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Medicine Dec 2021Antipseudomonal β-lactams have been used for the treatment of febrile neutropenia (FN); however, the efficacy and safety of antipseudomonal β-lactams in pediatric...
BACKGROUND
Antipseudomonal β-lactams have been used for the treatment of febrile neutropenia (FN); however, the efficacy and safety of antipseudomonal β-lactams in pediatric patients remain unclear. The aim of this study was to comprehensively compare the efficacy and side effects of optional antipseudomonal β-lactams for pediatric FN.
METHODS
PubMed, Embase, Medline, and Cochrane Library were systematically searched from their inception to December 18, 2020. Eligible randomized controlled trials in which pediatric FN patients were treated with an empiric monotherapy of antipseudomonal β-lactams were selected. Data synthesis was performed using WinBUGS 14.0 software and meta packages implemented in R 3.6.2. Random-effects network meta-analysis was performed, and dichotomous data were pooled as odds ratios with 95% confidence intervals. The primary outcome was treatment success without modification; the secondary outcomes were adverse events (AEs), all-cause mortality, and new infections. The GRADE tool was used to assess the quality of the evidence. The protocol was registered with PROSPERO ID CRD42021226763.
RESULTS
Eighteen studies with 2517 patients were included. The results showed no statistically significant difference between the optional antipseudomonal β-lactams in the outcomes of treatment success without modification, all AEs, all-cause mortality, and new infections for pediatric FN. Based on the results of Bayesian rank probability, meropenem was ranked highest among all the treatment options with regard to treatment success without modification benefit; ceftazidime and meropenem were associated with a lower risk of AEs; cefoperazone/sulbactam and piperacillin/tazobactam were associated with a lower risk of mortality, and piperacillin/tazobactam and meropenem were associated with a lower risk of new infections. The quality of evidence was moderate.
CONCLUSIONS
Meropenem and piperacillin/tazobactam were found to be better with regard to treatment success without modification, with a comparable safety profile. Therefore, our findings support the use of meropenem and piperacillin/tazobactam as a treatment option for pediatric FN patients.
Topics: Anti-Bacterial Agents; Ceftazidime; Child; Drug Therapy, Combination; Febrile Neutropenia; Female; Humans; Imipenem; Male; Meropenem; Network Meta-Analysis; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Treatment Outcome; beta-Lactams
PubMed: 34918626
DOI: 10.1097/MD.0000000000027266 -
The Cochrane Database of Systematic... Sep 2018Early diagnosis and treatment of lower respiratory tract infections are the mainstay of management of lung disease in cystic fibrosis. When sputum samples are... (Review)
Review
BACKGROUND
Early diagnosis and treatment of lower respiratory tract infections are the mainstay of management of lung disease in cystic fibrosis. When sputum samples are unavailable, treatment relies mainly on cultures from oropharyngeal specimens; however, there are concerns regarding the sensitivity of these to identify lower respiratory organisms.Bronchoscopy and related procedures (including bronchoalveolar lavage) though invasive, allow the collection of lower respiratory specimens from non-sputum producers. Cultures of bronchoscopic specimens provide a higher yield of organisms compared to those from oropharyngeal specimens. Regular use of bronchoscopy and related procedures may help in a more accurate diagnosis of lower respiratory tract infections and guide the selection of antimicrobials, which may lead to clinical benefits.This is an update of a previous review.
OBJECTIVES
To evaluate the use of bronchoscopy-guided antimicrobial therapy in the management of lung infection in adults and children with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of latest search: 30 August 2018.We also searched three registries of ongoing studies and the reference lists of relevant articles and reviews. Date of latest search: 10 April 2018.
SELECTION CRITERIA
We included randomized controlled studies including people of any age with cystic fibrosis, comparing outcomes following therapies guided by the results of bronchoscopy (and related procedures) with outcomes following therapies guided by the results of any other type of sampling (including cultures from sputum, throat swab and cough swab).
