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Semin Respir Crit Care Med 2019; 40(04): 548-557
DOI: 10.1055/s-0039-1695783
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Prevention of Intensive Care Unit-Acquired Pneumonia

Michael Klompas
1   Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts
2   Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
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Publication History

Publication Date:
04 October 2019 (online)

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Abstract

Intensive care unit (ICU) acquired pneumonia is one of the most common and morbid health care-associated infections. Despite decades of work developing and testing prevention strategies, ICU-acquired pneumonia remains stubbornly pervasive. Pneumonia prevention studies are difficult to interpret because all are at risk of bias due to the subjectivity and poor specificity of pneumonia definitions. Interventions associated with improvements in objective outcomes in addition to pneumonia, such as length of stay or mortality, should therefore be prioritized. Avoiding intubation, minimizing sedation, implementing early extubation strategies, and mobilizing patients do appear to improve some of these objective outcomes. Many of our other assumptions about how best to prevent ICU-acquired pneumonia, however, have recently been challenged. Elevating the head of the bed is supported by very little randomized trial data. Early reports suggested that subglottic secretion drainage may decrease time to extubation and ICU length of stay, but more recent analyses refute these findings. Novel endotracheal tube cuff designs do not clearly lower pneumonia rates. A large randomized trial of selective digestive decontamination in ICUs with high baseline rates of antimicrobial resistance did not identify any benefit. Oral care with chlorhexidine may increase mortality risk and stress ulcer prophylaxis may facilitate pneumonia. Early data on probiotics suggest a possible effect but there is no clear signal yet that they shorten duration of mechanical ventilation or lower mortality. Ventilator bundles on balance do appear to be beneficial but it is not clear which components are most important nor how best to implement them. This article will review recent studies that have challenged, refined, or complicated our understanding of how best to prevent ICU-acquired pneumonia.

Keywords

ventilator-associated pneumonia - ICU-acquired pneumonia - spontaneous breathing trials - oral care with chlorhexidine - subglottic secretion drainage - stress ulcer prophylaxis - endotracheal tube cuff design - selective digestive decontamination - probiotics
 

  • References

  • 1 Magill SS, O'Leary E, Janelle SJ. , et al; Emerging Infections Program Hospital Prevalence Survey Team. Changes in prevalence of health care-associated infections in U.S. hospitals. N Engl J Med 2018; 379 (18) 1732-1744
    CrossrefPubMedGoogle Scholar
  • 2 Olivieri A, Del Monte D, Benacchio L. , et al. An Observational Veneto Research on Ventilator-Associated Pneumonia (OVeRVAP): attributable mortality and cumulative incidence of ventilator-associated pneumonia. Minerva Anestesiol 2018; 84 (07) 811-819
    PubMedGoogle Scholar
  • 3 Melsen WG, Rovers MM, Groenwold RH. , et al. Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis 2013; 13 (08) 665-671
    CrossrefPubMedGoogle Scholar
  • 4 Schumacher M, Allignol A, Beyersmann J, Binder N, Wolkewitz M. Hospital-acquired infections--appropriate statistical treatment is urgently needed!. Int J Epidemiol 2013; 42 (05) 1502-1508
