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Identifier 000414154
Title Σύγκριση της αποτελεσματικότητας της εισπνεόμενης κολιστίνης σε συνδυασμό με ενδοφλέβια κολιστίνη έναντι της ενδοφλέβιας κολιστίνης μόνο, σε ασθενείς με πνευμονία σχετιζόμενη με αναπνευστήρα
Alternative Title Comparison of the effectiveness of inhaled colistin in combination with intravenous colistin versus intravenous colistin alone, in patients with ventilatorassociated pneumonia
Author Κορμπίλα, Ιωάννα Π.
Thesis advisor Σαμώνης, Γεώργιος
Γκίκας, Αχχιλέας
Γεωργόπουλος, Δημήτριος
Reviewer Γαλανάκης, Εμμανουήλ
Κουρούμαλης, Ηλίας
Κοφτερίδης, Διαμαντής
Μπριασούλης, Γεώργιος
Abstract ENGLISH TITLE Comparison of the effectiveness of inhaled colistin in combination with intravenous colistin versus intravenous colistin alone, in patients with ventilatorassociated pneumonia. ABSTRACT Introduction Ventilator-associated pneumonia is a common infectious complication in the intensive care unit, leading to increase in mortality, prolongation of hospital stay and increased costs. Ventilator-associated pneumonia is usually caused by multidrugresistant bacteria. In Greek hospitals, the most common pathogens are Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Intravenous colistin is one of the main therapeutic options. It is administered as a prodrug (colistimethate sodium) with complex pharmacokinetic properties, and has debatable efficacy and relatively high toxicity. Colistin can also be administered as an inhaled antibiotic, according to the experience in patients with cystic fibrosis. The use of inhaled colistin in patients with ventilator-associated pneumonia can theoretically lead to higher drug levels at the site of infection, without considerable risk for systemic toxicity Aim We aimed to evaluate the efficacy of treatment with inhaled colistin in combination with intravenous colistin, compared with intravenous colistin alone, for ventilator-associated pneumonia. Methods This was a retrospective, comparative cohort study, done at the intensive care unit of a tertiary-care hospital, in Athens, Greece. We included all patients with microbiologically-documented ventilator-associated pneumonia who received intravenous colistin for at least 3 days, with or without nebulized colistin, between May 2005 and August 2007. The usual dose of nebulized colistin was 1 MIU thrice daily and that of intravenous colistin was 3 MIU thrice daily for normal renal function. Patient data regarding demographics, comorbidities, laboratory, imaging and microbiological tests, antimicrobial treatments, invasive procedures, presence of 155 foreign bodies or catheters, special treatments, as well as the duration of mechanical ventilation and hospitalization were extracted and analyzed. The primary endpoint was clinical cure (resolution of pneumonia) at the end of colistin treatment. The secondary endpoint was all-cause mortality. The variables that were associated with the outcome were analyzed with multiple logistic regression. Results We included 121 patients, of whom 78 (64.5%) received inhaled colistin in combination with intravenous colistin, whereas 43 (35.5%) received intravenous colistin alone. Twenty-three (19.0%) of the 121 patients received concomitantly other active antibiotics. The causative pathogens were A. baumannii in 92 (76.0%) patients, P. aeruginosa in 22 (18. 2%), and K. pneumoniae in 7 (5,8%) patients. The patients who received inhaled colistin had fewer isolates that were susceptible only to colistin, had received fewer blood transfusions, while they received longer treatment with intravenous colistin. Clinical cure was more common in the inhaled colistin group [62/78 (79.5%) patients versus 26/43 (60.5%) patients in the intravenous colistin alone group (p=0.025)]. In multivariate analysis, the administration of inhaled colistin was the only independent predictor variable of clinical cure (OR 2.53, 95% CI 1.11-5.76). In the subgroup of 98 patients who received colistin as the only active antibiotic, clinical cure was also more common in those who received inhaled colistin [46/60 (76.7%) versus 22/38 (57.9%) in those who received intravenous colistin alone, p=0.049]. All-cause, in-hospital mortality was 31/78 (39.7%) in the inhaled colistin group, compared with 19/43 (44.2%) in the intravenous colistin alone group (p=0.63). All-cause mortality during intensive-care unit stay was 28/78 (35.9%) vs. 17/43 (39.5%), respectively (p=0.69). After adjustment for risk factors, treatment with inhaled colistin was not associated with in-hospital mortality. The variables that were independently associated with increased mortality were higher APACHE II score (OR 1.12, 95% CI 1.04-1.20), underlying malignancy (OR 4.11, 95% CI 1.18- 14.23) and lower daily dose of intravenous colistin [OR (per MIU) 0.81, 95% CI 0.68- 0.96]. Discussion The main finding of this study is that, among patients with ventilatorassociated pneumonia caused by multidrug-resistant Gram-negative bacteria, clinical cure was more common in those treated with inhaled colistin combined with intravenous colistin, than in those treated with intravenous colistin alone. The benefit of adjunctive inhaled colistin can be attributed to the limited and delayed penetration of intravenous colistin in lung parenchyma. On the contrary, inhaled colistin appears to achieve high lung concentrations and is associated with 156 low risk for nephrotoxicity. However, the mode of administration of nebulized antibiotics and the penetration in foci of serious pneumonia warrant further study. The survival of the patients with ventilator-associated pneumonia depends mainly on their underlying clinical condition, while the infection-attributable mortality appears to be relatively low. For the demonstration of potential differences in survival with the use of adjunctive inhaled colistin, a large sample size would be required. Most of the relevant in vivo and clinical studies support the idea that adjunctive inhaled colistin could be beneficial in ventilator-associated pneumonia, in terms of clinical improvement and microbiological eradication. There is however substantial heterogeneity between these studies as regards to the mode of administration of inhaled colistin, the dosage used, other concomitant antibiotics, and the susceptibility profile of the causative pathogens. Conclusions The use of inhaled colistin, as adjunctive to intravenous colistin, in ventilatorassociated pneumonia due to multidrug-resistant Gram-negative bacteria appears to be associated with a higher likelihood of clinical cure, without evidence for improved survival. These findings merit futher investigation in randomized clinical trials on the safety and efficacy of inhaled colistin.
Language Greek
Subject Bacteria
Inhaled antibiotics
Issue date 2018-03-28
Collection   Faculty/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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