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed their risk of bias and extracted data. We contacted study investigators for further information. The quality of the evidence was assessed using the GRADE criteria.
MAIN RESULTS
The search identified 11 studies, but we only included one study enrolling infants with cystic fibrosis under six months of age and diagnosed through newborn screening (170 enrolled); participants were followed until they were five years old (data from 157 children). The study compared outcomes following therapy directed by bronchoalveolar lavage for pulmonary exacerbations with standard treatment based on clinical features and oropharyngeal cultures.We considered this study to have a low risk of bias; however, the statistical power to detect a significant difference in the prevalence of Pseudomonas aeruginosa was limited due to the prevalence (of Pseudomonas aeruginosa isolation in bronchoalveolar lavage samples at five years age) being much lower in both the groups compared to that which was expected and which was used for the power calculation. The sample size was adequate to detect a difference in high-resolution computed tomography scoring. The quality of evidence for the key parameters was graded as low except high-resolution computed tomography scoring and cost of care analysis, which were graded as moderate quality.At five years of age, there was no clear benefit of bronchoalveolar lavage-directed therapy on lung function z scores or nutritional parameters. Evaluation of total and component high-resolution computed tomography scores showed no significant difference in evidence of structural lung disease in the two groups.In addition, this study did not show any difference between the number of isolates of Pseudomonas aeruginosa per child per year diagnosed in the bronchoalveolar lavage-directed therapy group compared to the standard therapy group. The eradication rate following one or two courses of eradication treatment was comparable in the two groups, as were the number of pulmonary exacerbations. However, the number of hospitalizations was significantly higher in the bronchoalveolar lavage-directed therapy group, but the mean duration of hospitalizations was significantly less compared to the standard therapy group.Mild adverse events were reported in a proportion of participants, but these were generally well-tolerated. The most common adverse event reported was transient worsening of cough after 29% of procedures. Significant clinical deterioration was documented during or within 24 hours of bronchoalveolar lavage in 4.8% of procedures.
AUTHORS' CONCLUSIONS
This review, limited to a single, well-designed randomized controlled study, shows no clear evidence to support the routine use of bronchoalveolar lavage for the diagnosis and management of pulmonary infection in pre-school children with cystic fibrosis compared to the standard practice of providing treatment based on results of oropharyngeal culture and clinical symptoms. No evidence was available for adult and adolescent populations.
Topics: Anti-Bacterial Agents; Bronchoalveolar Lavage; Bronchoscopy; Child, Preschool; Cystic Fibrosis; Humans; Infant; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic
PubMed: 30221745
DOI: 10.1002/14651858.CD009530.pub4 -
Microbial Pathogenesis Nov 2023Gram-negative bacteria are infectious and life-threatening agents after hematopoietic stem cell transplantation (HSCT). So, this study aimed to investigate the... (Review)
Review
Gram-negative bacteria are infectious and life-threatening agents after hematopoietic stem cell transplantation (HSCT). So, this study aimed to investigate the prevalence of Pseudomonas aeruginosa and its antibiotic resistance in patients who have received Hematopoietic Stem-Cell Transplantation through a systematic review. The systematic search was done with key words; Pseudomonas aeruginosa, hematopoietic stem cell transplantation from 2000 to the end of July 2023 in Google Scholar and PubMed/Medline, Scopus, and Web of Science. Twelve studies were able to include our study. Quality assessment of studies was done by Appraisal tool for Cross-Sectional Studies. The most of the included studies were conducted as allo-HSCT. Infections such as respiratory infection, urinary infection and bacteremia have occurred. The rate of prevalence with P. aeruginosa has varied between 3 and 100%. The average age of the participants was between 1 and 74 years. The rate of prevalence of P. aeruginosa resistant to several drugs has been reported to be variable, ranging from 20 to 100%. The highest antibiotic resistance was reported against cefotetan (100%), and the lowest was related to tobramycin (1.8%) followed by amikacin, levofloxacin and ciprofloxacin with the prevalence of 16.6%. Our findings showed a high prevalence and antibiotic resistance rate of P. aeruginosa in Hematopoietic stem cell transplantation. Therefore, more serious health measures should be taken in patients after transplantation.
