Ventilator-Associated Pneumonia

Abstract

Ventilator-associated pneumonia (VAP) is an iatrogenic pulmonary infection that develops in tracheally intubated patients on mechanical ventilation for at least 48 hours. VAP is the nosocomial infection with the greatest impact on patient outcomes and health care costs. Endogenous colonization by aerobic gram-negative pathogens, that is, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus play a pivotal role in the pathogenesis of VAP. Several preventive strategies have shown efficacy in decreasing VAP incidence and are often implemented altogether as a prevention bundle. In patients with clinical suspicion of VAP, respiratory samples should be promptly collected. The empiric treatment should be based on the local prevalence of pathogens, duration of hospital stay, and prior antimicrobial therapy. The antibiotics can be stopped or adjusted to more narrow-spectrum once cultures and susceptibilities are available.

Keywords

ventilator-associated pneumonia - nosocomial pneumonia - pseudomonas aeruginosa - endotracheal tube - mechanical ventilation

• References

• 1 American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171 (4) 388-416
• 2 Magill SS, Klompas M, Balk R , et al. Developing a new, national approach to surveillance for ventilator-associated events. Crit Care Med 2013; 41 (11) 2467-2475
• 3 Reignier J, Mercier E, Le Gouge A , et al; Clinical Research in Intensive Care and Sepsis (CRICS) Group. Effect of not monitoring residual gastric volume on risk of ventilator-associated pneumonia in adults receiving mechanical ventilation and early enteral feeding: a randomized controlled trial. JAMA 2013; 309 (3) 249-256
• 4 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 (1) 1-8
• 5 Lorente L, Lecuona M, Jiménez A , et al. Ventilator-associated pneumonia with or without toothbrushing: a randomized controlled trial. Eur J Clin Microbiol Infect Dis 2012; 31 (10) 2621-2629
• 6 Leblebicioglu H, Yalcin AN, Rosenthal VD , et al. Effectiveness of a multidimensional approach for prevention of ventilator-associated pneumonia in 11 adult intensive care units from 10 cities of Turkey: findings of the International Nosocomial Infection Control Consortium (INICC). Infection 2013; 41 (2) 447-456
• 7 Dudeck MA, Horan TC, Peterson KD , et al. National Healthcare Safety Network report, data summary for 2011, device-associated module. Am J Infect Control 2013; 41 (4) 286-300
• 8 Blot S, Koulenti D, Dimopoulos G , et al; EU-VAP Study Investigators. Prevalence, risk factors, and mortality for ventilator-associated pneumonia in middle-aged, old, and very old critically ill patients*. Crit Care Med 2014; 42 (3) 601-609
• 9 Koulenti D, Lisboa T, Brun-Buisson C , 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) 2360-2368
• 10 Forel JM, Voillet F, Pulina D , et al. Ventilator-associated pneumonia and ICU mortality in severe ARDS patients ventilated according to a lung-protective strategy. Crit Care 2012; 16 (2) R65
• 11 Kollef MH, Hamilton CW, Ernst FR. Economic impact of ventilator-associated pneumonia in a large matched cohort. Infect Control Hosp Epidemiol 2012; 33 (3) 250-256
• 12 Rello J, Ollendorf DA, Oster G , et al; VAP Outcomes Scientific Advisory Group. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest 2002; 122 (6) 2115-2121
• 13 Warren DK, Shukla SJ, Olsen MA , et al. Outcome and attributable cost of ventilator-associated pneumonia among intensive care unit patients in a suburban medical center. Crit Care Med 2003; 31 (5) 1312-1317
• 14 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 (8) 665-671
• 15 Bekaert M, Timsit JF, Vansteelandt S , et al; Outcomerea Study Group. Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis. Am J Respir Crit Care Med 2011; 184 (10) 1133-1139
