Ventilator-associated pneumonia (VAP) is a leading cause of morbidity and mortality in the intensive care unit. Prevention of VAP is possible through the use of several evidence-based strategies intended to minimize intubation, the duration of mechanical ventilation, and the risk of aspiration of oropharyngeal pathogens. Current data favor the quantitative analysis of lower respiratory tract cultures for the diagnosis of VAP, accompanied by the initiation of broad-spectrum empiric antimicrobial therapy based on patient risk factors for infection with multi-drug-resistant pathogens and data from unit-specific antibiograms. Eventual choice of antibiotic and duration of therapy are selected based on culture results and patient stability, with an emphasis on minimization of unnecessary antibiotic use.
KollefM.H., ShorrA., TabakY.P.Epidemiology and outcomes of health-care-associated pneumonia.Chest2005; 128: 3854–62.
3.
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 Med2005; 171: 388–416.
4.
VincentJ.L., BihariD.J., SuterP.M.The prevalence of nosocomial infection in intensive care units in Europe: Results of the European Prevalence of Infection in Intensive Care (EPIC) study.JAMA1995; 274: 639–44.
5.
RelloJ., OllendorfD.A., OsterG.Epidemiology and outcomes of ventilator-associated pneumonia in a large U.S. database.Chest2002; 122: 2115–21.
6.
ChastreJ., FagonJ-YVentilator-associated pneumonia.Am J Respir Crit Care Med2002; 165: 867–903.
7.
GeorgeD.L.Epidemiology of nosocomial pneumonia in intensive care units patients.Clin Chest Med1995; 16: 29–44.
8.
MeduriG.U., MauldinG.L., WunderinkR.G.Causes of fever and pulmonary densities in patients with clinical manifestations of ventilator-associated pneumonia.Chest1994; 106: 221–35.
9.
FagonJ.Y., ChastreJ., WolffM.Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia. A randomized trial.Ann Intern Med2000; 132: 621–30.
10.
SafdarN., DezfulianC., CollardH.R., SaintS.Clinical and economic consequences of ventilator-associated pneumonia: A systematic review.Crit Care Med2005; 33: 2184–93.
11.
National Nosocomial Infections Surveillance (NNIS).Data summary from January 1992–April 2000, issued June 2000.Am J Infect Control2000; 28: 429–48.
12.
CookD.J., WalterS.D., CookR.J.Incidence and risk factors for ventilator-associated pneumonia in critically ill patients.Ann Intern Med1998; 129: 433–40.
13.
CelisR., TorresA., GatellJ.M.Nosocomial pneumonia: A multivariate analysis of risk and prognosis.Chest1988; 93: 318–24.
14.
TorresA., AznarR., GatellJ.M.Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients.Am Rev Respir Dis1990; 142: 523–8.
15.
BrochardL., ManceboJ., WysockiM.Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease.N Engl J Med1995; 333: 817–22.
16.
AntonelliM., ContiG., RoccoM.A comparison of noninvasive positive pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure.N Engl J Med1998; 339: 429–35.
17.
HilbertG., GrusonD., VargasF.Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure.N Engl J Med2001; 344: 817–22.
18.
ChastreJ., TrouilletJ.L., VuagnatA.Nosocomial pneumonia in patients with acute respiratory distress syndrome.Am J Respir Crit Care Med1998; 157: 1165–72.
19.
DelclauxC., RoupieE., BlotF.Lower respiratory tract colonization and infection during severe acute respiratory distress syndrome: Incidence and diagnosis.Am J Respir Crit Care Med1997; 156: 1092–8.
20.
MarkowiczP., WolffM., DjedainiK.Multicenter prospective study of ventilator-associated pneumonia during acute respiratory distress syndrome. Incidence, prognosis, and risk factors. ARDS Study Group.Am J Respir Crit Care Med2000; 161: 1942–8.
21.
BarieP.S.Importance, morbidity, and mortality of pneumonia in the surgical intensive care unit.Am J Surg2000; 197: S2–7.