    CrossrefPubMedGoogle Scholar
  • 5 Ohannessian R, Gustin MP, Bénet T. , et al. Estimation of extra length of stay attributable to hospital-acquired infections in adult ICUs using a time-dependent multistate model. Crit Care Med 2018; 46 (07) 1093-1098
    CrossrefPubMedGoogle Scholar
  • 6 Cassini A, Plachouras D, Eckmanns T. , et al. Burden of six healthcare-associated infections on European population health: estimating incidence-based disability-adjusted life years through a population prevalence-based modelling study. PLoS Med 2016; 13 (10) e1002150
    CrossrefPubMedGoogle Scholar
  • 7 Klompas M. Hospital-acquired pneumonia in nonventilated patients: the next frontier. Infect Control Hosp Epidemiol 2016; 37 (07) 825-826
    CrossrefPubMedGoogle Scholar
  • 8 Ibn Saied W, Mourvillier B, Cohen Y. , et al; OUTCOMEREA Study Group. A comparison of the mortality risk associated with ventilator-acquired bacterial pneumonia and nonventilator ICU-acquired bacterial pneumonia. Crit Care Med 2019; 47 (03) 345-352
    PubMedGoogle Scholar
  • 9 Esperatti M, Ferrer M, Theessen A. , et al. Nosocomial pneumonia in the intensive care unit acquired by mechanically ventilated versus nonventilated patients. Am J Respir Crit Care Med 2010; 182 (12) 1533-1539
    CrossrefPubMedGoogle Scholar
  • 10 Corrado RE, Lee D, Lucero DE, Varma JK, Vora NM. Burden of adult community-acquired, health-care-associated, hospital-acquired, and ventilator-associated pneumonia: New York City, 2010 to 2014. Chest 2017; 152 (05) 930-942
    CrossrefPubMedGoogle Scholar
  • 11 Klompas M. The paradox of ventilator-associated pneumonia prevention measures. Crit Care 2009; 13 (05) 315
    CrossrefPubMedGoogle Scholar
  • 12 Bonten MJ. Healthcare epidemiology: ventilator-associated pneumonia: preventing the inevitable. Clin Infect Dis 2011; 52 (01) 115-121
    CrossrefPubMedGoogle Scholar
  • 13 Tejerina E, Esteban A, Fernández-Segoviano P. , et al. Accuracy of clinical definitions of ventilator-associated pneumonia: comparison with autopsy findings. J Crit Care 2010; 25 (01) 62-68
    CrossrefPubMedGoogle Scholar
  • 14 Stevens JP, Kachniarz B, Wright SB. , et al. When policy gets it right: variability in U.S. Hospitals' diagnosis of ventilator-associated pneumonia. Crit Care Med 2014; 42 (03) 497-503
    CrossrefPubMedGoogle Scholar
  • 15 Kerlin MP, Trick WE, Anderson DJ. , et al. Interrater reliability of surveillance for ventilator-associated events and pneumonia. Infect Control Hosp Epidemiol 2017; 38 (02) 172-178
    CrossrefPubMedGoogle Scholar
  • 16 Klompas M. Eight initiatives that misleadingly lower ventilator-associated pneumonia rates. Am J Infect Control 2012; 40 (05) 408-410
    CrossrefPubMedGoogle Scholar
  • 17 Klompas M, Kalil AC. Rethinking ventilator bundles. Crit Care Med 2018; 46 (07) 1201-1203
    CrossrefPubMedGoogle Scholar
  • 18 Kalil AC, Metersky ML, Klompas M. , 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 (05) e61-e111
    CrossrefPubMedGoogle Scholar
  • 19 Metersky ML, Wang Y, Klompas M, Eckenrode S, Bakullari A, Eldridge N. Trend in ventilator-associated pneumonia rates between 2005 and 2013. JAMA 2016; 316 (22) 2427-2429
    CrossrefPubMedGoogle Scholar
  • 20 Klompas M, Branson R, Eichenwald EC. , et al; Society for Healthcare Epidemiology of America (SHEA). Strategies to prevent ventilator-associated pneumonia in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol 2014; 35 (08) 915-936
    CrossrefPubMedGoogle Scholar
