Effectiveness of inhaled antibiotics combined with intravenous administration for treatment of ventilator-associated pneumonia: a systematic review_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 PENG Dongfeng , CHA Ritian , CHEN Xinhua , WEI Jinlian

Department of Respiratory Medicine, Wuhu No.1 Hospital, Wuhu, Anhui 241000, P.R.China;

Corresponding author：

PENG Dongfeng, Email: 1968360409@qq.com

Keywords：

Antibiotics; Inhalation; Intravenous injection; Ventilator-associated pneumonia

DOI：

10.7507/1671-6205.201608054

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Objective To evaluate the effects of inhalation combined intravenous antibiotics for the treatment of ventilator-associated pneumonia. Methods A computerized search was performed through Cochrane library, Joanna Briggs Institute Library, PubMed, MEDLINE, CINAHL, CBM, CNKI and Wangfang medical network about inhalation combined intravenous antibiotics therapy in ventilator-associated pneumonia in the literatures. The data extracting and quality assessment were performed by three researchers. The meta-analysis was performed by RevMan 5.3 software. Results Thirteen studies was included for analysis. The results showed that the cure rate was higher in the experimental group compared with the control group with significant difference (RR=1.16, 95%CI 1.07 to 1.56,P=0.000 5). There were no significant differences in the mortality (RR=1.04, 95%CI 0.82 to 1.32,P=0.74) or the incidence of kidney damage (RR=0.79, 95%CI 0.51 to 1.22,P=0.29). The difference in pathogenic bacteria removal was statistically significant (RR=1.38, 95%CI 1.09 to 1.74,P=0.007). The negative conversion rate of respiratory secretions was higher in the experimental group. Conclusion Inhalation combined intravenous antibiotics can improve the cure rate of patients with ventilator-associated pneumonia, clear pathogenic bacteria effectively, and is worthy of recommendation for clinical use.

Citation： PENG Dongfeng, CHA Ritian, CHEN Xinhua, WEI Jinlian. Effectiveness of inhaled antibiotics combined with intravenous administration for treatment of ventilator-associated pneumonia: a systematic review. Chinese Journal of Respiratory and Critical Care Medicine, 2017, 16(3): 228-236. doi: 10.7507/1671-6205.201608054 Copy

