-
International Journal of Antimicrobial... Jun 2021The global rise in nosocomial pneumonia caused by multidrug-resistant (MDR) Gram-negative pathogens and the increasingly limited antibiotic treatment options are growing...
The global rise in nosocomial pneumonia caused by multidrug-resistant (MDR) Gram-negative pathogens and the increasingly limited antibiotic treatment options are growing threats to modern medicine. As a result, older antibiotics such as polymyxins are being used as last-resort drugs for MDR nosocomial pneumonia. Polymyxins are bactericidal against most aerobic Gram-negative bacilli. High-dose intravenous (IV) adminsitration of polymyxins, however, results in subtherapeutic concentrations at the site of infection making treatment challenging. Alternative forms of polymyxin delivery have been considered in order to better achieve the necessary concentrations at the site of infection. Several studies have evaluated the effectiveness of aerosolised polymyxins in patients with nosocomial pneumonia caused by MDR Gram-negative pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. Here we evaluated the pharmacokinetic data supporting the use of inhaled polymyxins in nosocomial pneumonia and provide insight into the limitations and challenges that future studies should address. We have also reviewed the literature published between 2006 and 2020 on the use of aerosolised polymyxins for the treatment of nosocomial pneumonia, including ventilator-associated pneumonia, in patients without cystic fibrosis to evaluate their safety and efficacy as monotherapy or as an adjunct to IV antimicrobials. This review highlights the need for well-designed multicentre studies with standardised methodologies to further evaluate the effectiveness of inhaled polymyxins and to provide reliable pharmacokinetic/pharmacodynamic data in order to redefine appropriate dosing strategies.
Topics: Acinetobacter baumannii; Administration, Inhalation; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Klebsiella pneumoniae; Pneumonia, Ventilator-Associated; Polymyxins; Pseudomonas aeruginosa; Respiratory Tract Infections; Treatment Outcome
PubMed: 33785362
DOI: 10.1016/j.ijantimicag.2021.106328 -
Antimicrobial Resistance and Infection... Jan 2021Intensive care units (ICUs) in lower-middle income countries (LMICs) are suspected to constitute a special risk for patients of acquiring infection due to multiple...
BACKGROUND
Intensive care units (ICUs) in lower-middle income countries (LMICs) are suspected to constitute a special risk for patients of acquiring infection due to multiple antibiotic resistant organisms. The aim of this systematic scoping review was to present the data published on ICU-acquired infections and on antimicrobial resistance observed in ICUs in LMICs over a 13-year period. A systematic scoping review was conducted according to the PRISMA extension guideline for scoping reviews and registered in the Open Science Framework. Articles were sought that reported on ICU-acquired infection in LMICs between 2005 and 2018. Two reviewers parallelly reviewed 1961 titles and abstracts retrieved from five data banks, found 274 eligible and finally included 51. Most LMICs had not produced reports in Q1 or Q2 journals in this period, constituting a large gap in knowledge. However, from the reported evidence it is clear that the rate of ICU-acquired infections was comparable, albeit approximately 10% higher, in LMICs compared to high income countries. In contrast, ICU mortality was much higher in LMICs (33.6%) than in high income countries (< 20%). Multidrug-resistant Gram-negative species, especially Acinetobacter baumannii and Pseudomonas aeruginosa, and Klebsiella pneumoniae played a much more dominant role in LMIC ICUs than in those in high income countries. However, interventions to improve this situation have been shown to be feasible and effective, even cost-effective.
CONCLUSIONS
Compared to high income countries the burden of ICU-acquired infection is higher in LMICs, as is the level of antimicrobial resistance; the pathogen distribution is also different. However, there is evidence that interventions are feasible and may be quite effective in these settings. Protocol Registration The protocol was registered with Open Science Framework ( https://osf.io/c8vjk ).
Topics: Acinetobacter baumannii; Adult; Bacterial Infections; Cross Infection; Developing Countries; Drug Resistance, Bacterial; Humans; Intensive Care Units; Klebsiella pneumoniae; Pseudomonas aeruginosa
PubMed: 33514432
DOI: 10.1186/s13756-020-00871-x -
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 -
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 -
The Cochrane Database of Systematic... Sep 2020Staphylococcus aureus causes pulmonary infection in young children with cystic fibrosis. Prophylactic antibiotics are prescribed hoping to prevent such infection and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Staphylococcus aureus causes pulmonary infection in young children with cystic fibrosis. Prophylactic antibiotics are prescribed hoping to prevent such infection and lung damage. Antibiotics have adverse effects and long-term use might lead to infection with Pseudomonas aeruginosa. This is an update of a previously published review.
