Results of antibiotic susceptibility testing do not influence clinical outcome in children with cystic fibrosis.
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ABSTRACT: Introduction
Patients with CF experience pulmonary exacerbations. These are often initially empirically treated with intravenous antibiotics, with antibiotic choice refined after susceptibility testing.Methods
We completed a 5-year retrospective review of children attending the Paediatric CF Unit, Nottingham. The respiratory sampling, antibiotic prescribing and susceptibility testing guidance were audited. Episodes were classified according to the concordance between the antibiotics prescribed and antibiotic susceptibility testing.Results
Of 52 patients who had previously isolated Pseudomonas aeruginosa, 103 antibiotic courses were commenced that coincided with an isolation of P. aeruginosa. P. aeruginosa was fully susceptible, partially susceptible or fully resistant on 33%, 44.7% or 16.5% of occasions respectively. The antibiotic prescriptions were never changed following antibiotic susceptibility testing. We found no association between change in FEV(1) (p=0.54), change in BMI (p=0.12) or time to next exacerbation (p=0.66) and concordance between antibiotic susceptibility and the antibiotics administered.Conclusion
This study contributes to mounting evidence questioning the utility of routine antibiotic susceptibility testing.
SUBMITTER: Hurley MN
PROVIDER: S-EPMC3382712 | biostudies-literature | 2012 Jul
REPOSITORIES: biostudies-literature
Publications
Results of antibiotic susceptibility testing do not influence clinical outcome in children with cystic fibrosis.
Hurley M N MN Ariff A H Amin AH Bertenshaw C C Bhatt J J Smyth A R AR
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 20120320 4
<h4>Introduction</h4>Patients with CF experience pulmonary exacerbations. These are often initially empirically treated with intravenous antibiotics, with antibiotic choice refined after susceptibility testing.<h4>Methods</h4>We completed a 5-year retrospective review of children attending the Paediatric CF Unit, Nottingham. The respiratory sampling, antibiotic prescribing and susceptibility testing guidance were audited. Episodes were classified according to the concordance between the antibiot ...[more]
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Project description:BackgroundThe antibiotics used to treat pulmonary infections in people with cystic fibrosis are typically chosen 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.ObjectivesTo 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 methodsWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Most recent search: 19 June 2017.We also searched two ongoing trials registries and the reference lists of relevant articles and reviews. Most recent searches: 24 August 2017 and 05 September 2017.Selection criteriaRandomized controlled trials 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 analysisBoth authors independently selected trials, 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 resultsThe searches identified two multicentre, randomized, double-blind controlled clinical trials eligible for inclusion in the review with a total of 78 participants (adults and children); one trial was done in people who were clinically stable, the other in people experiencing pulmonary exacerbations. These trials 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 trials 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 trials 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' conclusionsThe 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.
| S-EPMC6485918 | biostudies-literature
Project description:BackgroundClinicians 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.ObjectivesTo 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 methodsWe 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 criteriaRandomized 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 analysisTwo 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 resultsThe 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' conclusionsThe 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.
| S-EPMC7388933 | biostudies-literature
Project description:Background and objectivesCystic fibrosis patients suffer from chronic lung infections that require long-term antibiotic therapy. Pseudomonas readily evolve resistance, rendering antibiotics ineffective. In vitro experiments suggest that resistant bacteria may be treated by exploiting their collateral sensitivity to other antibiotics. Here, we investigate correlations of sensitivity and resistance profiles of Pseudomonas aeruginosa that naturally adapted to antibiotics in the cystic fibrosis lung.MethodologyResistance profiles for 13 antibiotics were obtained using broth dilution, E-test and VITEK mass spectroscopy. Genetic variants were determined from whole-genome sequences and interrelationships among isolates were analyzed using 13 MLST loci.ResultOur study focused on 45 isolates from 13 patients under documented treatment with antibiotics. Forty percent of these were clinically resistant and 15% multi-drug resistant. Colistin resistance was found once, despite continuous colistin treatment and even though colistin resistance can readily evolve experimentally in the laboratory. Patients typically harbored multiple genetically and phenotypically distinct clones. However, genetically similar clones often had dissimilar resistance profiles. Isolates showed mutations in genes encoding cell wall synthesis, alginate production, efflux pumps and antibiotic modifying enzymes. Cross-resistance was commonly observed within antibiotic classes and between aminoglycosides and ?-lactam antibiotics. No evidence was found for consistent phenotypic resistance to one antibiotic and sensitivity to another within one genotype.Conclusions and implicationsEvidence supporting potential collateral sensitivity in clinical P. aeruginosa isolates remains equivocal. However, cross-resistance within antibiotic classes is common. Colistin therapy is promising since resistance to it was rare despite its intensive use in the studied patients.