22.
HaleyR.W., HootonT.M., CulverD.H.Nosocomial infections in U.S. hospitals, 1975–1976: Estimated frequency by selected characteristics of patients.Am J Med1981; 70: 947–59.
23.
PenningtonJ.E.Nosocomial respiratory infection. In: Man-dellG.L., DouglasR.G.Jr., BennetJ.E., eds. Principles and Practice of Infectious Diseases.St. Louis, MO: Churchill Livingstone, 1990, pp 2199–205.
24.
Centers for Disease Control and Prevention.Monitoring hospital acquired infections to promote patient safety: United States, 1990–1999.Morbid Mortal Wkly Rep2000; 49: 149–53.
25.
KollefM.H., MorrowL.E., NiedermanM.S.Clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia.Chest2006; 129: 1210–8.
26.
CravenD.E., KunchesL.M., KilinskyV.Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation.Am Rev Respir Dis1986; 133: 792–6.
27.
HeylandD.K., CookD.J., GriffithL.The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient.Am J Respir Crit Care Med1999; 159: 1249–56.
28.
KollefM.H., WardS., ShermanG.Inadequate treatment of nosocomial infections is associated with certain empiric antibiotic choices.Crit Care Med2000; 28: 3456–64.
29.
HugonnetS., EggimanP., BorstF.Impact of ventilator-associated pneumonia on resource utilization and patient outcome.Infect Control Hosp Epidemiol2004; 25: 1090–6.
30.
JohansonW.G., PierceA.K., SanfordJ.P.Changing pharyngeal bacterial flora of hospitalized patients: Emergence of gram negative bacilli.N Engl J Med1969; 281: 1137–40.
31.
JohansonW.G., PierceA.K., SanfordJ.P.Nosocomial respiratory infections with gram-negative bacilli: The significance of colonization of the respiratory tract.Ann Intern Med1972; 77: 701–6.
32.
BontenM.J., BergmansD.C., AmbergenA.W.Risk factors for pneumonia, and colonization of respiratory tract and stomach in mechanically ventilated ICU patients.Am J Respir Crit Care Med1996; 154: 1339–46.
33.
TrouilletJ.L., ChastreJ., VuagnatA.Ventilator-associated pneumonia caused by potentially drug-resistant bacteria.Am J Respir Crit Care Med1998; 157: 531–9.
34.
NeuhauserM.M., WeinsteinR.A., RydmanR.Antibiotic resistance among gram-negative bacilli in U.S. intensive care units: Implications for fluoroquinolone use.JAMA2003; 289: 885–8.
35.
Garnacho-MonteroJ., Ortiz-LeybaC., Jimenez-JimenezF.J.Treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia (VAP) with intravenous colistin: A comparison with imipenem-susceptible VAP.Clin Infect Dis2003; 36: 1111–8.
36.
RichardsM.J., EdwardsJ.R., CulverD.H.Nosocomial infections in medical intensive care units in the United States: National Nosocomial Infections Surveillance System.Crit Care Med1999; 27: 887–92.
FridkinS.K.Increasing prevalence of antimicrobial resistance in intensive care units.Crit Care Med2001; 29: N64–8.
39.
ScheldW.M.Maintaining fluoroquinolone class efficacy: Review of influencing factors.Emerg Infect Dis2003; 9: 1–9.
40.
National Nosocomial Infections Surveillance (NNIS) System Report.Data summary from January 1992 through June 2003, issued August 2003.Am J Infect Control2003; 31: 481–98.
41.
MarikP.E., CareauP.The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: A prospective study.Chest1999; 115: 178–83.
42.
El-EbiaryM., TorresA., FabregasN.Significance of the isolation of Candida species from respiratory samples in critically ill, non-neutropenic patients.Am J Respir Crit Care Med1997; 156: 583–90.
LentinoJ.R., RosenkranzM.A., MichaelsJ.A.A retrospective review of airborne disease secondary to road construction and contaminated air conditioners.Am J Epidemiol1982; 116: 430–7.
