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The Cochrane Database of Systematic... Sep 2019People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside...
BACKGROUND
People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher doses less often. This is an update of a previously published review.
OBJECTIVES
To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis.
SEARCH METHODS
We searched the Cystic Fibrosis Specialist Register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings.Date of the most recent search: 31 January 2019.We also searched online trial registries. Date of latest search: 25 February 2019.
SELECTION CRITERIA
All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
The two authors independently selected the studies to be included in the review and assessed the risk of bias of each study; authors also assessed the quality of the evidence using the GRADE criteria. Data were independently extracted by each author. Authors of the included studies were contacted for further information. As yet unpublished data were obtained for one of the included studies.
MAIN RESULTS
We identified 15 studies for possible inclusion in the review. Five studies reporting results from a total of 354 participants (aged 5 to 50 years) were included in this review. All studies compared once-daily dosing with thrice-daily dosing. One cross-over trial had 26 participants who received the first-arm treatment but only 15 received the second arm. One study had a low risk of bias for all criteria assessed; the remaining included studies had a high risk of bias from blinding, but for other criteria were judged to have either an unclear or a low risk of bias.There was little or no difference between treatment groups in: forced expiratory volume in one second, mean difference (MD) 0.33 (95% confidence interval (CI) -2.81 to 3.48, moderate-quality evidence); forced vital capacity, MD 0.29 (95% CI -6.58 to 7.16, low-quality evidence); % weight for height, MD -0.82 (95% CI -3.77 to 2.13, low-quality evidence); body mass index, MD 0.00 (95% CI -0.42 to 0.42, low-quality evidence); or in the incidence of ototoxicity, relative risk 0.56 (95% CI 0.04 to 7.96, moderate-quality evidence). Once-daily treatment in children probably improved the percentage change in creatinine, MD -8.20 (95% CI -15.32 to -1.08, moderate-quality evidence), but showed no difference in adults, MD 3.25 (95% CI -1.82 to 8.33, moderate-quality evidence). The included trials did not report antibiotic resistance patterns or quality of life.
AUTHORS' CONCLUSIONS
Once- and three-times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis. There is evidence of less nephrotoxicity in children.
Topics: Aminoglycosides; Anti-Bacterial Agents; Cystic Fibrosis; Drug Administration Schedule; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Injections, Intravenous; Lung Diseases; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Vital Capacity
PubMed: 31483853
DOI: 10.1002/14651858.CD002009.pub7 -
The Cochrane Database of Systematic... Jun 2017Antibiotic therapy for acute pulmonary exacerbations in people with cystic fibrosis is usually chosen based on the results of antimicrobial susceptibility testing of... (Review)
Review
BACKGROUND
Antibiotic therapy for acute pulmonary exacerbations in people with cystic fibrosis is usually chosen based on the results of antimicrobial susceptibility testing of individual drugs. Combination antimicrobial susceptibility testing assesses the efficacy of drug combinations including two or three antibiotics in vitro and can often demonstrate antimicrobial efficacy against bacterial isolates even when individual antibiotics have little or no effect. Therefore, choosing antibiotics based on combination antimicrobial susceptibility testing could potentially improve response to treatment in people with cystic fibrosis with acute exacerbations. This is an updated version of a previously published review.
OBJECTIVES
To compare antibiotic therapy based on conventional antimicrobial susceptibility testing to antibiotic therapy based on combination antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with cystic fibrosis and chronic infection with Pseudomonas aeruginosa.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 19 December 2016.We also searched ongoing trials registries. Date of latest search: 08 March 2017.
SELECTION CRITERIA
Randomised and quasi-randomised controlled studies of antibiotic therapy based on conventional antimicrobial susceptibility testing compared to antibiotic therapy based on combination antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in cystic fibrosis due to chronic infection with Pseudomonas aeruginosa.
DATA COLLECTION AND ANALYSIS
Both authors independently selected studies, assessed their quality and extracted data from eligible studies. Additionally, the authors contacted the study investigators to obtain further information.
