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The Cochrane Database of Systematic... Aug 2015Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review.
OBJECTIVES
To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013).
SELECTION CRITERIA
Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis.
DATA COLLECTION AND ANALYSIS
The authors independently selected trials, assessed them and extracted data.
MAIN RESULTS
Six trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P < 0.0001).
AUTHORS' CONCLUSIONS
Vaccines against Pseudomonas aeruginosa cannot be recommended.
Topics: Cystic Fibrosis; Humans; Pseudomonas Infections; Pseudomonas Vaccines; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic
PubMed: 26298311
DOI: 10.1002/14651858.CD001399.pub4 -
European Journal of Internal Medicine Aug 2021Inhaled antibiotics (IA) in non-cystic fibrosis bronchiectasis (NCFB) are recommended by some clinical practice guidelines for prevention or treatment of NCFB... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inhaled antibiotics (IA) in non-cystic fibrosis bronchiectasis (NCFB) are recommended by some clinical practice guidelines for prevention or treatment of NCFB exacerbations.
METHODS
We performed a systematic review and meta-analysis to evaluate the efficacy and safety of IA use for treatment of adults with NCFB and Pseudomonas aeruginosa chronic bronchial infection. The search was performed in the Cochrane Library, PubMed, and Web of Science databases from 2000 to 2019. Studies of IA for treatment of stable or exacerbated NCFB adults (≥18 years) with P. aeruginosa infection were considered eligible. PROSPERO Registration number: CRD42019136154.
RESULTS
Twelve trials (2476 participants) were included. IA therapy increased P. aeruginosa eradication from sputum in patients with exacerbations (OR: 3.19, 95%CI: 1.70-5.99) with similar effects on stable patients (OR: 7.22, 95%CI: 2.81-18.59), and a trend to reduced emergence of new respiratory pathogens (OR: 0.58, 95%CI: 0.28-1.18). IA achieved significant reduced exacerbation rates (RR: 0.90; 95%CI: 0.82-0.98) in stable patients, with a number needed to treat (NNT) of 59, but no significant changes in FEV, mortality, hospitalizations or quality of life were identified. In stable patients, IA use increased antimicrobial resistance (RR: 2.10, 95%CI: 1.35-3.27) at the end of therapy, with a number needed to treat of 6.
CONCLUSIONS
IA therapy achieved a statistically significant eradication of P. aeruginosa from sputum, with a 10% reduction of exacerbations in stable patients. This effect has to be balanced with significant increases in antimicrobial resistance. Our meta-analysis failed to show a significant benefit in terms of patient-centered outcomes.
Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Bronchiectasis; Cystic Fibrosis; Humans; Pseudomonas Infections; Pseudomonas aeruginosa; Quality of Life
PubMed: 33947626
DOI: 10.1016/j.ejim.2021.04.009 -
The Cochrane Database of Systematic... Mar 2011Inhaled antibiotics are commonly used to treat persistent airway infection that contributes to lung damage in people with cystic fibrosis (CF). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inhaled antibiotics are commonly used to treat persistent airway infection that contributes to lung damage in people with cystic fibrosis (CF).
OBJECTIVES
To examine the evidence that inhaled antibiotic treatment in people with CF reduces frequency of exacerbations of infection, and improves lung function, quality of life and survival. To examine adverse effects of inhaled antibiotic treatment.
SEARCH STRATEGY
Trials were identified from the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register.Last search: 31 January 2011.
SELECTION CRITERIA
Trials were selected if inhaled antibiotic treatment was used for at least four weeks in people with CF, treatment allocation was randomised or quasi-randomised, and there was a control group (either placebo, no placebo or another inhaled antibiotic).
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials, judged the risk of bias and extracted data from these trials.
MAIN RESULTS
The searches identified 176 citations to 78 trials. Nineteen trials, with 1724 participants, met the inclusion criteria. Adequate meta-analysis was not possible because of the variability of study design and reporting of results. Seventeen trials with 1562 participants compared an inhaled antibiotic with placebo or usual treatment for a duration between 1 and 32 months. Inhaled tobramycin was studied in eight trials. Lung function (measured as forced expired volume in one second) was higher and exacerbations of lung infection (by different measures) were less in the antibiotic-treated group. Resistance to antibiotics increased more in the antibiotic-treated group than in placebo group when results were reported. No auditory or renal impairment was found; analysis showed tinnitus, voice alteration, hemoptysis and cough were more frequent with tobramycin than placebo. One trial, compared tobramycin with colistin in 115 participants, after one month the mean difference in forced expiratory volume at one second was 6.33 (95% confidence interval -0.04 to 12.70) favouring tobramycin.