  • 21 Frat JP, Thille AW, Mercat A. , et al; FLORALI Study Group; REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015; 372 (23) 2185-2196
    CrossrefPubMedGoogle Scholar
  • 22 Monro-Somerville T, Sim M, Ruddy J, Vilas M, Gillies MA. The effect of high-flow nasal cannula oxygen therapy on mortality and intubation rate in acute respiratory failure: a systematic review and meta-analysis. Crit Care Med 2017; 45 (04) e449-e456
    CrossrefPubMedGoogle Scholar
  • 23 Girou E, Brun-Buisson C, Taillé S, Lemaire F, Brochard L. Secular trends in nosocomial infections and mortality associated with noninvasive ventilation in patients with exacerbation of COPD and pulmonary edema. JAMA 2003; 290 (22) 2985-2991
    CrossrefPubMedGoogle Scholar
  • 24 Burns KE, Meade MO, Premji A, Adhikari NK. Noninvasive ventilation as a weaning strategy for mechanical ventilation in adults with respiratory failure: a Cochrane systematic review. CMAJ 2014; 186 (03) E112-E122
    CrossrefPubMedGoogle Scholar
  • 25 Osadnik CR, Tee VS, Carson-Chahhoud KV, Picot J, Wedzicha JA, Smith BJ. Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2017; 7: CD004104
    CrossrefPubMedGoogle Scholar
  • 26 Perkins GD, Mistry D, Gates S. , et al; Breathe Collaborators. Effect of protocolized weaning with early extubation to noninvasive ventilation vs invasive weaning on time to liberation from mechanical ventilation among patients with respiratory failure: the breathe randomized clinical trial. JAMA 2018; 320 (18) 1881-1888
    CrossrefPubMedGoogle Scholar
  • 27 Vaschetto R, Longhini F, Persona P. , et al. Early extubation followed by immediate noninvasive ventilation vs. standard extubation in hypoxemic patients: a randomized clinical trial. Intensive Care Med 2019; 45 (01) 62-71
    CrossrefPubMedGoogle Scholar
  • 28 Ely EW, Baker AM, Dunagan DP. , et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996; 335 (25) 1864-1869
    CrossrefPubMedGoogle Scholar
  • 29 Girard TD, Kress JP, Fuchs BD. , et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008; 371 (9607): 126-134
    CrossrefPubMedGoogle Scholar
  • 30 Klompas M, Anderson D, Trick W. , et al; CDC Prevention Epicenters. The preventability of ventilator-associated events. Am J Respir Crit Care Med 2015; 191 (03) 292-301
    CrossrefPubMedGoogle Scholar
  • 31 Klompas M, Li L, Kleinman K, Szumita PM, Massaro AF. Associations between ventilator bundle components and outcomes. JAMA Intern Med 2016; 176 (09) 1277-1283
    CrossrefPubMedGoogle Scholar
  • 32 Guzmán-Herrador B, Molina CD, Allam MF, Navajas RF. Independent risk factors associated with hospital-acquired pneumonia in an adult ICU: 4-year prospective cohort study in a university reference hospital. J Public Health (Oxf) 2016; 38 (02) 378-383
    CrossrefPubMedGoogle Scholar
  • 33 Shehabi Y, Chan L, Kadiman S. , et al; Sedation Practice in Intensive Care Evaluation (SPICE) Study Group investigators. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study. Intensive Care Med 2013; 39 (05) 910-918
    CrossrefPubMedGoogle Scholar
  • 34 Balzer F, Weiß B, Kumpf O. , et al. Early deep sedation is associated with decreased in-hospital and two-year follow-up survival. Crit Care 2015; 19: 197
    CrossrefPubMedGoogle Scholar
  • 35 Shehabi Y, Bellomo R, Kadiman S. , et al; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality: a multinational prospective longitudinal cohort study. Crit Care Med 2018; 46 (06) 850-859
    CrossrefPubMedGoogle Scholar
  • 36 Hashem MD, Nelliot A, Needham DM. Early mobilization and rehabilitation in the ICU: moving back to the future. Respir Care 2016; 61 (07) 971-979