OBJECTIVES
To assess continuous oral antibiotic prophylaxis to prevent the acquisition of Staphylococcus aureus versus no prophylaxis in people with cystic fibrosis, we tested the following hypotheses to investigate whether prophylaxis: 1. improves clinical status, lung function and survival; 2. leads to fewer isolates of Staphylococcus aureus; 3. causes adverse effects (e.g. diarrhoea, skin rash, candidiasis); 4. leads to fewer isolates of other common pathogens from respiratory secretions; 5. leads to the emergence of antibiotic resistance and colonisation of the respiratory tract with Pseudomonas aeruginosa.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Companies manufacturing anti-staphylococcal antibiotics were contacted. Most recent search of the Group's Register: 27 February 2020. Online trials registries were also searched. Most recent search of online trials registries: 15 September 2020.
SELECTION CRITERIA
Randomised trials of continuous oral prophylactic antibiotics (given for at least one year) compared to intermittent antibiotics given 'as required', in people with cystic fibrosis of any disease severity.
DATA COLLECTION AND ANALYSIS
The authors assessed studies for eligibility and methodological quality and extracted data. The quality of the evidence was assessed using the GRADE criteria. The review's primary outcomes of interest were lung function by spirometry (forced expiratory volume in one second (FEV)) and the number of people with one or more isolates of Staphylococcus aureus (sensitive strains).
MAIN RESULTS
We included four studies, with a total of 401 randomised participants aged zero to seven years on enrolment; one study is ongoing. The two older included studies generally had a higher risk of bias across all domains, but in particular due to a lack of blinding and incomplete outcome data, than the two more recent studies. We only regarded the most recent study as being generally free of bias, although even here we were not certain of the effect of the per protocol analysis on the study results. Evidence quality was judged to be low for all outcomes assessed after being downgraded based on GRADE assessments. Downgrading decisions were due to limitations in study design (all outcomes), for imprecision and for inconsistency . Prophylactic anti-staphylococcal antibiotics probably make little or no difference to lung function measured as FEV % predicted after six years (mean difference (MD) -2.30, 95% confidence interval (CI) -13.59 to 8.99, one study, n = 119, low-quality evidence); but may reduce the number of children having one or more isolates of Staphylococcus aureus at two years (odds ratio (OR) 0.21, 95% CI 0.13 to 0.35, three studies, n = 315, low-quality evidence). At the same time point, there may be little or no effect on nutrition as reported using weight z score (MD 0.06, 95% CI -0.33 to 0.45, two studies, n = 140, low-quality evidence), additional courses of antibiotics (OR 0.18, 95% CI 0.01 to 3.60, one study, n = 119, low-quality evidence) or adverse effects (low-quality evidence). There was no difference in the number of isolates of Pseudomonas aeruginosa between groups at two years (OR 0.74, 95% CI 0.45 to 1.23, three studies, n = 312, low-quality evidence), though there was a trend towards a lower cumulative isolation rate of Pseudomonas aeruginosa in the prophylaxis group at two and three years and towards a higher rate from four to six years. As the studies reviewed lasted six years or less, conclusions cannot be drawn about the long-term effects of prophylaxis.
AUTHORS' CONCLUSIONS
Anti-staphylococcal antibiotic prophylaxis may lead to fewer children having isolates of Staphylococcus aureus, when commenced early in infancy and continued up to six years of age. The clinical importance of this finding is uncertain. Further research may establish whether the trend towards more children with CF with Pseudomonas aeruginosa, after four to six years of prophylaxis, is a chance finding and whether choice of antibiotic or duration of treatment might influence this.
Topics: Antibiotic Prophylaxis; Bias; Child; Child, Preschool; Cystic Fibrosis; Drug Resistance, Bacterial; Forced Expiratory Volume; Growth; Humans; Infant; Infant, Newborn; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus aureus
PubMed: 32997797
DOI: 10.1002/14651858.CD001912.pub5 -
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 -
The Cochrane Database of Systematic... Jul 2020Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This leads to lung destruction and eventually death through respiratory failure. There are no antibiotics in development that exert a new mode of action and many of the current antibiotics are ineffective in eradicating the bacteria once chronic infection is established. Antibiotic adjuvants - therapies that act by rendering the organism more susceptible to attack by antibiotics or the host immune system, by rendering it less virulent or killing it by other means, would be a significant therapeutic advance. This is an update of a previously published review.