45.
LooV.G., BertrandC., DixonC.Control of construction-associated nosocomial aspergillosis in an antiquated hematology unit.Infect Control Hosp Epidemiol1996; 17: 360–4.
46.
GirouE., LoyeauS., LegrandP.Efficacy of hand rubbing with alcohol based solution versus standard hand washing with antiseptic soap: Randomized clinical trial.Br Med J2002; 325: 362–6.
47.
PittetD., HugonnetS., HarbarthS.Effectiveness of a hospital-wide programme to improve compliance with hand hygiene.Lancet2000; 356: 1307–12.
48.
GirouE., Brun-BuissonC., TailleS.Secular trends in nosocomial infections and mortality associated with noninvasive ventilation in patients with exacerbations of COPD and pulmonary edema.JAMA2003; 290: 2985–91.
49.
KressJ., PohlmanA., O'ConnorM., HallJ.Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation.N Engl J Med2000; 342: 1471–7.
50.
MarelichG.P., MurinS., BattistellaF.Protocol weaning of mechanical ventilation in medical and surgical patients by respiratory care practitioners and nurses: Effect on weaning time and incidence of ventilator-associated pneumonia.Chest2000; 118: 459–67.
51.
HolzapfelL., ChevretS., MadinierG.Influence of long-term oro- or nasotracheal intubation on nosocomial maxillary sinusitis and pneumonia: Results of a prospective, randomized trial.Crit Care Med1993; 21: 1132–8.
52.
RoubyJ.J., LaurentP., GosnachM.Risk factors and clinical relevance of nosocomial maxillary sinusitis in the critically ill.Am J Respir Crit Care Med1994; 150: 776–83.
53.
CookD., De JongheB., BrochardL., Brun-BuissonC.Influence of airway management on ventilator-associated pneumonia: Evidence from randomized trials.JAMA1998; 279: 781–7.
54.
VallesJ., ArtigasA., RelloJ.Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia.Ann Intern Med1995; 122: 179–86.
55.
CookD., De JongheB., Brochard-FerrerM.Utility of selective digestive decontamination in mechanically ventilated patients.Ann Intern Med1994; 120: 389–95.
56.
MahulP., AuboyerC., JospeR.Prevention of nosocomial pneumonia in intubated patients: Respective role of mechanical subglottic secretions drainage and stress ulcer prophylaxis.Intensive Care Med1992; 18: 20–5.
57.
PneumatikosI., KoulourasV., NathanailC.Selective decontamination of subglottic area in mechanically ventilated patients with multiple trauma.Intensive Care Med2002; 28: 432–7.
58.
KollefM.H., SkubasN.J., SundtT.M.A randomized clinical trial of continuous aspiration of subglottic secretions in cardiac surgery patients.Chest1999; 116: 1339–46.
59.
SmuldersK., van der HoevenH., Weers-PothoffI.A randomized clinical trial of intermittent subglottic secretion drainage in patients receiving mechanical ventilation.Chest2002; 121: 858–62.
60.
TorresA., Serra-BatllesJ., RosE.Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: The effect of body position.Ann Intern Med1992; 116: 540–3.
61.
Orozco-LeviM., TorresA., FerrerM.Semirecumbent position protects from pulmonary aspiration but not completely from gastroesophageal reflux in mechanically ventilated patients.Am J Respir Crit Care Med1995; 152: 1387–90.
62.
DrakulovicM.B., TorresA., BauerT.T.Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: A randomised trial.Lancet1999; 354: 1851–8.
63.
HeylandD.K., DroverJ., MacDonaldS.Effect of post-pyloric feeding on gastroesophageal regurgitation and pulmonary microaspiration: Results of a randomized controlled trial.Crit Care Med2001; 29: 1495–501.
64.
KearnsP.J., ChinD., MuellerL.The incidence of ventilator-associated pneumonia and success in nutrient delivery with gastric versus small intestinal feeding: A randomized clinical trial.Crit Care Med2000; 28: 1742–6.
