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Clinical Pharmacokinetics Apr 2021Lower respiratory tract infections are common in adult patients with cystic fibrosis (CF) and are frequently caused by Pseudomonas aeruginosa, resulting in chronic lung...
BACKGROUND
Lower respiratory tract infections are common in adult patients with cystic fibrosis (CF) and are frequently caused by Pseudomonas aeruginosa, resulting in chronic lung inflammation and fibrosis. The progression of multidrug-resistant strains of P. aeruginosa and alterations in the pharmacokinetics of many antibiotics in CF make optimal antimicrobial therapy a challenge, as reflected by high between- and inter-individual variability (IIV).
OBJECTIVES
This review provides a synthesis of population pharmacokinetic models for various antibiotics prescribed in adult CF patients, and aims at identifying the most reported structural models, covariates and sources of variability influencing the dose-concentration relationship.
METHODS
A literature search was conducted using the PubMed database, from inception to August 2020, and articles were retained if they met the inclusion/exclusion criteria.
RESULTS
A total of 19 articles were included in this review. One-, two- and three-compartment models were reported to best describe the pharmacokinetics of various antibiotics. The most common covariates were lean body mass and creatinine clearance. After covariate inclusion, the IIV (range) in total body clearance was 27.2% (10.40-59.7%) and 25.9% (18.0-33.9%) for β-lactams and aminoglycosides, respectively. IIV in total body clearance was estimated at 36.3% for linezolid and 22.4% for telavancin. The IIV (range) in volume of distribution was 29.4% (8.8-45.9%) and 15.2 (11.6-18.0%) for β-lactams and aminoglycosides, respectively, and 26.9% for telavancin. The median (range) of residual variability for all studies, using a combined (proportional and additive) model, was 12.7% (0.384-30.80%) and 0.126 mg/L (0.007-1.88 mg/L), respectively.
CONCLUSION
This is the first review that highlights key aspects of different population pharmacokinetic models of antibiotics prescribed in adult CF patients, effectively proposing relevant information for clinicians and researchers to optimize antibiotic therapy in CF.
Topics: Adult; Anti-Bacterial Agents; Cystic Fibrosis; Humans; Pseudomonas aeruginosa
PubMed: 33447944
DOI: 10.1007/s40262-020-00970-3 -
The Cochrane Database of Systematic... 2004Chronic severe infection with Pseudomonas aeruginosa, affects many people with cystic fibrosis (CF). There is evidence from the laboratory and from other disease... (Review)
Review
BACKGROUND
Chronic severe infection with Pseudomonas aeruginosa, affects many people with cystic fibrosis (CF). There is evidence from the laboratory and from other disease processes that macrolide antibiotics, whilst not directly active against Pseudomonas aeruginosa, may have indirect actions against this organism.
OBJECTIVES
We aimed to test the hypotheses that, in people with CF, 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 STRATEGY
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 principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture macrolide antibiotics for unpublished or follow-up data (December 2003). Most recent search of the Group's register: January 2004
SELECTION CRITERIA
Published or unpublished randomised controlled trials of macrolide antibiotics compared to placebo, another class of antibiotic or another macrolide antibiotic. Studies comparing regimens of the same macrolide antibiotic at different doses will also be included.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data and assessed study quality. Three groups were contacted for missing data and we hope to include these in future reviews.
MAIN RESULTS
Searches identified 14 studies, four were included in this review (296 participants). Two studies enrolled adults, one children (a significant number of whom were not colonised with Pseudomonas aeruginosa) and one both adults and children. All the clinical studies reported small but significant improvements in respiratory function with azithromycin versus placebo. Meta-analysis at the one-month and six-month time points demonstrates a significant benefit with respect to relative change in FEV1 (at six months, for n = 104, azithromycin and n = 114, placebo; WMD 5.82% (95% CI 2.45 to 9.20)). The largest study reported a significant increase in mild adverse events (nausea, diarrhoea and wheezing).
REVIEWERS' CONCLUSIONS
There is clear evidence from these studies of a small but significant improvement in respiratory function following treatment with azithromycin. The largest study employed a three times a week dose and, in this study, treatment with azithromycin was associated with a significant increase in mild adverse events. Further studies are needed to clarify the precise role of azithromycin in the treatment of CF lung disease.
Topics: Anti-Bacterial Agents; Cystic Fibrosis; Humans; Macrolides; Outcome Assessment, Health Care; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic
PubMed: 15106170
DOI: 10.1002/14651858.CD002203.pub2 -
The Cochrane Database of Systematic... May 2014Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children... (Review)
Review
BACKGROUND
Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis.