AUTHORS' CONCLUSIONS
Inhaled antibiotic treatment probably improves lung function and reduces exacerbation rate, but a pooled estimate of the level of benefit is not possible. The best evidence is for inhaled tobramycin. More evidence, from trials of longer duration, is needed to determine whether this benefit is maintained and to determine the significance of development of antibiotic-resistant organisms.
Topics: Administration, Inhalation; Administration, Intranasal; Aerosols; Anti-Bacterial Agents; Cystic Fibrosis; Humans; Nebulizers and Vaporizers; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Tract Infections
PubMed: 21412868
DOI: 10.1002/14651858.CD001021.pub2 -
The Cochrane Database of Systematic... Feb 2024Cystic fibrosis (CF) is a life-limiting genetic condition, affecting over 90,000 people worldwide. CF affects several organs in the body, but airway damage has the most... (Review)
Review
BACKGROUND
Cystic fibrosis (CF) is a life-limiting genetic condition, affecting over 90,000 people worldwide. CF affects several organs in the body, but airway damage has the most profound impact on quality of life (QoL) and survival. Causes of lower airway infection in people with CF are, most notably, Staphylococcus aureus in the early course of the disease and Pseudomonas aeruginosa at a later stage. Macrolide antibiotics, e.g. azithromycin and clarithromycin, are usually taken orally, have a broad spectrum of action against gram-positive (e.g. S aureus) and some gram-negative bacteria (e.g. Haemophilus influenzae), and may have a modifying role in diseases involving airway infection and inflammation such as CF. They are well-tolerated and relatively inexpensive, but widespread use has resulted in the emergence of resistant bacteria. This is an updated review.
OBJECTIVES
To assess the potential effects of macrolide antibiotics on clinical status in terms of benefit and harm in people with CF. 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 last searched the Group's Cystic Fibrosis Trials Register on 2 November 2022. We last searched the trial registries WHO ICTRP and clinicaltrials.gov on 9 November 2022. We contacted investigators known to work in the field, previous authors and pharmaceutical companies manufacturing macrolide antibiotics for unpublished or follow-up data, where possible.
SELECTION CRITERIA
We included randomised controlled trials of macrolide antibiotics in adults and children with CF. We compared them to: placebo; another class of antibiotic; another macrolide antibiotic; or the same macrolide antibiotic at a different dose or type of administration.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias. We assessed the certainty of evidence using GRADE.
MAIN RESULTS
We included 14 studies (1467 participants) lasting 28 days to 36 months. All the studies assessed azithromycin: 11 compared oral azithromycin to placebo (1167 participants); one compared a high dose to a low dose (47 participants); one compared nebulised to oral azithromycin (45 participants); and one looked at weekly versus daily dose (208 participants). Oral azithromycin versus placebo There is a slight improvement in forced expiratory volume (FEV % predicted) in one second in the azithromycin group at up to six months compared to placebo (mean difference (MD) 3.97, 95% confidence interval (CI) 1.74 to 6.19; high-certainty evidence), although there is probably no difference at three months, (MD 2.70%, 95% CI -0.12 to 5.52), or 12 months (MD -0.13, 95% CI -4.96 to 4.70). Participants in the azithromycin group are probably at a decreased risk of pulmonary exacerbation with a longer time to exacerbation (hazard ratio (HR) 0.61, 95% CI 0.50 to 0.75; moderate-certainty evidence). Mild side effects were common, but there was no difference between groups (moderate-certainty evidence). There is no difference in hospital admissions at six months (odds ratio (OR) 0.61, 95% CI 0.36 to 1.04; high-certainty evidence), or in new acquisition of P aeruginosa at 12 months (HR 1.00, 95% CI 0.64 to 1.55; moderate-certainty evidence). High-dose versus low-dose azithromycin We are uncertain whether there is any difference in FEV % predicted at six months between the two groups (no data available) or in the rate of exacerbations per child per month (MD -0.05 (95% CI -0.20 to 0.10)); very low-certainty evidence for both outcomes. Only children were included in the study and the study did not report on any of our other clinically important outcomes. Nebulised azithromycin versus oral azithromycin We were unable to include any of the data into our analyses and have reported findings directly from the paper; we graded all evidence as being of very low certainty. The authors reported that there was a greater mean change in FEV % predicted at one month in the nebulised azithromycin group (P < 0.001). We are uncertain whether there was a change in P aeruginosa count. Weekly azithromycin versus daily azithromycin There is probably a lower mean change in FEV % predicted at six months in the weekly group compared to the daily group (MD -0.70, 95% CI -0.95 to -0.45) and probably also a longer period of time until first exacerbation in the weekly group (MD 17.30 days, 95% CI 4.32 days to 30.28 days). Gastrointestinal side effects are probably more common in the weekly group and there is likely no difference in admissions to hospital or QoL. We graded all evidence as moderate certainty.