65.
MontejoJ.C., GrauT., AcostaJ.Multicenter, prospective, randomized, single-blind study comparing the efficacy and gastrointestinal complications of early jejunal feeding with early gastric feeding in critically ill patients.Crit Care Med2002; 30: 796–800.
66.
HeylandD.K., DhaliwalR., DroverJ.W.Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients.J Parenter Enter Nutr2003; 27: 355–73.
67.
TablanO.C., AndersonL.J., BesserR., Healthcare Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. Guidelines for preventing healthcare-associated pneumonia, 2003: Recommendations of the CDC and the Healthcare Infection Control Practices Advisory Committee.Morbid Mortal Wkly Recomm Rep2004; 53(RR-3): 1–36.
68.
BerneJ.D., NorwoodS.H., McAuleyC.E.Erythromycin reduces delayed gastric emptying in critically ill trauma patients: A randomized, controlled trial.J Trauma2002; 53: 422–5.
69.
IbrahimE.H., MehringerL., PrenticeD.Early versus late enteral feeding of mechanically ventilated patients: results of a clinical trial.J Parenter Enter Nutr2002; 26: 174–81.
70.
ShorrA.F., DuhM.S., KellyK.M., KollefM.H.Red blood cell transfusion and ventilator-associated pneumonia: A potential link?Crit Care Med2004; 32: 666–74.
71.
Abele-HornM., DauberA., BauernfeindA.Decrease in nosocomial pneumonia in ventilated patients by selective oropharyngeal decontamination (SOD).Intensive Care Med1997; 23: 187–95.
72.
PuginJ., AuckenthalerR., LewD.P., SuterP.M.Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia: A randomized, placebo-controlled, double-blind clinical trial.JAMA1991; 265: 2704–10.
73.
Rodriguez-RoldanJ.M., Altuna-CuestaA., LopezA.Prevention of nosocomial lung infection in ventilated patients: Use of an antimicrobial pharyngeal nonabsorbable paste.Crit Care Med1990; 18: 1239–42.
74.
KruegerW.A., LenhartF.P., NeeserG.Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients: A prospective, stratified, randomized, double-blind, placebo-controlled clinical trial.Am J Respir Crit Care Med2002; 166: 1029–37.
75.
de JongeE., SchultzM., SpanjaardL.Effects of selective decontamination of the digestive tract on mortality and acquisition of resistant bacteria in intensive care: A randomized controlled trial.Lancet2003; 362: 1011–6.
76.
de la CalM.A., CerdaE., Garcia-HierroP.Survival benefit in critically ill burned patients receiving selective decontamination of the digestive tract: A randomized, placebo-controlled, double-blind trial.Ann Surg2005; 241: 424–30.
77.
van NieuwenhovenC.A., BuskensE., van TielF.H., BontenM.J.Relationship between methodological trial quality and the effects of selective digestive decontamination on pneumonia and mortality in critically ill patients.JAMA2001; 286: 335–40.
78.
VerwaestC., VerhaegenJ., FerdinandeP.Randomized, controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multidisciplinary intensive care unit.Crit Care Med1997; 25: 63–71.
79.
MissetB., KitzisM.D., ConscienceG.Mechanisms of failure to decontaminate the gut with polymixin E, gentamycin and amphotericin B in patients in intensive care.Eur J Clin Microbiol Infect Dis1994; 13: 165–70.
80.
LingnauW., BergerJ., JavorskyF.Changing bacterial ecology during a five year period of selective intestinal decontamination.J Hosp Infect1998; 39: 195–206.
81.
DeRisoA.J., LadowskiJ.S., DillonT.A.Chlorhexidine gluconate 0.12% oral rinse reduces the incidence of total nosocomial respiratory infection and nonprophylactic systemic antibiotic use in patients undergoing heart surgery.Chest1996; 109: 1556–61.
82.