    CrossrefPubMedGoogle Scholar
  • 37 Schweickert WD, Gehlbach BK, Pohlman AS, Hall JB, Kress JP. Daily interruption of sedative infusions and complications of critical illness in mechanically ventilated patients. Crit Care Med 2004; 32 (06) 1272-1276
    CrossrefPubMedGoogle Scholar
  • 38 Quenot JP, Ladoire S, Devoucoux F. , et al. Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia. Crit Care Med 2007; 35 (09) 2031-2036
    CrossrefPubMedGoogle Scholar
  • 39 Devlin JW, Skrobik Y, Gélinas C. , et al. Executive summary: clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med 2018; 46 (09) 1532-1548
    CrossrefPubMedGoogle Scholar
  • 40 Tipping CJ, Harrold M, Holland A, Romero L, Nisbet T, Hodgson CL. The effects of active mobilisation and rehabilitation in ICU on mortality and function: a systematic review. Intensive Care Med 2017; 43 (02) 171-183
    CrossrefPubMedGoogle Scholar
  • 41 Trogrlić Z, van der Jagt M, Bakker J. , et al. A systematic review of implementation strategies for assessment, prevention, and management of ICU delirium and their effect on clinical outcomes. Crit Care 2015; 19: 157
    CrossrefPubMedGoogle Scholar
  • 42 Pun BT, Balas MC, Barnes-Daly MA. , et al. Caring for critically ill patients with the ABCDEF bundle: results of the ICU Liberation Collaborative in over 15,000 adults. Crit Care Med 2019; 47 (01) 3-14
    CrossrefPubMedGoogle Scholar
  • 43 Hsieh SJ, Otusanya O, Gershengorn HB. , et al. Staged implementation of awakening and breathing, coordination, delirium monitoring and management, and early mobilization bundle improves patient outcomes and reduces hospital costs. Crit Care Med 2019; 47 (07) 885-893
    PubMedGoogle Scholar
  • 44 Krein SL, Greene MT, Apisarnthanarak A. , et al. Infection prevention practices in Japan, Thailand, and the United States: results from national surveys. Clin Infect Dis 2017; 64 (Suppl. 02) S105-S111
    CrossrefPubMedGoogle Scholar
  • 45 Saint S, Greene MT, Fowler KE. , et al. What US hospitals are currently doing to prevent common device-associated infections: results from a national survey. BMJ Qual Saf. 2019; 28 (09) 741-749 (e-pub ahead of print). doi:10.1136/bmjqs-2018-009111
    CrossrefPubMedGoogle Scholar
  • 46 Drakulovic MB, Torres A, Bauer TT, Nicolas JM, Nogué S, Ferrer M. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. Lancet 1999; 354 (9193): 1851-1858
    CrossrefPubMedGoogle Scholar
  • 47 van Nieuwenhoven CA, Vandenbroucke-Grauls C, van Tiel FH. , et al. Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: a randomized study. Crit Care Med 2006; 34 (02) 396-402
    CrossrefPubMedGoogle Scholar
  • 48 Keeley L. Reducing the risk of ventilator-acquired pneumonia through head of bed elevation. Nurs Crit Care 2007; 12 (06) 287-294
    CrossrefPubMedGoogle Scholar
  • 49 Wang L, Li X, Yang Z. , et al. Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation. Cochrane Database Syst Rev 2016; (01) CD009946
    PubMedGoogle Scholar
  • 50 Panigada M, Berra L, Greco G, Stylianou M, Kolobow T. Bacterial colonization of the respiratory tract following tracheal intubation-effect of gravity: an experimental study. Crit Care Med 2003; 31 (03) 729-737
    CrossrefPubMedGoogle Scholar
  • 51 Li Bassi G, Zanella A, Cressoni M, Stylianou M, Kolobow T. Following tracheal intubation, mucus flow is reversed in the semirecumbent position: possible role in the pathogenesis of ventilator-associated pneumonia. Crit Care Med 2008; 36 (02) 518-525