Topics: Humans; Anti-Bacterial Agents; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Hematopoietic Stem Cell Transplantation; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections
PubMed: 37769854
DOI: 10.1016/j.micpath.2023.106368 -
Clinical Microbiology and Infection :... Aug 2019Pseudomonas aeruginosa is mostly a nosocomial pathogen affecting predisposed patients. However, community-onset bloodstream infections (CO-BSI) caused by this organism... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pseudomonas aeruginosa is mostly a nosocomial pathogen affecting predisposed patients. However, community-onset bloodstream infections (CO-BSI) caused by this organism are not exceptional.
OBJECTIVES
To assess the predisposing factors for CO-BSI due to P. aeruginosa (CO-BSI-PA) and the impact in mortality of inappropriate empirical antimicrobial therapy.
DATA SOURCE
A systematic literature search was performed in the Medline, Embase, Cochrane Library, Scopus and Web of Science databases. Study eligibility criteria and participants: Articles published between 1 January 2002 and 31 January 2018 reporting at least of 20 adult patients with CO-BSI due to P. aeruginosa were considered.
INTERVENTION
Empiric antimicrobial therapy for CO-BSI-PA.
METHODS
A systematic review and a meta-analysis were conducted for risk factors and to evaluate if inappropriate empiric antimicrobial therapy increased mortality in CO-BSI-PA using a Mantel-Haenszel effects model.
RESULTS
Twelve studies assessing data of 1120 patients were included in the systematic review. Solid tumour (33.1%), haematologic malignancy (26.4%), neutropenia (31.7%) and previous antibiotic use (44.8%) were the most prevalent predisposing factors. Septic shock was present in 42.3% of cases, and 30-day crude mortality was 33.8%. Mortality in meta-analysis (four studies) was associated with septic shock at presentation (odds ratio, 22.31; 95% confidence interval, 3.52-141.35; p 0.001) and with inappropriate empiric antibiotic therapy (odds ratio, 1.83; 95% confidence interval, 1.12-2.98l p 0.02).
CONCLUSIONS
CO-BSI-PA mostly occurred in patients with predisposing factors and had a 30-day mortality comparable to hospital-acquired cases. Inappropriate empirical antibiotic therapy was associated with increased mortality. Appropriate identification of patients at risk for CO-BSI-PA is needed for empirical treatment decisions.
Topics: Anti-Bacterial Agents; Bacteremia; Cross Infection; Humans; Inappropriate Prescribing; Pseudomonas Infections; Pseudomonas aeruginosa; Risk Factors; Shock, Septic
PubMed: 30995530
DOI: 10.1016/j.cmi.2019.04.005 -
The Lancet. Infectious Diseases Apr 2013Many meta-analyses have shown reductions in infection rates and mortality associated with the use of selective digestive decontamination (SDD) or selective oropharyngeal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many meta-analyses have shown reductions in infection rates and mortality associated with the use of selective digestive decontamination (SDD) or selective oropharyngeal decontamination (SOD) in intensive care units (ICUs). These interventions have not been widely implemented because of concerns that their use could lead to the development of antimicrobial resistance in pathogens. We aimed to assess the effect of SDD and SOD on antimicrobial resistance rates in patients in ICUs.
METHODS
We did a systematic review of the effect of SDD and SOD on the rates of colonisation or infection with antimicrobial-resistant pathogens in patients who were critically ill. We searched for studies using Medline, Embase, and Cochrane databases, with no limits by language, date of publication, study design, or study quality. We included all studies of selective decontamination that involved prophylactic application of topical non-absorbable antimicrobials to the stomach or oropharynx of patients in ICUs, with or without additional systemic antimicrobials. We excluded studies of interventions that used only antiseptic or biocide agents such as chlorhexidine, unless antimicrobials were also included in the regimen. We used the Mantel-Haenszel model with random effects to calculate pooled odds ratios.
