Aerosolized Amikacin as Adjunctive Therapy of Ventilator-associated Pneumonia Caused by Multidrug-resistant Gram-negative Bacteria

Abstract

Background:Aerosolized amikacin (AA) is a current option for the management of ventilator-associated pneumonia (VAP) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB), as it is reported that AA could increase the alveolar level of the drug without increasing systemic toxicity. This study aimed to evaluate the efficacy and safety of AA as an adjunctive therapy for VAP caused by MDR-GNB.Methods:In this single-center, double-blind study conducted in a 36-bed general Intensive Care Unit (ICU) in a tertiary hospital from June 2014 to June 2016, 52 ICU patients with confirmed MDR-GNB VAP were randomized to two groups (AA group, n = 27 and placebo group, n = 25). Amikacin (400 mg, q8h) or saline placebo (4 ml, q8h) was aerosolized for 7 days. The attending physician determined the administration of systemic antibiotics for VAP. Patients were followed up for 28 days. Bacteriological eradication, clinical pulmonary infection score (CPIS), and serum creatinine were assessed on day 7 of therapy. New resistance to amikacin, cure rate of VAP, weaning rate, and mortality were assessed on day 28.Results:The baseline characteristics of patients in both groups were similar. At the end of the treatment, 13 of the 32 initially detected bacterial isolates were eradicated in AA group, compared to 4 of 28 in placebo group (41% vs. 14%, P = 0.024). As for patients, 11 of 27 patients treated with AA and 4 of 25 patients treated with placebo have eradication (41% vs. 16%, P = 0.049). The adjunction of AA reduced CPIS (4.2 ± 1.6 vs. 5.8 ± 2.1, P = 0.007). New drug resistance to amikacin and the change in serum creatinine were not detected in AA group. No significant differences in the clinical cure rate in survivors (48% vs. 35%, P = 0.444), weaning rate (48% vs. 32%, P = 0.236), and mortality (22% vs. 32%, P = 0.427) were detected between the two groups on day 28.Conclusions:As an adjunctive therapy of MDR-GNB VAP, AA successfully eradicated existing MDR organisms without inducing new resistance to amikacin or change in serum creatinine. However, the improvement of mortality was not found.

Generation of high concentrations of respirable solid-phase aerosols from viscous fluids

“…Aerosol inhalation provides a delivery route for anti-infectives that requires a substantial dose to be delivered to the lungs (Maselli et al 2017) and/or have considerable systemic toxicity when administered intravenously. Colistin (40–80 mg) (Gurjar 2015) and Amikacin (400 mg) (Liu et al 2017) and its liposomal formulation, Amikacin (560 mg) (Clancy et al 2013) are potential candidates for improved aerosol delivery to treat respiratory infections. Mucolytics such as N-acetlycysteine (350 mg) (Tomioka et al 2005) and mannitol (400 mg) (Zhu et al 2015) have been used to treat patients with cystic fibrosis.…”

Amikacin nebulization for the adjunctive therapy of gram-negative pneumonia in mechanically ventilated patients: a systematic review and meta-analysis of randomized controlled trials

“…The literature search yielded 325 records through database searching, of which 24 full-text were considered for text-trials review. Finally, 13 RCTs with a total of 1733 patients met the inclusion criteria and were included in our study 11 , 14 , 18 , 19 , 26 – 34 (Fig. 1 ).…”

“…A total of 1733 patients were included in intention-to-treat analysis while 1,450 patients were included in clinically evaluable. As to the type of nebulizer devices employed in the NA group, vibrating-mesh nebulizer (3 studies) 11 , 19 , 26 , ultrasonic nebulizer (2 study) 20 , 34 , and jet nebulizer (8 study) 14 , 24 , 25 , 27 – 33 were used. During the treatment period, patients received concomitant intravenous antibiotics variable among the included studies, decided by the clinician, or based on pathogen-specific treatment criteria.…”

“…Recently, several studies on this topic have been published and some of them have a modest sample size, while the conclusions are inconsistent 14 , 19 , 20 . Thus, with the help of the strengthened power of meta-analytic techniques, the present meta-analysis aimed to review the available published RCTs to investigate the efficacy and safety of NA as adjunctive therapy in the treatment of critically ill ventilated patients with GNP.…”

Mechanical Insufflation-exsufflation for the Prevention of Ventilator-associated Pneumonia in Intensive Care Units: A Retrospective Cohort Study

“…The incidence of VAP was determined using the clinical pulmonary infection score (CPIS); a CPIS >6 indicates the presence of pneumonia. 14 Clinical pulmonary infection score is based on body temperature, blood leukocyte count, tracheal secretion, oxygenation (PaO 2 /FiO 2 ), pulmonary radiography, and positive tracheal aspirate culture. To determine VAP incidence, CPIS was calculated from the date of bacterial culture testing of specimens collected by endotracheal aspiration or bronchoalveolar lavage.…”