    CrossrefPubMedGoogle Scholar
  • 52 Li Bassi G, Panigada M, Ranzani OT. , et al; Gravity-VAP Network. Randomized, multicenter trial of lateral Trendelenburg versus semirecumbent body position for the prevention of ventilator-associated pneumonia. Intensive Care Med 2017; 43 (11) 1572-1584
    CrossrefPubMedGoogle Scholar
  • 53 Kollef MH. Ventilator-associated pneumonia. A multivariate analysis. JAMA 1993; 270 (16) 1965-1970
    CrossrefPubMedGoogle Scholar
  • 54 Torres A, Serra-Batlles J, Ros E. , et al. Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med 1992; 116 (07) 540-543
    CrossrefPubMedGoogle Scholar
  • 55 Jaillette E, Girault C, Brunin G. , et al; BestCuff Study Group and the BoRéal Network. Impact of tapered-cuff tracheal tube on microaspiration of gastric contents in intubated critically ill patients: a multicenter cluster-randomized cross-over controlled trial. Intensive Care Med 2017; 43 (11) 1562-1571
    CrossrefPubMedGoogle Scholar
  • 56 Klompas M, Berra L, Branson R. Beware the siren's song of novel endotracheal tube designs. Intensive Care Med 2017; 43 (11) 1708-1711
    CrossrefPubMedGoogle Scholar
  • 57 Zanella A, Scaravilli V, Isgrò S. , et al. Fluid leakage across tracheal tube cuff, effect of different cuff material, shape, and positive expiratory pressure: a bench-top study. Intensive Care Med 2011; 37 (02) 343-347
    CrossrefPubMedGoogle Scholar
  • 58 Blot SI, Rello J, Koulenti D. The value of polyurethane-cuffed endotracheal tubes to reduce microaspiration and intubation-related pneumonia: a systematic review of laboratory and clinical studies. Crit Care 2016; 20 (01) 203
    CrossrefPubMedGoogle Scholar
  • 59 Philippart F, Gaudry S, Quinquis L. , et al; TOP-Cuff Study Group. Randomized intubation with polyurethane or conical cuffs to prevent pneumonia in ventilated patients. Am J Respir Crit Care Med 2015; 191 (06) 637-645
    CrossrefPubMedGoogle Scholar
  • 60 Maertens B, Blot K, Blot S. Prevention of ventilator-associated and early postoperative pneumonia through tapered endotracheal tube cuffs: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med 2018; 46 (02) 316-323
    PubMedGoogle Scholar
  • 61 Letvin A, Kremer P, Silver PC, Samih N, Reed-Watts P, Kollef MH. Frequent versus infrequent monitoring of endotracheal tube cuff pressures. Respir Care 2018; 63 (05) 495-501
    CrossrefPubMedGoogle Scholar
  • 62 Nseir S, Lorente L, Ferrer M. , et al. Continuous control of tracheal cuff pressure for VAP prevention: a collaborative meta-analysis of individual participant data. Ann Intensive Care 2015; 5 (01) 43
    CrossrefPubMedGoogle Scholar
  • 63 Lacherade JC, Azais MA, Pouplet C, Colin G. Subglottic secretion drainage for ventilator-associated pneumonia prevention: an underused efficient measure. Ann Transl Med 2018; 6 (21) 422
    CrossrefPubMedGoogle Scholar
  • 64 Powell J, Garnett JP, Mather MW. , et al. Excess mucin impairs subglottic epithelial host defense in mechanically ventilated patients. Am J Respir Crit Care Med 2018; 198 (03) 340-349
    CrossrefPubMedGoogle Scholar
  • 65 Dezfulian C, Shojania K, Collard HR, Kim HM, Matthay MA, Saint S. Subglottic secretion drainage for preventing ventilator-associated pneumonia: a meta-analysis. Am J Med 2005; 118 (01) 11-18
    CrossrefPubMedGoogle Scholar
  • 66 Frost SA, Azeem A, Alexandrou E. , et al. Subglottic secretion drainage for preventing ventilator associated pneumonia: a meta-analysis. Aust Crit Care 2013; 26 (04) 180-188
    CrossrefPubMedGoogle Scholar