FINDINGS
We analysed 64 unique studies of SDD and SOD in ICUs, of which 47 were randomised controlled trials and 35 included data for the detection of antimicrobial resistance. When comparing data for patients in intervention groups (those who received SDD or SOD) versus data for those in control groups (who received no intervention), we identified no difference in the prevalence of colonisation or infection with Gram-positive antimicrobial-resistant pathogens of interest, including meticillin-resistant Staphylococcus aureus (odds ratio 1·46, 95% CI 0·90-2·37) and vancomycin-resistant enterococci (0·63, 0·39-1·02). Among Gram-negative bacilli, we detected no difference in aminoglycoside-resistance (0·73, 0·51-1·05) or fluoroquinolone-resistance (0·52, 0·16-1·68), but we did detect a reduction in polymyxin-resistant Gram-negative bacilli (0·58, 0·46-0·72) and third-generation cephalosporin-resistant Gram-negative bacilli (0·33, 0·20-0·52) in recipients of selective decontamination compared with those who received no intervention.
INTERPRETATION
We detected no relation between the use of SDD or SOD and the development of antimicrobial-resistance in pathogens in patients in the ICU, suggesting that the perceived risk of long-term harm related to selective decontamination cannot be justified by available data. However, our study indicates that the effect of decontamination on ICU-level antimicrobial resistance rates is understudied. We recommend that future research includes a non-crossover, cluster randomised controlled trial to assess long-term ICU-level changes in resistance rates.
FUNDING
None.
Topics: Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents, Local; Cephalosporins; Clinical Trials as Topic; Cross Infection; Decontamination; Digestive System; Disease Transmission, Infectious; Drug Resistance, Bacterial; Enterobacteriaceae; Europe; Fluoroquinolones; Gentamicins; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Intensive Care Units; Methicillin-Resistant Staphylococcus aureus; Neomycin; Nystatin; Odds Ratio; Oropharynx; Polymyxins; Prevalence; Primary Prevention; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; South Africa; Tobramycin; United States; Vancomycin
PubMed: 23352693
DOI: 10.1016/S1473-3099(12)70322-5 -
Clinical Therapeutics Oct 2016In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas... (Comparative Study)
Comparative Study Meta-Analysis Review
Comparison of Inhaled Antibiotics for the Treatment of Chronic Pseudomonas aeruginosa Lung Infection in Patients With Cystic Fibrosis: Systematic Literature Review and Network Meta-analysis.
PURPOSE
In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF). Levofloxacin inhalation solution (LIS) is the most recently approved inhaled antibiotic for adult patients with CF. A systematic literature review and Bayesian network meta-analysis (NMA) was conducted to compare the relative short-term (4 weeks) and long-term (24 weeks) outcomes of these inhaled antibiotics versus LIS.
METHODS
A systematic literature search was conducted on February 16, 2016, using EMBASE and Medline via OvidSP. All randomized controlled trials comparing any of the aforementioned inhaled antibiotics with 4 or 24 weeks of follow-up were evaluated. NMA was performed for the following outcomes: relative and absolute percent changes from baseline in forced expiratory volume in 1 second (FEV%) predicted, change in P aeruginosa sputum density, respiratory symptoms score from the CF questionnaire-revised, hospitalization, additional antibiotics use, and study withdrawal rates.
