Effect of extended infusion of meropenem and nebulized amikacin on Gram-negative multidrug-resistant ventilator-associated pneumonia

Abstract

Background:Ventilator-associated pneumonia (VAP) due to multidrug-resistant organisms (MDROs) is associated with a significant mortality in the Intensive Care Unit (ICU). The aim of this study was to compare the efficacy and safety of extended infusion of meropenem and nebulized amikacin on VAP caused by Gram-negative MDRO versus intravenous (IV) meropenem and amikacin alone.Methodology:A randomized nonblinded controlled trial was performed on ninety patients with VAP. Patients were randomized into three equal groups: Group I received IV amikacin 20 mg/kg/24 h and meropenem 2 g over 30 min/8 h. Group II received the same as Group I in addition to nebulized amikacin 25 mg/kg/day every 8 h. Group III received IV amikacin 20 mg/kg/24 h, nebulized amikacin 25 mg/kg/day every 8 h, and meropenem 2 g diluted in 240 ml normal saline over 3 h/8 h. The primary outcome was the clinical outcome of VAP. Secondary outcomes were microbiological outcome, VAP-related mortality, duration of MV, ICU stay, and nephrotoxicity.Results:Group II and Group III compared to Group I showed higher incidence of clinical cure (53.33% in Group II and 66.67% in Group III vs. 26.67% in Group I, P = 0.007). Group II compared to Group I showed significant reduction in ventilator days (5.32 ± 1.86 vs. 7.3 ± 2.1 days, respectively, P < 0.001) and reduction in ICU days (11.87 ± 2.6 vs. 15.3 ± 3.1 days, respectively, P < 0.001). Group III compared to Group II showed significant reduction in ventilator days (4.22 ± 1.32 vs. 5.32 ± 1.86, respectively, P = 0.011) and highly significant reduction in ICU days (9.21 ± 1.17 vs. 11.87 ± 2.6, respectively, P < 0.001). All groups were comparable as regards nephrotoxicity or mortality.Conclusions:Adding nebulized amikacin to systemic antibiotics in patients with VAP caused by Gram-negative MDRO may offer efficacy benefits, and the use of extended infusions of meropenem could improve the clinical outcomes in critically ill populations.

A comparative study between effect of combined intravenous and nebulized amikacin versus intravenous amikacin alone in mechanically ventilated patients with ventilator-associated pneumonia (VAP)

“…In the study by Diamantis et al, the VAP-related mortality was 16% in the nebulized group versus 26% in the control group without significant differences ( p 0.289) (Kofteridis et al, 2010 ). In Ammar and Abdalla, the VAP-related mortality was 8% in the IV group ( p 0.347) versus 5% in the IV and nebulized group ( p 0.197) versus 4% in the nebulized and extended IV infusion group ( p 0.717) with no significant differences (Ammar & Abdalla, 2018 ).…”

“…Group C received IV amikacin 20 mg/kg/day, nebulized amikacin 25 mg/kg/day, and extended infusion of meropenem 2 g/kg/8 h over 3 h. Group B showed a highly statistically significant reduction in ventilator days 5.31 ± 1.86 vs 7.3 ± 2.1 days ( p < 0.001) while group C also showed significant fewer ventilator days compared to group A, 4.22±1.32 vs 5.32 ± 1.86 ( p < 0.011). Also, this similarity may be attributed to the larger sample size, combined use of nebulized and IV routes, and the use of jet nebulizers (Ammar & Abdalla, 2018 ).…”

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.…”