Antibiotic treatment adequacy and death among patients with Pseudomonas aeruginosa airway infection

Autoři: Josefin Eklöf aff001;  Kirstine Møller Gliese aff002;  Truls Sylvan Ingebrigtsen aff001;  Uffe Bodtger aff004;  Jens-Ulrik Stæhr Jensen aff001
Působiště autorů: Department of Internal Medicine, Section of Respiratory Medicine, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark aff001;  Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark aff002;  Department of Respiratory Medicine, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark aff003;  Department of Respiratory Medicine, Naestved Hospital, University of Southern Denmark, Naestved, Denmark aff004;  Department of Medicine, Zealand University Hospital Roskilde, Roskilde, Denmark aff005;  Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark aff006;  Department of Infectious Diseases, CHIP & PERSIMUNE, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark aff007
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0226935



The effect of antibiotics on survival in patients with pulmonary Pseudomonas aeruginosa is controversial. The aim of this study is to i) determine the prevalence of adequate antibiotic treatment of P. aeruginosa in an unselected group of adult non-cystic fibrosis patients and ii) to assess the overall mortality in study patients treated with adequate vs. non-adequate antibiotics.


Prospective, observational study of all adult patients with culture verified P. aeruginosa from 1 January 2010–31 December 2012 in Region Zealand, Denmark. Patients with cystic fibrosis were excluded. Adequate therapy was defined as any antibiotic treatment including at least one antipseudomonal beta-lactam for a duration of at least 10 days. Furthermore, P. aeruginosa had to be tested susceptible to the given antipseudomonal drug and treatment had to be approved by senior clinician to fulfil the adequate-criteria.


A total of 250 patients were identified with pulmonary P. aeruginosa. The vast majority (80%) were treated with non-adequate antibiotic therapy. All-cause mortality rate after 12 months was 49% in adequate treatment group vs. 52% in non-adequate treatment group. Cox regression analysis adjusted for age, gender, bacteraemia, comorbidities and bronchiectasis showed no significant difference in mortality between treatment groups (adequate vs. non-adequate: hazard ratio 0.95, 95% CI 0.59–1.52, P = 0.82).


Adequate antipseudomonal therapy was only provided in a minority of patients with pulmonary P. aeruginosa. Adequate therapy did not independently predict a favourable outcome. New research initiatives are needed to improve the prognosis of this vulnerable group of patients.

Klíčová slova:

Antibiotics – Death rates – Denmark – Drug therapy – Chronic obstructive pulmonary disease – Prognosis – Pseudomonas aeruginosa – Pseudomonas infections


1. Arancibia F, Bauer TT, Ewig S, Mensa J, Gonzalez J, Niederman MS, et al. Community-acquired pneumonia due to gram-negative bacteria and Pseudomonas aeruginosa: Incidence, risk, and prognosis. Arch Intern Med. 2002;162(16):1849–58. doi: 10.1001/archinte.162.16.1849 12196083

2. Holm JP, Hilberg O, Noerskov-Lauritsen N, Bendstrup E. Pseudomonas aeruginosa in patients without cystic fibrosis is strongly associated with chronic obstructive lung disease. Dan Med J. 2013;60(6):1–5.

3. Folkesson A, Jelsbak L, Yang L, Johansen HK, Ciofu O, Hoiby N, et al. Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: An evolutionary perspective. Nat Rev Microbiol. 2012;10(12):841–51. doi: 10.1038/nrmicro2907 23147702

4. Martínez‐Solano L, Macia MD, Fajardo A, Oliver A, Martinez JL. Chronic Pseudomonas aeruginosa Infection in Chronic Obstructive Pulmonary Disease. Clin Infect Dis. 2008;47(12):1526–33. doi: 10.1086/593186 18990062

5. Murphy TF, Brauer AL, Eschberger K, Lobbins P, Grove L, Cai X, et al. Pseudomonas aeruginosa in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177(8):853–60. doi: 10.1164/rccm.200709-1413OC 18202344

6. Rakhimova E, Wiehlmann L, Brauer AL, Sethi S, Murphy TF, Tümmler B. Pseudomonas aeruginosa Population Biology in Chronic Obstructive Pulmonary Disease. J Infect Dis. 2009;200(12):1928–35. doi: 10.1086/648404 19919307

7. Polverino E, Goeminne PC, McDonnell MJ, Aliberti S, Marshall SE, Loebinger MR, et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017;50(3).