MAIN RESULTS
The search identified one multicentre study eligible for inclusion in the review. This study prospectively assessed whether the use of multiple combination bactericidal antibiotic testing improved clinical outcomes in participants with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria. A total of 132 participants were randomised in the study. The study investigators provided data specific to the 82 participants who were only infected with Pseudomonas aeruginosa for their primary outcome of time until next pulmonary exacerbation. For participants specifically infected with only Pseudomonas aeruginosa, the hazard ratio of a subsequent exacerbation was 0.82, favouring the control group (95% confidence interval 0.44 to 1.51) (P = 0.52). No further data for any of this review's outcomes specific to participants infected with Pseudomonas aeruginosa were available. The risk of bias for the included study was deemed to be low. The quality of the evidence was moderate for the only outcome providing data solely for individuals with infection due to Pseudomonas aeruginosa. For other outcomes, we were unable to judge the quality of the evidence as no data were available for the relevant subset of participants.
AUTHORS' CONCLUSIONS
The current evidence, limited to one study, shows that there is insufficient evidence to determine effect of choosing antibiotics based on combination antimicrobial susceptibility testing compared to choosing antibiotics based on conventional antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with cystic fibrosis with chronic Pseudomonas aeruginosa infection. A large international and multicentre study is needed to further investigate this issue.The only study included in the review was published in 2005, and we have not identified any further relevant studies up to March 2017. We therefore do not plan to update this review until new studies are published.
Topics: Anti-Bacterial Agents; Chronic Disease; Cystic Fibrosis; Disease Progression; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic
PubMed: 28628280
DOI: 10.1002/14651858.CD006961.pub4 -
Le Infezioni in Medicina Sep 2020The present study aims to investigate the prevalence of Pseudomonas aeruginosa in Iranian Cystic Fibrosis (CF) patients. We conducted a systematic search on this topic... (Meta-Analysis)
Meta-Analysis
The present study aims to investigate the prevalence of Pseudomonas aeruginosa in Iranian Cystic Fibrosis (CF) patients. We conducted a systematic search on this topic in Web of Science, PubMed, Embase, Scopus, and Google Scholar electronic databases to the end of July 2019. Then, 14 articles with eligible criteria were selected for data extraction and analysis by Comprehensive Meta-Analysis Software. The pooled prevalence of P. aeruginosa was 40.6% (95% CI: 32.4%-49.4%) ranging from 32.4% to 49.4%. There was a significant heterogeneity among the studies (χ2 =21.02; p <0.001; I2 = 86.07%). The funnel plot for publication bias showed no evidence of asymmetry. Based on the results of Begg's and Egger's test no significant publication bias was observed. The study demonstrated a relative prevalence of P. aeruginosa among CF patients in Iran. Due to the rapid spread and infection severity of P. aeruginosa and other opportunistic pathogens, efforts are required to identify risk factors, reservoirs, transmission routes and source of infection.
Topics: Cystic Fibrosis; Humans; Iran; Prevalence; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 32920566
DOI: No ID Found -
Respiratory Medicine Jan 2021Non-cystic fibrosis bronchiectasis (NCFBE) is a chronic and progressive disease characterized by the permanent destruction of small and mid-sized airways. Many patients... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Non-cystic fibrosis bronchiectasis (NCFBE) is a chronic and progressive disease characterized by the permanent destruction of small and mid-sized airways. Many patients are chronically colonized by Pseudomona aueruginosa, for which oral antibiotics are given. Evidence to support the use of inhaled antibiotics is contradictory.
OBJECTIVE
To describe the clinical effects of inhaled Tobramycin in P. aeruginosa density in sputum and eradication, lung function, bacterial resistance, and exacerbations requiring hospital admission, in the context of patients with NCFBE colonized by P. aeruginosa.
METHODS
We included RCTs comparing inhaled tobramycin to other antibiotics and placebo in patients with NCFBE.
MAIN FINDINGS
5 studies with 211 participants were included. 2 studies reported a significant but transitory decrease in P. aeruginosa density in sputum as compared to placebo. There was a small difference in the eradication of P. aeruginosa among groups, although with very wide confidence intervals. Tobramycin reduced the rate of hospital admissions but no frequency of exacerbations. There was no evidence of an increased rate of bacterial resistance but was associated to respiratory adverse effects.