FourrierF., DuboisD., PronnierP.Effect of gingival and dental plaque antiseptic decontamination on nosocomial infections acquired in the intensive care unit: A double-blind placebo-controlled multicenter study.Crit Care Med2005; 33: 1728–35.
83.
ChlebickiM.P., SafdarN.Topical chlorhexidine for prevention of ventilator-associated pneumonia: A meta-analysis.Crit Care Med2007; 35: 595–602.
84.
BontenM.J., GaillardC.A., de LeeuwP.W., StobberinghE.E.Role of colonization of the upper intestinal tract in the pathogenesis of ventilator-associated pneumonia.Clin Infect Dis1997; 24: 309–19.
85.
Prod'homG., LeuenbergerP., KoerferJ.Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine or sucralfate as prophylaxis for stress ulcer: A randomized controlled trial.Ann Intern Med1994; 120: 653–62.
86.
CookD., GuyattG., MarshallJ.A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation.N Engl J Med1998; 338: 791–7.
87.
DriksM.R., CravenD.E., CelliB.R.Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers: The role of gastric colonization.N Engl J Med1987; 317: 1376–82.
88.
TrybaM.Risks of acute stress bleeding and nosocomial pneumonia in ventilated intensive care unit patients: Sucralfate versus antacids.Am J Med1987; 83: 117–24.
89.
BontenM.J., GaillardC.A., van der GeestS.The role of intragastric acidity and stress ulcer prophylaxis on colonization and infection in mechanically ventilated ICU patients: A stratified, randomized, double-blind study of sucralfate versus antacids.Am J Respir Crit Care Med1995; 152: 1825–34.
90.
BontenM.J.M., GaillardC.A., van TielF.H.The stomach is not a source for colonization of the upper respiratory tract and pneumonia in ICU patients.Chest1994; 105: 878–84.
91.
BragaM., VignaliA., RadaelliG.Association between perioperative blood transfusion and postoperative infection in patients having elective operations for gastrointestinal cancer.Eur J Surg1992; 158: 531–6.
92.
OttinoG., De PaulisR., PansiniS.Major sternal wound infection after open heart surgery: A multivariate analysis of risk factors in 2,579 consecutive procedures.Ann Thorac Surg1987; 44: 173–9.
93.
DellingerE.P., MillerS.D., WertzM.J.Risk of infection after open fracture of the arm or leg.Arch Surg1988; 123: 1320–7.
94.
ClaridgeJ.A., SawyerR.G., SchulmanA.M.Blood transfusions correlate with infections in trauma patients in a dose-dependent manner.Am Surg2002; 68: 566–72.
95.
TaylorR.W., ManganaroL., O'BrienJ.Impact of allogenic packed red blood cell transfusion on nosocomial infection rates in the critically ill patient.Crit Care Med2002; 30: 2249–54.
96.
EarleyA.S., GraciasV.H., HautE.Anemia management program reduces transfusion volumes, incidence of ventilator-associated pneumonia, and cost in trauma patients.J Trauma2006; 61: 1–7.
97.
CarletJ., Ben AliA., ChalfineA.Epidemiology and control of antibiotic resistance in the intensive care unit.Curr Opin Infect Dis2004; 17: 309–16.
98.
FridkinS.K., GaynesR.P.Antimicrobial resistance in intensive care units.Clin Chest Med1999; 20: 303–16.
99.
KollefM.H., VlasnikJ., SharplessL.Scheduled rotation of antibiotic classes: A strategy to decrease the incidence of ventilator-associated pneumonia due to antibiotic-resistant gram-negative bacteria.Am J Respir Crit Care Med1997; 156: 1040–8.
100.
GrusonD., HilbertG., VargasF.Strategy of antibiotic rotation: Long term effect on incidence and susceptibilities of gram-negative bacilli responsible for ventilator-associated pneumonia.Crit Care Med2003; 31: 1908–14.
101.
RaymondD.P., PelletierS.J., CrabtreeT.D.Impact of a rotating empiric antibiotic schedule on infectious mortality in an intensive care unit.Crit Care Med2001; 29: 1101–8.
