Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis
Información
- DOI:
- https://doi.org/10.1002/14651858.CD009528.pub5Copiar DOI
- Base de datos:
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- Cochrane Database of Systematic Reviews
- Versión publicada:
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- 10 junio 2020see what's new
- Tipo:
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- Intervention
- Etapa:
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- Review
- Grupo Editorial Cochrane:
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Grupo Cochrane de Fibrosis quística y enfermedades genéticas
- Copyright:
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- Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cifras del artículo
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Autores
Contributions of authors
| Roles and responsibilities | |
|---|---|
| TASK | WHO WILL UNDERTAKE THE TASK? |
| Protocol stage: draft the protocol | Valerie Waters |
| Review stage: select which trials to include (2 + 1 arbiter) | Valerie Waters and Felix Ratjen (+ Nikki Jahnke) |
| Review stage: extract data from trials (2 people) | Valerie Waters and Felix Ratjen |
| Review stage: enter data into RevMan | Valerie Waters |
| Review stage: carry out the analysis | Valerie Waters and Felix Ratjen |
| Review stage: interpret the analysis | Valerie Waters and Felix Ratjen |
| Review stage: draft the final review | Valerie Waters and Felix Ratjen |
| Update stage | Valerie Waters, Felix Ratjen, Sherie Smith, Nikki Jahnke NJ extracted data and assessed risk of bias for Yau 2014 Sherie Smith generated the Summary of Findings table and incorporated the GRADE findings into the text of the review |
Sources of support
Internal sources
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No sources of support supplied
External sources
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National Institute for Health Research, UK
This systematic review was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Cystic Fibrosis and Genetic Disorders Group.
Declarations of interest
Two authors of this review (VW, FR) are investigators in the included biofilm trial which was funded by a grant from Innovotech Inc. and the National Research Council Industrial Research Assistance Program (NRC‐IRAP) of Alberta (Yau 2014). The funders had no involvement in the trial design, interpretation of data, writing of the manuscript or decision to submit the manuscript for publication.
SS: none known.
VW: declares grant funding from Cystic Fibrosis Foundation, Cystic Fibrosis Canada, Canadian Institutes of Health Research and Gilead Sciences. VW also declares consultancy fees from Tevapharm (who do not make anything related to antibiotic susceptibility testing).
NJ: none known.
FR: I have acted as a consultant to Novartis, Roche, Vertex, Boehringer Ingelheim, Bayer, Genentech. I have been paid for lectures by Genentech. I have also received grants as PI for an early intervention study targeting Pseudomonas sponsored by Novartis and as PI for other grants sponsored by Vertex. While I have received grants from Vertex, they do not produce antibiotics that would be eligible for consideration in this review.
Acknowledgements
The authors acknowledge the kind assistance of Dr Samuel Moskowitz and Dr Julia Emerson who provided us with the details of the allocation assignments and additional outcome measures for their trial.
This project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Cystic Fibrosis and Genetic Disorders Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.
Version history
| Published | Title | Stage | Authors | Version |
| 2020 Jun 10 | Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis | Review | Sherie Smith, Valerie Waters, Nikki Jahnke, Felix Ratjen | |
| 2017 Oct 05 | Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis | Review | Valerie Waters, Felix Ratjen | |
| 2015 Mar 05 | Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis | Review | Valerie Waters, Felix Ratjen | |
| 2012 Nov 14 | Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis | Review | Valerie Waters, Felix Ratjen | |
| 2011 Dec 07 | Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis | Protocol | Valerie Waters, Felix Ratjen | |
Differences between protocol and review
In a post hoc change the review authors additionally decided to report data as change from start of treatment and not just absolute values for their primary outcome of lung function as these data are more useful to users of the review than just endpoint values which do not relate to previous levels of lung function. Furthermore, a summary of findings table has been added in line with Cochrane guidance (2017) and the final secondary outcome 'Use of oral antibiotics' has been removed since oral antibiotics are considered an antibiotic therapy eligible for consideration following the testing (2020).