CONCLUSIONS
Evidence is not robust enough to confirm a benefit of inhaled Tobramycin in reducing P. aeruginosa sputum density or eradication. There was a high attrition rate, in part due to respiratory adverse events after drug administration, which affects interpretation of the data and raises concerns about the tolerability of the drug. Further network meta-analysis should be done to compare the efficacy and safety of different inhaled antibiotics.
Topics: Administration, Inhalation; Bronchiectasis; Chronic Disease; Disease Progression; Female; Humans; Male; Middle Aged; Pseudomonas Infections; Pseudomonas aeruginosa; Sputum; Tobramycin; Treatment Outcome
PubMed: 33307314
DOI: 10.1016/j.rmed.2020.106283 -
International Journal of Infectious... Sep 2020Alternative dosing strategies for β-lactams - the most common antibiotics used to treat critically ill patients with respiratory tract infections - have been... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of extended versus intermittent infusion of antipseudomonal beta-lactams for the treatment of critically ill patients with respiratory infections: A systematic review and meta-analysis.
OBJECTIVES
Alternative dosing strategies for β-lactams - the most common antibiotics used to treat critically ill patients with respiratory tract infections - have been recommended to maximize the duration of exposure and reduce drug resistance. The objective of this study was to evaluate whether extended infusion of antipseudomonal β-lactams improves mortality and clinical efficacy.
METHODS
Two independent authors identified eligible trials by searching the PubMed, Cochrane Library, Scopus, and ICHUSHI databases, in both English and Japanese, up to June 2019. Data were extracted from both randomized controlled and observational trials comparing extended infusion (≥3h) with intermittent infusion in critically ill patients. The primary outcome was all-cause mortality. Risk differences (RD) and 95% confidential intervals (CI) were calculated using a random-effects model and subgroup analyses were performed. Sensitivity and heterogeneity were also evaluated.
RESULTS
Nine studies involving 1508 participants were included in the meta-analysis. Mortality was lower for extended infusion than for intermittent infusion (RD -0.10; 95% CI -0.15 to -0.04). However, no significant between-group differences in clinical success, length of ICU stay, length of hospital stay, and antibiotic duration were observed.
CONCLUSIONS
Extended infusions of β-lactams were associated with reduced mortality rates but not with clinical success.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Critical Illness; Data Management; Humans; Infusion Pumps; Length of Stay; Middle Aged; Pseudomonas; Respiratory Tract Infections; Time Factors; Treatment Outcome; beta-Lactams
PubMed: 32535299
DOI: 10.1016/j.ijid.2020.06.022 -
The Cochrane Database of Systematic... Dec 2019Chronic infection with Pseudomonas aeruginosa (PA) in cystic fibrosis (CF) is a source of much morbidity and mortality. Eradication of early PA infection is possible,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic infection with Pseudomonas aeruginosa (PA) in cystic fibrosis (CF) is a source of much morbidity and mortality. Eradication of early PA infection is possible, but can recur in many individuals. We sought to examine strategies to delay the time to PA recurrence in people with CF.
OBJECTIVES
To establish whether secondary prevention strategies, using antibiotics or other therapies, increase the chances of people with CF remaining free from PA infection following successful eradication therapy.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 21 August 2019.
SELECTION CRITERIA
Randomised controlled trials (and quasi-randomised trials where the risk of bias was low) comparing any treatment modality aimed at preventing recurrence of PA infection with placebo, standard therapy or any other treatment modality in people with CF who have undergone successful eradication of PA.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias. Quality of the evidence was assessed using GRADE. Conflicts were resolved by discussion and the opinion of a third review author was sought where necessary. Only a subset of participants in the included trial were eligible, therefore individual participant data were requested and obtained from the trial investigators.