102.
van LoonH.J., VriensM.R., FluitA.C.Antibiotic rotation and development of gram-negative antibiotic resistance.Am J Respir Crit Care Med2005; 171: 480–7.
103.
KollefM.H.Is antibiotic cycling the answer to preventing the mergence of bacterial resistance in the intensive care unit?Clin Infect Dis2006; 43: S82–8.
104.
ZazkJ.E., GarrisonT., TrovillionE.Effect of an education program aimed at reducing the occurrence of ventilator-associated pneumonia.Crit Care Med2002; 30: 2407–12.
105.
NiedermanM.S.Appropriate use of antimicrobial agents: Challenges and strategies for improvement.Crit Care Med2003; 31: 608–16.
106.
Alvarez-LermaF.Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit: ICU-Acquired Pneumonia Study Group.Intensive Care Med1996; 22: 387–94.
107.
FabregasN., EwigS., TorresA.Clinical diagnosis of ventilatory associated pneumonia revisitited: Comparative value using immediate post mortem lung biopsies.Thorax1999; 54: 867–73.
108.
FagonJ.Y., ChastreJ., HanceA.J.Evaluation of clinical judgment in the identification and treatment of nosocomial pneumonia in ventilated patients.Chest1993; 103: 547–55.
109.
BaughmanR.P.Diagnosis of ventilator-associated pneumonia.Curr Opin Crit Care2003; 95: 397–402.
110.
MabieM., WunderinkR.G.Use and limitations of clinical and radiologic diagnosis of pneumonia.Semin Respir Infect2003; 18: 72–9.
111.
FagonJ.Y., ChastreJ., DomartY.Nosocomial pneumonia in patients receiving continuous mechanical ventilation. Prospective analysis of 52 episodes with use of a protected specimen brush and quantitative culture techniques.Am Rev Respir Dis1989; 139: 877–84.
112.
Rodriguez de CastroF., Sole-ViolanJ., Aranda LeonA.Do quantitative cultures of protected brush specimens modify the initial empirical therapy in ventilated patients with suspected pneumonia?Eur Respir J1996; 9: 37–41.
113.
PuginJ., AuckenthalerR., MiliN.Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid.Am Rev Respir Dis1991; 143: 1121–9.
114.
SinghN., RogersP., AtwoodC.W.Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit.Am J Respir Crit Care Med2000; 162: 505–11.
115.
FartoukhM., MaitreB., HonoreS.Diagnosing pneumonia during mechanical ventilation: The clinical pulmonary infection score revisited.Am J Respir Crit Care Med2003; 168: 173–9.
116.
LuytC.E., ChastreJ., FagonJ.Value of the clinical pulmonary infection score for the identification and management of ventilator-associated pneumonia.Intensive Care Med2004; 30: 844–52.
117.
VeinsteinA., Brun-BuissonC., DerrodeN.Validation of an algorithm based on direct examination of specimens in suspected ventilator-associated pneumonia.Intensive Care Med2006; 32: 676–83.
118.
Centers for Disease Control and Prevention.National Nosocomial Infections Surveillance System (NNIS). Available at http://www.cdc.gov/ncidod/dhqp/nnis.html; Accessed March 10, 2007.
119.
MillerP.R., JohnsonJ.C.III, KarchmerT.National nosocomial infection surveillance system: From benchmark to bedside in trauma patients.J Trauma2006; 60: 98–103.
120.
BlotF.B., RaynardB., ChachatyE.Value of gram stain examination of lower respiratory tract secretions for early diagnosis of nosocomial pneumonia.Am J Respir Crit Care Med2000; 162: 1731–7.
121.
TorresA., MustafaE.Bronchoscopic BAL in the diagnosis of ventilator-associated pneumonia.Chest2000; 117: 198–202.
122.
NiedermanM.S.Gram-negative colonization of the respiratory tract: Pathogenesis and clinical consequences.Semin Respir Infect1990; 5: 173–84.
123.
