate sodium DPI and tobramycin DPI were reported to be non-inferior to nebulised tobramycin for the outcome forced expiratory volume in first second percentage predicted (FEV1%). It was not possible to draw any firm conclusions as to the relative efficacy of colistimethate sodium DPI compared with tobramycin DPI. The economic analysis suggests that colistimethate sodium DPI produces fewer quality-adjusted life-years (QALYs) than nebulised tobramycin. Given the incremental discounted lifetime cost of tobramycin DPI compared with nebulised tobramycin, it highly unlikely that tobramycin DPI has an incremental cost-effectiveness ratio that is better than £30,000 per QALY gained.
LIMITATION
The uncertainty surrounding the short-term evidence base inevitably results in uncertainty surrounding the long-term clinical effectiveness and cost-effectiveness of colistimethate sodium DPI.
CONCLUSIONS
Both DPI formulations have been shown to be non-inferior to nebulised tobramycin as measured by FEV1%. The results of these trials should be interpreted with caution owing to the means by which the results were analysed, the length of follow-up, and concerns about the ability of FEV1% to accurately represent changes in lung health. Although the increase in QALYs is expected to be lower with colistimethate sodium DPI than with nebulised tobramycin, a price for this intervention had not been agreed at the time of the assessment. Depending on the price of colistimethate sodium DPI, this results either in a situation whereby colistimethate sodium DPI is dominated by nebulised tobramycin or in one whereby the incremental cost-effectiveness of nebulised tobramycin compared with colistimethate sodium DPI is in the range of £24,000-277,000 per QALY gained. The economic analysis also suggests that, given its price, it is unlikely that tobramycin DPI has a cost-effectiveness ratio of < £30,000 per QALY gained when compared with nebulised tobramycin. A RCT to assess the longer-term (≥ 12 months) efficacy of colistimethate sodium DPI and tobramycin DPI in comparison with nebulised treatments would be beneficial. Such a study should include the direct assessment of HRQoL using a relevant preference-based instrument. Future studies should ensure that the European Medicines Agency guidelines are adhered to. In addition, high-quality research concerning the relationship between forced expiratory volume in first second % (FEV1%) predicted or other measures of lung function and survival/health-related quality of life (HRQoL) would be useful.
STUDY REGISTRATION
PROSPERO CRD42011001350.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Administration, Inhalation; Child; Colistin; Cost-Benefit Analysis; Cystic Fibrosis; Disease Progression; Humans; Outcome Assessment, Health Care; Pseudomonas Infections; Pseudomonas aeruginosa; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Therapeutic Equivalency; Tobramycin; United Kingdom
PubMed: 24290164
DOI: 10.3310/hta17560 -
The Cochrane Database of Systematic... Nov 2012Macrolide antibiotics may have a modifying role in diseases which involve airway infection and inflammation, like cystic fibrosis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Macrolide antibiotics may have a modifying role in diseases which involve airway infection and inflammation, like cystic fibrosis.
OBJECTIVES
To test the hypotheses that, in people with cystic fibrosis, macrolide antibiotics: 1. improve clinical status compared to placebo or another antibiotic; 2. do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.We contacted investigators known to work in the field, previous authors and pharmaceutical companies manufacturing macrolide antibiotics for unpublished or follow-up data (May 2010).Latest search of the Group's Cystic Fibrosis Trials Register: 29 February 2012.
SELECTION CRITERIA
Randomised controlled trials of macrolide antibiotics compared to: placebo; another class of antibiotic; another macrolide antibiotic; or the same macrolide antibiotic at a different dose.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias. Seven groups were contacted and provided additional data which were incorporated into the review.
MAIN RESULTS
Ten of 31 studies identified were included (959 patients). Five studies with a low risk of bias examined azithromycin versus placebo and demonstrated consistent improvement in forced expiratory volume in one second over six months (mean difference at six months 3.97% (95% confidence interval 1.74% to 6.19%; n = 549, from four studies)). Patients treated with azithromycin were approximately twice as likely to be free of pulmonary exacerbation at six months, odds ratio 1.96 (95% confidence interval 1.15 to 3.33). With respect to secondary outcomes, there was a significant reduction in need for oral antibiotics and greater weight gain in those taking azithromycin. Adverse events were uncommon and not obviously associated with azithromycin, although a once-weekly high dose regimen was associated with more frequent gastrointestinal adverse events. Treatment with azithromycin was associated with reduced identification of Staphylococcus aureus on respiratory culture, but also a significant increase in macrolide resistance.
AUTHORS' CONCLUSIONS
This review provides evidence of improved respiratory function after six months of azithromycin. Data beyond six months were less clear, although reduction in pulmonary exacerbation was sustained. Treatment appeared safe over a six-month period; however, emergence of macrolide resistance was a concern. A multi-centre trial examining long-term effects of this antibiotic treatment is needed, especially for infants recognised through newborn screening.
Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Cystic Fibrosis; Disease Progression; Humans; Macrolides; Outcome Assessment, Health Care; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic
PubMed: 23152214
DOI: 10.1002/14651858.CD002203.pub4 -
The Cochrane Database of Systematic... Jul 2012Pseudomonas aeruginosa is the commonest micro-organism associated with respiratory infections in cystic fibrosis. Retrospective studies have suggested that using an... (Review)
Review
BACKGROUND
Pseudomonas aeruginosa is the commonest micro-organism associated with respiratory infections in cystic fibrosis. Retrospective studies have suggested that using an aggressive policy of intravenous anti-pseudomonal antibiotics at regular intervals, irrespective of symptoms, increases survival.