• 16 Kollef MH, Silver P, Murphy DM, Trovillion E. The effect of late-onset ventilator-associated pneumonia in determining patient mortality. Chest 1995; 108 (6) 1655-1662
• 17 Lisboa T, Diaz E, Sa-Borges M , et al. The ventilator-associated pneumonia PIRO score: a tool for predicting ICU mortality and health-care resources use in ventilator-associated pneumonia. Chest 2008; 134 (6) 1208-1216
• 18 Esperatti M, Ferrer M, Giunta V , et al. Validation of predictors of adverse outcomes in hospital-acquired pneumonia in the ICU. Crit Care Med 2013; 41 (9) 2151-2161
• 19 Zimlichman E, Henderson D, Tamir O , et al. Health care-associated infections: a meta-analysis of costs and financial impact on the US health care system. JAMA Intern Med 2013; 173 (22) 2039-2046
• 20 Gal TJ. Effects of endotracheal intubation on normal cough performance. Anesthesiology 1980; 52 (4) 324-329
• 21 Konrad F, Schreiber T, Brecht-Kraus D, Georgieff M. Mucociliary transport in ICU patients. Chest 1994; 105 (1) 237-241
• 22 Meisel C, Schefold JC, Pschowski R , et al. Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med 2009; 180 (7) 640-648
• 23 Leentjens J, Kox M, Koch RM , et al. Reversal of immunoparalysis in humans in vivo: a double-blind, placebo-controlled, randomized pilot study. Am J Respir Crit Care Med 2012; 186 (9) 838-845
• 24 DiazGranados CA, Jones MY, Kongphet-Tran T , et al. Outbreak of Pseudomonas aeruginosa infection associated with contamination of a flexible bronchoscope. Infect Control Hosp Epidemiol 2009; 30 (6) 550-555
• 25 Guyot A, Turton JF, Garner D. Outbreak of Stenotrophomonas maltophilia on an intensive care unit. J Hosp Infect 2013; 85 (4) 303-307
• 26 Kikuchi T, Nagashima G, Taguchi K , et al. Contaminated oral intubation equipment associated with an outbreak of carbapenem-resistant Pseudomonas in an intensive care unit. J Hosp Infect 2007; 65 (1) 54-57
• 27 Bou R, Ramos P. Outbreak of nosocomial Legionnaires' disease caused by a contaminated oxygen humidifier. J Hosp Infect 2009; 71 (4) 381-383
• 28 Rogues AM, Maugein J, Allery A , et al. Electronic ventilator temperature sensors as a potential source of respiratory tract colonization with Stenotrophomonas maltophilia. J Hosp Infect 2001; 49 (4) 289-292
• 29 Pegues CF, Pegues DA, Ford DS , et al. Burkholderia cepacia respiratory tract acquisition: epidemiology and molecular characterization of a large nosocomial outbreak. Epidemiol Infect 1996; 116 (3) 309-317
• 30 Enoch DA, Summers C, Brown NM , et al. Investigation and management of an outbreak of multidrug-carbapenem-resistant Acinetobacter baumannii in Cambridge, UK. J Hosp Infect 2008; 70 (2) 109-118
• 31 Johanson Jr WG, Pierce AK, Sanford JP, Thomas GD. Nosocomial respiratory infections with gram-negative bacilli. The significance of colonization of the respiratory tract. Ann Intern Med 1972; 77 (5) 701-706
• 32 Johanson WG, Pierce AK, Sanford JP. Changing pharyngeal bacterial flora of hospitalized patients. Emergence of gram-negative bacilli. N Engl J Med 1969; 281 (21) 1137-1140
• 33 Feldman C, Kassel M, Cantrell J , et al. The presence and sequence of endotracheal tube colonization in patients undergoing mechanical ventilation. Eur Respir J 1999; 13 (3) 546-551
• 34 Li Bassi G, Ranzani OT, Marti JD , et al. An in vitro study to assess determinant features associated with fluid sealing in the design of endotracheal tube cuffs and exerted tracheal pressures. Crit Care Med 2013; 41 (2) 518-526
• 35 Ouanes I, Lyazidi A, Danin PE , et al. Mechanical influences on fluid leakage past the tracheal tube cuff in a benchtop model. Intensive Care Med 2011; 37 (4) 695-700
• 36 Pitts R, Fisher D, Sulemanji D, Kratohvil J, Jiang Y, Kacmarek R. Variables affecting leakage past endotracheal tube cuffs: a bench study. Intensive Care Med 2010; 36 (12) 2066-2073