OBJECTIVES
To determine if antibiotic adjuvants improve clinical and microbiological outcome of pulmonary infection in people with cystic fibrosis.
SEARCH METHODS
We searched the Cystic Fibrosis Trials Register which is compiled from database searches, hand searches of appropriate journals and conference proceedings. Date of most recent search: 16 January 2020. We also searched MEDLINE (all years) on 14 February 2019 and ongoing trials registers on 06 April 2020.
SELECTION CRITERIA
Randomised controlled trials and quasi-randomised controlled trials of a therapy exerting an antibiotic adjuvant mechanism of action compared to placebo or no therapy for people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two of the authors independently assessed and extracted data from identified trials.
MAIN RESULTS
We identified 42 trials of which eight (350 participants) that examined antibiotic adjuvant therapies are included. Two further trials are ongoing and five are awaiting classification. The included trials assessed β-carotene (one trial, 24 participants), garlic (one trial, 34 participants), KB001-A (a monoclonal antibody) (two trials, 196 participants), nitric oxide (two trials, 30 participants) and zinc supplementation (two trials, 66 participants). The zinc trials recruited children only, whereas the remaining trials recruited both adults and children. Three trials were located in Europe, one in Asia and four in the USA. Three of the interventions measured our primary outcome of pulmonary exacerbations (β-carotene, mean difference (MD) -8.00 (95% confidence interval (CI) -18.78 to 2.78); KB001-A, risk ratio (RR) 0.25 (95% CI 0.03 to 2.40); zinc supplementation, RR 1.85 (95% CI 0.65 to 5.26). β-carotene and KB001-A may make little or no difference to the number of exacerbations experienced (low-quality evidence); whereas, given the moderate-quality evidence we found that zinc probably makes no difference to this outcome. Respiratory function was measured in all of the included trials. β-carotene and nitric oxide may make little or no difference to forced expiratory volume in one second (FEV) (low-quality evidence), whilst garlic probably makes little or no difference to FEV (moderate-quality evidence). It is uncertain whether zinc or KB001-A improve FEV as the certainty of this evidence is very low. Few adverse events were seen across all of the different interventions and the adverse events that were reported were mild or not treatment-related (quality of the evidence ranged from very low to moderate). One of the trials (169 participants) comparing KB001-A and placebo, reported on the time to the next course of antibiotics; results showed there is probably no difference between groups, HR 1.00 (95% CI 0.69 to 1.45) (moderate-quality evidence). Quality of life was only reported in the two KB001-A trials, which demonstrated that there may be little or no difference between KB001-A and placebo (low-quality evidence). Sputum microbiology was measured and reported for the trials of KB001-A and nitric oxide (four trials). There was very low-quality evidence of a numerical reduction in Pseudomonas aeruginosa density with KB001-A, but it was not significant. The two trials looking at the effects of nitric oxide reported significant reductions in Staphylococcus aureus and near-significant reductions in Pseudomonas aeruginosa, but the quality of this evidence is again very low.
AUTHORS' CONCLUSIONS
We could not identify an antibiotic adjuvant therapy that we could recommend for treating of lung infection in people with cystic fibrosis. The emergence of increasingly resistant bacteria makes the reliance on antibiotics alone challenging for cystic fibrosis teams. There is a need to explore alternative strategies, such as the use of adjuvant therapies. Further research is required to provide future therapeutic options.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Antibodies, Monoclonal; Bacterial Infections; Chemotherapy, Adjuvant; Child; Cystic Fibrosis; Disease Progression; Garlic; Humans; Immunoglobulin Fab Fragments; Lung Diseases; Nitric Oxide; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Vitamins; Young Adult; Zinc; beta Carotene
PubMed: 32671834
DOI: 10.1002/14651858.CD008037.pub4 -
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 -
Burns : Journal of the International... May 2021The pathogenesis of Pseudomonas aeruginosa is multifactorial and attributed to the production of several cell-associated and extracellular virulence factors including... (Meta-Analysis)
Meta-Analysis
PURPOSE
The pathogenesis of Pseudomonas aeruginosa is multifactorial and attributed to the production of several cell-associated and extracellular virulence factors including those implicated in adherence, iron uptake, exoenzymes (Exo) and exotoxins. The present study aimed to determine the prevalence of type III secretion systems (T3SS) effectors in Iranian burn patients with P. aeruginosa wound infection.