RESULTS
Of the 685 articles identified, 7 unique studies were included in the 4 weeks' NMA and 9 unique studies were included in the 24 weeks' NMA. Aztreonam was predicted to result in the greatest numerically increase in FEV% predicted at 4 weeks, whereas LIS were predicted to be numerically greater than colistimethate sodium, tobramycin inhaled solution (TIS), and tobramycin inhaled powder (TIP). However, all of the 95% credibility intervals (CrIs) of these comparisons included zero. At 24 weeks, none of the treatments was significantly more effective than LIS. The estimates for the mean change from baseline to 24 weeks in relative FEV% versus LIS was -0.55 (95% CrI, -3.91 to 2.80) for TIS, -2.36 (95% CrI, -7.32 to 2.63) for aztreonam, -2.95 (95% CrI, -10.44 to 4.51) for TIP, and -9.66 (95% CrI, -15.01 to -4.33) for placebo. Compared with LIS, the odds ratio for hospitalization at 24 weeks was 1.92 (95% CrI, 1.01-3.30) for TIS, 2.25 (95% CrI, 1.01-4.34) for TIP, and 3.16 (95% CrI, 1.53-5.78) for placebo, all statistically worse than LIS. P aeruginosa sputum density scores, additional use of antipseudomonal antibiotics, and study withdrawal rates were comparable among all inhaled antibiotics at all times.
IMPLICATIONS
Based on this NMA, the analyses for many of the outcomes did not provide significant evidence to indicate that the other approved inhaled antibiotics were more effective than LIS for the treatment of chronic P aeruginosa lung infection in patients with CF. Study withdrawal rates seemed to be comparable among these inhaled antibiotics.
Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Bayes Theorem; Chronic Disease; Cystic Fibrosis; Europe; Forced Expiratory Volume; Humans; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Tract Infections
PubMed: 27692977
DOI: 10.1016/j.clinthera.2016.08.014 -
Clinical Infectious Diseases : An... Feb 2019Carbapenem-resistant Enterobacteriaceae (CRE), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPsA) are a serious cause of healthcare-associated...
Control of Carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa in Healthcare Facilities: A Systematic Review and Reanalysis of Quasi-experimental Studies.
Carbapenem-resistant Enterobacteriaceae (CRE), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPsA) are a serious cause of healthcare-associated infections, although the evidence for their control remains uncertain. We conducted a systematic review and reanalysis to assess infection prevention and control (IPC) interventions on CRE-CRAB-CRPsA in inpatient healthcare facilities to inform World Health Organization guidelines. Six major databases and conference abstracts were searched. Before-and-after studies were reanalyzed as interrupted time series if possible. Effective practice and organization of care (EPOC) quality criteria were used. Seventy-six studies were identified, of which 17 (22%) were EPOC-compatible and interrupted time series analyses, assessing CRE (n = 11; 65%), CRAB (n = 5; 29%) and CRPsA (n = 3; 18%). IPC measures were often implemented using a multimodal approach (CRE: 10/11; CRAB: 4/5; CRPsA: 3/3). Among all CRE-CRAB-CRPsA EPOC studies, the most frequent intervention components included contact precautions (90%), active surveillance cultures (80%), monitoring, audit and feedback of measures (80%), patient isolation or cohorting (70%), hand hygiene (50%), and environmental cleaning (40%); nearly all studies with these interventions reported a significant reduction in slope and/or level. The quality of EPOC studies was very low to low.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Health Facilities; Humans; Pseudomonas aeruginosa
PubMed: 30475989
DOI: 10.1093/cid/ciy752 -
International Journal of Infectious... Feb 2024The objective of this systematic review and meta-analysis was to estimate the global prevalence of multi-drug resistant (MDR) Pseudomonas aeruginosa causing... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The objective of this systematic review and meta-analysis was to estimate the global prevalence of multi-drug resistant (MDR) Pseudomonas aeruginosa causing ventilator-associated pneumonia (VAP).
METHODS
The systematic search was conducted in four databases. Original studies describing MDR P. aeruginosa VAP prevalence in adults from 2012- 2022 were included. A meta-analysis, using the random effects model, was conducted for overall, subgroups (country, published year, study duration, and study design), and European data, respectively. Univariate meta-regression based on pooled estimates was also conducted. Systematic review registered in International Prospective Register of Systematic Review (CRD42022384035).
