[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 54.197.171.35. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Download PDF
Figure 1.
Potential sources of bacteria causing ventilator-associated pneumonia. Bacteria residing in the oropharynx and gastrointestinal tract can contaminate the subglottic secretion pool, as demonstrated. Subglottic secretions above the endotracheal tube cuff are aspirated into the trachea and disseminated into the distal airways and lung parenchyma by the force of the ventilator (inset).

Potential sources of bacteria causing ventilator-associated pneumonia. Bacteria residing in the oropharynx and gastrointestinal tract can contaminate the subglottic secretion pool, as demonstrated. Subglottic secretions above the endotracheal tube cuff are aspirated into the trachea and disseminated into the distal airways and lung parenchyma by the force of the ventilator (inset).

Figure 2.
Recommended empirical antibiotic therapy for ventilator-associated pneumonia. Recommendations are adapted from the American Thoracic Society consensus statement of 1995. Risk factors consist of previous use of antibiotic drugs, use of corticosteroids, clinical shock, immunosuppression, and neutropenia. Asterisk indicates β-lactam±β-lactamase inhibitors, imipenem, meropenem, ceftazidime, cefoperazone sodium, cefepime, and aztreonam (avoid a combination of aztreonam and an aminoglycoside if gram-positive cocci are suspected); dagger, use only fluoroquinolones with reliable antipseudomonal activity. See the "Antibiotic Selection" subsection for details.

Recommended empirical antibiotic therapy for ventilator-associated pneumonia. Recommendations are adapted from the American Thoracic Society consensus statement of 1995.85 Risk factors consist of previous use of antibiotic drugs, use of corticosteroids, clinical shock, immunosuppression, and neutropenia. Asterisk indicates β-lactam±β-lactamase inhibitors, imipenem, meropenem, ceftazidime, cefoperazone sodium, cefepime, and aztreonam (avoid a combination of aztreonam and an aminoglycoside if gram-positive cocci are suspected); dagger, use only fluoroquinolones with reliable antipseudomonal activity. See the "Antibiotic Selection" subsection for details.

Table 1. 
Ventilator-Associated Pneumonia Mortality in Relation to Appropriateness of Antibiotic Therapy*
Ventilator-Associated Pneumonia Mortality in Relation to Appropriateness of Antibiotic Therapy*
Table 2. 
Bacteriologic Isolates of Proven Ventilator-Associated Pneumonia From Selected Series*
Bacteriologic Isolates of Proven Ventilator-Associated Pneumonia From Selected Series*
Table 3. 
Summary of Evidence for Efficacy of Interventions for the Prevention of Ventilator-Associated Pneumonia*
Summary of Evidence for Efficacy of Interventions for the Prevention of Ventilator-Associated Pneumonia*
1.
Vincent  JLBihari  DJSuter  PM  et al.  The prevalence of nosocomial infection in intensive care units in Europe: results of the European Prevalence of Infection in Intensive Care (EPIC) Study: EPIC International Advisory Committee. JAMA. 1995;274639- 644Article
2.
Baker  AMMeredith  JWHaponik  EF Pneumonia in intubated trauma patients: microbiology and outcomes. Am J Respir Crit Care Med. 1996;153343- 349Article
3.
Papazian  LBregeon  FThirion  X  et al.  Effect of ventilator-associated pneumonia on mortality and morbidity. Am J Respir Crit Care Med. 1996;15491- 97Article
4.
Fagon  JYChastre  JHance  AJMontravers  PNovara  AGibert  C Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay. Am J Med. 1993;94281- 288Article
5.
Timsit  JFChevret  SValcke  J  et al.  Mortality of nosocomial pneumonia in ventilated patients: influence of diagnostic tools. Am J Respir Crit Care Med. 1996;154116- 123Article
6.
Craven  DEKunches  LMKilinsky  VLichtenberg  DAMake  BJMcCabe  WR Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation. Am Rev Respir Dis. 1986;133792- 796
7.
Kollef  MH Ventilator-associated pneumonia: a multivariate analysis. JAMA. 1993;2701965- 1970Article
8.
Torres  AAznar  RGatell  JM  et al.  Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis. 1990;142523- 528Article
9.
Fagon  JYChastre  JDomart  Y  et al.  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 Dis. 1989;139877- 884Article
10.
Fagon  JYChastre  JVuagnat  ATrouillet  JLNovara  AGibert  C Nosocomial pneumonia and mortality among patients in intensive care units. JAMA. 1996;275866- 869Article
11.
