Nebulization of antimicrobial agents in mechanically ventilated adults in 2017: an international cross-sectional survey

  • Joana Alves
  • Emine Alp
  • Despoina Koulenti
  • Zhongheng Zhang
  • Stephan Ehrmann
  • Stijn Blot
  • Matteo Bassetti
  • Andrew Conway-Morris
  • Rosa Reina
  • Enrique Teran
  • Candela Sole-Lleonart
  • Maria Ruiz-Rodríguez
  • Jordi Rello
  • SANEME-2 Investigators
Original Article


2017 ESCMID practice guidelines reported safety concerns and weak evidence of benefit supporting use of aerosolized antibiotics in mechanically ventilated patients. Our primary goal was to assess current patterns of aerosolized antibiotic prescription in mechanically ventilated patients. A sequential global survey was performed prior to the release of the ESCMID guidelines, from the 1st of February to the 30th of April 2017, using an electronic platform. Responses were analyzed comparing geographical regions. A total of 410 units responded, with 261 (177 from Europe) being eligible for the full survey. 26.8% of units reported not using aerosolized antibiotics. The two major indications amongst prescribing units were ventilator-associated pneumonia and ventilator-associated tracheobronchitis (74.3% and 49.4%, respectively). 63.6% of units indicated prescription solely in response to multi-drug resistant organisms. In comparison with a survey undertaken in 2014, there was a significant reduction in use of aerosolized antibiotics for prophylaxis (50.6% vs 7.7%, p < 0.05) and colonization (52.9% vs 25.3%, p < 0.05). The large majority of units (91.7%) reported only prescribing in patients with positive pulmonary cultures. Asia appeared to be an outlier, with 53.3% of units reporting empirical use. The most commonly used device was the jet nebulizer. The most commonly prescribed drugs were colistin methanesulfonate (57.6%), colistin base (41.9%) and amikacin (31.4%), although there was considerable heterogeneity across geographical areas. A significant gap exists between ESCMID clinical practice recommendations and the use of aerosolized antibiotics in clinical practice. Our findings indicate an urgent need for high-quality education to bring practice into line with evidence-based guidelines.



This work was supported in part by a research grant (CB06/06/36) from PCI Pneumonia, CIBERES, Instituto de Salud Carlos III, Madrid, Spain.

Compliance with ethical standards

Guarantor statement and author contribution

The first author (JA) undertook the literature search, data analysis, first draft manuscript preparation and is the guarantor for this article. CSL, MRR and JR were responsible for the study design. MRR and JA performed quality assessment. A steering committee (Appendix 2) approved the protocol, provided advice and was responsible for dissemination of the survey. All authors contributed scientifically in subsequent drafts and have approved the final version of the manuscript.

Conflict of interest

JR has received research grants and consulting fees from Bayer and Genentech. ZZ has received grants from Zhejiang provincial natural science foundation of China (LGF18H150005). ACM is supported by a Wellcome Trust Clinical Research Career Development Fellowship (WT 2055214/Z/16/Z). MB has participated in advisory boards and/or received speaker honoraria from Achaogen, Angelini, Astellas, AstraZeneca, Bayer, Basilea, Cidara, Gilead, Menarini, MSD, Pfizer, The Medicine Company, Paratek, Tetraphase and Vifor. SE has received research grants and research support: Aerogen Ltd., Fisher and Paykel Healthcare, Hamiton Medical; and consulting, honoraria or lecture fees from Aerogen, La diffusion technique française, and Baxter. SB has received fees for advisory board activity from the Bayer advisory board on nebulized amikacin. The remaining authors did not disclose conflicts of interest.

Ethical approval

Because this analysis was based on a clinical practice survey, institutional review board approval was not required.

Informed consent

As this study does not have individual specific data of patients, informed consent was not applicable.

Supplementary material

10096_2017_3175_MOESM1_ESM.docx (112 kb)
ESM 1 (DOCX 111 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Joana Alves
    • 1
    • 2
  • Emine Alp
    • 3
  • Despoina Koulenti
    • 4
    • 5
  • Zhongheng Zhang
    • 6
  • Stephan Ehrmann
    • 7
    • 8
  • Stijn Blot
    • 9
    • 10
  • Matteo Bassetti
    • 11
  • Andrew Conway-Morris
    • 12
  • Rosa Reina
    • 13
  • Enrique Teran
    • 14
  • Candela Sole-Lleonart
    • 15
    • 16
  • Maria Ruiz-Rodríguez
    • 17
  • Jordi Rello
    • 18
    • 19
  • SANEME-2 Investigators
  1. 1.Infectious Diseases DepartmentCentro Hospitalar São JoãoPortoPortugal
  2. 2.Faculty of Medicine of University of PortoPortoPortugal
  3. 3.Department of Infectious Diseases and Clinical Microbiology, Faculty of MedicineErciyes UniversityKayseriTurkey
  4. 4.BTCCRC, UQCCR, Faculty of MedicineThe University of QueenslandBrisbaneAustralia
  5. 5.2nd Critical Care DepartmentAttikon Univesrity HospitalAthensGreece
  6. 6.Department of Emergency Medicine, Sir Run-Run Shaw HospitalZhejiang University School of MedicineHangzhouChina
  7. 7.Médecine Intensive RéanimationCHRU de Tours and CRICS-TriggerSEP NetworkToursFrance
  8. 8.Centre d’étude des pathologies respiratoires, INSERM U1100, Aérosolthérapie et biomédicaments à visée respiratoire, Faculté de médecine de ToursUniversité François RabelaisToursFrance
  9. 9.Department of Internal Medicine, Faculty of Medicine & Health ScienceGhent UniversityGhentBelgium
  10. 10.Burns Trauma and Critical Care Research CentreThe University of QueenslandBrisbaneAustralia
  11. 11.Infectious Diseases DivisionDepartment of Medicine University of Udine and Azienda Sanitaria Universitaria IntegrataUdineItaly
  12. 12.University Division of Anaesthesia, Department of MedicineUniversity of CambridgeCambridgeUK
  13. 13.Terapia IntensivaHospital Interzonal de Agudos “General San Martín”La PlataArgentina
  14. 14.Colegio de Ciencias de la SaludUniversidad San Francisco de QuitoQuitoEcuador
  15. 15.Centre Hospitalier Universitaire VaudoiseGeneveSwitzerland
  16. 16.Universitat Autonoma de BarcelonaBarcelonaSpain
  17. 17.Department of Clinical Research & Innovation in Pneumonia and SepsisVall d’Hebron Institut of ResearchBarcelonaSpain
  18. 18.Critical Care DepartmentVall d’Hebron Institut of ResearchBarcelonaSpain
  19. 19.Centro de Investigacion Biomedica en Red (CIBERES)BarcelonaSpain

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