[en] 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.
Disciplines :
Immunology & infectious disease
Author, co-author :
Alves, Joana; Infectious Diseases Department, Centro Hospitalar São João, Porto, Portugal ; Faculty of Medicine of University of Porto, Porto, Portugal
Alp, Emine; Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
Koulenti, Despoina; BTCCRC, UQCCR, Faculty of Medicine, The University of Queensland, Brisbane, Australia ; 2nd Critical Care Department, Attikon Univesrity Hospital, Athens, Greece
Zhang, Zhongheng; Department of Emergency Medicine, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China
Ehrmann, Stephan; Médecine Intensive Réanimation, CHRU de Tours and CRICS-TriggerSEP Network, Tours, France ; Centre d'étude des pathologies respiratoires, INSERM U1100, Aérosolthérapie et biomédicaments à visée respiratoire, Faculté de médecine de Tours, Université François Rabelais, Tours, France
Blot, Stijn; Department of Internal Medicine, Faculty of Medicine & Health Science, Ghent University, Ghent, Belgium ; Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
Bassetti, Matteo; Infectious Diseases Division, Department of Medicine University of Udine and Azienda Sanitaria Universitaria Integrata, Udine, Italy
Conway-Morris, Andrew; University Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK
Reina, Rosa; Terapia Intensiva, Hospital Interzonal de Agudos "General San Martín", La Plata, Argentina
Teran, Enrique; Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Quito, Ecuador
Sole-Lleonart, Candela; Centre Hospitalier Universitaire Vaudoise, Geneve, Switzerland ; Universitat Autonoma de Barcelona, Barcelona, Spain
Ruiz-Rodríguez, Maria; Department of Clinical Research & Innovation in Pneumonia and Sepsis, Vall d'Hebron Institut of Research, Barcelona, Spain
Rello, Jordi ; Critical Care Department, Vall d'Hebron Institut of Research, Barcelona, Spain. jrello@crips.es ; Centro de Investigacion Biomedica en Red (CIBERES), Ps Vall d'Hebron 119, AMI- 14a Planta, 08035, Barcelona, Spain. jrello@crips.es
SANEME-2 investigators
Layios, Nathalie ; Centre Hospitalier Universitaire de Liège - CHU > > Service des soins intensifs ; Université de Liège - ULiège > Faculté de Médecine > Doct. scienc. biom. pharma.
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.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 fran?aise, 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.Funding This work was supported in part by a research grant (CB06/06/ 36) from PCI Pneumonia, CIBERES, Instituto de Salud Carlos III, Madrid, Spain.
Barbier F, Andremont A, Wolff M, Bouadma L (2013) Hospital-acquired pneumonia and ventilator-associated pneumonia: recent advances in epidemiology and management. Curr Opin Pulm Med 19(3):216–228. https://doi.org/10.1097/MCP.0b013e32835f27be
Warren DK, Shukla SJ, Olsen MA, Kollef MH, Hollenbeak CS, Cox MJ, Cohen MM, Fraser VJ (2003) Outcome and attributable cost of ventilator-associated pneumonia among intensive care unit patients in a suburban medical center. Crit Care Med 31(5):1312–1317. https://doi.org/10.1097/01.CCM.0000063087.93157.06
Chastre J, Fagon JY (2002) Ventilator-associated pneumonia. Am J Respir Crit Care Med 165(7):867–903. https://doi.org/10.1164/ajrccm.165.7.2105078
Valcke Y, Pauwels R, Van der Straeten M (1990) Pharmacokinetics of antibiotics in the lungs. Eur Respir J 3(6):715–722