Cook  DGuyatt  GLaupacis  ASackett  DGoldberg  R Clinical recommendations using levels of evidence for antithrombotic agents. Chest. 1995;108(suppl 4)S227- S230Article
12.
Rogers  D The changing patterns of life-threatening microbial disease. N Engl J Med. 1959;261677- 683Article
13.
Kneeland  YPrice  K Antibiotics and terminal pneumonia: a postmortem microbiologic study. Am J Med. 1960;29967- 979Article
14.
Kollef  MHVon Harz  BPrentice  D  et al.  Patient transport from intensive care increases the risk of developing ventilator-associated pneumonia. Chest. 1997;112765- 773Article
15.
Rello  JSonora  RJubert  PArtigas  ARue  MValles  J Pneumonia in intubated patients: role of respiratory airway care. Am J Respir Crit Care Med. 1996;154111- 115Article
16.
Cook  DJWalter  SDCook  RJ  et al.  Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med. 1998;129433- 440Article
17.
Joshi  NLocalio  ARHamory  BH A predictive risk index for nosocomial pneumonia in the intensive care unit. Am J Med. 1992;93135- 142Article
18.
Rello  JMirelis  BAlonso  CPrats  G Lack of usefulness of blood cultures to diagnose ventilator-associated pneumonia. Eur Respir J. 1991;41020
19.
Chendrasekhar  A Are routine blood cultures effective in the evaluation of patients clinically diagnosed to have nosocomial pneumonia? Am Surg. 1996;62373- 376
20.
Pham  LHBrun-Buisson  CLegrand  P  et al.  Diagnosis of nosocomial pneumonia in mechanically ventilated patients: comparison of a plugged telescoping catheter with the protected specimen brush. Am Rev Respir Dis. 1991;1431055- 1061Article
21.
Fagon  JYChastre  JHance  AJ  et al.  Detection of nosocomial lung infection in ventilated patients: use of a protected specimen brush and quantitative culture techniques in 147 patients. Am Rev Respir Dis. 1988;138110- 116Article
22.
Torres  Ael-Ebiary  MPadro  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;149324- 331Article
23.
Andrews  CPCoalson  JJSmith  JDJohanson  WG  Jr Diagnosis of nosocomial bacterial pneumonia in acute, diffuse lung injury. Chest. 1981;80254- 258Article
24.
Johanson  WPierce  ASanford  JThomas  G Nosocomial respiratory infections with gram-negative bacilli: the significance of colonization of the respiratory tract. Ann Intern Med. 1972;77701- 706Article
25.
Johanson  WPierce  ASanford  J Changing oropharyngeal bacterial flora of hospitalized patients. N Engl J Med. 1969;2811137- 1140Article
26.
Petring  OAdelhoj  BJensen  BPedersen  NLomholt  N Prevention of silent aspiration due to leaks around cuffs of endotracheal tubes. Anesth Analg. 1986;65777- 780Article
27.
Spray  SZuidema  GCameron  J Aspiration pneumonia. Am J Surg. 1976;131701- 703Article
28.
Feldman  CKassel  MCantrell  J  et al.  The presence and sequence of endotracheal tube colonization in patients undergoing mechanical ventilation. Eur Respir J. 1999;13546- 551Article
29.
Inglis  TMillar  MJones  JJones  JRobinson  D Tracheal tube biofilm as a source of bacterial colonization of the lung. J Clin Microbiol. 1989;272014- 2018
30.
Jourdain  BNovara  AJoly-Guillou  ML  et al.  Role of quantitative cultures of endotracheal aspirates in the diagnosis of nosocomial pneumonia. Am J Respir Crit Care Med. 1995;152241- 246Article
31.
Marquette  CHGeorges  HWallet  F  et al.  Diagnostic efficiency of endotracheal aspirates with quantitative bacterial cultures in intubated patients with suspected pneumonia: comparison with the protected specimen brush. Am Rev Respir Dis. 1993;148138- 144Article
32.
el-Ebiary  MTorres  AGonzalez  J  et al.  Quantitative cultures of endotracheal aspirates for the diagnosis of ventilator-associated pneumonia. Am Rev Respir Dis. 1993;1481552- 1557Article
33.
Rouby  JDeLassale  EPoete  P  et al.  Nosocomial bronchopneumonia in the critically ill: histologic and bacteriologic aspects. Am Rev Respir Dis. 1992;1461059- 1066Article
34.