METHODS
A systematic search was conducted to identify papers published by Iranian authors in the Web of Science, PubMed, Scopus, Embase, and Google Scholar electronic databases during the period of January, 2000 to December, 2018. Publications which met our inclusion criteria were selected for data extraction and analysis by Comprehensive Meta-Analysis Software. The inclusion criteria were articles that include burn patients with a wound infection caused by P. aeruginosa, and reported the prevalence of aimed exoenzymes.
RESULTS
Ten publications were selected out of 15 full-text reviewed articles with the inclusion criteria. Of ten studies, the pooled prevalence of ExoS producing isolates was estimated at 57.1% (95% CI: 40.3-72.5%). Five studies reported the prevalence of ExoU and ExoT, from which, the pooled prevalence of ExoU and ExoT producing isolates was estimated at 51.4% (95% CI: 31.4-70.9%) and 86.4% (95% CI: 48.1-97.8%), respectively. Four studies reported the prevalence of ExoY, from which, the pooled prevalence of ExoY producing isolates was estimated at 79.0% (95% CI: 48.6-93.8%).
CONCLUSION
Our results showed a remarkable prevalence of T3SS-positive genotype in patients with burn injuries. These findings provided attractive targets for new therapeutic strategies for burn patients who were infected with cytotoxin-producing P. aeruginosa.
Topics: Anti-Bacterial Agents; Burns; Humans; Pseudomonas aeruginosa; Type III Secretion Systems; Wound Infection
PubMed: 32532479
DOI: 10.1016/j.burns.2020.04.024 -
The Cochrane Database of Systematic... Jun 2020Clinicians typically select the antibiotics used to treat pulmonary infections in people with cystic fibrosis based on the results of antimicrobial susceptibility... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clinicians typically select the antibiotics used to treat pulmonary infections in people with cystic fibrosis based on the results of antimicrobial susceptibility testing performed on bacteria traditionally grown in a planktonic mode (grown in a liquid). However, there is considerable evidence to suggest that Pseudomonas aeruginosa actually grows in a biofilm (or slime layer) in the airways of people with cystic fibrosis with chronic pulmonary infections. Therefore, choosing antibiotics based on biofilm rather than conventional antimicrobial susceptibility testing could potentially improve response to treatment of Pseudomonas aeruginosa in people with cystic fibrosis. This is an update of a previously published Cochrane Review.
OBJECTIVES
To compare biofilm antimicrobial susceptibility testing-driven therapy to conventional antimicrobial susceptibility testing-driven therapy in the treatment of Pseudomonas aeruginosa infection in people 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. Most recent search: 07 April 2020. We also searched two ongoing trials registries and the reference lists of relevant articles and reviews. Most recent searches: 07 April 2020 and 05 September 2017.
SELECTION CRITERIA
Randomized controlled trials (RCTs) of antibiotic therapy based on biofilm antimicrobial susceptibility testing compared to antibiotic therapy based on conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infection in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two authors independently selected RCTs, assessed their risk of bias and extracted data from eligible trials. Additionally, the review authors contacted the trial investigators to obtain further information. The quality of the evidence was assessed using the GRADE criteria.
MAIN RESULTS
The searches identified two multicentre, double-blind RCTs eligible for inclusion in the review with a total of 78 participants (adults and children); one RCT was undertaken in people who were clinically stable, the second was in people experiencing pulmonary exacerbations. Both RCTs prospectively assessed whether the use of biofilm antimicrobial susceptibility testing improved microbiological and clinical outcomes in participants with cystic fibrosis who were infected with Pseudomonas aeruginosa. The primary outcome was the change in sputum Pseudomonas aeruginosa density from the beginning to the end of antibiotic therapy. Although the intervention was shown to be safe, the data from these two RCTs did not provide evidence that biofilm susceptibility testing was superior to conventional susceptibility testing either in terms of microbiological or lung function outcomes. One of the trials also measured risk and time to subsequent exacerbation as well as quality of life measures and did not demonstrate any difference between groups in these outcomes. Both RCTs had an overall low risk of bias and the quality of the evidence using GRADE criteria was deemed to be moderate to high for the outcomes selected.
AUTHORS' CONCLUSIONS
The current evidence is insufficient to recommend choosing antibiotics based on biofilm antimicrobial susceptibility testing rather than conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infections in people with cystic fibrosis. Biofilm antimicrobial susceptibility testing may be more appropriate in the development of newer, more effective formulations of drugs which can then be tested in clinical trials.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Biofilms; Cystic Fibrosis; Female; Humans; Male; Microbial Sensitivity Tests; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Sputum
PubMed: 32520436
DOI: 10.1002/14651858.CD009528.pub5