Aerosolized Plus Intravenous Polymyxin B Versus Colistin in the Treatment of Pandrug-Resistant Klebsiella Pneumonia-mediated Ventilator-Associated Pneumonia: A Retrospective Cohort Study in Bangladesh

Overview

Journal J Crit Care Med (Targu Mures)

Publisher Sciendo

Specialty Critical Care

Date 2023 Aug 18

PMID 37593252

Authors

Md Jahidul Hasan

Chandra Datta Sumi

Shihan Mahmud Redwanul Huq

Ahmad Mursel Anam

Raihan Rabbani

Affiliations

Soon will be listed here.

Abstract

Background: Pandrug-resistant Klebsiella pneumoniae ventilator associated pneumonia (VAP) is associated with high rate of mortality in intensive care unit (ICU) and has been recognized as a difficult-to-treat infection worldwide. Polymyxin B or colistin-based combination therapies are frequently used worldwide though microbial eradication rate is not promising.

Aim: The aim of this study is to compare the clinical outcome of intravenous with aerosolized polymyxin B versus colistin in the treatment of pandrug-resistant K. pneumoniae VAP.

Methods: This retrospective cohort study was conducted on 222 mechanically ventilated patients admitted from May 11, 2019 to October 19, 2020. K. pneumoniae isolates were resistant to all available antibiotics, including polymyxins in culture sensitivity tests. As treatment, polymyxin B and colistin was administered in intravenous and aerosolized form concurrently twice daily in 106 patients and 116 patients in PMB and CLN group, respectively for 14 days. Survival rate, safety, and clinical outcomes were compared among the groups. The Cox proportional-hazard model was performed to calculate hazard ratio (HR) with 95% confidence intervals (CI).

Results: Patients in PMB group showed more microbial eradication than the patients CLN group [68.1% (n=116)/83% (n=106), respectively; P <0.05). The median day of intubation and ICU stay in PMB group was shorter than that in CLN group [10 (IQR: 9-12.25) vs. 14 (IQR: 11-19), P <0.05; 12 (IQR: 10-14) vs. 15 (IQR: 9-18.5), P=0.072, respectively] with reduced 60-day all-cause mortality rate [15% (n=106) vs. 21.55% (n=116)]. Polymyxin B improved survival compared to colistin (multivariate HR: 0.662; 95% CI=0.359-1.222, P=0.195).

Conclusions: Concurrent administration of intravenous and aerosolized polymyxin B in patients with pandrug-resistant K. pneumoniae-associated VAP revealed better microbial eradication, reduced the length of intubation and ICU stay, and improved survival rate compared to colistin.

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References

Fernando S, Tran A, Cheng W, Klompas M, Kyeremanteng K, Mehta S . Diagnosis of ventilator-associated pneumonia in critically ill adult patients-a systematic review and meta-analysis. Intensive Care Med. 2020; 46(6):1170-1179. PMC: 7223448. DOI: 10.1007/s00134-020-06036-z. View

Imberti R, Cusato M, Villani P, Carnevale L, Iotti G, Langer M . Steady-state pharmacokinetics and BAL concentration of colistin in critically Ill patients after IV colistin methanesulfonate administration. Chest. 2010; 138(6):1333-9. DOI: 10.1378/chest.10-0463. View

Wu D, Wu C, Zhang S, Zhong Y . Risk Factors of Ventilator-Associated Pneumonia in Critically III Patients. Front Pharmacol. 2019; 10:482. PMC: 6521332. DOI: 10.3389/fphar.2019.00482. View

Xu Q, Xu T, Zhuang Y, Liu X, Li Y, Chen Y . In Vivo Development of Polymyxin B Resistance in owing to a 42 bp Deletion in the Sequence of . Biomed Res Int. 2020; 2020:5868479. PMC: 7193288. DOI: 10.1155/2020/5868479. View

Athanassa Z, Markantonis S, Fousteri M, Myrianthefs P, Boutzouka E, Tsakris A . Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients. Intensive Care Med. 2012; 38(11):1779-86. DOI: 10.1007/s00134-012-2628-7. View

Leuppi-Taegtmeyer A, Decosterd L, Osthoff M, Mueller N, Buclin T, Corti N . Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy. Antimicrob Agents Chemother. 2018; 63(2). PMC: 6355613. DOI: 10.1128/AAC.01957-18. View