Papazion  LThomas  PGarbe  L  et al.  Bronchoscopic or blind sampling techniques for the diagnosis of ventilator-associated pneumonia. Am J Respir Crit Care Med. 1995;1521982- 1991Article
35.
Johanson  WG  JrSeidenfeld  JJGomez  Pde los Santos  RCoalson  JJ Bacteriologic diagnosis of nosocomial pneumonia following prolonged mechanical ventilation. Am Rev Respir Dis. 1988;137259- 264Article
36.
Chastre  JViau  FBrun  P  et al.  Prospective evaluation of the protected specimen brush for the diagnosis of pulmonary infections in ventilated patients. Am Rev Respir Dis. 1984;130924- 929
37.
Chastre  JFagon  JYBornet-Lecso  M  et al.  Evaluation of bronchoscopic techniques for the diagnosis of nosocomial pneumonia. Am J Respir Crit Care Med. 1995;152231- 240Article
38.
Kirtland  SHCorley  DEWinterbauer  RH  et al.  The diagnosis of ventilator-associated pneumonia: a comparison of histologic, microbiologic, and clinical criteria. Chest. 1997;112445- 457Article
39.
Jourdain  BJoly-Guillou  MLDombret  MC  et al.  Usefulness of quantitative cultures of BAL fluid for diagnosing nosocomial pneumonia in ventilated patients. Chest. 1997;111411- 418Article
40.
Souweine  BVeber  BBedos  JP  et al.  Diagnostic accuracy of protected specimen brush and bronchoalveolar lavage in nosocomial pneumonia: impact of previous antimicrobial treatments. Crit Care Med. 1998;26236- 244Article
41.
Meduri  GUBeals  DHMaijub  AGBaselski  V Protected bronchoalveolar lavage: a new bronchoscopic technique to retrieve uncontaminated distal airway secretions. Am Rev Respir Dis. 1991;143855- 864Article
42.
Cantral  DETape  TGReed  ECSpurzem  JRRennard  SIThompson  AB Quantitative culture of bronchoalveolar lavage fluid for the diagnosis of bacterial pneumonia. Am J Med. 1993;95601- 607Article
43.
Meduri  GUReddy  RCStanley  TEl-Zeky  F Pneumonia in acute respiratory distress syndrome: a prospective evaluation of bilateral bronchoscopic sampling. Am J Respir Crit Care Med. 1998;158870- 875Article
44.
Prekates  ANanas  SArgyropoulou  A  et al.  The diagnostic value of Gram stain of bronchoalveolar lavage samples. Scand J Infect Dis. 1998;3043- 47Article
45.
Gerbeaux  PLedoray  VBoussuges  AMolenat  FJean  PSainty  J Diagnosis of nosocomial pneumonia in mechanically ventilated patients: repeatability of the bronchoalveolar lavage. Am J Respir Crit Care Med. 1998;15776- 80Article
46.
Timsit  JFMisset  BFrancoual  SGoldstein  FWVaury  PCarlet  J Is protected specimen brush a reproducible method to diagnose ICU-acquired pneumonia? Chest. 1993;104104- 108Article
47.
Marquette  CHHerengt  FMathieu  DSaulnier  FCourcol  RRamon  P Diagnosis of pneumonia in mechanically ventilated patients: repeatability of the protected specimen brush. Am Rev Respir Dis. 1993;147211- 214Article
48.
Sole-Violan  JRodriguez de Castro  FRey  AMartin-Gonzalez  JCCabrera-Navarro  P Usefulness of microscopic examination of intracellular organisms in lavage fluid in ventilator-associated pneumonia. Chest. 1994;106889- 894
49.
Papazian  LMartin  CMeric  BDumon  JFGouin  F A reappraisal of blind bronchial sampling in the microbiologic diagnosis of nosocomial bronchopneumonia: a comparative study in ventilated patients. Chest. 1993;103236- 242Article
50.
Dotson  RGPingleton  SK The effect of antibiotic therapy on recovery of intracellular bacteria from bronchoalveolar lavage in suspected ventilator-associated nosocomial pneumonia. Chest. 1993;103541- 546Article
51.
Papazian  LAutillo-Touati  AThomas  P  et al.  Diagnosis of ventilator-associated pneumonia: an evaluation of direct examination and presence of intracellular organisms. Anesthesiology. 1997;87268- 276Article
52.
Marquette  CHHerengt  FSaulnier  F  et al.  Protected specimen brush in the assessment of ventilator-associated pneumonia: selection of a certain lung segment for bronchoscopic sampling is unnecessary. Chest. 1993;103243- 247Article
53.
