Use of High-Dose Nebulized Colistimethate in Patients with Colistin-Only Susceptible <i>Acinetobacter baumannii</i> VAP: Clinical, Pharmacokinetic and Microbiome Features
Gennaro De Pascale,
Gabriele Pintaudi,
Lucia Lisi,
Flavio De Maio,
Salvatore Lucio Cutuli,
Eloisa Sofia Tanzarella,
Simone Carelli,
Gianmarco Lombardi,
Melania Cesarano,
Veronica Gennenzi,
Gabriella Maria Pia Ciotti,
Domenico Luca Grieco,
Brunella Posteraro,
Maurizio Sanguinetti,
Pierluigi Navarra,
Massimo Antonelli
Affiliations
Gennaro De Pascale
Dipartimento di Scienze Dell’emergenza, Anestesiologiche e Della Rianimazione,
Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
Gabriele Pintaudi
Dipartimento di Scienze Dell’emergenza, Anestesiologiche e Della Rianimazione,
Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
Lucia Lisi
Section of Pharmcology, Department of Healthcare Surveillance and Bioethics,
Catholic University Medical School, Fondazione Policlinico Universitario A. Gemelli IRCCS,
L.go A. Gemelli 8, 00168 Rome, Italy
Flavio De Maio
Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
Salvatore Lucio Cutuli
Dipartimento di Scienze Dell’emergenza, Anestesiologiche e Della Rianimazione,
Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
Eloisa Sofia Tanzarella
Dipartimento di Scienze Dell’emergenza, Anestesiologiche e Della Rianimazione,
Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
Simone Carelli
Dipartimento di Scienze Dell’emergenza, Anestesiologiche e Della Rianimazione,
Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
Gianmarco Lombardi
Dipartimento di Scienze Dell’emergenza, Anestesiologiche e Della Rianimazione,
Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
Melania Cesarano
Dipartimento di Scienze Dell’emergenza, Anestesiologiche e Della Rianimazione,
Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
Veronica Gennenzi
Dipartimento di Scienze Dell’emergenza, Anestesiologiche e Della Rianimazione,
Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
Gabriella Maria Pia Ciotti
Section of Pharmcology, Department of Healthcare Surveillance and Bioethics,
Catholic University Medical School, Fondazione Policlinico Universitario A. Gemelli IRCCS,
L.go A. Gemelli 8, 00168 Rome, Italy
Domenico Luca Grieco
Dipartimento di Scienze Dell’emergenza, Anestesiologiche e Della Rianimazione,
Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
Brunella Posteraro
Dipartimento di Scienze Biotecnologiche di base Cliniche Intensivologiche e Perioperatorie,
Universita’ Cattolica del Sacro Cuore, Rome, L.go F. Vito 1, 00168 Rome, Italy
Maurizio Sanguinetti
Dipartimento di Scienze Dell’emergenza, Anestesiologiche e Della Rianimazione,
Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
Pierluigi Navarra
Section of Pharmcology, Department of Healthcare Surveillance and Bioethics,
Catholic University Medical School, Fondazione Policlinico Universitario A. Gemelli IRCCS,
L.go A. Gemelli 8, 00168 Rome, Italy
Massimo Antonelli
Dipartimento di Scienze Dell’emergenza, Anestesiologiche e Della Rianimazione,
Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy
(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.