Rottboll LA, Friis C (2016) Penetration of antimicrobials to pulmonary epithelial lining fluid and muscle and impact of drug physicochemical properties determined by microdialysis. J Pharmacol Toxicol Methods 78:58–65. https://doi.org/10.1016/j.vascn.2015.11.007
Kiem S, Schentag JJ (2008) Interpretation of antibiotic concentration ratios measured in epithelial lining fluid. Antimicrob Agents Chemother 52(1):24–36. https://doi.org/10.1128/AAC.00133-06
Valachis A, Samonis G, Kofteridis DP (2015) The role of aerosolized colistin in the treatment of ventilator-associated pneumonia: a systematic review and metaanalysis. Crit Care Med 43(3):527–533. https://doi.org/10.1097/CCM.0000000000000771
Palmer LB, Smaldone GC, Chen JJ, Baram D, Duan T, Monteforte M, Varela M, Tempone AK, O'Riordan T, Daroowalla F, Richman P (2008) Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit. Crit Care Med 36(7):2008–2013. https://doi.org/10.1097/CCM.0b013e31817c0f9e
Palmer LB, Smaldone GC (2014) Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit. Am J Respir Crit Care Med 189(10):1225–1233. https://doi.org/10.1164/rccm.201312-2161OC
Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O'Grady NP, Bartlett JG, Carratala J, El Solh AA, Ewig S, Fey PD, File TM Jr, Restrepo MI, Roberts JA, Waterer GW, Cruse P, Knight SL, Brozek JL (2016) 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 63(5):e61–e111. https://doi.org/10.1093/cid/ciw353
Sole-Lleonart C, Rouby JJ, Blot S, Poulakou G, Chastre J, Palmer LB, Bassetti M, Luyt CE, Pereira JM, Riera J, Felton T, Dhanani J, Welte T, Garcia-Alamino JM, Roberts JA, Rello J (2017) Nebulization of Antiinfective agents in invasively mechanically ventilated adults: a systematic review and meta-analysis. Anesthesiology 126(5):890–908. https://doi.org/10.1097/ALN.0000000000001570
Rello J, Sole-Lleonart C, Rouby JJ, Chastre J, Blot S, Poulakou G, Luyt CE, Riera J, Palmer LB, Pereira JM, Felton T, Dhanani J, Bassetti M, Welte T, Roberts JA (2017) Use of nebulized antimicrobials for the treatment of respiratory infections in invasively mechanically ventilated adults: a position paper from the European Society of Clinical Microbiology and Infectious Diseases. Clin Microbiol Infect 23(9):629–639. https://doi.org/10.1016/j.cmi.2017.04.011
Sole-Lleonart C, Roberts JA, Chastre J, Poulakou G, Palmer LB, Blot S, Felton T, Bassetti M, Luyt CE, Pereira JM, Riera J, Welte T, Qiu H, Rouby JJ, Rello J, Investigators E (2016) Global survey on nebulization of antimicrobial agents in mechanically ventilated patients: a call for international guidelines. Clin Microbiol Infect 22(4):359–364. https://doi.org/10.1016/j.cmi.2015.12.016
Sole-Lleonart C, Rouby JJ, Chastre J, Poulakou G, Palmer LB, Blot S, Felton T, Bassetti M, Luyt CE, Pereira JM, Riera J, Welte T, Roberts JA, Rello J (2016) Intratracheal administration of antimicrobial agents in mechanically ventilated adults: an international survey on delivery practices and safety. Respir Care 61(8):1008–1014. https://doi.org/10.4187/respcare.04519
Pulcini C, Leibovici L, Office CMIE (2016) CMI guidance for authors of surveys. Clin Microbiol Infect 22(11):901–902. https://doi.org/10.1016/j.cmi.2016.08.015
Rello J, Ruiz-Rodriguez M, Zhang Z (2017) 2017 global survey on nebulization of antimicrobial agents in mechanically ventilated patients—SANEME 2 study protocol. Journal of Emergency and Critical Care Medicine 1 (5). https://doi.org/10.21037/jeccm.2017.04.01