1.	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.
2.	Czosnowski QA, Wood GC, Magnotti LJ, et al. Adjunctive aerosolized antibiotics for treatment of ventilator-associated pneumonia. Pharmacotherapy, 2009, 29(9): 1054-1060.
3.	Rouby JJ, Bouhemad B, Monsel A, et al. Aerosolized antibiotics for ventilator-associated pneumonia: lessons from experimental studies. Anesthesiology, 2012, 117(6): 1364-1380.
4.	Luyt CE, Combes A, Nieszkowska A, et al. Aerosolized antibiotics to treat ventilator-associated pneumonia. Curr Opin Infect Dis, 2009, 22(2): 154-158.
5.	杨春辉, 李虎, 薛杨勇, 等. 雾化吸入阿米卡星气道分泌物及血药动力学特点. 内科急危重症杂志, 2013, 19(3): 165-167.
6.	Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med, 2002, 165(7): 867-903.
7.	Kalanuria AA, Ziai W, Mirski M. Ventilator-associated pneumonia in the ICU. Crit Care, 2014, 18(2): 208.
8.	Restrepo MI, Keyt H, Reyes LF. Aerosolized Antibiotics. Respir Care, 2015, 60(6): 762-761; discussion 771-773.
9.	Ferrari F, Lu Q, Girardi C, et al. Nebulized ceftazidime in experimental pneumonia caused by partially resistant Pseudomonas aeruginosa. Intensive Care Med, 2009, 35(10): 1792-1800.
10.	Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis, 2016, 14: 1-51.
11.	Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration, 2011, 81-387.
12.	Lu Q, Yang J, Liu Z, et al. Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med, 2011, 184(1): 106-115.
13.	Niederman MS, Chastre J, Corkery K, et al. BAY41-6551 achieves bactericidal tracheal aspirate amikacin concentrations in mechanically ventilated patients with Gram-negative pneumonia. Intensive Care Med, 2012, 38(2): 263-271.
14.	Hallal A, Cohn SM, Namias N, et al. Aerosolized tobramycin in the treatment of ventilator-associated pneumonia: a pilot study. Surg Infect (Larchmt), 2007, 8(1): 73-82.
15.	Palmer LB, Smaldone GC, Chen JJ, et al. Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit. Crit Care Med, 2008, 36(7): 2008-2013.
16.	Abdellatif S, Trifi A, Daly F, et al. Efficacy and toxicity of aerosolised colistin in ventilator-associated pneumonia: a prospective, randomised trial. Ann Intensive Care, 2016, 6(1): 26.
17.	Rattanaumpawan P, Lorsutthitham J, Ungprasert P, et al. Randomized controlled trial of nebulized colistimethate sodium as adjunctive therapy of ventilator-associated pneumonia caused by Gram-negative bacteria. J Antimicrob Chemother, 2010, 65(12): 2645-2649.
18.	Palmer LB, Smaldone GC. Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit. Am J Respir Crit Care Med, 2014, 189(10): 1225-1233.
19.	柳梅, 郑萍. 静脉注射联合吸入抗生素治疗呼吸机相关性肺炎 97 例. 实用医学杂志, 2012, 28(1): 129-131.
20.	李虎, 杨春辉, 薛杨勇, 等. 雾化吸入抗生素治疗呼吸机相关性肺炎的临床疗效观察. 中国呼吸与危重监护杂志, 2015, 14(3): 273-277.
21.	曹广科, 赵玉良, 李之海, 等. 雾化吸入阿米卡星治疗鲍曼不动杆菌呼吸机相关肺炎的效果和安全性分析. 中国当代医药, 2014, 21(32): 66-68.
22.	刘建民, 郭奕芬. 雾化吸入妥布霉素联合静脉使用抗生素治疗呼吸机相关性肺炎的疗效. 实用临床医学, 2015, 16(9): 20-21.
23.	Kofteridis DP, Alexopoulou C, Valachis A, et al. Aerosolized plus intravenous colistin versus intravenous colistin alone for the treatment of ventilator-associated pneumonia: a matched case-control study. Clin Infect Dis, 2010, 51(11): 1238-1244.
24.	Korbila IP, Michalopoulos A, Rafailidis PI, et al. Inhaled colistin as adjunctive therapy to intravenous colistin for the treatment of microbiologically documented ventilator-associated pneumonia: a comparative cohort study. Clin Microbiol Infect, 2010, 16(8): 1230-1236.
25.	Palmer LB. Aerosolized antibiotics in critically ill ventilated patients. Curr Opin Crit Care, 2009, 15(5): 413-418.
26.	Lu Q, Luo R, Bodin L, et al. Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology, 2012, 117(6): 1335-1347.
27.	Michalopoulos A, Metaxas EI, Falagas ME. Aerosol delivery of antimicrobial agents during mechanical ventilation: current practice and perspectives. Curr Drug Deliv, 2011, 8(2): 208-212.
28.	Kuzovlev AN, Moroz VV, Golubev AM. Inhailed antibiotics in treatment of nosocomial pneumonia. Anesteziol Reanimatol, 2015, 60(4): 55-61.
29.	李虎, 杨春辉, 唐建国. 雾化吸入治疗呼吸机相关肺炎的疗效观察. 中国危重病急救医学, 2011, 23(1): 60-62.
30.	Montgomery AB, Vallance S, Abuan T, et al. A randomized double-blind placebo-controlled dose-escalation phase 1 study of aerosolized amikacin and fosfomycin delivered via the PARI investigational eFlow® inline nebulizer system in mechanically ventilated patients. J Aerosol Med Pulm Drug Deliv, 2014, 27(6): 441-448.
31.	Bassetti M, Luyt CE, Nicolau DP, Pugin J. Characteristics of an ideal nebulized antibiotic for the treatment of pneumonia in the intubated patient. Ann Intensive Care, 2016, 6(1): 35.
32.	Kollef MH, Hamilton CW, Montgomery AB. Aerosolized antibiotics: do they add to the treatment of pneumonia?. Curr Opin Infect Dis, 2013, 26(6): 538-544.