RESULTS
In total of 31 studies, containing a total of 7951 cases from 16 countries, were included. The overall pooled prevalence of MDR among P. aeruginosa causing VAP was 33% (95% confidence interval [CI] 27.7-38.3%). The highest prevalence was for Iran at 87.5% (95% CI 69-95.7%), and the lowest was for the USA at 19.7% (95% CI 18.6-20.7%). The European prevalence was 29.9% (95% CI 23.2-36.7%).
CONCLUSIONS
This review indicates that the prevalence of MDR P. aeruginosa in patients with VAP is generally high and varies significantly between countries; however, data are insufficient for many countries. The data in this study can provide a reference for VAP management and drug customisation strategies.
Topics: Adult; Humans; Anti-Bacterial Agents; Pneumonia, Ventilator-Associated; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections
PubMed: 38013153
DOI: 10.1016/j.ijid.2023.11.023 -
The Cochrane Database of Systematic... Oct 2013Pseudomonas aeruginosa is the most common bacterial pathogen causing lung infections in people with CF and appropriate antibiotic therapy is vital. Antibiotics for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pseudomonas aeruginosa is the most common bacterial pathogen causing lung infections in people with CF and appropriate antibiotic therapy is vital. Antibiotics for pulmonary exacerbations are usually given intravenously, and for long-term treatment, via a nebuliser. Oral anti-pseudomonal antibiotics with the same efficacy and safety as intravenous or nebulised antibiotics would benefit people with CF due to ease of treatment and avoidance of hospitalisation.
OBJECTIVES
To determine the benefit or harm of oral anti-pseudomonal antibiotic therapy for people with CF, colonised with Pseudomonas aeruginosa, in the:1. treatment of a pulmonary exacerbation; and 2. long-term treatment of chronic infection.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We contacted pharmaceutical companies and checked reference lists of identified trials.Date of last search: 28 June 2013.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials comparing any dose of oral anti-pseudomonal antibiotics, to other combinations of inhaled, oral or intravenous antibiotics, or to placebo or usual treatment for pulmonary exacerbations and long-term treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently selected the trials, extracted data and assessed quality. We contacted trial authors to obtain missing information.
MAIN RESULTS
We included three trials examining pulmonary exacerbations (171 participants) and two trials examining long-term therapy (85 participants). We regarded the most important outcomes as quality of life and lung function. The analysis did not identify any statistically significant difference between oral anti-pseudomonal antibiotics and other treatments for these outcome measures for either pulmonary exacerbations or long-term treatment. One of the included trials reported significantly better lung function when treating a pulmonary exacerbation with ciprofloxacin when compared with intravenous treatment; however, our analysis did not confirm this finding. We found no evidence of difference between oral anti-pseudomonal antibiotics and other treatments regarding adverse events or development of antibiotic resistance, but trials were not adequately powered to detect this. None of the studies had a low risk of bias from blinding which may have an impact particularly on subjective outcomes such as quality of life. The risk of bias for other criteria could not be clearly stated across the studies.
AUTHORS' CONCLUSIONS
We found no conclusive evidence that an oral anti-pseudomonal antibiotic regimen is more or less effective than an alternative treatment for either pulmonary exacerbations or long-term treatment of chronic infection with P. aeruginosa. Until results of adequately-powered future trials are available, treatment needs to be selected on a pragmatic basis, based upon any available non-RCT evidence, the clinical circumstances of the individual, the known effectiveness of drugs against local strains and upon individual preference.
Topics: Adult; Anti-Bacterial Agents; Child; Cystic Fibrosis; Humans; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Treatment Outcome
PubMed: 24170644
DOI: 10.1002/14651858.CD005405.pub3 -
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