Zhang Z (2016) Univariate description and bivariate statistical inference: the first step delving into data. Ann Transl Med 4(5):91. https://doi.org/10.21037/atm.2016.02.11
Povoa FCC, Cardinal-Fernandez P, Maia IS, Reboredo MM, Pinheiro BV (2017) Effect of antibiotics administered via the respiratory tract in the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis. J Crit Care 43:240–245. https://doi.org/10.1016/j.jcrc.2017.09.019
Kollef MH, Ricard JD, Roux D, Francois B, Ischaki E, Rozgonyi Z, Boulain T, Ivanyi Z, Janos G, Garot D, Koura F, Zakynthinos E, Dimopoulos G, Torres A, Danker W, Montgomery AB (2017) A randomized trial of the amikacin Fosfomycin inhalation system for the adjunctive therapy of gram-negative ventilator-associated pneumonia: IASIS trial. Chest 151(6):1239–1246. https://doi.org/10.1016/j.chest.2016.11.026
Bayer (2017) Phase III study program with amikacin inhale in addition to standard of care in intubated and mechanically ventilated patients with gram-negative pneumonia does not meet primary endpoint of superiority. Press Release PRNewswire
Abdellatif S, Trifi A, Daly F, Mahjoub K, Nasri R, Ben Lakhal S (2016) Efficacy and toxicity of aerosolised colistin in ventilator-associated pneumonia: a prospective, randomised trial. Ann Intensive Care 6(1):26. https://doi.org/10.1186/s13613-016-0127-7
Lu Q, Luo R, Bodin L, Yang J, Zahr N, Aubry A, Golmard JL, Rouby JJ, Nebulized Antibiotics Study G (2012) Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology 117(6):1335–1347. https://doi.org/10.1097/ALN.0b013e31827515de
Falagas ME, Siempos II, Rafailidis PI, Korbila IP, Ioannidou E, Michalopoulos A (2009) Inhaled colistin as monotherapy for multidrug-resistant gram (−) nosocomial pneumonia: a case series. Respir Med 103(5):707–713. https://doi.org/10.1016/j.rmed.2008.11.018
Michalopoulos A, Fotakis D, Virtzili S, Vletsas C, Raftopoulou S, Mastora Z, Falagas ME (2008) Aerosolized colistin as adjunctive treatment of ventilator-associated pneumonia due to multidrug-resistant gram-negative bacteria: a prospective study. Respir Med 102(3):407–412. https://doi.org/10.1016/j.rmed.2007.10.011
Rattanaumpawan P, Lorsutthitham J, Ungprasert P, Angkasekwinai N, Thamlikitkul V (2010) Randomized controlled trial of nebulized colistimethate sodium as adjunctive therapy of ventilator-associated pneumonia caused by gram-negative bacteria. J Antimicrob Chemother 65(12):2645–2649. https://doi.org/10.1093/jac/dkq360
Korbila IP, Michalopoulos A, Rafailidis PI, Nikita D, Samonis G, Falagas ME (2010) Inhaled colistin as adjunctive therapy to intravenous colistin for the treatment of microbiologically documented ventilator-associated pneumonia: a comparative cohort study. Clin Microbiol Infect 16(8):1230–1236. https://doi.org/10.1111/j.1469-0691.2009.03040.x
Rello J, Rouby JJ, Sole-Lleonart C, Chastre J, Blot S, Luyt CE, Riera J, Vos MC, Monsel A, Dhanani J, Roberts JA (2017) Key considerations on nebulization of antimicrobial agents to mechanically ventilated patients. Clin Microbiol Infect 23(9):640–646. https://doi.org/10.1016/j.cmi.2017.03.018
Dugernier J, Ehrmann S, Sottiaux T, Roeseler J, Wittebole X, Dugernier T, Jamar F, Laterre PF, Reychler G (2017) Aerosol delivery during invasive mechanical ventilation: a systematic review. Crit Care 21(1):264. https://doi.org/10.1186/s13054-017-1844-5