OBJECTIVES
To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 17 March 2014.
SELECTION CRITERIA
Randomised and quasi-randomised studies.
DATA COLLECTION AND ANALYSIS
The authors independently extracted data and assessed risk of bias.
MAIN RESULTS
One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. We judged there to be a low risk of bias with respect to the concealment of the randomization schedule (although it was not clear how this was generated) and to blinding of participants and study personnel. There is also a low risk of bias with regards to incomplete outcome data. However, we judged there to be a high risk of bias from selective reporting (summary statements presented but no data) and the fact that this industry-supported study has not been published as a full report in a peer-reviewed journal.At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while five and four children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio.
AUTHORS' CONCLUSIONS
We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with cystic fibrosis. While the overall incidence of adverse events was similar in both groups, it is not possible to draw firm conclusions on the safety and tolerability of respiratory syncytial virus prophylaxis with palivizumab in infants with cystic fibrosis. Six months after treatment, the authors reported no clinically meaningful differences in outcomes. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with cystic fibrosis.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Cystic Fibrosis; Drug Administration Schedule; Humans; Infant; Palivizumab; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 24851825
DOI: 10.1002/14651858.CD007743.pub5 -
Current Opinion in Pulmonary Medicine Nov 2014Newer 'innovative' formulations of antibiotics for Pseudomonas aeruginosa lung infection in patients with cystic fibrosis include colistimethate sodium and tobramycin in... (Review)
Review
PURPOSE OF REVIEW
Newer 'innovative' formulations of antibiotics for Pseudomonas aeruginosa lung infection in patients with cystic fibrosis include colistimethate sodium and tobramycin in the form of dry powders for inhalation (DPIs). Whilst these DPIs are anticipated to improve patient adherence because of increased convenience and ease of administration, questions remain concerning whether they are as clinically effective, safe and cost-effective as nebulized antibiotics.
RECENT FINDINGS
This review describes the recent findings of a health technology assessment of the clinical effectiveness and cost-effectiveness of colistimethate sodium and tobramycin DPIs with regard to how innovative treatments may be judged to be incrementally better than existing treatments. The original assessment was undertaken to inform the National Institute for Health and Care Excellence's Technology Appraisal Programme to inform national clinical guidance on the use of these new treatments in the National Health Service.
SUMMARY
Three trials were included in the systematic review. Issues surrounding the clinical effectiveness and cost-effectiveness of colistimethate sodium DPI and tobramycin DPI are discussed in light of the considerable uncertainties associated with the available evidence.
Topics: Administration, Inhalation; Anti-Bacterial Agents; Colistin; Cost-Benefit Analysis; Cystic Fibrosis; Dry Powder Inhalers; Humans; Medication Adherence; Pseudomonas Infections; Pseudomonas aeruginosa; Tobramycin; Treatment Outcome
PubMed: 25221853
DOI: 10.1097/MCP.0000000000000109 -
International Journal of Antimicrobial... Aug 2009The treatment of multidrug-resistant (MDR), extensively drug-resistant or pandrug-resistant non-fermenting Gram-negative bacterial infections constitutes a challenge in... (Review)
Review
Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies.
The treatment of multidrug-resistant (MDR), extensively drug-resistant or pandrug-resistant non-fermenting Gram-negative bacterial infections constitutes a challenge in an era of few new antibiotic choices. This mandates the re-evaluation of already existing antibiotics such as fosfomycin. We systematically reviewed the literature to assess the clinical and microbiological effectiveness of fosfomycin in the treatment of these infections by searching PubMed, Scopus and the Cochrane Library databases. In 23 microbiological studies identified, 1859 MDR non-fermenting Gram-negative bacterial isolates were examined. The susceptibility rate to fosfomycin of MDR Pseudomonas aeruginosa isolates was >or=90% and 50-90% in 7/19 and 4/19 relevant studies, respectively. Cumulatively, 511/1693 (30.2%) MDR P. aeruginosa isolates were susceptible to fosfomycin. Serotype O12 isolates exhibited greater susceptibility. Only 3/85 (3.5%) MDR Acinetobacter baumannii and 0/31 MDR Burkholderia spp. isolates were susceptible to fosfomycin. Variable criteria of susceptibility were used in the included studies. Fosfomycin was synergistic in combination with a beta-lactam, aminoglycoside or ciprofloxacin in 46/86 (53.5%) MDR P. aeruginosa isolates. One animal study found a good therapeutic effect of the combination fosfomycin/gentamicin against MDR P. aeruginosa endocarditis. In six clinical studies, 33 patients with MDR P. aeruginosa infections (mainly pulmonary exacerbations of cystic fibrosis) received fosfomycin (25/33 in combination with other antibiotics); 91% of the patients clinically improved. In conclusion, fosfomycin could have a role as a therapeutic option against MDR P. aeruginosa infections. Further research is needed to clarify the potential utility of this agent.