AUTHORS' CONCLUSIONS
Azithromycin therapy is associated with a small but consistent improvement in respiratory function, a decreased risk of exacerbation and longer time to exacerbation at six months; but evidence for treatment efficacy beyond six months remains limited. Azithromycin appears to have a good safety profile (although a weekly dose was associated with more gastrointestinal side effects, which makes it less acceptable for long-term therapy), with a relatively minimal treatment burden for people with CF, and it is inexpensive. A wider concern may be the emergence of macrolide resistance reported in the most recent study which, combined with the lack of long-term data, means we do not feel that the current evidence is strong enough to support azithromycin therapy for all people with CF. Future research should report over longer time frames using validated tools and consistent reporting, to allow for easier synthesis of data. In particular, future trials should report important adverse events such as hearing impairment or liver disease. More data on the effects of azithromycin given in different ways and reporting on our primary outcomes would benefit decision-making on whether and how to give macrolide antibiotics. Finally, it is important to assess azithromycin therapy for people with CF who are established on the relatively new cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies which correct the underlying molecular defect associated with CF (none of the trials included in the review are relevant to this population).
Topics: Child; Adult; Humans; Azithromycin; Anti-Bacterial Agents; Cystic Fibrosis; Macrolides; Quality of Life; Drug Resistance, Bacterial; Pseudomonas aeruginosa
PubMed: 38411248
DOI: 10.1002/14651858.CD002203.pub5 -
Chronic Respiratory Disease May 2017To provide an update on efficacy and safety of antibiotic treatments for stable non-cystic fibrosis (CF) bronchiectasis (BE). Systematic review based on the Preferred... (Review)
Review
To provide an update on efficacy and safety of antibiotic treatments for stable non-cystic fibrosis (CF) bronchiectasis (BE). Systematic review based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was done. Twenty-six studies (1.898 patients) fulfilled the inclusion criteria. Studies of inhaled tobramycin have revealed conflicting results regarding quality of life (QoL), exacerbations and admissions, but may result in sputum cultures negative for Pseudomonas aeruginosa, whereas studies investigating the effect of inhaled gentamycin have shown positive effects on sputum bacterial density, decrease in sputum cultures positive for P. aeruginosa, QoL and exacerbation rate, but no improvement in forced expiratory volume in first second (FEV). Oral azithromycin can reduce exacerbations, together with minor improvements in QoL and FEV. Furthermore, oral erythromycin reduces exacerbations, but has no effect on lung function, symptoms or QoL. Inhaled ciprofloxacin may reduce P. aeruginosa in sputum cultures, but without changes in lung function, exacerbations or QoL. Although with limited evidence, inhaled colistin may have effects on P. aeruginosa density, exacerbations and QoL, whereas studies on aztreonam revealed no significant clinical improvements in the outcomes of interest, including exacerbation rate. Adverse events, including bronchospasm, have been reported in association with tobramycin and aztreonam. Several antibiotic treatment regimens have been shown to improve QoL and exacerbation rate, whereas findings regarding sputum production, lung function and admissions have been conflicting. Evidence-based treatment algorithms for antibiotic treatment of stable non-CF BE will have to await large-scale, long-term controlled studies.