8. Pasteur MC, Bilton D, Hill AT. British Thoracic Society guideline for non-CFbronchiectasis. Thorax. 2010;65(Suppl 1):i1–58.

9. Woodhead M, Blasi F, Ewig S, Garau J, Huchon G, Ieven M, et al. Guidelines for the management of adult lower respiratory tract infections—Full version. Clin Microbiol Infect. 2011;17:E1–59.

10. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44(Supplement 2):S27–72.

11. 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):e61–111. doi: 10.1093/cid/ciw353 27418577

12. Renom F, Yáñez A, Garau M, Rubí M, Centeno MJ, Gorriz MT, et al. Prognosis of COPD patients requiring frequent hospitalization: Role of airway infection. Respir Med. 2010;104(6):840–8. doi: 10.1016/j.rmed.2009.12.010 20106648

13. Finch S, McDonnell MJ, Abo-Leyah H, Aliberti S, Chalmers JD. A comprehensive analysis of the impact of Pseudomonas aeruginosa colonization on prognosis in adult bronchiectasis. Ann Am Thorac Soc. 2015;12(11):1602–11. doi: 10.1513/AnnalsATS.201506-333OC 26356317

14. Loebinger MR, Wells AU, Hansell DM, Chinyanganya N, Devaraj A, Meister M, et al. Mortality in bronchiectasis: A long-term study assessing the factors influencing survival. Eur Respir J. 2009;34(4):843–9. doi: 10.1183/09031936.00003709 19357155

15. Montero M, Domínguez M, Orozco-Levi M, Salvadó M, Knobel H. Mortality of COPD patients infected with multi-resistant pseudomonas aeruginosa: A case and control study. Infection. 2009;37(1):16–9. doi: 10.1007/s15010-008-8125-9 19139809

16. Patel IS, Seemungal TA, Wilks M, Lloyd-Owen SJ, Donaldson GC, Wedzicha JA. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax. 2002;57(9):759–64. doi: 10.1136/thorax.57.9.759 12200518

17. Miravitlles M. Relationship Between Bacterial Flora in Sputum and Functional Impairment in Patients With Acute Exacerbations of COPD. CHEST J. 1999;116(1):40.

18. Groenewegen KH, Schols AMWJ, Wouters EFM. Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD. Chest. 2003;124(2):459–67. doi: 10.1378/chest.124.2.459 12907529

19. Connors AF, Dawson NV, Thomas C, Harrell FE, Desbiens N, Fulkerson WJ, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments). Am J Respir Crit Care Med.1996;154:959–67. doi: 10.1164/ajrccm.154.4.8887592 8887592

20. Garnacho-Montero J, Sa-Borges M, Sole-Violan J, Barcenilla F, Escoresca-Ortega A, Ochoa M, et al. Optimal management therapy for Pseudomonas aeruginosa ventilator-associated pneumonia: An observational, multicenter study comparing monotherapy with combination antibiotic therapy. Crit Care Med. 2007;35(8):1888–95. doi: 10.1097/01.CCM.0000275389.31974.22 17581492

21. Park SY, Park HJ, Moon SM, Park KH, Chong YP, Kim MN, et al. Impact of adequate empirical combination therapy on mortality from bacteremic Pseudomonas aeruginosa pneumonia. BMC Infect Dis. 2012;12(1):1.

22. Llor C, Moragas A, Hernández S, Bayona C, Miravitlles M. Efficacy of Antibiotic Therapy for Acute Exacerbations of Mild to Moderate Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2012;186(8):716–23. doi: 10.1164/rccm.201206-0996OC 22923662

23. Anthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK, Nelson NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 1987;106(2):196–204. doi: 10.7326/0003-4819-106-2-196 3492164

24. Chastre J, Wolff M, Fagon J-Y, Chevret S, Thomas F, Wermert D, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290(19):2588–98. doi: 10.1001/jama.290.19.2588 14625336

25. GOLD- Global initirativ for chronic obstrucitve lung disease. 2018 New GOLD reports. Date last assessed: April 1 2018.

Článok vyšiel v časopise


2019 Číslo 12