Marik  PEBrown  WJ A comparison of bronchoscopic vs blind protected specimen brush sampling in patients with suspected ventilator-associated pneumonia. Chest. 1995;108203- 207Article
54.
Kollef  MHBock  KRRichards  RDHearns  ML The safety and diagnostic accuracy of minibronchoalveolar lavage in patients with suspected ventilator-associated pneumonia. Ann Intern Med. 1995;122743- 748Article
55.
Torres  AMartos  APuig 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;147952- 957Article
56.
Sterling  TRHo  EJBrehm  WTKirkpatrick  MB Diagnosis and treatment of ventilator-associated pneumonia—impact on survival: a decision analysis. Chest. 1996;1101025- 1034Article
57.
Kollef  MHWard  S The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia. Chest. 1998;113412- 420Article
58.
Luna  CMVujacich  PNiederman  MS  et al.  Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest. 1997;111676- 685Article
59.
Heyland  DCook  DMarshall  J  et al.  The clinical utility of invasive diagnostic techniques in the setting of ventilator-associated pneumonia. Chest. 1999;1151076- 1084Article
60.
Croce  MAFabian  TCShaw  B  et al.  Analysis of charges associated with diagnosis of nosocomial pneumonia: can routine bronchoscopy be justified? J Trauma. 1994;37721- 727Article
61.
Bonten  MJBergmans  DCStobberingh  EE  et al.  Implementation of bronchoscopic techniques in the diagnosis of ventilator-associated pneumonia to reduce antibiotic use. Am J Respir Crit Care Med. 1997;1561820- 1824Article
62.
Sanchez-Nieto  JMTorres  AGarcia-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;157371- 376Article
63.
Pugin  JAuckenthaler  RMili  NJanssens  JPLew  PDSuter  PM Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am Rev Respir Dis. 1991;1431121- 1129Article
64.
Rumbak  MJBass  RL Tracheal aspirate correlates with protected specimen brush in long-term ventilated patients who have clinical pneumonia. Chest. 1994;106531- 534Article
65.
Cunnion  KMWeber  DJBroadhead  WEHanson  LCPieper  CFRutala  WA Risk factors for nosocomial pneumonia: comparing adult critical-care populations. Am J Respir Crit Care Med. 1996;153158- 162Article
66.
Kappstein  ISchulgen  GBeyer  UGeiger  KSchumacher  MDaschner  FD Prolongation of hospital stay and extra costs due to ventilator-associated pneumonia in an intensive care unit. Eur J Clin Microbiol Infect Dis. 1992;11504- 508Article
67.
Craig  CConnelly  S Effect of intensive care unit nosocomial pneumonia on duration of stay and mortality. Am J Infect Control. 1984;12233- 238Article
68.
Heyland  DCook  DGriffith  LKeenan  SBrun-Buisson  C The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. Am J Respir Crit Care Med. 1999;1591249- 1256Article
69.
Alvarez-Lerma  F Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit: ICU-Acquired Pneumonia Study Group. Intensive Care Med. 1996;22387- 394Article
70.
Celis  RTorres  AGatell  JMAlmela  MRodriguez-Roisin  RAgusti-Vidal  A Nosocomial pneumonia: a multivariate analysis of risk and prognosis. Chest. 1988;93318- 324Article
71.
Rello  JGallego  MMariscal  DSonora  RValles  J The value of routine microbial investigation in ventilator-associated pneumonia. Am J Respir Crit Care Med. 1997;156196- 200Article
72.
Crouch Brewer  SWunderink  RGJones  CBLeeper  KV  Jr Ventilator-associated pneumonia due to Pseudomonas aeruginosa. Chest. 1996;1091019- 1029Article
73.
Kollef  MHSilver  PMurphy  DMTrovillion  E The effect of late-onset ventilator-associated pneumonia in determining patient mortality. Chest. 1995;1081655- 1662Article
74.
Jimenez  PTorres  ARodriguez-Roisin  R  et al.  Incidence and etiology of pneumonia acquired during mechanical ventilation. Crit Care Med. 1989;17882- 885Article
75.
Trouillet  JLChastre  JVuagnat  A  et al.  Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. Am J Respir Crit Care Med. 1998;157531- 539Article
76.
Dore  PRobert  RGrollier  G  et al.  Incidence of anaerobes in ventilator-associated pneumonia with use of a protected specimen brush. Am J Respir Crit Care Med. 1996;1531292- 1298Article
77.
