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. 2023 Jan 9;12(1):125.
doi: 10.3390/antibiotics12010125.

Use of High-Dose Nebulized Colistimethate in Patients with Colistin-Only Susceptible Acinetobacter baumannii VAP: Clinical, Pharmacokinetic and Microbiome Features

Gennaro De Pascale  1   2 , Gabriele Pintaudi  1 , Lucia Lisi  3 , Flavio De Maio  4 , Salvatore Lucio Cutuli  1 , Eloisa Sofia Tanzarella  1 , Simone Carelli  1 , Gianmarco Lombardi  1 , Melania Cesarano  1 , Veronica Gennenzi  1 , Gabriella Maria Pia Ciotti  3 , Domenico Luca Grieco  1 , Brunella Posteraro  2   5 , Maurizio Sanguinetti  1   4 , Pierluigi Navarra  3 , Massimo Antonelli  1   2
Affiliations

Use of High-Dose Nebulized Colistimethate in Patients with Colistin-Only Susceptible Acinetobacter baumannii VAP: Clinical, Pharmacokinetic and Microbiome Features

Gennaro De Pascale et al. Antibiotics (Basel). .

Abstract

(1) Background: Colistin-only susceptible (COS) Acinetobacter baumannii (AB) ventilator-associated pneumonia (VAP) represents a clinical challenge in the Intensive Care Unit (ICU) due to the negligible lung diffusion of this molecule and the low-grade evidence on efficacy of its nebulization. (2) Methods: We conducted a prospective observational study on 134 ICU patients with COS-AB VAP to describe the 'real life' clinical use of high-dose (5 MIU q8) aerosolized colistin, using a vibrating mesh nebulizer. Lung pharmacokinetics and microbiome features were investigated. (3) Results: Patients were enrolled during the COVID-19 pandemic with the ICU presenting a SAPS II of 42 [32-57]. At VAP diagnosis, the median PaO2/FiO2 was 120 [100-164], 40.3% were in septic shock, and 24.6% had secondary bacteremia. The twenty-eight day mortality was 50.7% with 60.4% and 40.3% rates of clinical cure and microbiological eradication, respectively. We did not observe any drug-related adverse events. Epithelial lining fluid colistin concentrations were far above the CRAB minimal-inhibitory concentration and the duration of nebulized therapy was an independent predictor of microbiological eradication (12 [9.75-14] vs. 7 [4-13] days, OR (95% CI): 1.069 (1.003-1.138), p = 0.039). (4) Conclusions: High-dose and prolonged colistin nebulization, using a vibrating mesh, was a safe adjunctive therapeutic strategy for COS-AB VAP. Its right place and efficacy in this setting warrant investigation in interventional studies.

Keywords: Acinetobacter baumannii; colistin; nebulization; ventilator-associated pneumonia.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Lung microbiome composition of a representative patient with microbiological eradication.
Figure 2
Figure 2
Colistin (A) and colistimethate (B) ELF concentrations. Data available from 7 patients’ ELF (epithelial lining fluid).
See this image and copyright information in PMC

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