Topics: Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Burkholderia; Drug Resistance, Multiple, Bacterial; Drug Synergism; Endocarditis, Bacterial; Fosfomycin; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 19403273
DOI: 10.1016/j.ijantimicag.2009.03.009 -
The Cochrane Database of Systematic... Feb 2012Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children... (Review)
Review
BACKGROUND
Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis.
OBJECTIVES
To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 25 October 2011.
SELECTION CRITERIA
Randomised and quasi-randomised studies.
DATA COLLECTION AND ANALYSIS
The authors independently extracted data and assessed risk of bias.
MAIN RESULTS
One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while 5 and 4 children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio.
AUTHORS' CONCLUSIONS
We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with cystic fibrosis. While the overall incidence of adverse events was similar in both groups, it is not possible to draw conclusions on the safety and tolerability of respiratory syncytial virus prophylaxis with palivizumab in infants with cystic fibrosis because the trial did not specify how adverse events were classified. Six months after treatment, the authors reported no clinically meaningful differences in outcomes; however no data were provided. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with cystic fibrosis.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Cystic Fibrosis; Humans; Infant; Palivizumab; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 22336832
DOI: 10.1002/14651858.CD007743.pub3 -
The Cochrane Database of Systematic... Dec 2012Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may prove an alternative in people with poor access to their veins.
OBJECTIVES
To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis improves their quality of life, reduces time off school or work and improves their long-term survival.
SEARCH METHODS
We searched ClinicalTrials.gov and the Australia and New Zealand Clinical Trials Registry for relevant trials. Date of last search: 15 March 2012We also searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last search: 01 June 2012.
SELECTION CRITERIA
Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled antibiotic for between one and four weeks.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted data. Authors of the included trials were contacted for more information.
MAIN RESULTS
Six trials with 208 participants were included in the review. Trials were heterogenous in design and interventions (however, all included trials compared inhaled versus intravenous antibiotic regimens). Risk of bias was difficult to assess in most trials. Results were not fully reported and only limited data were available for analysis. Four trials reported some results on forced expiratory volume at one second and found no significant differences between the inhaled antibiotic and the comparison intervention. In two of these trials using 300 mg of inhaled tobramycin, the change in forced expiratory volume at one second was similar to intravenous tobramycin; and in one trial the time until the next exacerbation was not different. No important adverse effects were reported.
AUTHORS' CONCLUSIONS
There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.
Topics: Administration, Inhalation; Amikacin; Anti-Bacterial Agents; Carbenicillin; Ceftazidime; Cystic Fibrosis; Disease Progression; Humans; Injections, Intravenous; Pseudomonas Infections; Pseudomonas aeruginosa; Respiratory Tract Infections; Ticarcillin; Tobramycin
PubMed: 23235659
DOI: 10.1002/14651858.CD008319.pub2 -
Photodiagnosis and Photodynamic Therapy Dec 2023Pseudomonas aeruginosa is a Gram-negative bacillus that causes superficial and deep infections, which can be minor to life-threatening. Recently, P. aeruginosa has... (Review)
Review
BACKGROUND
Pseudomonas aeruginosa is a Gram-negative bacillus that causes superficial and deep infections, which can be minor to life-threatening. Recently, P. aeruginosa has gained significant relevance due to the increased incidence of multidrug-resistant (MDR) strains that complicate antibiotic treatment. Due to MDR strains, alternative therapies, such as antimicrobial photodynamic therapy (PDT), are presented as a good option to treat nonsystemic infections. PDT combines a photosensitizer agent (PS), light, and oxygen to generate free radicals that destroy bacterial structures such as the envelope, matrix, and genetic material. This work aimed to identify the development stage of the PDT applied to P. aeruginosa to conclude which research stage should be emphasized more.
METHODS
Systematic bibliographic search in various public databases was performed. Related articles were identified using keywords, and relevant ones were selected using inclusion and exclusion criteria according to the PRISMA protocol.
RESULTS
We found 29 articles that meet the criteria, constituting a good body of evidence associated with using PDT against P. aeruginosa in vitro and less developed for in vivo research.