VidaurL., GualisB., RodriquezA.Clinical resolution in patients with suspicion of VAP: A cohort study comparing patients with and without ARDS.Crit Care Med2005; 33: 1248–53.
124.
SouweineB., VeberB., BedosJ.P.Diagnostic accuracy of protected specimen brush and bronchoalveolar lavage in nosocomial pneumonia: Impact of previous antimicrobial treatment.Crit Care Med1998; 26: 236–44.
125.
ElatrousS., BoukefR., BesbesL.O.Diagnosis of ventilator-associated pneumonia: Agreement between quantitative cultures of endotracheal aspiration and plugged telescoping catheter.Intensive Care Med2004; 30: 853–8.
126.
WuC.L., YangD.I., WangN.Y.Quantitative culture of endotracheal aspirates in the diagnosis of ventilator associated pneumonia in patients with treatment failure.Chest2002; 122: 662–8.
127.
Brun-BuissonC., FartoukhM., LechaptE.Contribution of blinded, protected quantitative specimens to the diagnostic and therapeutic management of ventilator-associated pneumonia.Chest2005; 128: 533–44.
128.
Sanchez-NietoJ.M., TorresA., Garcia-CordobaF.Impact of invasive and noninvasive quantitative culture sampling on outcome of ventilator-associated pneumonia.Am J Respir Crit Care Med1998; 157: 371–6.
129.
CampbellG.D.Blinded invasive diagnostic procedures in ventilator-associated pneumonia.Chest2000; 117: 207S–11S.
130.
RuizM., TorresA., EwigS.Noninvasive versus invasive microbial investigation in ventilator-associated pneumonia: Evaluation of outcome.Am J Respir Crit Care Med2000; 162: 119–25.
131.
ShorrA.F., ShernerJ.H., JacksonW.L., KollefM.H.Invasive approaches to the diagnosis of ventilator-associated pneumonia: A meta-analysis.Crit Care Med2005; 33: 46–53.
132.
The Canadian Critical Care Trials Group.A randomized trial of diagnostic techniques for ventilator-associated pneumonia.N Engl J Med2006; 355: 2619–30.
133.
BontenM.J., BergmansD.C., StobberinghE.E.Implementation of bronchoscopic techniques in the diagnosis of ventilator-associated pneumonia to reduce antibiotic use.Am J Respir Crit Care Med1997; 156: 1820–4.
134.
CroceM.A., FabianT.C., SchurrM.J.Using broncho-alveolar lavage to distinguish nosocomial pneumonia from systemic inflammatory response syndrome: A prospective analysis.J Trauma1995; 39: 1134–9.
135.
KollefM.H., KollefK.E.Antibiotic utilization and outcomes for patients with clinically suspected VAP and negative quantitative BAL cultures results.Chest2005; 128: 2706–13.
136.
IreguiM., WardS., ShermanG.Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia.Chest2002; 122: 262–8.
137.
IbrahimE.H., WardS., ShermanG.Experience with a clinical guideline for the treatment of ventilator associated pneumonia.Crit Care Med2001; 29: 1109–15.
138.
GrusonD., HilbertG., VargasF.Rotation and restricted use of antibiotics in a medical intensive care unit: Impact on the incidence of ventilator-associated pneumonia caused by antibiotic resistant gram-negative bacteria.Am J Respir Crit Care Med2000; 162: 837–43.
139.
RelloJ., Sa-BorgesM., CorreaH.Variations in etiology of ventilator-associated pneumonia across four treatment Sites. Implications for antimicrobial prescribing practices.Am J Respir Crit Care Med1999; 160: 608–13.
140.
PaladinoJ.A.Pharmacoeconomic comparison of sequential IV/oral ciprofloxacin versus ceftazidime in the treatment of nosocomial pneumonia.Can J Hosp Pharm1995; 48: 276–83.
141.
BrownR.B., KruseJ.A., CountsG.W., Endotracheal Tobramycin Study Group. Double-blind study of endotracheal tobramycin in the treatment of gram-negative bacterial pneumonia.Antimicrob Agents Chemother1990; 34: 269–72.