• 37 Lucangelo U, Zin WA, Antonaglia V , et al. Effect of positive expiratory pressure and type of tracheal cuff on the incidence of aspiration in mechanically ventilated patients in an intensive care unit. Crit Care Med 2008; 36 (2) 409-413
• 38 De Souza PR, De Andrade D, Cabral DB, Watanabe E. Endotracheal tube biofilm and ventilator-associated pneumonia with mechanical ventilation. Microsc Res Tech 2014; 77 (4) 305-312
• 39 Gil-Perotin S, Ramirez P, Marti V , et al. Implications of endotracheal tube biofilm in ventilator-associated pneumonia response: a state of concept. Crit Care 2012; 16 (3) R93
• 40 Høiby N, Ciofu O, Johansen HK , et al. The clinical impact of bacterial biofilms. Int J Oral Sci 2011; 3 (2) 55-65
• 41 Fux CA, Stoodley P, Hall-Stoodley L, Costerton JW. Bacterial biofilms: a diagnostic and therapeutic challenge. Expert Rev Anti Infect Ther 2003; 1 (4) 667-683
• 42 Fux CA, Costerton JW, Stewart PS, Stoodley P. Survival strategies of infectious biofilms. Trends Microbiol 2005; 13 (1) 34-40
• 43 Inglis TJ, Millar MR, Jones JG, Robinson DA. Tracheal tube biofilm as a source of bacterial colonization of the lung. J Clin Microbiol 1989; 27 (9) 2014-2018
• 44 Ng KS, Kumarasinghe G, Inglis TJ. Dissemination of respiratory secretions during tracheal tube suctioning in an intensive care unit. Ann Acad Med Singapore 1999; 28 (2) 178-182
• 45 Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE. Defining the normal bacterial flora of the oral cavity. J Clin Microbiol 2005; 43 (11) 5721-5732
• 46 Tenovuo J. Antimicrobial function of human saliva—how important is it for oral health?. Acta Odontol Scand 1998; 56 (5) 250-256
• 47 Edgerton M, Koshlukova SE. Salivary histatin 5 and its similarities to the other antimicrobial proteins in human saliva. Adv Dent Res 2000; 14: 16-21
• 48 Caccavo D, Pellegrino NM, Altamura M , et al. Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application. J Endotoxin Res 2002; 8 (6) 403-417
• 49 De Smet K, Contreras R. Human antimicrobial peptides: defensins, cathelicidins and histatins. Biotechnol Lett 2005; 27 (18) 1337-1347
• 50 Terezakis E, Needleman I, Kumar N, Moles D, Agudo E. The impact of hospitalization on oral health: a systematic review. J Clin Periodontol 2011; 38 (7) 628-636
• 51 Fourrier F, Duvivier B, Boutigny H, Roussel-Delvallez M, Chopin C. Colonization of dental plaque: a source of nosocomial infections in intensive care unit patients. Crit Care Med 1998; 26 (2) 301-308
• 52 Golin V, Mimica IM, Mimica LM. Oropharynx microbiota among alcoholics and non-alcoholics. Sao Paulo Med J 1998; 116 (3) 1727-1733
• 53 Mackowiak PA, Martin RM, Smith JW. The role of bacterial interference in the increased prevalence of oropharyngeal gram-negative bacilli among alcoholics and diabetics. Am Rev Respir Dis 1979; 120 (3) 589-593
• 54 Scannapieco FA, Bush RB, Paju S. Associations between periodontal disease and risk for nosocomial bacterial pneumonia and chronic obstructive pulmonary disease. A systematic review. Ann Periodontol 2003; 8 (1) 54-69
• 55 Leibovitz A, Plotnikov G, Habot B , et al. Saliva secretion and oral flora in prolonged nasogastric tube-fed elderly patients. Isr Med Assoc J 2003; 5 (5) 329-332
• 56 Michishige F, Yoshinaga S, Harada E , et al. Relationships between activity of daily living, and oral cavity care and the number of oral cavity microorganisms in patients with cerebrovascular diseases. J Med Invest 1999; 46 (1-2) 79-85
• 57 Helovuo H, Hakkarainen K, Paunio K. Changes in the prevalence of subgingival enteric rods, staphylococci and yeasts after treatment with penicillin and erythromycin. Oral Microbiol Immunol 1993; 8 (2) 75-79