Topics: Aminoglycosides; Anti-Bacterial Agents; Aztreonam; Bronchiectasis; Ciprofloxacin; Colistin; Disease Progression; Forced Expiratory Volume; Humans; Macrolides; Pseudomonas Infections; Pseudomonas aeruginosa; Quality of Life; Sputum
PubMed: 27507832
DOI: 10.1177/1479972316661923 -
American Journal of Otolaryngology 2015Culture-directed antibiotic therapy represents an important component in the management paradigm of chronic rhinosinusitis (CRS). The objective of this study was to... (Review)
Review
BACKGROUND
Culture-directed antibiotic therapy represents an important component in the management paradigm of chronic rhinosinusitis (CRS). The objective of this study was to systematically review the literature to assess culture yield of the most common aerobic and anaerobic pathogens.
METHODS
A total of 43 studies between 1975 and 2010 were included.
RESULTS
The composite data comprised 3528 patients with 6005 total culture specimens. The cultures were obtained in operating room in 33 (76.7%) and clinic in 10 (23.3%) of the studies, respectively. The most common site of culture was the maxillary sinus in 18 (41.9%) of the studies. The most common assay techniques reported were swab in 19 (44.2%) and aspirate in 12 (27.9%) studies. The most common gram positive aerobes reported were coagulase negative Staphylococcus and Staphylococcus aureus in 630 (34.7%) and 481 (26.5%) of the cultures, respectively. The most common gram negative aerobes included Haemophilus influenzae and Pseudomonas aeruginosa in 245 (27.0%) and 198 (21.6%) cultures, respectively. The most common anaerobes reported were Peptostreptococcus species in 156 (19.6%) and Bacteroides species in 153 (19.2%) cultures.
CONCLUSION
This study provides a composite snapshot of the literature accrued on the microbiology of CRS. It should serve to apprise clinicians on the most common aerobic and anaerobic organisms in CRS patients when employing culture-directed antimicrobial therapy.
Topics: Anti-Infective Agents; Chronic Disease; Endoscopy; Humans; Pseudomonas Infections; Pseudomonas aeruginosa; Rhinitis; Sinusitis; Staphylococcal Infections; Staphylococcus aureus
PubMed: 25964173
DOI: 10.1016/j.amjoto.2015.04.010 -
International Journal of Molecular... Oct 2023is the primary opportunistic human pathogen responsible for a range of acute and chronic infections; it poses a significant threat to immunocompromised patients and is... (Review)
Review
is the primary opportunistic human pathogen responsible for a range of acute and chronic infections; it poses a significant threat to immunocompromised patients and is the leading cause of morbidity and mortality for nosocomial infections. Its high resistance to a diverse array of antimicrobial agents presents an urgent health concern. Among the mechanisms contributing to resistance in , the horizontal acquisition of antibiotic resistance genes (ARGs) via mobile genetic elements (MGEs) has gained recognition as a substantial concern in clinical settings, thus indicating that a comprehensive understanding of ARG dissemination within the species is strongly required for surveillance. Here, two approaches, including a systematic literature analysis and a genome database survey, were employed to gain insights into ARG dissemination. The genome database enabled scrutinizing of all the available sequence information and various attributes of isolates, thus providing an extensive understanding of ARG dissemination within the species. By integrating both approaches, with a primary focus on the genome database survey, mobile ARGs that were linked or correlated with MGEs, important sequence types (STs) carrying diverse ARGs, and MGEs responsible for ARG dissemination were identified as critical factors requiring strict surveillance. Although human isolates play a primary role in dissemination, the importance of animal and environmental isolates has also been suggested. In this study, 25 critical mobile ARGs, 45 critical STs, and associated MGEs involved in ARG dissemination within the species, are suggested as critical factors. Surveillance and management of these prioritized factors across the One Health sectors are essential to mitigate the emergence of multidrug-resistant (MDR) and extensively resistant (XDR) in clinical settings.
Topics: Animals; Humans; Pseudomonas aeruginosa; Drug Resistance, Microbial; Anti-Bacterial Agents
PubMed: 37894890
DOI: 10.3390/ijms242015209 -
Journal of Molecular Biology Nov 2015We have become increasingly aware that, during infection, pathogenic bacteria often grow in multicellular biofilms that are often highly resistant to antibacterial... (Review)
Review
We have become increasingly aware that, during infection, pathogenic bacteria often grow in multicellular biofilms that are often highly resistant to antibacterial strategies. In order to understand how biofilms form and contribute to infection, many research groups around the world have heavily used in vitro biofilm systems such as microtitre plate assays and flow cells. Whilst these methods have greatly increased our understanding of the biology of biofilms, it is becoming increasingly apparent that many of our in vitro methods do not accurately represent in vivo conditions. Here we present a systematic review of the most widely used in vitro biofilm systems, and we discuss why they are not always representative of the in vivo biofilms found in chronic infections. We present examples of methods that will help us to bridge the gap between in vitro and in vivo biofilm work so that we can ultimately use our benchside data to improve bedside treatment.
