The Potential Role of Aerosolized Colistin in the Ventilator-Associated Pneumonia Management Caused by Multidrug-Resistant Gram-Negative Bacteria: A Randomized Clinical Trial
Background: Infections caused by multidrug-resistant (MDR) pathogen have caused a resurgence of interest in colistin. To date, information about the effectiveness of Aerosolized Colistin (AS) is very limited in the treatment of Ventilator-Associated Pneumonia (VAP). The aim of this study is to evaluate the eﬃcacy and safety of AS in conjunction with intravenous (IV) colistin in patients with VAP, caused by MDR Gram-Negative Bacteria (GNB).Methods: This parallel randomized clinical trial was conducted on patients with VAP in the Intensive Care Unit (ICU) ward. 27 patients allocated to the intervention or the control group. Patients in the intervention group received IV Colistin based on glomerular ﬁltration rate along with aerosolized Colistin, 2 million units three times a day. In the control group, only IV Colistin was administered. For all patients, Procalcitonin (PCT), sputum culture, and Clinical Pulmonary Infection Score (CPIS) were evaluated and compared as outcome measures at the specified period of time.Results: Negative sputum culture was achieved in 9 (80%) out of 11 patients in the AS-IV Colistin group after seven days of therapy versus 9 (56.25%) out of 16 in the control group (P= 0.01). PCT and CPIS scores were not significantly different between two groups (P=0.21, P= 0.62). Furthermore, nephrotoxicity and neurotoxicity were not seen.Conclusion: AS Colistin lead to earlier negative sputum culture without increasing risk of nephrotoxicity and neurotoxicity, and could potentially be a beneficial adjunctive approach in the management of MDR-VAP.
2. Melsen WG, Rovers MM, Groenwold RH, et al. Attributable mortality of ventilator associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis 2013;13(8):665-71.
3. Boucher HW, Talbot GH, Bradley JS, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 2009;48(1):1-2.
4. Florescu DF, Qiu F, McCartan MA, Mindru C, Fey PD, Kalil AC. What is the efficacy and safety of colistin for the treatment of ventilator-associated pneumonia? A systematic review and meta-regression. Clin Infect Dis 2012;54(5):670-80.
5. Karnik ND, Sridharan K, Jadhav SP, et al. Pharmacokinetics of colistin in critically ill patients with multidrug-resistant Gram-negative bacilli infection. Eur J Clin Pharmacol 2013;69(7):1429-36.
6. Leong KW, Ong S, Chee HL, Lee W, Kwa AL. Hypersensitivity pneumonitis due to high-dose colistin aerosol therapy. Int J Infect Dis 2010;14(11):e1018-9.
7. Koenig SM, Truwit JD. Ventilator-associated pneumonia: diagnosis, treatment, and prevention. Clin Microbiol Rev 2006;19(4):637-57.
8. WS Yapa S, Li J, Patel K, et al. Pulmonary and systemic pharmacokinetics of inhaled and intravenous colistin methanesulfonate in cystic fibrosis patients: targeting advantage of inhalational administration. Antimicrob Agents Chemother 2014;58(5):2570-9.
9. Visser Kift E, Maartens G, Bamford C. Systematic review of the evidence for rational dosing of colistin. S Afr Med J 2014;104(3):183-6.
10. Arthur LE, Kizor RS, Selim AG, van Driel ML, Seoane L. Antibiotics for ventilator‐associated pneumonia. Cochrane Database Syst Rev 2016;10(10):CD004267.
11. Lu Q, Girardi C, Zhang M, et al. Nebulized and intravenous colistin in experimental pneumonia caused by Pseudomonas aeruginosa. Intensive Care Med 2010;36(7):1147-55.
12. Rouby JJ, Bouhemad B, Monsel A, Brisson H, Arbelot C, Lu Q. Nebulized Antibiotics Study Group. Aerosolized antibiotics for ventilator-associated pneumonia: lessons from experimental studies. Anesthesiology 2012;117(6):1364-80.
13. 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):1792-800.
14. Chuang YC, Cheng CY, Sheng Wh, et al. Effectiveness of tigecycline-based versus colistin-based therapy for treatment of pneumonia caused by multidrug-resistant Acinetobacter baumannii in a critical setting: a matched cohort analysis. BMC Infect Dis 2014;14(1):1-8.
15. Korbila IP, Michalopoulos A, Rafailidis PI, Nikita D, Samonis G, Falagas ME. 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):1230-6.
16. Arnold HM, Sawyer AM, Kollef MH. 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.
17. 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):1238-44.
18. Tumbarello M, De Pascale G, Trecarichi EM, et al. Effect of aerosolized colistin as adjunctive treatment on the outcomes of microbiologically documented ventilator-associated pneumonia caused by colistin-only susceptible gram-negative bacteria. Chest 2013;144(6):1768-75.
19. Polat M, Kara SS, Tapısız A, Tezer H, Kalkan G, Dolgun A. Treatment of ventilator-associated pneumonia using intravenous colistin alone or in combination with inhaled colistin in critically ill children. Paediatr Drugs 2015;17(4):323-30.
20. Valachis A, Samonis G, Kofteridis DP. The role of aerosolized colistin in the treatment of ventilator-associated pneumonia: a systematic review and meta analysis. Crit Care Med 2015;43(3):527-33.
21. Gu WJ, Wang F, Tang L, Bakker J, Liu JC. Colistin for the treatment of ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: a systematic review and meta-analysis. Int J Antimicrob Agents 2014;44(6):477-85.
22. Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care 2006;10(1):1-3.
23. Dalfino L, Puntillo F, Mosca A, et al. High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy? A preliminary study. Clin Infect Dis 2012;54(12):1720-6.
24. Trifi A, Abdellatif S, Daly F, Mahjoub K, et al. Efficacy and toxicity of high-dose colistin in multidrug-resistant gram-negative bacilli infections: a comparative study of a matched series. Chemotherapy 2016;61(4):190-6.
25. Falagas ME, Trigkidis KK, Vardakas KZ. Inhaled antibiotics beyond aminoglycosides, polymyxins and aztreonam: a systematic review. Int J Antimicrob Agents 2015;45(3):221-33.
26. Florescu DF, Qiu F, McCartan MA, Mindru C, Fey PD, Kalil AC. What is the efficacy and safety of colistin for the treatment of ventilator-associated pneumonia? A systematic review and meta-regression. Clin Infect Dis 2012;54(5):670-80.
27. Lu Q, Luo R, Bodin L, et al. Nebulized Antibiotics Study Group. Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology 2012;117(6):1335-47.
|Issue||Vol 9, No 3 (Summer 2021)|
|Colistin; Multiple Drug Resistance; Ventilator-Associated Pneumonia|
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