1. 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.
2. Czosnowski QA, Wood GC, Magnotti LJ, et al. Adjunctive aerosolized antibiotics for treatment of ventilator-associated pneumonia. Pharmacotherapy, 2009, 29(9): 1054-1060.
3. Rouby JJ, Bouhemad B, Monsel A, et al. Aerosolized antibiotics for ventilator-associated pneumonia: lessons from experimental studies. Anesthesiology, 2012, 117(6): 1364-1380.
4. Luyt CE, Combes A, Nieszkowska A, et al. Aerosolized antibiotics to treat ventilator-associated pneumonia. Curr Opin Infect Dis, 2009, 22(2): 154-158.
5. 杨春辉, 李虎, 薛杨勇, 等. 雾化吸入阿米卡星气道分泌物及血药动力学特点. 内科急危重症杂志, 2013, 19(3): 165-167.
6. Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med, 2002, 165(7): 867-903.
7. Kalanuria AA, Ziai W, Mirski M. Ventilator-associated pneumonia in the ICU. Crit Care, 2014, 18(2): 208.
8. Restrepo MI, Keyt H, Reyes LF. Aerosolized Antibiotics. Respir Care, 2015, 60(6): 762-761; discussion 771-773.
9. Ferrari F, Lu Q, Girardi C, et al. Nebulized ceftazidime in experimental pneumonia caused by partially resistant Pseudomonas aeruginosa. Intensive Care Med, 2009, 35(10): 1792-1800.
10. Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis, 2016, 14: 1-51.
11. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration, 2011, 81-387.
12. Lu Q, Yang J, Liu Z, et al. Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med, 2011, 184(1): 106-115.
13. Niederman MS, Chastre J, Corkery K, et al. BAY41-6551 achieves bactericidal tracheal aspirate amikacin concentrations in mechanically ventilated patients with Gram-negative pneumonia. Intensive Care Med, 2012, 38(2): 263-271.
14. Hallal A, Cohn SM, Namias N, et al. Aerosolized tobramycin in the treatment of ventilator-associated pneumonia: a pilot study. Surg Infect (Larchmt), 2007, 8(1): 73-82.
15. Palmer LB, Smaldone GC, Chen JJ, et al. Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit. Crit Care Med, 2008, 36(7): 2008-2013.
16. Abdellatif S, Trifi A, Daly F, et al. Efficacy and toxicity of aerosolised colistin in ventilator-associated pneumonia: a prospective, randomised trial. Ann Intensive Care, 2016, 6(1): 26.
17. Rattanaumpawan P, Lorsutthitham J, Ungprasert P, et al. Randomized controlled trial of nebulized colistimethate sodium as adjunctive therapy of ventilator-associated pneumonia caused by Gram-negative bacteria. J Antimicrob Chemother, 2010, 65(12): 2645-2649.
18. Palmer LB, Smaldone GC. Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit. Am J Respir Crit Care Med, 2014, 189(10): 1225-1233.
19. 柳梅, 郑萍. 静脉注射联合吸入抗生素治疗呼吸机相关性肺炎 97 例. 实用医学杂志, 2012, 28(1): 129-131.
20. 李虎, 杨春辉, 薛杨勇, 等. 雾化吸入抗生素治疗呼吸机相关性肺炎的临床疗效观察. 中国呼吸与危重监护杂志, 2015, 14(3): 273-277.
21. 曹广科, 赵玉良, 李之海, 等. 雾化吸入阿米卡星治疗鲍曼不动杆菌呼吸机相关肺炎的效果和安全性分析. 中国当代医药, 2014, 21(32): 66-68.
22. 刘建民, 郭奕芬. 雾化吸入妥布霉素联合静脉使用抗生素治疗呼吸机相关性肺炎的疗效. 实用临床医学, 2015, 16(9): 20-21.
23. Kofteridis DP, Alexopoulou C, Valachis A, et al. Aerosolized plus intravenous colistin versus intravenous colistin alone for the treatment of ventilator-associated pneumonia: a matched case-control study. Clin Infect Dis, 2010, 51(11): 1238-1244.
24. Korbila IP, Michalopoulos A, Rafailidis PI, et al. Inhaled colistin as adjunctive therapy to intravenous colistin for the treatment of microbiologically documented ventilator-associated pneumonia: a comparative cohort study. Clin Microbiol Infect, 2010, 16(8): 1230-1236.
25. Palmer LB. Aerosolized antibiotics in critically ill ventilated patients. Curr Opin Crit Care, 2009, 15(5): 413-418.
26. Lu Q, Luo R, Bodin L, et al. Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology, 2012, 117(6): 1335-1347.
27. Michalopoulos A, Metaxas EI, Falagas ME. Aerosol delivery of antimicrobial agents during mechanical ventilation: current practice and perspectives. Curr Drug Deliv, 2011, 8(2): 208-212.
28. Kuzovlev AN, Moroz VV, Golubev AM. Inhailed antibiotics in treatment of nosocomial pneumonia. Anesteziol Reanimatol, 2015, 60(4): 55-61.
29. 李虎, 杨春辉, 唐建国. 雾化吸入治疗呼吸机相关肺炎的疗效观察. 中国危重病急救医学, 2011, 23(1): 60-62.
30. Montgomery AB, Vallance S, Abuan T, et al. A randomized double-blind placebo-controlled dose-escalation phase 1 study of aerosolized amikacin and fosfomycin delivered via the PARI investigational eFlow® inline nebulizer system in mechanically ventilated patients. J Aerosol Med Pulm Drug Deliv, 2014, 27(6): 441-448.
31. Bassetti M, Luyt CE, Nicolau DP, Pugin J. Characteristics of an ideal nebulized antibiotic for the treatment of pneumonia in the intubated patient. Ann Intensive Care, 2016, 6(1): 35.
32. Kollef MH, Hamilton CW, Montgomery AB. Aerosolized antibiotics: do they add to the treatment of pneumonia?. Curr Opin Infect Dis, 2013, 26(6): 538-544.

Chinese Journal of Respiratory and Critical Care Medicine

Effectiveness of inhaled antibiotics combined with intravenous administration for treatment of ventilator-associated pneumonia: a systematic review

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