| S-EPMC4906436 | biostudies-literature
Project description:Pseudomonas aeruginosa (P.a) is one of the most critical antibiotic resistant bacteria in the world and is the most prevalent pathogen in cystic fibrosis (CF), causing chronic lung infections that are considered one of the major causes of mortality in CF patients. Although several studies have contributed to understanding P.a within-host adaptive evolution at a genomic level, it is still difficult to establish direct relationships between the observed mutations, expression of clinically relevant phenotypes, and clinical outcomes. Here, we performed a comparative untargeted LC/HRMS-based metabolomics analysis of sequential isolates from chronically infected CF patients to obtain a functional view of P.a adaptation. Metabolic profiles were integrated with expression of bacterial phenotypes and clinical measurements following multiscale analysis methods. Our results highlighted significant associations between P.a "metabotypes", expression of antibiotic resistance and virulence phenotypes, and frequency of clinical exacerbations, thus identifying promising biomarkers and therapeutic targets for difficult-to-treat P.a infections.
| S-EPMC7909822 | biostudies-literature
Project description:The lungs of cystic fibrosis (CF) patients are often chronically colonized by multiple microbial species that can form biofilms, including the major CF pathogen Pseudomonas aeruginosa. Herewith, lower microbial diversity in CF airways is typically associated with worse health outcomes. In an attempt to treat CF lung infections patients are frequently exposed to antibiotics, which may affect microbial diversity. This study aimed at understanding if common antibiotics that target P. aeruginosa influence microbial diversity. To this end, a microaerophilic multispecies biofilm model of frequently co-isolated members of the CF lung microbiome (Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus anginosus, Achromobacter xylosoxidans, Rothia mucilaginosa, and Gemella haemolysans) was exposed to antipseudomonal antibiotics. We found that antibiotics that affected several dominant species (i.e. ceftazidime, tobramycin) resulted in higher species evenness compared to colistin, which is only active against P. aeruginosa. Furthermore, susceptibility of individual species in the multispecies biofilm following antibiotic treatment was compared to that of the respective single-species biofilms, showing no differences. Adding three anaerobic species (Prevotella melaninogenica, Veillonella parvula, and Fusobacterium nucleatum) to the multispecies biofilm did not influence antibiotic susceptibility. In conclusion, our study demonstrates antibiotic-dependent effects on microbial community diversity of multispecies biofilms comprised of CF microbiome members.
| S-EPMC7798459 | biostudies-literature
Project description:BACKGROUND:Although antimicrobial susceptibility testing (AST) frequently guides cystic fibrosis (CF) pulmonary exacerbation (PEx) management, its clinical utility is unclear. This study examined associations between AST and antimicrobial switching during PEx treatment and time and occurrence of next PEx as treatment outcomes. METHODS:This retrospective cohort study utilized Pediatric Health Information System data. Children and adolescents aged 1-18?years admitted for a PEx from 2011 to 2016 were studied. Antimicrobial switching was defined as any intra-admission change in intravenous (IV), oral, and/or inhaled antimicrobials. Time to next PEx was defined as the time between index PEx hospital discharge and subsequent hospital admission requiring IV antimicrobials. Odds of antimicrobial switching ?5?days after treatment initiation were determined by generalized linear mixed models, and associations between AST and time to next PEx were studied using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS:AST occurred in 2518 (39%) of 6451 PEx at 36 hospitals and was associated with increased odds of antimicrobial switching (OR 1.33, 95% CI 1.16-1.52; p?=?0.001) and increased hazard of future PEx (HR 1.32, 95% CI 1.16-1.50; p?<?0.001). However, antimicrobial switching was not associated with a longer time to next PEx. CONCLUSIONS:AST was associated with both increased probability of antimicrobial regimen change and increased PEx hazard. There was no evidence that antimicrobial regimen change was associated with clinical benefit as assessed by time to next PEx. However, these results indicate residual indication bias remained after adjustment for available disease covariates. Additional studies of the clinical value of AST are warranted.
| S-EPMC6881516 | biostudies-literature
Project description:Allergic reactions to antibiotics are more common in cystic fibrosis (CF) than in the general population. This in part is due to the improving survival in adults with CF and the increased use of high dose intravenous antibiotics. While some are immediate anaphylaxis type (IgE mediated) reactions, the majority are late onset and may have non-specific features such as rash and fever. Piperacillin has consistently been found to have the highest rate of reported reactions (30-50%). There is a low risk of cross reactions between penicillins and other non-beta-lactam classes of antibiotics in penicillin skin prick positive patients. Carbapenems should only be used with extreme caution in patients with positive skin prick tests to penicillin. However, aztreonam can be used safely in patients who are penicillin allergic with positive skin prick reactions. The aminoglycosides are a relatively uncommon cause of allergic reactions, but patients who react to one member of the family may cross react with other aminoglycosides. Desensitisation relies on the incremental introduction of small quantities of the allergen and has been used for penicillins, ceftazidime, tobramycin and ciprofloxacin and must be repeated before each course. Personalized cards should be regularly updated for patients who develop allergic reactions. Written instructions on the emergency treatment of allergic reactions should be provided to patients self-administering intravenous antibiotics at home. Further research is required to identify risk factors and predictors for antibiotic allergy.