• 58 Dennesen P, van der Ven A, Vlasveld M , et al. Inadequate salivary flow and poor oral mucosal status in intubated intensive care unit patients. Crit Care Med 2003; 31 (3) 781-786
• 59 Scannapieco FA. Role of oral bacteria in respiratory infection. J Periodontol 1999; 70 (7) 793-802
• 60 Quinn MO, Miller VE, Dal Nogare AR. Increased salivary exoglycosidase activity during critical illness. Am J Respir Crit Care Med 1994; 150 (1) 179-183
• 61 Weinmeister KD, Dal Nogare AR. Buccal cell carbohydrates are altered during critical illness. Am J Respir Crit Care Med 1994; 150 (1) 131-134
• 62 Gibbons RJ, Hay DI, Childs III WC, Davis G. Role of cryptic receptors (cryptitopes) in bacterial adhesion to oral surfaces. Arch Oral Biol 1990; 35 (Suppl): 107S-114S
• 63 Heyland DK, Cook DJ, Schoenfeld PS, Frietag A, Varon J, Wood G ; Canadian Critical Care Trials Group. The effect of acidified enteral feeds on gastric colonization in critically ill patients: results of a multicenter randomized trial. Crit Care Med 1999; 27 (11) 2399-2406
• 64 Torres A, El-Ebiary M, Soler N, Montón C, Fàbregas N, Hernández C. Stomach as a source of colonization of the respiratory tract during mechanical ventilation: association with ventilator-associated pneumonia. Eur Respir J 1996; 9 (8) 1729-1735
• 65 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 (7) 540-543
• 66 Ferrer M, Bauer TT, Torres A, Hernández C, Piera C. Effect of nasogastric tube size on gastroesophageal reflux and microaspiration in intubated patients. Ann Intern Med 1999; 130 (12) 991-994
• 67 Di Pasquale M, Ferrer M, Esperatti M , et al. Assessment of severity of ICU-acquired pneumonia and association with etiology. Crit Care Med 2014; 42 (2) 303-312
• 68 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
• 69 Combes A, Figliolini C, Trouillet JL , et al. Incidence and outcome of polymicrobial ventilator-associated pneumonia. Chest 2002; 121 (5) 1618-1623
• 70 Teixeira PJ, Seligman R, Hertz FT, Cruz DB, Fachel JM. Inadequate treatment of ventilator-associated pneumonia: risk factors and impact on outcomes. J Hosp Infect 2007; 65 (4) 361-367
• 71 Makris D, Desrousseaux B, Zakynthinos E, Durocher A, Nseir S. The impact of COPD on ICU mortality in patients with ventilator-associated pneumonia. Respir Med 2011; 105 (7) 1022-1029
• 72 Nseir S, Ader F, Lubret R, Marquette CH. Pathophysiology of airway colonization in critically ill COPD patient. Curr Drug Targets 2011; 12 (4) 514-520
• 73 Fagon JY, Chastre J. Diagnosis and treatment of nosocomial pneumonia in ALI/ARDS patients. Eur Respir J Suppl 2003; 42: 77s-83s
• 74 Lepelletier D, Roquilly A, Demeure dit latte D , et al. Retrospective analysis of the risk factors and pathogens associated with early-onset ventilator-associated pneumonia in surgical-ICU head-trauma patients. J Neurosurg Anesthesiol 2010; 22 (1) 32-37
• 75 Pelosi P, Barassi A, Severgnini P , et al. Prognostic role of clinical and laboratory criteria to identify early ventilator-associated pneumonia in brain injury. Chest 2008; 134 (1) 101-108
• 76 Nseir S, Blazejewski C, Lubret R, Wallet F, Courcol R, Durocher A. Risk of acquiring multidrug-resistant Gram-negative bacilli from prior room occupants in the intensive care unit. Clin Microbiol Infect 2011; 17 (8) 1201-1208
• 77 Rello J, Sa-Borges M, Correa H, Leal SR, Baraibar J. Variations in etiology of ventilator-associated pneumonia across four treatment sites: implications for antimicrobial prescribing practices. Am J Respir Crit Care Med 1999; 160 (2) 608-613
• 78 Delisle MS, Williamson DR, Albert M , et al. Impact of Candida species on clinical outcomes in patients with suspected ventilator-associated pneumonia. Can Respir J 2011; 18 (3) 131-136
• 79 Ong DS, Mc Klein Klouwenberg P, Spitoni C, Bonten MJ, Cremer OL. Nebulised amphotericin B to eradicate Candida colonisation from the respiratory tract in critically ill patients receiving selective digestive decontamination: a cohort study. Crit Care 2013; 17 (5) R233