MAIN RESULTS
We included one trial (n = 306) in the review; however, only 253 participants had undergone successful eradication of PA, so fulfilling the inclusion criteria for our review. Information presented relates only to the included subset of participants. The trial recruited children aged one to 12 years (mean (standard deviation (SD)) age of 5.8 (3.5) years), 129 participants (51.0%) were female and the median follow-up was 494 days. We compared cycled therapy with tobramycin inhalation solution (TIS), in which participants underwent 28 days of TIS every three months, with culture-based therapy, in which participants were only prescribed medication when a quarterly sputum sample was positive for PA. Reasons for downgrading the quality of the evidence included applicability (only included children), incomplete outcome data and a small number of participants. The time to next isolation of PA was probably shorter with cycled TIS therapy than with culture-based therapy, hazard ratio (HR) 2.04 days (95% confidence interval (CI) 1.28 to 3.26) (moderate-quality evidence). This is in contrast to the main publication of the only included trial, which examined rate of PA positivity rather than time to PA infection and included participants not eligible for inclusion in this review. At the end of the trial, there was no difference between the cycled and culture-based groups in the change from baseline in forced expiratory volume in one second (FEV) L, mean difference (MD) 0.0 L (95% CI -0.09 to 0.09) or in FEV % predicted, MD 0.70% (95% CI -4.33 to 5.73) (both very low-quality evidence). There was no difference in the change from baseline for FVC between the groups. There was also no difference in the frequency of pulmonary exacerbations between groups, MD -0.18 (95% CI -0.51 to 0.14) (moderate-quality evidence). Similarly, there was no difference between groups in the risk of participants developing novel resistant bacteria, RR 1.00 (95% CI 0.67 to 1.5) (moderate-quality evidence). There were more severe adverse events in the cycled group, but the type of treatment probably makes little or no difference to the results, RR 0.65 (95% CI 0.39 to 1.11) (moderate-quality evidence). There was no difference between groups in the change in weight or height from baseline or in rates of adherence to tobramycin or all trial medicines. The included trial did not assess changes in quality of life, the time to chronic infection with PA or the cost-effectiveness of treatment.
AUTHORS' CONCLUSIONS
Cycled TIS therapy may be beneficial in prolonging the time to recurrence of PA after successful eradication, but further trials are required, specifically addressing this question and in both adults and children.
Topics: Administration, Inhalation; Anti-Bacterial Agents; Cystic Fibrosis; Forced Expiratory Volume; Humans; Pseudomonas Infections; Pseudomonas aeruginosa; Quality of Life; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Tobramycin
PubMed: 31845758
DOI: 10.1002/14651858.CD012300.pub2 -
BMC Infectious Diseases Jun 2021Effective treatment of sepsis due to carbapenem-resistant Gram-negative bacteria (CR-GNB) remains a challenge for clinicians worldwide. In recent years, the combination...
BACKGROUND
Effective treatment of sepsis due to carbapenem-resistant Gram-negative bacteria (CR-GNB) remains a challenge for clinicians worldwide. In recent years, the combination of antibiotics has become the preferred treatment strategy for CR-GNB infection. However, robust evidence to support this approach is lacking. This systematic review aimed at critically evaluating all available antibiotic options for CR-GNB sepsis with particular focus on combination.
METHODS
We systematically searched published literature from January 1945 until December 2018 for observational comparative and non-comparative studies and randomized trials examining any antibiotic option for CR-GNB. Studies were included if reporting microbiologically-confirmed infection caused by Acinetobacter baumannii, Enterobacteriaceae/Klebsiella spp., or Pseudomonas aeruginosa, reporting at least one of the study outcomes, and definitive antibiotic treatment. Carbapenem-resistance was defined as phenotypically-detected in vitro resistance to at least one of the following carbapenems: doripenem, ertapenem, imipenem, meropenem. Each antibiotic regimen was classified as "defined" when at least the molecular class(es) composing the regimen was detailed. Primary outcomes were 30-day and attributable mortality. Bayesian network meta-analysis (NMA) approach was selected for quantitative synthesis to explore feasibility of pooling data on antibiotic regimens.