Marik  PCareau  P The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: a prospective study. Chest. 1999;115178- 183Article
78.
Mastro  TDFields  BSBreiman  RFCampbell  JPlikaytis  BDSpika  JS Nosocomial Legionnaires' disease and use of medication nebulizers. J Infect Dis. 1991;163667- 671Article
79.
Muder  RRYu  VLWoo  AH Mode of transmission of Legionella pneumophila: a critical review. Arch Intern Med. 1986;1461607- 1612Article
80.
Roig  JAguilar  XRuiz  J  et al.  Comparative study of Legionella pneumophila and other nosocomial-acquired pneumonias. Chest. 1991;99344- 350Article
81.
Goetz  AMStout  JEJacobs  SL  et al.  Nosocomial Legionnaires' disease discovered in community hospitals. Am J Infect Control. 1998;268- 11Article
82.
Bregeon  FPapazian  LVisconti  AGregoire  RThirion  XGouin  F Relationship of microbiologic diagnostic criteria to morbidity and mortality in patients with ventilator-associated pneumonia. JAMA. 1997;277655- 662Article
83.
Talon  DMulin  BRouget  CBailly  PThouverez  MViel  JF Risks and routes for ventilator-associated pneumonia with Pseudomonas aeruginosa. Am J Respir Crit Care Med. 1998;157978- 984Article
84.
Rello  JAusina  VRicart  MCastella  JPrats  G Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. Chest. 1993;1041230- 1235Article
85.
Not Available, Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventative strategies: a consensus statement, American Thoracic Society, November 1995. Am J Respir Crit Care Med. 1996;1531711- 1725Article
86.
Jaccard  CTroillet  NHarbarth  S  et al.  Prospective randomized comparison of imipenem-cilastatin and piperacillin-tazobactam in nosocomial pneumonia or peritonitis. Antimicrob Agents Chemother. 1998;422966- 2972
87.
Cometta  ABaumgartner  JDLew  D  et al.  Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patients. Antimicrob Agents Chemother. 1994;381309- 1313Article
88.
Norrby  SRFinch  RGGlauser  M Monotherapy in serious hospital-acquired infections: a clinical trial. J Antimicrob Chemother. 1993;31927- 937Article
89.
Rubinstein  ELode  HGrassi  C Ceftazidime monotherapy vs. ceftriaxone/tobramycin for serious hospital-acquired gram-negative infections: Antibiotic Study Group. Clin Infect Dis. 1995;201217- 1228Article
90.
Fink  MPSnydman  DRNiederman  MS  et al.  Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. Antimicrob Agents Chemother. 1994;38547- 557Article
91.
Brun-Buisson  CSollet  JPSchweich  HBriere  SPetit  C Treatment of ventilator-associated pneumonia with piperacillin-tazobactam/amikacin versus ceftazidime/amikacin: a multicenter, randomized controlled trial: VAP Study Group. Clin Infect Dis. 1998;26346- 354Article
92.
Rello  JMariscal  DMarch  F  et al.  Recurrent Pseudomonas aeruginosa pneumonia in ventilated patients: relapse or reinfection? Am J Respir Crit Care Med. 1998;157912- 916Article
93.
Chow  JFine  MShlaes  D  et al.  Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy. Ann Intern Med. 1991;115585- 590Article
94.
Rello  JSa-Borges  MCorrea  HLeal  SRBaraibar  J Variations in etiology of ventilator-associated pneumonia across four treatment sites: implications for antimicrobial prescribing practices. Am J Respir Crit Care Med. 1999;160608- 613Article
95.
Rello  JTorres  ARicart  M  et al.  Ventilator-associated pneumonia by Staphylococcus aureus: comparison of methicillin-resistant and methicillin-sensitive episodes. Am J Respir Crit Care Med. 1994;1501545- 1549Article
96.
Archibald  LPhillips  LMonnet  DMcGowan  JTenover  FGaynes  R Antimicrobial resistance in isolates from inpatients and outpatients in the United States: increasing importance of the intensive care unit. Clin Infect Dis. 1997;24211- 215Article
97.
Cailleaux  VMulin  BCapellier  GJulliot  MThouverez  MTalon  D Epidemiological study of variations in β-lactam antibiotic susceptibility of Pseudomonas aeruginosa in two intensive care units. J Hosp Infect. 1997;37217- 224Article
98.