• 80 Hamet M, Pavon A, Dalle F , et al. Candida spp. airway colonization could promote antibiotic-resistant bacteria selection in patients with suspected ventilator-associated pneumonia. Intensive Care Med 2012; 38 (8) 1272-1279
• 81 Luyt CE, Bréchot N, Chastre J. What role do viruses play in nosocomial pneumonia?. Curr Opin Infect Dis 2014; 27 (2) 194-199
• 82 Sinuff T, Muscedere J, Cook DJ , et al; Canadian Critical Care Trials Group. Implementation of clinical practice guidelines for ventilator-associated pneumonia: a multicenter prospective study. Crit Care Med 2013; 41 (1) 15-23
• 83 Bouadma L, Mourvillier B, Deiler V , et al. A multifaceted program to prevent ventilator-associated pneumonia: impact on compliance with preventive measures. Crit Care Med 2010; 38 (3) 789-796
• 84 Barrera L, Zingg W, Mendez F, Pittet D. Effectiveness of a hand hygiene promotion strategy using alcohol-based handrub in 6 intensive care units in Colombia. Am J Infect Control 2011; 39 (8) 633-639
• 85 Slekovec C, Gbaguidi-Haore H, Coignard B, Bertrand X, Talon D. Relationship between prevalence of device-associated infections and alcohol-based hand-rub consumption: a multi-level approach. J Hosp Infect 2011; 78 (2) 133-137
• 86 Koff MD, Corwin HL, Beach ML, Surgenor SD, Loftus RW. Reduction in ventilator associated pneumonia in a mixed intensive care unit after initiation of a novel hand hygiene program. J Crit Care 2011; 26 (5) 489-495
• 87 Kollef MH, Von Harz B, Prentice D , et al. Patient transport from intensive care increases the risk of developing ventilator-associated pneumonia. Chest 1997; 112 (3) 765-773
• 88 Bercault N, Wolf M, Runge I, Fleury JC, Boulain T. Intrahospital transport of critically ill ventilated patients: a risk factor for ventilator-associated pneumonia—a matched cohort study. Crit Care Med 2005; 33 (11) 2471-2478
• 89 Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342 (20) 1471-1477
• 90 Schweickert WD, Pohlman MC, Pohlman AS , et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 2009; 373 (9678) 1874-1882
• 91 Hilbert G, Gruson D, Vargas F , et al. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med 2001; 344 (7) 481-487
• 92 Brochard L, Mancebo J, Wysocki M , et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1995; 333 (13) 817-822
• 93 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 (3) E112-E122
• 94 Dullenkopf A, Gerber A, Weiss M. Fluid leakage past tracheal tube cuffs: evaluation of the new Microcuff endotracheal tube. Intensive Care Med 2003; 29 (10) 1849-1853
• 95 Zanella A, Cressoni M, Epp M, Stylianou M, Kolobow T. A double-layer tracheal tube cuff designed to prevent leakage: a bench-top study. Intensive Care Med 2008; 34 (6) 1145-1149
• 96 Young PJ, Burchett K, Harvey I, Blunt MC. The prevention of pulmonary aspiration with control of tracheal wall pressure using a silicone cuff. Anaesth Intensive Care 2000; 28 (6) 660-665
• 97 Lorente L, Lecuona M, Jiménez A, Mora ML, Sierra A. Influence of an endotracheal tube with polyurethane cuff and subglottic secretion drainage on pneumonia. Am J Respir Crit Care Med 2007; 176 (11) 1079-1083
• 98 Young PJ, Blunt MC. Improving the shape and compliance characteristics of a high-volume, low-pressure cuff improves tracheal seal. Br J Anaesth 1999; 83 (6) 887-889
• 99 Bowton DL, Hite RD, Martin RS. The impact of hospital-wide use of a tapered cuff endotracheal tube on VAP incidence. Respir Care 2013; 58 (10) 1582-1587
• 100 Valencia M, Ferrer M, Farre R , et al. Automatic control of tracheal tube cuff pressure in ventilated patients in semirecumbent position: a randomized trial. Crit Care Med 2007; 35 (6) 1543-1549