  • 67 Muscedere J, Rewa O, McKechnie K, Jiang X, Laporta D, Heyland DK. Subglottic secretion drainage for the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis. Crit Care Med 2011; 39 (08) 1985-1991
    CrossrefPubMedGoogle Scholar
  • 68 Wang F, Bo L, Tang L. , et al. Subglottic secretion drainage for preventing ventilator-associated pneumonia: an updated meta-analysis of randomized controlled trials. J Trauma Acute Care Surg 2012; 72 (05) 1276-1285
    CrossrefPubMedGoogle Scholar
  • 69 Caroff DA, Li L, Muscedere J, Klompas M. Subglottic secretion drainage and objective outcomes: a systematic review and meta-analysis. Crit Care Med 2016; 44 (04) 830-840
    CrossrefPubMedGoogle Scholar
  • 70 Vallés J, Artigas A, Rello J. , et al. Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. Ann Intern Med 1995; 122 (03) 179-186
    PubMedGoogle Scholar
  • 71 Klompas M. Does this patient have ventilator-associated pneumonia?. JAMA 2007; 297 (14) 1583-1593
    CrossrefPubMedGoogle Scholar
  • 72 Plantinga NL, de Smet AMGA, Oostdijk EAN. , et al. Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients: individual patient data meta-analysis. Clin Microbiol Infect 2018; 24 (05) 505-513
    CrossrefPubMedGoogle Scholar
  • 73 Price R, MacLennan G, Glen J. ; SuDDICU Collaboration. Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis. BMJ 2014; 348: g2197
    CrossrefPubMedGoogle Scholar
  • 74 Bos LD, Stips C, Schouten LR. , et al. Selective decontamination of the digestive tract halves the prevalence of ventilator-associated pneumonia compared to selective oral decontamination. Intensive Care Med 2017; 43 (10) 1535-1537
    CrossrefPubMedGoogle Scholar
  • 75 Daneman N, Sarwar S, Fowler RA, Cuthbertson BH. ; SuDDICU Canadian Study Group. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infect Dis 2013; 13 (04) 328-341
    CrossrefPubMedGoogle Scholar
  • 76 Sánchez-Ramírez C, Hípola-Escalada S, Cabrera-Santana M. , et al. Long-term use of selective digestive decontamination in an ICU highly endemic for bacterial resistance. Crit Care 2018; 22 (01) 141
    CrossrefPubMedGoogle Scholar
  • 77 Buitinck S, Jansen R, Rijkenberg S. , et al. The ecological effects of selective decontamination of the digestive tract (SDD) on antimicrobial resistance: a 21-year longitudinal single-centre study. Crit Care 2019; 23 (01) 208
    CrossrefPubMedGoogle Scholar
  • 78 Lloréns-Villar Y, Tusell F, Canut A. , et al. Antibiotic susceptibility trend before and after long-term use of selective digestive decontamination: a 16 year ecological study. J Antimicrob Chemother 2019; 74 (08) 2289-2294
    CrossrefPubMedGoogle Scholar
  • 79 Oostdijk EAN, Kesecioglu J, Schultz MJ. , et al. Effects of decontamination of the oropharynx and intestinal tract on antibiotic resistance in ICUs: a randomized clinical trial. JAMA 2014; 312 (14) 1429-1437
    CrossrefPubMedGoogle Scholar
  • 80 Oostdijk EAN, Kesecioglu J, Schultz MJ. , et al. Notice of retraction and replacement: Oostdijk et al. Effects of decontamination of the oropharynx and intestinal tract on antibiotic resistance in ICUs: a randomized clinical trial. JAMA. 2014;312(14):1429-1437. JAMA 2017; 317 (15) 1583-1584
    CrossrefPubMedGoogle Scholar
  • 81 Torres A, Niederman MS, Chastre J. , et al. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J 2017; 50 (03) 1700582
    CrossrefPubMedGoogle Scholar
  • 82 Wittekamp BH, Plantinga NL, Cooper BS. , et al. Decontamination strategies and bloodstream infections with antibiotic-resistant microorganisms in ventilated patients: a randomized clinical trial. JAMA 2018; 320 (20) 2087-2098