| S-EPMC1747437 | biostudies-literature
Project description:OBJECTIVE:To investigate the relationship between abdominal ultrasound findings and demographic, historical, and clinical features in children with cystic fibrosis (CF). STUDY DESIGN:Children age 3-12 years with CF without known cirrhosis, were enrolled in a prospective, multicenter study of ultrasound to predict hepatic fibrosis. Consensus ultrasound patterns were assigned by 3 radiologists as normal, heterogeneous, homogeneous, or cirrhosis. Data were derived from direct collection and US or Toronto CF registries. ?(2) or ANOVA were used to compare variables among ultrasound groups and between normal and abnormal. Logistic regression was used to study risk factors for having abnormal ultrasound. RESULTS:Findings in 719 subjects were normal (n = 590, 82.1%), heterogeneous (64, 8.9%), homogeneous (41, 5.7%), and cirrhosis (24, 3.3%). Cirrhosis (P = .0004), homogeneous (P < .0001), and heterogeneous (P = .03) were older than normal. More males were heterogeneous (P = .001). More heterogeneous (15.0%, P = .009) and cirrhosis (25.0%, P = .005) had CF-related diabetes or impaired glucose tolerance vs normal (5.4%). Early infection with Pseudomonas aeruginosa (<2 years old) was associated with a lower risk (OR 0.42, P = .0007) of abnormal. Ursodeoxycholic acid use (OR 3.69, P < .0001) and CF-related diabetes (OR 2.21, P = .019) were associated with increased risk of abnormal. CONCLUSIONS:Unsuspected cirrhosis is seen in 3.3% of young patients with CF, heterogeneous in 8.9%. Abnormal ultrasound is associated with CF-related diabetes, and early P aeruginosa is associated with normal ultrasound. Prospective assessment of these risk factors may identify potential interventional targets. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01144507.
| S-EPMC4586395 | biostudies-literature
Project description:Bacteremia is a life-threatening condition for which antibiotics must be prescribed within hours of clinical diagnosis. Since the current gold standard for bacteremia diagnosis is based on conventional methods developed in the mid-1800s-growth on agar or in broth-identification and susceptibility profiling for both Gram-positive and Gram-negative bacterial species requires at least 48-72 h. Recent advancements in accelerated phenotypic antibiotic susceptibility testing have centered on the microscopic growth analysis of small bacterial populations. These approaches are still inherently limited by the bacterial growth rate. Our approach is fundamentally different. By applying environmental stress to bacteria in a microfluidic platform, we can correctly assign antibiotic susceptibility profiles of clinically relevant Gram-negative bacteria within two hours of antibiotic introduction rather than 8-24 h. The substantial expansion to include a number of clinical isolates of important Gram-negative species-Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa-reported here underscores the broad utility of our approach, complementing the method's proven utility for Gram-positive bacteria. We also demonstrate that the platform is compatible with antibiotics that have varying mechanisms of action-meropenem, gentamicin, and ceftazidime-highlighting the versatility of this platform.
| S-EPMC5556039 | biostudies-other
Project description:RationaleConsensus is lacking regarding antistaphylococcal antibiotic prophylaxis use for young children with cystic fibrosis. Prophylaxis is recommended in the United Kingdom, but it is recommended against in the United States.ObjectivesTo test the hypothesis that antistaphylococcal antibiotic prophylaxis is associated with a decreased risk of Staphylococcus aureus acquisition but no increased risk of Pseudomonas aeruginosa acquisition.MethodsWe undertook a longitudinal observational study of children with cystic fibrosis who were recruited from birth (or from their first registry entry in the period) and followed until the age of 4 years (1,500 d) using 2000-2009 data from the UK Cystic Fibrosis Trust and Cystic Fibrosis Foundation registries. Children were excluded if they had a positive culture result for S. aureus or P. aeruginosa, or if they were receiving inhaled antibiotics, at the first encounter. Time to first S. aureus and P. aeruginosa detection in the UK/U.S. cohorts was compared using a Cox proportional hazards model. A UK-based analysis compared the same for those receiving flucloxacillin with those who received no prophylaxis. We included the following covariates: sex, age at registry entry, dornase alfa use, genotype, and center size.ResultsThe primary analysis comprised 1,074 UK and 3,677 U.S. children. The risk of first detection was greater in U.S. children than in UK children for S. aureus (hazard ratio [HR], 5.79; 95% confidence interval [CI], 4.85, 6.90; P < 0.001) and P. aeruginosa (HR, 1.92; 95% CI, 1.65, 2.24; P < 0.001). In the UK analysis, we compared 278 children receiving flucloxacillin and 306 receiving no prophylaxis. Flucloxacillin was not associated with a reduced risk of S. aureus detection (HR, 1.22; 95% CI, 0.74, 2.0; P = 0.43), but it was associated with an increased risk of P. aeruginosa detection (HR, 2.53; 95% CI, 1.71, 3.74; P < 0.001). None of the covariates significantly affected the risk estimate in either analysis.ConclusionsThe risk of first detection of S. aureus and P. aeruginosa was greater in the United States than in the United Kingdom. In the United Kingdom, the risk of first P. aeruginosa detection was increased among those receiving flucloxacillin compared with those who received no prophylaxis. These observational findings should be examined in randomized controlled trials.
| S-EPMC5822417 | biostudies-literature