Inhalatory and intravenous colistin in treating ventilator-associated pneumonia due to Acinetobacter species: should we combine them?

Jovan Matijašević; Srdjan Gavrilović; Ilija Andrijević; Ana Andrijević; Svetislava  Milić; Marija Vukoja

doi:10.2298/VSP180910161M

Jovan Matijašević Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia
Srdjan Gavrilović Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia
Ilija Andrijević Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia
Ana Andrijević Institute for pulmonary diseases of Vojvodina, Sremska Kamenica, SerbiaInstitute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia
Svetislava Milić Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia
Marija Vukoja Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia

DOI: https://doi.org/10.2298/VSP180910161M

Keywords: pneumonia, ventilator-associated, acinetobacter, colistin, administration, inhalation, infusions, intravenous, treatment outcome

Abstract

Background/Aim. Acinetobacter is one of the most common causes of nosocomial infections, especially ventilator-associated pneumonia (VAP). Considering the increased presence of multidrug-resistant microorganisms and the lack of novel antibiotics, colistin merged as the last-resort antibiotic for life threatening nosocomial infections. Intravenous use of antibiotics is accepted as a gold standard for the treatment of pneumonia, but additional administration of inhaled antibiotics in the treatment of VAP has shown to be advantageous in some clinical trials. The aim of this study was to investigate the effect of inhalatory colistin as an adjunct to intravenous colistin on the survival of patients with VAP caused by Acinetobacter species. Methods. We conducted a retrospective study to evaluate the efficacy of combination of inhalatory and intravenous colistin vs. intravenous colistin alone in 69 patients in the Intensive Care Units (ICU) with VAP caused by Acinetobacter baumannii. The patients were treated in the ICU at the Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica (Serbia) in the period from January, 2013 to March, 2018. Baseline demographic data, severity of the disease, comorbidities, colistin regimen and length of the treatment were collected. The primary outcome was 28-day mortality. Results. Twenty seven of total 69 (39.1%) patients received combined intravenous and inhalatory colistin. Forty two (60.9%) patients received only intravenous colistin. Compared to the combined use of the drug (intravenous and inhalatory colistin), patients receiving intravenous colistin alone had a significantly increased risk of death during 28 days [25.9% vs. 61.9%, respectively; odds ratio (OR) 4.464, 95% confidence interval (CI) 1.539–2.925; p = 0.006]. Length of colistin use (> 7 days) was also associated with reduced survival (OR 0.22; 95% CI 0.080–0.606; p = 0.003). After adjusting for baseline severity of the illness (APACHE score) and length of colistin treatment, patients receiving only intravenous colistin had greater 28-day mortality rate compared to patients receiving both intravenous and inhalatory colistin (OR 6.305; 95% CI 1.795–22.153; p = 0.004). Conclusion. Our results suggest that adding inhalatory to intravenous colistin might be beneficial in the treatment of VAP caused by Acinetobacter species.

References

Arthur LE, Kizor RS, Selim AG, van Driel ML, Seoane L. Anti-biotics for ventilator-associated pneumonia. Cochrane Data-base Syst Rev 2016; 10: CD004267.

Lanspa MJ, Brown SM. Asking the right questions: the relation-ship between incident ventilator-associated pneumonia and mortality. Crit Care 2012; 16 (2): 123.

Kollef KE, Schramm GE, Wills AR, Reichley RM, Micek ST, Kollef MH. Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria. Chest 2008; 134(2): 281–7.

Koulenti D, Lisboa T, Brun-Buisson C, Krueger W, Macor A, Sole-Violan J, et al. EU-VAP/CAP Study Group. Spectrum of practice in the diagnosis of nosocomial pneumonia in patients requiring mechanical ventilation in European intensive care units. Crit Care Med 2009; 37(8): 2360–8.

Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, 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; 63(5): e61–e111.

Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Fer-rer R, et al. Surviving Sepsis Campaign: international guide-lines for management of sepsis and septic shock: 2016. Inten-sive Care Med 2017; 43(3): 304–77.

Vincent JL, Bassetti M, François B, Karam G, ChastreJ, Torres A, et al. Advances in antibiotic therapy in the critically ill. Crit Care 2016; 20(1): 133.

Shete VB, Ghadage DP, Muley VA, Bhore AV. Multi-drug re-sistant Acinetobacter ventilator-associated pneumonia. Lung India 2010; 27(4): 217–20.

Sader HS, Farrell DJ, Flamm RK, Jones RN. Antimicrobial sus-ceptibility of gram-negative organisms isolated from patients hospitalized in intensive care units in United States and Euro-pean hospitals (2009–2011). Diagn Microbiol Infect Dis 2014; 78(4): 443–8.

Kempf M, Rolain JM. Emergence of resistance to carbapenems in Acinetobacter baumannii in Europe: clinical impact and therapeutic options. Int J Antimicrob Agents 2012; 39(2): 105–14.

Mehrad B, Clark NM, Zhanel GG, Lynch JP 3rd. Antimicrobial resistance in hospital-acquired gram-negative bacterial infec-tions. Chest 2015; 147(5): 1413–21.

Michalopoulos A, Falagas ME. Colistin and polymyxin B in crit-ical care. Crit Care Clin 2008; 24(2): 377–91.

Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bac-terial infections. Clin Infect Dis 2005; 40(9): 1333–41.