    CrossrefPubMedGoogle Scholar
  • 83 Roquilly A, Marret E, Abraham E, Asehnoune K. Pneumonia prevention to decrease mortality in intensive care unit: a systematic review and meta-analysis. Clin Infect Dis 2015; 60 (01) 64-75
    CrossrefPubMedGoogle Scholar
  • 84 Klompas M. Oropharyngeal decontamination with antiseptics to prevent ventilator-associated pneumonia: rethinking the benefits of chlorhexidine. Semin Respir Crit Care Med 2017; 38 (03) 381-390
    Article in Thieme ConnectPubMedGoogle Scholar
  • 85 Klompas M, Speck K, Howell MD, Greene LR, Berenholtz SM. Reappraisal of routine oral care with chlorhexidine gluconate for patients receiving mechanical ventilation: systematic review and meta-analysis. JAMA Intern Med 2014; 174 (05) 751-761
    CrossrefPubMedGoogle Scholar
  • 86 Harris BD, Thomas GA, Greene MH, Spires SS, Talbot TR. Ventilator bundle compliance and risk of ventilator-associated events. Infect Control Hosp Epidemiol 2018; 39 (06) 637-643
    CrossrefPubMedGoogle Scholar
  • 87 Azevedo JR, Montenegro WS, Sousa CA. , et al. Ventilator-associated events: prevalence, outcome, and preventability. Intensive Care Med Exp 2017; 5 (Suppl. 02) 44
    CrossrefPubMedGoogle Scholar
  • 88 Deschepper M, Waegeman W, Eeckloo K, Vogelaers D, Blot S. Effects of chlorhexidine gluconate oral care on hospital mortality: a hospital-wide, observational cohort study. Intensive Care Med 2018; 44 (07) 1017-1026
    CrossrefPubMedGoogle Scholar
  • 89 Plantinga NL, Wittekamp BHJ, Leleu K. , et al. Oral mucosal adverse events with chlorhexidine 2% mouthwash in ICU. Intensive Care Med 2016; 42 (04) 620-621
    CrossrefPubMedGoogle Scholar
  • 90 Bouadma L, Klompas M. Oral care with chlorhexidine: beware!. Intensive Care Med 2018; 44 (07) 1153-1155
    CrossrefPubMedGoogle Scholar
  • 91 Seguin P, Laviolle B, Dahyot-Fizelier C. , et al; Study of Povidone Iodine to Reduce Pulmonary Infection in Head Trauma and Cerebral Hemorrhage Patients (SPIRIT) ICU Study Group; AtlanRéa Group. Effect of oropharyngeal povidone-iodine preventive oral care on ventilator-associated pneumonia in severely brain-injured or cerebral hemorrhage patients: a multicenter, randomized controlled trial. Crit Care Med 2014; 42 (01) 1-8
    CrossrefPubMedGoogle Scholar
  • 92 Resar R, Pronovost P, Haraden C, Simmonds T, Rainey T, Nolan T. Using a bundle approach to improve ventilator care processes and reduce ventilator-associated pneumonia. Jt Comm J Qual Patient Saf 2005; 31 (05) 243-248
    PubMedGoogle Scholar
  • 93 Alhazzani W, Alshamsi F, Belley-Cote E. , et al. Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials. Intensive Care Med 2018; 44 (01) 1-11
    CrossrefPubMedGoogle Scholar
  • 94 Sasabuchi Y, Matsui H, Lefor AK, Fushimi K, Yasunaga H. Risks and benefits of stress ulcer prophylaxis for patients with severe sepsis. Crit Care Med 2016; 44 (07) e464-e469
    CrossrefPubMedGoogle Scholar
  • 95 Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA 2009; 301 (20) 2120-2128
    CrossrefPubMedGoogle Scholar
  • 96 Huang HB, Jiang W, Wang CY, Qin HY, Du B. Stress ulcer prophylaxis in intensive care unit patients receiving enteral nutrition: a systematic review and meta-analysis. Crit Care 2018; 22 (01) 20
    CrossrefPubMedGoogle Scholar
  • 97 Alhazzani W, Guyatt G, Alshahrani M. , et al; Canadian Critical Care Trials Group. Withholding pantoprazole for stress ulcer prophylaxis in critically ill patients: a pilot randomized clinical trial and meta-analysis. Crit Care Med 2017; 45 (07) 1121-1129