Pontikis K, Karaiskos I, Bastani S, Dimopoulos G, Kalogirou M, Katsiari M . Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrug-resistant and extensively drug-resistant carbapenemase-producing Gram-negative bacteria. Int J Antimicrob Agents. 2013; 43(1):52-9. DOI: 10.1016/j.ijantimicag.2013.09.010. View

Lin Y, Zhou Q, Onufrak N, Wirth V, Chen K, Wang J . Aerosolized Polymyxin B for Treatment of Respiratory Tract Infections: Determination of Pharmacokinetic-Pharmacodynamic Indices for Aerosolized Polymyxin B against Pseudomonas aeruginosa in a Mouse Lung Infection Model. Antimicrob Agents Chemother. 2017; 61(8). PMC: 5527630. DOI: 10.1128/AAC.00211-17. View

Hasan M, Rabbani R, Anam A, Santini A, Huq S . The Susceptibility of MDR- To Polymyxin B Plus Its Nebulised Form Versus Polymyxin B Alone in Critically Ill South Asian Patients. J Crit Care Med (Targu Mures). 2021; 7(1):28-36. PMC: 8519379. DOI: 10.2478/jccm-2020-0044. View

10.

Ding C, Zhang Y, Yang Z, Wang J, Jin A, Wang W . Incidence, temporal trend and factors associated with ventilator-associated pneumonia in mainland China: a systematic review and meta-analysis. BMC Infect Dis. 2017; 17(1):468. PMC: 5496595. DOI: 10.1186/s12879-017-2566-7. View

11.

Martin-Loeches I, Rodriguez A, Torres A . New guidelines for hospital-acquired pneumonia/ventilator-associated pneumonia: USA vs. Europe. Curr Opin Crit Care. 2018; 24(5):347-352. DOI: 10.1097/MCC.0000000000000535. View

12.

Kalil A, Metersky M, Klompas M, Muscedere J, Sweeney D, Palmer L . 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; 63(5):e61-e111. PMC: 4981759. DOI: 10.1093/cid/ciw353. View

13.

Tran T, Velkov T, Nation R, Forrest A, Tsuji B, Bergen P . Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: are we there yet?. Int J Antimicrob Agents. 2016; 48(6):592-597. PMC: 5154767. DOI: 10.1016/j.ijantimicag.2016.09.010. View

14.

Navon-Venezia S, Kondratyeva K, Carattoli A . Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol Rev. 2017; 41(3):252-275. DOI: 10.1093/femsre/fux013. View

15.

Juan C, Fang S, Chou C, Tsai T, Lin Y . Clinical characteristics of patients with pneumonia caused by in Taiwan and prevalence of antimicrobial-resistant and hypervirulent strains: a retrospective study. Antimicrob Resist Infect Control. 2020; 9(1):4. PMC: 6942382. DOI: 10.1186/s13756-019-0660-x. View

16.

Tuon F, Graf M, Merlini A, Rocha J, Stallbaum S, Arend L . Risk factors for mortality in patients with ventilator-associated pneumonia caused by carbapenem-resistant Enterobacteriaceae. Braz J Infect Dis. 2016; 21(1):1-6. PMC: 9425544. DOI: 10.1016/j.bjid.2016.09.008. View

17.

Yapa S, Li J, Patel K, Wilson J, Dooley M, George J . 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. PMC: 3993267. DOI: 10.1128/AAC.01705-13. View

18.

Sarda C, Fazal F, Rello J . Management of ventilator-associated pneumonia (VAP) caused by resistant gram-negative bacteria: which is the best strategy to treat?. Expert Rev Respir Med. 2019; 13(8):787-798. DOI: 10.1080/17476348.2019.1632195. View

19.

Capone A, Giannella M, Fortini D, Giordano A, Meledandri M, Ballardini M . High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality. Clin Microbiol Infect. 2012; 19(1):E23-E30. DOI: 10.1111/1469-0691.12070. View

20.

Zimlichman E, Henderson D, Tamir O, Franz C, Song P, Yamin C . Health care-associated infections: a meta-analysis of costs and financial impact on the US health care system. JAMA Intern Med. 2013; 173(22):2039-46. DOI: 10.1001/jamainternmed.2013.9763. View