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
- Anti-Bacterial Agents [*therapeutic use];
- Biofilms [*drug effects, growth & development];
- Cystic Fibrosis [*complications];
- Microbial Sensitivity Tests [methods];
- Pseudomonas aeruginosa [*drug effects, physiology];
- Pseudomonas Infections [complications, *drug therapy];
- Randomized Controlled Trials as Topic;
- Respiratory Tract Infections [*drug therapy, microbiology];
- Sputum [microbiology];
Medical Subject Headings Check Words
Adolescent; Adult; Female; Humans; Male;
PICO
Comparison 1: Biofilm testing versus standard testing, Outcome 1: FEV₁ (L) change from start of treatment
Comparison 1: Biofilm testing versus standard testing, Outcome 2: FEV1 (% predicted) change from start of treatment
Comparison 1: Biofilm testing versus standard testing, Outcome 3: FVC (% predicted) change from start of treatment
Comparison 1: Biofilm testing versus standard testing, Outcome 4: FVC (L) change from start of treatment
Comparison 1: Biofilm testing versus standard testing, Outcome 5: Time to next exacerbation (days)
Comparison 1: Biofilm testing versus standard testing, Outcome 6: Pulmonary exacerbations (number of participants)
Comparison 1: Biofilm testing versus standard testing, Outcome 7: Adverse events
Comparison 1: Biofilm testing versus standard testing, Outcome 8: Change in P aeruginosa sputum density (log₁₀ CFU/g)
Comparison 1: Biofilm testing versus standard testing, Outcome 9: CFQ‐R change from start of treatment
| Biofilm antimicrobial susceptibility testing compared with standard antimicrobial susceptibility testing for guiding antibiotic therapy in cystic fibrosis | ||||||
| Patient or population: adults and children with cystic fibrosis and P aeruginosa Settings: outpatients Intervention: antibiotics chosen on the basis of biofilm antimicrobial susceptibility testing Comparison: antibiotics chosen on the basis of standard antimicrobial susceptibility testing | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk | Corresponding risk | |||||
| Standard antimicrobial susceptibility testing | Biofilm antimicrobial susceptibility testing | |||||
| FEV1 change from start of treatment (L) Follow‐up: 14 days | The mean change in FEV1 ranged across control groups from 0.12 L to 2.75 L. | The mean change in FEV1 in the intervention groups was | NA | 68 | ⊕⊕⊕⊕ | |
| FEV1 change from start of treatment (% predicted) Follow‐up: 14 days | The mean (SD) change in FEV1 in the control group was 9.62 (10.12)% predicted. | The mean change in FEV1 in the intervention groups was | NA | 34 | ⊕⊕⊕⊝ | Data provided by the authors for this outcome. |
| Time to next exacerbation Follow‐up: 5 years | The median time to subsequent exacerbation was 185 days in the standard testing group and 162 days in the biofilm group. The difference in survival curves was not significant (P = 0.8). The HR for subsequent exacerbation also showed no significant difference between groups, HR 0.54 (95% CI 0.25 to 1.16). | NA | 39 | ⊕⊕⊕⊝ | ||
| Adverse events: number of moderate adverse events Follow‐up: duration of antibiotic treatment (14 days) | 129 per 1000 | 46 per 1000 | RR 0.36 (0.07 to 1.77) | 73 | ⊕⊕⊕⊝ | There was no significant difference in the number of mild events between standard or biofilm groups. There were no severe adverse events observed in either group. |