    CrossrefPubMedGoogle Scholar
  • 98 Selvanderan SP, Summers MJ, Finnis ME. , et al. Pantoprazole or placebo for stress ulcer prophylaxis (POP-UP): randomized double-blind exploratory study. Crit Care Med 2016; 44 (10) 1842-1850
    CrossrefPubMedGoogle Scholar
  • 99 Young PJ, Bagshaw SM, Forbes A. , et al; Australian and New Zealand Intensive Care Society Clinical Trials Group on behalf of the PEPTIC investigators. A cluster randomised, crossover, registry-embedded clinical trial of proton pump inhibitors versus histamine-2 receptor blockers for ulcer prophylaxis therapy in the intensive care unit (PEPTIC study): study protocol. Crit Care Resusc 2018; 20 (03) 182-189
    PubMedGoogle Scholar
  • 100 Krag M, Perner A, Wetterslev J. , et al; SUP-ICU investigators. Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial. Trials 2016; 17 (01) 205
    CrossrefPubMedGoogle Scholar
  • 101 Krag M, Marker S, Perner A. , et al; SUP-ICU trial group. Pantoprazole in patients at risk for gastrointestinal bleeding in the ICU. N Engl J Med 2018; 379 (23) 2199-2208
    CrossrefPubMedGoogle Scholar
  • 102 Weng H, Li JG, Mao Z. , et al. Probiotics for preventing ventilator-associated pneumonia in mechanically ventilated patients: a meta-analysis with trial sequential analysis. Front Pharmacol 2017; 8: 717
    CrossrefPubMedGoogle Scholar
  • 103 Cook DJ, Johnstone J, Marshall JC. , et al; PROSPECT Investigators and the Canadian Critical Care Trials Group. Probiotics: prevention of severe pneumonia and endotracheal colonization trial-PROSPECT: a pilot trial. Trials 2016; 17: 377
    CrossrefPubMedGoogle Scholar
  • 104 Lherm T, Monet C, Nougière B. , et al. Seven cases of fungemia with Saccharomyces boulardii in critically ill patients. Intensive Care Med 2002; 28 (06) 797-801
    CrossrefPubMedGoogle Scholar
  • 105 Muñoz P, Bouza E, Cuenca-Estrella M. , et al. Saccharomyces cerevisiae fungemia: an emerging infectious disease. Clin Infect Dis 2005; 40 (11) 1625-1634
    CrossrefPubMedGoogle Scholar
  • 106 Salminen MK, Rautelin H, Tynkkynen S. , et al. Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG. Clin Infect Dis 2004; 38 (01) 62-69
    CrossrefPubMedGoogle Scholar
  • 107 Cassone M, Serra P, Mondello F. , et al. Outbreak of Saccharomyces cerevisiae subtype boulardii fungemia in patients neighboring those treated with a probiotic preparation of the organism. J Clin Microbiol 2003; 41 (11) 5340-5343
    CrossrefPubMedGoogle Scholar
  • 108 Graf C, Gavazzi G. Saccharomyces cerevisiae fungemia in an immunocompromised patient not treated with Saccharomyces boulardii preparation. J Infect 2007; 54 (03) 310-311
    CrossrefPubMedGoogle Scholar
  • 109 Klompas M. Ventilator-associated pneumonia: is zero possible?. Clin Infect Dis 2010; 51 (10) 1123-1126
    CrossrefPubMedGoogle Scholar
  • 110 Pileggi C, Mascaro V, Bianco A, Nobile CGA, Pavia M. Ventilator bundle and its effects on mortality among ICU patients: a meta-analysis. Crit Care Med 2018; 46 (07) 1167-1174
    CrossrefPubMedGoogle Scholar
  • 111 Poelaert J, Depuydt P, De Wolf A, Van de Velde S, Herck I, Blot S. Polyurethane cuffed endotracheal tubes to prevent early postoperative pneumonia after cardiac surgery: a pilot study. J Thorac Cardiovasc Surg 2008; 135 (04) 771-776
    CrossrefPubMedGoogle Scholar
  • 112 Damas P, Frippiat F, Ancion A. , et al. Prevention of ventilator-associated pneumonia and ventilator-associated conditions: a randomized controlled trial with subglottic secretion suctioning. Crit Care Med 2015; 43 (01) 22-30
    PubMedGoogle Scholar