Biswas S, Brunel J, Dubus J, Reynaud-Gaubert M, Rolain J. Col-istin: An Update on the Antibiotic of the 21st Century. Ex-pert Rev Anti Infect Ther 2012; 10(8): 917–34.

Gutiérrez-Pizarraya A, Amaya-Villar R, Garnacho-Montero J. Nebulized colistin in ventilator-associated pneumonia: Should we trust it? J Crit Care 2017; 41: 328–9.

Gurjar M. Colistin for lung infection: an update. J Intensive Care 2015; 3(1): 3.

Demirdal T, Sari US, Nemli SA. Is inhaled colistin beneficial in ventilator associated pneumonia or nosocomial pneumonia caused by Acinetobacter baumannii? Ann Clin Microbiol An-timicrob 2016; 15: 11.

Falagas ME, Kasiakou SK, Tsiodras S, Michalopoulos A. The use of intravenous and aerosolized polymyxins for the treatment of infections in critically ill patients: a review of the recent lit-erature. Clin Med Res 2006; 4(2): 138–46.

Luyt CE, Combes A, Nieszkowska A, Trouillet JL , Chastre J. Aerosolized antibiotics to treat ventilator-associated pneumo-nia. Curr Opin Infect Dis 2009; 22(2): 154–8.

Yahav D, Farbman L, Leibovici L, Paul M. Colistin: new lessons on an old antibiotic. Clin Microbiol Infect 2012; 18(1): 18–29.

Kofteridis DP, Alexopoulou C, Valachis A, Maraki S, Dimopoulou D, Georgopoulos D, et al. Aerosolized plus intravenous colistin versus intravenous colistin alone for the treatment of ventila-tor-associated pneumonia: a matched case-control study. Clin Infect Dis 2010; 51(11): 1238–44.

Landersdorfer CB, Nation RL. Colistin: how should it be dosed for the critically ill? Semin Respir Crit Care Med 2015; 36(1): 126–35.

Álvarez-Marín R, López-Rojas R, Márquez J, Gómez M, Molina J, Cisneros J, et al. Colistin Dosage without Loading Dose Is Ef-ficacious when Treating Carbapenem-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia Caused by Strains with High Susceptibility to Colistin. PLoS One 2016; 11(12): e0168468.

Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985; 13(10): 818–29.

Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bru-ining H, et al. The SOFA (Sepsis-related Organ Failure As-sessment) score to describe organ dysfunction/failure. On be-half of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996; 22(7): 707–10.

ARDS Definition Task Force. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute res-piratory distresssyndrome: the Berlin Definition. JAMA 2012; 307(23): 2526–33.

Singer M, Deutschman C, Seymour C, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315(8): 801–10.

Kidney Disease: Improving Global Outcomes (KDIGO). Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012; 2: 1–138.

Michalopoulos A, Kasiakou SK, Mastora Z, Rellos K, Kapaskelis AM, Falagas ME. Aerosolized colistin for the treatment of nosocomial pneumonia due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis. Crit Care 2005; 9(1): R53–R59.

Tumbarello M, De Pascale G, Trecarichi EM, De Martino S, Bello G, Maviglia R, et al. Effect of aerosolized colistin as adjunc-tive treatment on the outcomes of microbiologically docu-mented ventilator-associated pneumonia caused by colistin-only susceptible gram-negative bacteria. Chest 2013; 144(6): 1768–75.

Michalopoulos A, Fotakis D, Virtzili S, Vletsas C, Raftopoulou S, Mastora Z, et al. Aerosolized colistin as adjunctive treatment of ventilator-associated pneu monia due to multidrug-resistant gram-negative bacteria: a prospective study. Respir Med 2008; 102(3): 407–12.

Lin CC, Liu TC, Kuo CF, Liu CP, Lee CM. Aerosolized col-istin for the treatment of multidrug-resistant Acinetobacter baumannii pneumonia: experience in a tertiary care hospital in northern Taiwan. J Microbiol Immunol Infect 2010; 43(4): 323–31.

Mendes CA, Burdmann EA. Polymyxins - review with emphasis on nephrotoxicity. Rev Assoc Med Bras (1992) 2009; 55(6): 752–9. (Portuguese)

Lu Q, Luo R, Bodin L, Yang J, Zahr N, Aubry A, et al. Nebu-lized Antibiotics Study Group. Efficacy of high-dose nebu-lized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobac-ter baumannii. Anesthesiology 2012; 117(6): 1335–47.

Durante-Mangoni E, Andini R, Signoriello S, Cavezza G, Murino P, Buono S, et al. Acute kidney injury during colistin therapy: a prospective study in patients with extensively-drug resistant Acinetobacter baumannii infections. Clin Microbiol Infect 2016; 22(12): 984–9.

Korbila IP, Michalopoulos A, Rafailidis PI, Nikita D, Samonis G, Falagas ME. Inhaled colistin as adjunctive therapy to intrave-nous colistin for the treatment of microbiologically docu-mented ventilator-associated pneumonia: a comparative co-hort study. Clin Microbiol Infect 2010; 16(8): 1230–6.

Abdellatif S, Trifi A, Daly F, Mahjoub K, Nasri R, Ben Lakhal S. Efficacy and toxicity of aerosolized colistin in ventilator-associated pneumonia: a prospective, randomized trial. Ann Intensive Care 2016; 6(1): 26.

Doshi NM, Cook CH, Mount KL, Stawicki SP, Frazee EN, Per-sonett HA, et al. Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: a retro-spective study. BMC Anesthesiol 2013; 13(1): 45.