| Sputum density: change in P aeruginosa sputum density (log1₀ CFU/g) Follow‐up: 14 days | The mean change in sputum density ranged across control groups from ‐3.27 to ‐3.83 log1₀ CFU/g. | The mean change in sputum density in the intervention groups was 0.8 log1₀ CFU/g higher (0.59 log1₀ CFU/g lower to 2.18 log1₀ CFU/g higher). | NA | 70 | ⊕⊕⊕⊕ | |
| Quality of life: change in CFQ‐R score from start of treatment Follow‐up: 14 days | The mean change in CFQ‐R score in the control group was 26.39 points. | The mean change in CFQ‐R score in the intervention group was 15.04 points lower (15.04 points lower to 1.71 points lower. | NA | 38 | ⊕⊕⊕⊝ | There was a significant difference in change in CFQ‐R scores between groups (P = 0.03) favouring the standard susceptibility testing group. |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| a Downgraded once due to small number of participants from 1 trial. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 FEV₁ (L) change from start of treatment Show forest plot | 2 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.1.1 At day 7 | 1 | 23 | Mean Difference (IV, Fixed, 95% CI) | ‐0.12 [‐0.36, 0.13] |
| 1.1.2 At day 14 | 2 | 68 | Mean Difference (IV, Fixed, 95% CI) | 0.04 [‐0.08, 0.16] |
| 1.1.3 At 1 month | 1 | 27 | Mean Difference (IV, Fixed, 95% CI) | 0.17 [‐0.03, 0.37] |
| 1.2 FEV1 (% predicted) change from start of treatment Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.2.1 At day 7 | 1 | 23 | Mean Difference (IV, Fixed, 95% CI) | ‐3.09 [‐10.60, 4.41] |
| 1.2.2 At day 14 | 1 | 34 | Mean Difference (IV, Fixed, 95% CI) | ‐2.47 [‐9.29, 4.34] |
| 1.2.3 At 1 month | 1 | 27 | Mean Difference (IV, Fixed, 95% CI) | 4.93 [‐2.42, 12.28] |
| 1.3 FVC (% predicted) change from start of treatment Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.3.1 At day 7 | 1 | 23 | Mean Difference (IV, Fixed, 95% CI) | ‐6.35 [‐13.04, 0.34] |
| 1.3.2 At day 14 | 1 | 34 | Mean Difference (IV, Fixed, 95% CI) | ‐2.27 [‐9.06, 4.51] |
| 1.3.3 At 1 month | 1 | 27 | Mean Difference (IV, Fixed, 95% CI) | 5.80 [‐4.59, 16.19] |
| 1.4 FVC (L) change from start of treatment Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.4.1 At day 7 | 1 | 23 | Mean Difference (IV, Fixed, 95% CI) | ‐0.13 [‐0.42, 0.17] |
| 1.4.2 At day 14 | 1 | 34 | Mean Difference (IV, Fixed, 95% CI) | ‐0.03 [‐0.32, 0.26] |
| 1.4.3 At 1 month | 1 | 27 | Mean Difference (IV, Fixed, 95% CI) | 0.26 [‐0.07, 0.60] |
| 1.5 Time to next exacerbation (days) Show forest plot | 1 | Hazard Ratio (IV, Fixed, 95% CI) | Subtotals only | |
| 1.6 Pulmonary exacerbations (number of participants) Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.6.1 At end of study | 1 | 39 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.57, 1.22] |
| 1.7 Adverse events Show forest plot | 2 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.7.1 Mild | 2 | 73 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.70 [0.48, 1.04] |
| 1.7.2 Moderate | 2 | 73 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.36 [0.07, 1.77] |
| 1.7.3 Severe | 2 | 73 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 1.8 Change in P aeruginosa sputum density (log₁₀ CFU/g) Show forest plot | 2 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.8.1 At day 14 | 2 | 70 | Mean Difference (IV, Fixed, 95% CI) | 0.80 [‐0.59, 2.18] |
| 1.8.2 At 1 month | 1 | 30 | Mean Difference (IV, Fixed, 95% CI) | 0.35 [‐0.53, 1.23] |
| 1.9 CFQ‐R change from start of treatment Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.9.1 At day 14 | 1 | 38 | Mean Difference (IV, Fixed, 95% CI) | ‐15.04 [‐28.38, ‐1.71] |
| 1.9.2 At 1 month | 1 | 27 | Mean Difference (IV, Fixed, 95% CI) | ‐17.03 [‐30.13, ‐3.92] |