Topics: Animals; Bacterial Infections; Bacteriological Techniques; Biofilms; Chronic Disease; Disease Models, Animal; Humans; In Vitro Techniques; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 26344834
DOI: 10.1016/j.jmb.2015.09.002 -
World Journal of Urology Oct 2021Pathophysiology and risk factors for Ureteral Stent-Associated Urinary Tract Infection (USAUTI) have been poorly investigated. This situation results in highly diverse...
PURPOSE
Pathophysiology and risk factors for Ureteral Stent-Associated Urinary Tract Infection (USAUTI) have been poorly investigated. This situation results in highly diverse practices regarding USAUTI prevention, diagnosis and treatment. The aim of the present study was to describe the epidemiology and risk factors for USAUTI in non-transplanted patients.
METHODS
We conducted a systematic literature review based on a comprehensive PubMed® bibliographic strategy, between October 1998 and March 2020. The methodological quality of the studies included was analyzed according to dedicated grids. The main endpoints were the correlation between different potential risk factors and infection ureteral stent-associated urinary tract infection or colonization rate. Conclusions and their level of evidence were reported on the basis of a critical analysis of the best available scientific evidence. This work has been submitted to a national review, which enabled the potentially divergent opinions of experts to be collected, thereby ensuring adequate quality of data.
RESULTS AND CONCLUSION
Twenty-six studies out of the 505 articles identified, were included in the final analysis. Staphylococcus spp, E. coli, Klebsiella spp, Pseudomona aeruginosa, Enterococcus spp. and Candida spp. were the microorganisms most often responsible for asymptomatic bacteriuria (ABU) or USAUTI. Longer indwelling time, diabetes mellitus, female gender, chronic renal failure, diabetic nephropathy and cancer were identified as risk factors for ABU and ureteral stent colonization. No specific risk factor for UTI was identified in the literature studied. A causal relationship between ureteral stent colonization and USAUTI or urosepsis remains to be demonstrated.
Topics: Asymptomatic Infections; Bacteriuria; Candida; Candidiasis; Enterococcus; Escherichia coli; Escherichia coli Infections; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Klebsiella; Klebsiella Infections; Pseudomonas Infections; Pseudomonas aeruginosa; Risk Factors; Staphylococcal Infections; Staphylococcus; Stents; Ureter; Ureteroscopy; Urinary Tract Infections
PubMed: 33991215
DOI: 10.1007/s00345-021-03693-7 -
International Journal of Chronic... 2022Chronic bronchial infection is frequent in chronic obstructive pulmonary disease (COPD), but the impact of the isolation of pathogenic bacteria, and in particular (PA)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic bronchial infection is frequent in chronic obstructive pulmonary disease (COPD), but the impact of the isolation of pathogenic bacteria, and in particular (PA) in respiratory samples on the prognosis of COPD is unclear.
METHODS
We conducted a systematic review of prognostic studies including patients with isolation of PA in sputum in stable state or during exacerbations of COPD. The main outcomes were all-cause mortality, respiratory mortality, and number and severity of future exacerbations. Data were expressed as hazard ratio (HR) (95% confidence interval [CI]) whenever possible.
RESULTS
Of 2773 studies, eight were finally included (23,228 individuals). The mean age ranged from 65.5 to 73 years. Six studies reported data for all-cause mortality. The adjusted risk of death was almost double in patients with PA isolation (HR 1.95, 95% CI, 1.34 to 2.84; quality of evidence moderate). Patients with PA isolation showed a three times higher adjusted risk of readmission at 30 days after discharge (OR 3.60, 95% CI, 3.60 to 12.03, 1 study; quality of evidence very low), and more than double adjusted risk of death and hospitalization at two years (HR 2.80, 95% CI, 2.20 to 3.56, 1 study; quality of evidence very low).
CONCLUSION
There is moderate certainty that the isolation of PA in sputum is associated with an adjusted increased risk of death in patients with COPD.
Topics: Aged; Bronchitis, Chronic; Disease Progression; Humans; Pseudomonas aeruginosa; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 35210766
DOI: 10.2147/COPD.S346294