CONCLUSIONS
We conclude that PDT could become an effective adjunct to antimicrobial therapy against P. aeruginosa. This effectiveness depends on the PS used and the location of the infection. Many PS already demonstrated efficacy in PDT, but the evidence is supported significantly by in vitro and very few in vivo studies. Therefore, we conclude that further research efforts should focus on demonstrating the safety and efficacy of these PSs in vivo in animal infection models.
Topics: Animals; Pseudomonas Infections; Photosensitizing Agents; Photochemotherapy; Anti-Bacterial Agents; Gram-Negative Bacteria; Pseudomonas aeruginosa
PubMed: 37709240
DOI: 10.1016/j.pdpdt.2023.103803 -
The Cochrane Database of Systematic... Jul 2016Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children... (Review)
Review
BACKGROUND
Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. This is an update of a previously published review.
OBJECTIVES
To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 05 May 2016.
SELECTION CRITERIA
Randomised and quasi-randomised studies.
DATA COLLECTION AND ANALYSIS
The authors independently extracted data and assessed risk of bias.
MAIN RESULTS
One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. We judged there to be a low risk of bias with respect to the concealment of the randomization schedule (although it was not clear how this was generated) and to blinding of participants and study personnel. There is also a low risk of bias with regards to incomplete outcome data. However, we judged there to be a high risk of bias from selective reporting (summary statements presented but no data) and the fact that this industry-supported study has not been published as a full report in a peer-reviewed journal.At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while five and four children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio.
AUTHORS' CONCLUSIONS
We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with cystic fibrosis. While the overall incidence of adverse events was similar in both groups, it is not possible to draw firm conclusions on the safety and tolerability of respiratory syncytial virus prophylaxis with palivizumab in infants with cystic fibrosis. Six months after treatment, the authors reported no clinically meaningful differences in outcomes. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with cystic fibrosis.
Topics: Antiviral Agents; Cystic Fibrosis; Drug Administration Schedule; Humans; Infant; Palivizumab; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 27439110
DOI: 10.1002/14651858.CD007743.pub6 -
The Cochrane Database of Systematic... 2003Persistent infection by Pseudomonas aeruginosa contributes to lung damage, resulting in illness and death in people with cystic fibrosis (CF). Nebulised antibiotics are... (Review)
Review
BACKGROUND
Persistent infection by Pseudomonas aeruginosa contributes to lung damage, resulting in illness and death in people with cystic fibrosis (CF). Nebulised antibiotics are commonly used to treat this infection.
OBJECTIVES
To examine the evidence that nebulised anti-pseudomonal antibiotic treatment in people with CF reduces frequency of exacerbations of infection, improves lung function, quality of life and survival. To examine adverse effects of nebulised anti-pseudomonal antibiotic treatment.
SEARCH STRATEGY
Trials were identified from the Cochrane Cystic Fibrosis and Genetic Disorders Group clinical trials register. Companies that marketed nebulised anti-pseudomonal antibiotics were contacted for information on unpublished trials. Most recent search of the Group's trials register: August 2002.
SELECTION CRITERIA
Trials were selected if, nebulised anti-pseudomonal antibiotics treatment was used for four weeks or more in people with CF, allocation to treatment was randomised or quasi-randomised, and there was a placebo or a no placebo control group or another nebulised antibiotic comparison.
DATA COLLECTION AND ANALYSIS
For the first version of this review, two reviewers independently selected and judged the quality of, the trials to be included in the review. One reviewer extracted data from these trials and performed all tasks for the updated version of the review.
MAIN RESULTS
Out of 33 trials identified, there were 11, with 873 participants, that met the inclusion criteria. Ten trials with 758 participants compared a nebulised anti-pseudomonal antibiotic with placebo or usual treatment. One of these trials accounted for 68% of the total participants and seven of these trials used a cross-over design. Tobramycin was studied in four trials and follow up ranged from 1 to 32 months. Lung function, measured as forced expired volume in one second (FEV1) was better in the treated group than in control group in nine of these. Resistance to antibiotics increased more in the antibiotic treated group than in placebo group. Tinnitus and voice alteration were more frequent with tobramycin than placebo. One short-term trial of one month, with 115 participants, compared tobramycin and colistin, and showed a trend towards greater improvement in FEV1 in the tobramycin group.
REVIEWER'S CONCLUSIONS
Nebulised anti-pseudomonal antibiotic treatment improves lung function. However, more evidence, from longer duration trials, is needed to determine if this benefit is maintained as well as to determine the significance of development of antibiotic resistant organisms. There is insufficient evidence for recommendations about type of drug and dose regimens.
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: 12917897
DOI: 10.1002/14651858.CD001021