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Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: a
Neha M Doshi1, Charles H Cook, Kari L Mount
1Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH, USA. claire.murphy@osumc.edu.
Background:
The incidence of multi-drug resistant (MDR) gram-negative (GN) organisms including Pseudomonas and Acinetobacter spp has increased in the last decade, prompting re-evaluation of colistin for the management of these infections. Aerosolized colistin as an adjunct to intravenous therapy is a current option for the management of MDR-GN pneumonia, although data supporting this practice is limited. This study evaluates the efficacy of adjunctive aerosolized colistin in combination with intravenous colistin in critically ill patients with MDR-GN pneumonia.
Methods:
A retrospective multi-center cohort analysis comparing critically ill patients with MDR-GN pneumonia who received intravenous colistin (IV) alone or in combination with adjunctive aerosolized colistin (IV/AER) with a primary endpoint of clinical cure at the end of colistin therapy. Secondary endpoints included microbiologic cure, duration of mechanical ventilation, length of stay, and hospital mortality. A post-hoc subgroup analysis was performed for patients with high quality cultures used for diagnosis of MDR-GN pneumonia. Dichotomous data were compared using Fisher's exact test while the student's t-test or Mann-Whitney U test were used for continuous variables.
Results:
Ninety-five patients met criteria for evaluation with 51 patients receiving IV and 44 receiving IV/AER. Baseline characteristics were similar between the two groups. Twenty patients (39.2%) receiving IV and 24 (54.5%) receiving IV/AER achieved clinical cure (p = 0.135). There was no difference in microbiologic cure rates between the IV and IV/AER colistin groups (40.7vs. 44.4%, p = 0.805). The IV group demonstrated a trend towards higher pneumonia attributable mortality (70.4 vs. 40%, p = 0.055). In the subgroup analysis of patients with high quality respiratory cultures, there was a significantly lower clinical cure rate for those in the IV group as compared to the IV/AER group (31.3 vs. 57.1%, p = 0.033).
Conclusions:
Addition of aerosolized colistin to IV colistin may improve clinical cure and mortality for patients with MDR-GN pneumonia. Larger, prospective trials are warranted to confirm the benefit of adjunctive aerosolized colistin in critically ill patients with MDR-GN pneumonia.
Insights
Adding aerosolized colistin to intravenous colistin may improve clinical cure and reduce mortality in critically ill patients with multi-drug resistant gram-negative pneumonia. Further research is needed to confirm these findings.
Area of Science:
- Critical Care Medicine
- Infectious Diseases
- Pharmacology
Background:
- Rising incidence of multi-drug resistant (MDR) gram-negative (GN) organisms necessitates re-evaluation of colistin therapy.
- Aerosolized colistin is used as an adjunct for MDR-GN pneumonia, but supporting data is limited.
- This study assesses the efficacy of adjunctive aerosolized colistin with intravenous colistin in critically ill patients.
Purpose of the Study:
- To evaluate the efficacy of adjunctive aerosolized colistin combined with intravenous colistin.
- To compare clinical and microbiologic cure rates, ventilation duration, length of stay, and mortality.
- To analyze outcomes in patients with high-quality diagnostic cultures.
Main Methods:
- Retrospective multi-center cohort analysis.
- Comparison of critically ill patients receiving intravenous colistin alone versus intravenous plus aerosolized colistin.
- Primary endpoint: clinical cure; Secondary endpoints: microbiologic cure, ventilation duration, length of stay, mortality.
Main Results:
- 51 patients received intravenous colistin, 44 received intravenous plus aerosolized colistin.
- Clinical cure rates were 39.2% (IV) vs. 54.5% (IV/AER), not statistically significant (p=0.135).
- In high-quality culture subgroups, clinical cure was significantly higher with IV/AER (57.1%) vs. IV (31.3%) (p=0.033). A trend towards lower mortality was observed with IV/AER.
Conclusions:
- Adjunctive aerosolized colistin may improve clinical cure and reduce mortality in MDR-GN pneumonia.
- Further large, prospective trials are required to validate the benefits of aerosolized colistin.
- The findings suggest a potential role for aerosolized colistin in managing complex Gram-negative infections.
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