RESULTS
A total of 6306 records were retrieved and 134 studies including 11,546 patients were included: 54 studies were on Acinetobacter, 52 on Enterobacteriaceae/Klebsiella, 21 on mixed Gram-negative, and 7 on Pseudomonas. Nine (7%) were RCTs; 19 prospective cohorts (14%), 89 (66%) retrospective, and 17 (13%) case series. Forty-one studies (31%) were multicentric. Qualitative synthesis showed an heterogeneous and scattered reporting of key-clinical and microbiological variables across studies. Ninety-two distinct antibiotic regimens were identified with 47 of them (51%, 5863 patients) not reporting any details on numbers, type, dosage and in vitro activity of the included antibiotic molecules. The NMAs could not be performed for any of the selected outcome given the presence of too many disconnected components.
CONCLUSION
The existing evidence is insufficient to allowing for the formulation of any evidence-based therapeutic recommendation for CR-GNB sepsis. Future studies must provide a standardized definition of antibiotic regimen to drive recommendations for using combination of antibiotics that can be reliably applied to clinical practice.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Carbapenems; Clinical Studies as Topic; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Pseudomonas aeruginosa
PubMed: 34107899
DOI: 10.1186/s12879-021-06253-x -
The Cochrane Database of Systematic... May 2020Antibiotic therapy for acute pulmonary exacerbations in people with cystic fibrosis is usually chosen based on the results of antimicrobial susceptibility testing of...
BACKGROUND
Antibiotic therapy for acute pulmonary exacerbations in people with cystic fibrosis is usually chosen based on the results of antimicrobial susceptibility testing of individual drugs. Combination antimicrobial susceptibility testing assesses the efficacy of drug combinations including two or three antibiotics in vitro and can often demonstrate antimicrobial efficacy against bacterial isolates even when individual antibiotics have little or no effect. Therefore, choosing antibiotics based on combination antimicrobial susceptibility testing could potentially improve response to treatment in people with cystic fibrosis with acute exacerbations. This is an updated version of a previously published review.
OBJECTIVES
To compare antibiotic therapy based on conventional antimicrobial susceptibility testing to antibiotic therapy based on combination antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with cystic fibrosis and chronic infection with Pseudomonas aeruginosa.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 19 March 2020. We also searched ongoing trials registries. Date of latest search: 07 April 2020.
SELECTION CRITERIA
Randomised and quasi-randomised controlled studies of antibiotic therapy based on conventional antimicrobial susceptibility testing compared to antibiotic therapy based on combination antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in cystic fibrosis due to chronic infection with Pseudomonas aeruginosa.
DATA COLLECTION AND ANALYSIS
Both authors independently selected studies, assessed their quality and extracted data from eligible studies. Additionally, the authors contacted the study investigators to obtain further information.
MAIN RESULTS
The search identified one multicentre study eligible for inclusion in the review. This study prospectively assessed whether the use of multiple combination bactericidal antibiotic testing improved clinical outcomes in participants with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria. A total of 132 participants were randomised in the study. The study investigators provided data specific to the 82 participants who were only infected with Pseudomonas aeruginosa for their primary outcome of time until next pulmonary exacerbation. For participants specifically infected with only Pseudomonas aeruginosa, the hazard ratio of a subsequent exacerbation was 0.82, favouring the control group (95% confidence interval 0.44 to 1.51) (P = 0.52). No further data for any of this review's outcomes specific to participants infected with Pseudomonas aeruginosa were available. The risk of bias for the included study was deemed to be low. The quality of the evidence was moderate for the only outcome providing data solely for individuals with infection due to Pseudomonas aeruginosa. For other outcomes, we were unable to judge the quality of the evidence as no data were available for the relevant subset of participants.
AUTHORS' CONCLUSIONS
The current evidence, limited to one study, shows that there is insufficient evidence to determine effect of choosing antibiotics based on combination antimicrobial susceptibility testing compared to choosing antibiotics based on conventional antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with cystic fibrosis with chronic Pseudomonas aeruginosa infection. A large international and multicentre study is needed to further investigate this issue. The only study included in the review was published in 2005, and we have not identified any further relevant studies up to March 2017. We therefore do not plan to update this review until new studies are published.
Topics: Anti-Bacterial Agents; Chronic Disease; Cystic Fibrosis; Disease Progression; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic
PubMed: 32412092
DOI: 10.1002/14651858.CD006961.pub5