Effect of Extended Infusion of Meropenem and Nebulized Amikacin on Gram-negative Multidrug-resistant Ventilator-associated Pneumonia

Overview

Journal Saudi J Anaesth

Specialty Anesthesiology

Date 2018 Feb 9

PMID 29416463

Citations 3

Authors

Mona Ahmed Ammar

Waleed Abdalla

Affiliations

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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, = 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, < 0.001) and reduction in ICU days (11.87 ± 2.6 vs. 15.3 ± 3.1 days, respectively, < 0.001). Group III compared to Group II showed significant reduction in ventilator days (4.22 ± 1.32 vs. 5.32 ± 1.86, respectively, = 0.011) and highly significant reduction in ICU days (9.21 ± 1.17 vs. 11.87 ± 2.6, respectively, < 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.

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References

Korbila I, Michalopoulos A, Rafailidis P, Nikita D, Samonis G, Falagas M . Inhaled colistin as adjunctive therapy to intravenous colistin for the treatment of microbiologically documented ventilator-associated pneumonia: a comparative cohort study. Clin Microbiol Infect. 2009; 16(8):1230-6. DOI: 10.1111/j.1469-0691.2009.03040.x. View

Chastre J, Fagon J . Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002; 165(7):867-903. DOI: 10.1164/ajrccm.165.7.2105078. View

Nicasio A, Eagye K, Nicolau D, Shore E, Palter M, Pepe J . Pharmacodynamic-based clinical pathway for empiric antibiotic choice in patients with ventilator-associated pneumonia. J Crit Care. 2009; 25(1):69-77. DOI: 10.1016/j.jcrc.2009.02.014. View

Vincent J, Bihari D, Suter P, Bruining H, White J, Wolff M . The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA. 1995; 274(8):639-44. View

Arnold H, Sawyer A, Kollef M . Use of adjunctive aerosolized antimicrobial therapy in the treatment of Pseudomonas aeruginosa and Acinetobacter baumannii ventilator-associated pneumonia. Respir Care. 2012; 57(8):1226-33. DOI: 10.4187/respcare.01556. View

Bercault N, Boulain T . Mortality rate attributable to ventilator-associated nosocomial pneumonia in an adult intensive care unit: a prospective case-control study. Crit Care Med. 2002; 29(12):2303-9. DOI: 10.1097/00003246-200112000-00012. View

. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005; 171(4):388-416. DOI: 10.1164/rccm.200405-644ST. View

Palmer L, Smaldone G . Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit. Am J Respir Crit Care Med. 2014; 189(10):1225-33. DOI: 10.1164/rccm.201312-2161OC. View

Safdar N, Dezfulian C, Collard H, Saint S . Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med. 2005; 33(10):2184-93. DOI: 10.1097/01.ccm.0000181731.53912.d9. View

10.

Cook D, Walter S, Cook R, Griffith L, Guyatt G, Leasa D . Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med. 1998; 129(6):433-40. DOI: 10.7326/0003-4819-129-6-199809150-00002. View

11.

Lu Q, Yang J, Liu Z, Gutierrez C, Aymard G, Rouby J . Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2011; 184(1):106-15. DOI: 10.1164/rccm.201011-1894OC. View

12.

Palmer L . Aerosolized antibiotics in critically ill ventilated patients. Curr Opin Crit Care. 2009; 15(5):413-8. DOI: 10.1097/MCC.0b013e328330abcf. View

13.

Jaruratanasirikul S, Sriwiriyajan S . Comparison of the pharmacodynamics of meropenem in healthy volunteers following administration by intermittent infusion or bolus injection. J Antimicrob Chemother. 2003; 52(3):518-21. DOI: 10.1093/jac/dkg378. View

14.

Valles J, Pobo A, Garcia-Esquirol O, Mariscal D, Real J, Fernandez R . Excess ICU mortality attributable to ventilator-associated pneumonia: the role of early vs late onset. Intensive Care Med. 2007; 33(8):1363-8. DOI: 10.1007/s00134-007-0721-0. View