• 101 Rouzé A, Nseir S. Continuous control of tracheal cuff pressure for the prevention of ventilator-associated pneumonia in critically ill patients: where is the evidence?. Curr Opin Crit Care 2013; 19 (5) 440-447
• 102 Manzano F, Fernández-Mondéjar E, Colmenero M , et al. Positive-end expiratory pressure reduces incidence of ventilator-associated pneumonia in nonhypoxemic patients. Crit Care Med 2008; 36 (8) 2225-2231
• 103 Kollef MH, Afessa B, Anzueto A , et al; NASCENT Investigation Group. Silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the NASCENT randomized trial. JAMA 2008; 300 (7) 805-813
• 104 Lacherade JC, De Jonghe B, Guezennec P , et al. Intermittent subglottic secretion drainage and ventilator-associated pneumonia: a multicenter trial. Am J Respir Crit Care Med 2010; 182 (7) 910-917
• 105 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 (8) 1985-1991
• 106 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
• 107 Orozco-Levi M, Torres A, Ferrer M , et al. Semirecumbent position protects from pulmonary aspiration but not completely from gastroesophageal reflux in mechanically ventilated patients. Am J Respir Crit Care Med 1995; 152 (4 Pt 1) 1387-1390
• 108 Torres A, Ewig S, Lode H, Carlet J ; European HAP working group. Defining, treating and preventing hospital acquired pneumonia: European perspective. Intensive Care Med 2009; 35 (1) 9-29
• 109 Krag M, Perner A, Wetterslev J, Møller MH. Stress ulcer prophylaxis in the intensive care unit: is it indicated? A topical systematic review. Acta Anaesthesiol Scand 2013; 57 (7) 835-847
• 110 Alhazzani W, Almasoud A, Jaeschke R , et al. Small bowel feeding and risk of pneumonia in adult critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care 2013; 17 (4) R127
• 111 Labeau SO, Van de Vyver K, Brusselaers N, Vogelaers D, Blot SI. Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis. Lancet Infect Dis 2011; 11 (11) 845-854
• 112 Shi Z, Xie H, Wang P , et al. Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database Syst Rev 2013; 8: CD008367
• 113 Koeman M, van der Ven AJ, Hak E , et al. Oral decontamination with chlorhexidine reduces the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med 2006; 173 (12) 1348-1355
• 114 Tantipong H, Morkchareonpong C, Jaiyindee S, Thamlikitkul V. Randomized controlled trial and meta-analysis of oral decontamination with 2% chlorhexidine solution for the prevention of ventilator-associated pneumonia. Infect Control Hosp Epidemiol 2008; 29 (2) 131-136
• 115 de Smet AM, Kluytmans JA, Cooper BS , et al. Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med 2009; 360 (1) 20-31
• 116 de Jonge E, Schultz MJ, Spanjaard L , et al. Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet 2003; 362 (9389) 1011-1016
• 117 Liberati A, D'Amico R, Pifferi S, Torri V, Brazzi L, Parmelli E. Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care. Cochrane Database Syst Rev 2009; (4) CD000022
• 118 D'Amico R, Pifferi S, Leonetti C, Torri V, Tinazzi A, Liberati A. Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials. BMJ 1998; 316 (7140) 1275-1285
• 119 Grgurich PE, Hudcova J, Lei Y, Sarwar A, Craven DE. Diagnosis of ventilator-associated pneumonia: controversies and working toward a gold standard. Curr Opin Infect Dis 2013; 26 (2) 140-150
• 120 Fàbregas N, Torres A, El-Ebiary M , et al. Histopathologic and microbiologic aspects of ventilator-associated pneumonia. Anesthesiology 1996; 84 (4) 760-771
• 121 Torres A, el-Ebiary M, González J , et al. Gastric and pharyngeal flora in nosocomial pneumonia acquired during mechanical ventilation. Am Rev Respir Dis 1993; 148 (2) 352-357
• 122 Meduri GU, Mauldin GL, Wunderink RG , et al. Causes of fever and pulmonary densities in patients with clinical manifestations of ventilator-associated pneumonia. Chest 1994; 106 (1) 221-235
