A Systematic Review and Meta-analysis to Assess the Safety and Efficacy of Nebulised Colistin as an Adjunct for the Treatment of Ventilator Associated Pneumonia (VAP)
Bibliographic record
Abstract
Abstract Rationale: Ventilator-associated pneumonia, particularly when caused by multidrug-resistant pathogens, can result in mortality rates as high as 76%. Nebulised colistin has been studied as a potential adjunct therapy for patients with ventilator-associated pneumonia (VAP); however, there is still a lack of evidence either supporting or opposing the use of nebulised colistin. This systematic review and meta-analysis were conducted to evaluate the safety and efficacy of nebulised colistin as an adjunct to intravenous (IV) antibiotics, compared to IV antibiotics alone, in patients with VAP. Methods: We systematically searched PubMed, Web of Science, Google Scholar, Embase, and the Cochrane Library to retrieve studies published at any time until April 18, 2024. The studies included in this analysis were selected based on the PICOS principle, which stands for Population, Intervention, Comparator, Outcome, and Study design. Only dual-arm studies on adults, where the intervention group received nebulised colistin with at least one IV antibiotic and the comparator group received IV antibiotics alone, were included in the analysis. The primary outcome was clinical response. Secondary outcomes included microbiological eradication and adverse events. To assess the quality of case-control/cohort studies, the Newcastle-Ottawa Quality Assessment Scale was utilised, while the Cochrane risk-of-bias tool was used for RCTs. Results: A total of 11 studies (four randomised controlled trials [RCTs] and seven observational studies) were included. The meta-analysis revealed that nebulised colistin significantly improved the clinical response in VAP patients [Odds Ratio (OR): 1.37; 95% Confidence Interval (CI): 1.05-1.80; p = 0.02]. Subgroup analysis showed significant improvement in observational studies, but no statistical significance in RCTs (OR: 1.13; 95% CI: 0.75-1.69; p = 0.16). Nebulised colistin also enhanced microbiological eradication (OR: 2.13; 95% CI: 1.27-3.56; p = 0.004). Although the incidence of bronchospasm was higher (OR: 5.19; 95% CI: 1.05-25.52; p = 0.04), the overall risk of adverse events was not significantly increased compared to IV antibiotics alone (OR: 0.89; 95% CI: 0.66-1.2; p = 0.46). Most of the included publications had a low risk of bias, and the risk of publication bias was also not serious. The quality of evidence was graded moderate for RCTs and very low for observational studies, due to inadequate sample sizes and heterogeneity. Conclusion: In conclusion, adding nebulised colistin to intravenous antibiotics can improve treatment outcomes in VAP. Despite the potential for bronchospasm, the overall risk of adverse effects is not excessively high. Further research is necessary to determine suitable nebulised doses and appropriate ventilator settings.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.017 | 0.042 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.026 | 0.042 |
| Bibliometrics | 0.011 | 0.010 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".