OBJECTIVES
To determine whether there is evidence that an elective (regular) versus symptomatic intravenous antibiotic regimen is associated with an improvement in clinical status and survival rates in people with cystic fibrosis. To identify any adverse effects associated with the use of elective intravenous antibiotics, including an increase in the development of resistant organisms.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 15 March 2012.
SELECTION CRITERIA
All randomised or quasi-randomised controlled trials describing the use of elective compared with symptomatic intravenous antibiotic policies for any duration or dose regimen. Elective versus symptomatic intravenous antibiotic regimens against any organisms were considered. People with cystic fibrosis of any age or disease severity were included.
DATA COLLECTION AND ANALYSIS
Both authors independently assessed trial eligibility and quality; both extracted the data.
MAIN RESULTS
Searches identified four studies. Two studies reporting results from a total of 79 participants were included in the review. Differences in study design and objectives meant that data could not be pooled for meta-analysis. Neither study demonstrated significant differences in outcome measures between intervention and comparison groups.
AUTHORS' CONCLUSIONS
Studies are insufficient to identify conclusive evidence favouring a policy of elective intravenous antibiotic administration, despite its widespread use, neither are the potential risks adequately evaluated. The results should be viewed with caution, as participant numbers are small. Clearly there is a need for a well-designed, adequately-powered, multicentred randomised controlled trial to evaluate these issues.
Topics: Anti-Bacterial Agents; Cystic Fibrosis; Humans; Injections, Intravenous; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 22786481
DOI: 10.1002/14651858.CD002767.pub2 -
The Cochrane Database of Systematic... Nov 2010Several beta-lactams are recommended as single agents for the treatment of febrile neutropenia. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several beta-lactams are recommended as single agents for the treatment of febrile neutropenia.
OBJECTIVES
To compare the effectiveness of different anti-pseudomonal beta-lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta-lactams.
SEARCH STRATEGY
We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing an antipseudomonal beta-lactam to another antipseudomonal beta-lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients.
DATA COLLECTION AND ANALYSIS
Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all-cause mortality. Risk of bias was assessed using a domain-based evaluation and its effect of results was assessed through sensitivity analyses.
MAIN RESULTS
Forty-four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin-tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double-blinded. The risk for all-cause mortality was significantly higher with cefepime compared to other beta-lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non-significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin-tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all-cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile.
AUTHORS' CONCLUSIONS
Current evidence supports the use of piperacillin-tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic-associated and Clostridium difficile-associated diarrhea. There is a high level of evidence that all-cause mortality is higher with cefepime compared to other beta-lactams and it should not be used as monotherapy for patients with febrile neutropenia.
Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Fever; Humans; Imipenem; Meropenem; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Thienamycins; beta-Lactams
PubMed: 21069685
DOI: 10.1002/14651858.CD005197.pub3 -
BMC Pulmonary Medicine Aug 2010Pneumonia, and particularly nosocomial (NP) and ventilator-associated pneumonias (VAP), results in high morbidity and costs. NPs in particular are likely to be caused by... (Review)
Review
BACKGROUND
Pneumonia, and particularly nosocomial (NP) and ventilator-associated pneumonias (VAP), results in high morbidity and costs. NPs in particular are likely to be caused by Pseudomonas aeruginosa (PA), ~20% of which in observational studies are resistant to imipenem. We sought to identify the burden of PA imipenem resistance in pneumonia.
METHODS
We conducted a systematic literature review of randomized controlled trials (RCT) of imipenem treatment for pneumonia published in English between 1993 and 2008. We extracted study, population and treatment characteristics, and proportions caused by PA. Endpoints of interest were: PA resistance to initial antimicrobial treatment, clinical success, microbiologic eradication and on-treatment emergence of resistance of PA.
RESULTS
Of the 46 studies identified, 20 (N = 4,310) included patients with pneumonia (imipenem 1,667, PA 251; comparator 1,661, PA 270). Seven were double blind, and 7 included US data. Comparator arms included a β-lactam (17, [penicillin 6, carbapenem 4, cephalosporin 7, monobactam 1]), aminoglycoside 2, vancomycin 1, and a fluoroquinolone 5; 5 employed double coverage. Thirteen focused exclusively on pneumonia and 7 included pneumonia and other diagnoses. Initial resistance was present in 14.6% (range 4.2-24.0%) of PA isolates in imipenem and 2.5% (range 0.0-7.4%) in comparator groups. Pooled clinical success rates for PA were 45.2% (range 0.0-72.0%) for imipenem and 74.9% (range 0.0-100.0%) for comparator regimens. Microbiologic eradication was achieved in 47.6% (range 0.0%-100.0%) of isolates in the imipenem and 52.8% (range 0.0%-100.0%) in the comparator groups. Resistance emerged in 38.7% (range 5.6-77.8%) PA isolates in imipenem and 21.9% (range 4.8-56.5%) in comparator groups.
CONCLUSIONS
In the 15 years of RCTs of imipenem for pneumonia, PA imipenem resistance rates are high, and PA clinical success and microbiologic eradication rates are directionally lower for imipenem than for comparators. Conversely, initial and treatment-emergent resistance is more likely with the imipenem than the comparator regimens.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Imipenem; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 20796312
DOI: 10.1186/1471-2466-10-45