• 123 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 (1) 62-68
• 124 Fàbregas N, Ewig S, Torres A , et al. Clinical diagnosis of ventilator associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies. Thorax 1999; 54 (10) 867-873
• 125 Torres A, el-Ebiary M, Padró L , et al. Validation of different techniques for the diagnosis of ventilator-associated pneumonia. Comparison with immediate postmortem pulmonary biopsy. Am J Respir Crit Care Med 1994; 149 (2 Pt 1) 324-331
• 126 Fartoukh M, Maitre B, Honoré S, Cerf C, Zahar JR, Brun-Buisson C. Diagnosing pneumonia during mechanical ventilation: the clinical pulmonary infection score revisited. Am J Respir Crit Care Med 2003; 168 (2) 173-179
• 127 Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid. Am Rev Respir Dis 1991; 143 (5 Pt 1) 1121-1129
• 128 Shan J, Chen HL, Zhu JH. Diagnostic accuracy of clinical pulmonary infection score for ventilator-associated pneumonia: a meta-analysis. Respir Care 2011; 56 (8) 1087-1094
• 129 Garrouste-Orgeas M, Chevret S, Arlet G , et al. Oropharyngeal or gastric colonization and nosocomial pneumonia in adult intensive care unit patients. A prospective study based on genomic DNA analysis. Am J Respir Crit Care Med 1997; 156 (5) 1647-1655
• 130 Jourdain B, Novara A, Joly-Guillou ML , et al. Role of quantitative cultures of endotracheal aspirates in the diagnosis of nosocomial pneumonia. Am J Respir Crit Care Med 1995; 152 (1) 241-246
• 131 Torres A, Martos A, Puig de la Bellacasa J , et al. Specificity of endotracheal aspiration, protected specimen brush, and bronchoalveolar lavage in mechanically ventilated patients. Am Rev Respir Dis 1993; 147 (4) 952-957
• 132 Muscedere J, Sinuff T, Heyland DK , et al; Canadian Critical Care Trials Group. The clinical impact and preventability of ventilator-associated conditions in critically ill patients who are mechanically ventilated. Chest 2013; 144 (5) 1453-1460
• 133 Klein Klouwenberg PM, van Mourik MS, Ong DS , et al; MARS Consortium. Electronic implementation of a novel surveillance paradigm for ventilator-associated events. Feasibility and validation. Am J Respir Crit Care Med 2014; 189 (8) 947-955
• 134 Boyer A, Medrano J, Mzali F , et al. Direct testing of bronchoalveolar lavages from ventilator-associated pneumonia patients. Diagn Microbiol Infect Dis 2012; 73 (2) 107-110
• 135 Bouza E, Torres MV, Radice C , et al. Direct E-test (AB Biodisk) of respiratory samples improves antimicrobial use in ventilator-associated pneumonia. Clin Infect Dis 2007; 44 (3) 382-387
• 136 Cercenado E, Cercenado S, Marín M, Rico MV, Vicente T, Bouza E. Evaluation of direct E-test on lower respiratory tract samples: a rapid and accurate procedure for antimicrobial susceptibility testing. Diagn Microbiol Infect Dis 2007; 58 (2) 211-216
• 137 Reygaert W. Methicillin-resistant Staphylococcus aureus (MRSA): identification and susceptibility testing techniques. Clin Lab Sci 2009; 22 (2) 120-124
• 138 Bogaerts P, Hamels S, de Mendonca R , et al. Analytical validation of a novel high multiplexing real-time PCR array for the identification of key pathogens causative of bacterial ventilator-associated pneumonia and their associated resistance genes. J Antimicrob Chemother 2013; 68 (2) 340-347
• 139 Ost DE, Poch D, Fadel A, Wettimuny S, Ginocchio C, Wang XP. Mini-bronchoalveolar lavage quantitative polymerase chain reaction for diagnosis of methicillin-resistant Staphylococcus aureus pneumonia. Crit Care Med 2010; 38 (7) 1536-1541
• 140 Muscedere JG, Shorr AF, Jiang X, Day A, Heyland DK ; Canadian Critical Care Trials Group. The adequacy of timely empiric antibiotic therapy for ventilator-associated pneumonia: an important determinant of outcome. J Crit Care 2012; 27 (3) e7-e14