142.
GuillemotD., CarbonC., BalkauB.Low dosage and long treatment duration of β-lactam: Risk factors for carriage of penicillin-resistant Streptococcus pneumoniae.JAMA1998; 279: 365–70.
RubinsteinE., CammarataS., OliphantT., WunderinkR., Linezolid Nosocomial Pneumonia Study Group. Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double blind, multicenter study.Clin Infect Dis2001; 32: 402–12.
145.
WunderinkR.G., CammarataS.K., OliphantT.H., KollefM.H.Linezolid versus vancomycin in the treatment of patients with nosocomial pneumonia: Continuation of a randomized, double-blind, multicenter study.Clin Ther2003; 25: 980–92.
146.
KollefM.H., RelloJ., CammarataS.Clinical cure and survival in Gram-positive ventilator-associated pneumonia: Retrospective analysis of two double-blind studies comparing linezolid with vancomycin.Intensive Care Med2004; 30: 388–94.
147.
MachadoA.R., ArnsC., FolladorW., GuerraA.Cost-effectiveness of linezolid versus vancomycin in mechanical ventilation-associated nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus.Braz J Infect Dis2005; 9: 191–200.
148.
GrauS., Alvarez-LermaF., del CastilloA.Cost-effectiveness analysis of the treatment of ventilator-associated pneumonia with linezolid or vancomycin in Spain.J Chemother2005; 17: 203–11.
149.
NsierS., PompeoC., SoubrierS.First-generation fluoroquinolone use and subsequent emergence of multiple drug-resistant bacteria in the intensive care unit.Crit Care Med2005; 33: 283–9.
150.
TrouilletJ., VuagnatA., CombesA.Pseudomonas aeruginosa ventilator-associated pneumonia: Comparison of episodes due to piperacillin-resistant versus piperacillin-susceptible organisms.Clin Infect Dis2002; 34: 1047–54.
151.
DanielF., SahmD., CritchleyI.Evaluation of current activities of fluoroquinolones against gram-negative bacilli using centralized in vitro testing and electronic surveillance.Antimicrob Agents Chemother2001; 45: 267–74.
152.
HilfM., YuV.L., SharpJ.Antibiotic therapy for Pseudomonas aeruginosa bacteremia: Outcome correlations in a prospective study of 200 patients.Am J Med1989; 87: 540–6.
153.
FowlerR.A., FlavinK.E., BarrJ.Variability in antibiotic prescribing patterns and outcomes in patients with clinically suspected ventilator-associated pneumonia.Chest2003; 123: 835–44.
154.
PaulM., Benuri-SilibigerI., Soares-WeiserK., LeiboviciL.β-Lactam monotherapy versus β-lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: Systematic review and meta-analysis of randomized trials.Br Med J2004; 328: 668–81.
155.
LunaC.M., BlanzacoD., NiedermanM.S.Resolution of ventilator-associated pneumonia: Prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome.Crit Care Med2003; 31: 676–82.
156.
DennesenP.J.W., van der VenJ.A., AlphonsG.H.Resolution of infectious parameters after antimicrobial therapy in patients with ventilator-associated pneumonia.Am J Respir Crit Care Med2001; 163: 1371–5.
157.
ChastreJ., WolffM., FagonJ.Y.Comparison of 8 vs. 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: A randomized trial.JAMA2002; 290: 2588–98.
158.
RelloJ., GallegoM., MariscalD.The value of routine microbial investigation in ventilator-associated pneumonia.Am J Respir Crit Care Med1997; 156: 196–200.
159.
EvansR.S., PestotnikS.L., ClassenD.C.A computer-assisted management program for antibiotics and other anti-infective agents.N Engl J Med1998; 338: 232–8.
160.
MicekS.T., WardS., FraserV., KollefM.A randomized controlled trial of an antibiotic discontinuation policy for clinically suspected ventilator-associated pneumonia.Chest2004; 125: 1791–9.