• 141 Bouza E, Giannella M, Bunsow E , et al; Gregorio Marañón Task Force for Pneumonia (GANG). Ventilator-associated pneumonia due to meticillin-resistant Staphylococcus aureus: risk factors and outcome in a large general hospital. J Hosp Infect 2012; 80 (2) 150-155
• 142 Mueller EW, Hanes SD, Croce MA, Wood GC, Boucher BA, Fabian TC. Effect from multiple episodes of inadequate empiric antibiotic therapy for ventilator-associated pneumonia on morbidity and mortality among critically ill trauma patients. J Trauma 2005; 58 (1) 94-101
• 143 Sanchez-Nieto JM, Torres A, Garcia-Cordoba F , et al. Impact of invasive and noninvasive quantitative culture sampling on outcome of ventilator-associated pneumonia: a pilot study. Am J Respir Crit Care Med 1998; 157 (2) 371-376
• 144 Ferrer M, Liapikou A, Valencia M , et al. Validation of the American Thoracic Society-Infectious Diseases Society of America guidelines for hospital-acquired pneumonia in the intensive care unit. Clin Infect Dis 2010; 50 (7) 945-952
• 145 Kollef MH, Morrow LE, Niederman MS , et al. Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia. Chest 2006; 129 (5) 1210-1218
• 146 Damas P, Garweg C, Monchi M , et al. Combination therapy versus monotherapy: a randomised pilot study on the evolution of inflammatory parameters after ventilator associated pneumonia [ISRCTN31976779]. Crit Care 2006; 10 (2) R52
• 147 Aarts MA, Hancock JN, Heyland D, McLeod RS, Marshall JC. Empiric antibiotic therapy for suspected ventilator-associated pneumonia: a systematic review and meta-analysis of randomized trials. Crit Care Med 2008; 36 (1) 108-117
• 148 Heyland DK, Dodek P, Muscedere J, Day A, Cook D ; Canadian Critical Care Trials Group. Randomized trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia. Crit Care Med 2008; 36 (3) 737-744
• 149 Magnotti LJ, Schroeppel TJ, Clement LP , et al. Efficacy of monotherapy in the treatment of Pseudomonas ventilator-associated pneumonia in patients with trauma. J Trauma 2009; 66 (4) 1052-1058 , discussion 1058–1059
• 150 Walkey AJ, O'Donnell MR, Wiener RS. Linezolid vs glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a meta-analysis of randomized controlled trials. Chest 2011; 139 (5) 1148-1155
• 151 Kalil AC, Klompas M, Haynatzki G, Rupp ME. Treatment of hospital-acquired pneumonia with linezolid or vancomycin: a systematic review and meta-analysis. BMJ Open 2013; 3 (10) e003912
• 152 Wunderink RG, Niederman MS, Kollef MH , et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis 2012; 54 (5) 621-629
• 153 Haque NZ, Zuniga LC, Peyrani P , et al; Improving Medicine through Pathway Assessment of Critical Therapy of Hospital-Acquired Pneumonia (IMPACT-HAP) Investigators. Relationship of vancomycin minimum inhibitory concentration to mortality in patients with methicillin-resistant Staphylococcus aureus hospital-acquired, ventilator-associated, or health-care-associated pneumonia. Chest 2010; 138 (6) 1356-1362
• 154 Hidayat LK, Hsu DI, Quist R, Shriner KA, Wong-Beringer A. High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. Arch Intern Med 2006; 166 (19) 2138-2144
• 155 Lu Q, Luo R, Bodin L , et al; Nebulized Antibiotics Study Group. Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology 2012; 117 (6) 1335-1347
• 156 Lu Q, Yang J, Liu Z, Gutierrez C, Aymard G, Rouby JJ ; Nebulized Antibiotics Study Group. Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med 2011; 184 (1) 106-115
• 157 Radhakrishnan M, Jaganath A, Rao GS, Kumari HB. Nebulized imipenem to control nosocomial pneumonia caused by Pseudomonas aeruginosa. J Crit Care 2008; 23 (1) 148-150
• 158 Papazian L, Roch A, Charles PE , et al; STATIN-VAP Study Group. Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial. JAMA 2013; 310 (16) 1692-1700