Lee  SFung  CLiu  P  et al.  Nosocomial infections with ceftazidime-resistant Pseudomonas aeruginosa: risk factors and outcome. Infect Control Hosp Epidemiol. 1999;20205- 207Article
99.
D'Agata  EVenkataraman  LDeGirolami  P  et al.  Colonization with broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units during a nonoutbreak period: prevalence, risk factors, and rate of infection. Crit Care Med. 1999;271090- 1095Article
100.
Rajal  JUrban  CHorn  D  et al.  Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella. JAMA. 1998;2801233- 1237Article
101.
Troillet  NSamore  MCarmeli  Y Imipenem-resistant Pseudomonas aeruginosa: risk fac tors and antibiotic susceptibility patterns. Clin Infect Dis. 1997;251094- 1098Article
102.
Kollef  MHVlasnik  JSharpless  LPasque  CMurphy  DFraser  V Scheduled change of antibiotic classes: a strategy to decrease the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med. 1997;1561040- 1048Article
103.
Boyce  JMPotter-Bynoe  GDziobek  LSolomon  SL Nosocomial pneumonia in Medicare patients: hospital costs and reimbursement patterns under the prospective payment system. Arch Intern Med. 1991;1511109- 1114Article
104.
Haley  RWWhite  JWCulver  DHHughes  JM The financial incentive for hospitals to prevent nosocomial infections under the prospective payment system: an empirical determination from a nationally representative sample. JAMA. 1987;2571611- 1614Article
105.
Boyce  JMWhite  RLSpruill  EYWall  M Cost-effective application of the Centers for Disease Control Guideline for Prevention of Nosocomial Pneumonia. Am J Infect Control. 1985;13228- 232Article
106.
Craven  DESteger  KA Hospital-acquired pneumonia: perspectives for the healthcare epidemiologist. Infect Control Hosp Epidemiol. 1997;18783- 795Article
107.
Gaynes  RPSolomon  S Improving hospital-acquired infection rates: the CDC experience. Jt Comm J Qual Improv. 1996;22457- 467
108.
Kelleghan  SISalemi  CPadilla  S  et al.  An effective continuous quality improvement approach to the prevention of ventilator-associated pneumonia. Am J Infect Control. 1993;21322- 330Article
109.
Joiner  GASalisbury  DBollin  GE Utilizing quality assurance as a tool for reducing the risk of nosocomial ventilator-associated pneumonia. Am J Med Qual. 1996;11100- 103Article
110.
Kollef  M The prevention of ventilator-associated pneumonia. N Engl J Med. 1999;340627- 634Article
111.
Bonten  MJGaillard  CAvan Tiel  FHSmeets  HGvan der Geest  SStobberingh  EE The stomach is not a source for colonization of the upper respiratory tract and pneumonia in ICU patients. Chest. 1994;105878- 884Article
112.
Bonten  MGaillard  CJohanson  W  et al.  Colonization in patients receiving and not receiving topical antibiotic prophylaxis. Am J Respir Crit Care Med. 1994;1501332- 1340Article
113.
Pingleton  SKHinthorn  DRLiu  C Enteral nutrition in patients receiving mechanical ventilation: multiple sources of tracheal colonization include the stomach. Am J Med. 1986;80827- 832Article
114.
Flynn  DMWeinstein  RANathan  CGaston  MAKabins  SA Patients' endogenous flora as the source of "nosocomial" Enterobacter in cardiac surgery. J Infect Dis. 1987;156363- 368Article
115.
Weber  DWilson  MRutala  WThomann  C Manual ventilation bags as a source for bacterial colonization of intubated patients. Am Rev Respir Dis. 1990;142892- 894Article
116.
Craven  DGoularte  TMake  B Contaminated condensate in mechanical ventilator circuits: a risk factor for nosocomial pneumonia? Am Rev Respir Dis. 1984;129625- 628
117.
Cross  ARoup  B Role of respiratory assistance devices in endemic nosocomial pneumonia. Am J Med. 1981;70681- 685Article
118.
Craven  DLichtenberg  DGoularte  TMake  BMcCabe  W Contaminated medication nebulizers in mechanical ventilator circuits: source of bacterial aerosols. Am J Med. 1984;77834- 838Article
119.
Doebbeling  BNStanley  GLSheetz  CT  et al.  Comparative efficacy of alternative hand-washing agents in reducing nosocomial infections in intensive care units. N Engl J Med. 1992;32788- 93Article
120.
Patterson  JEVecchio  JPantelick  EL  et al.  Association of contaminated gloves with transmission of Acinetobacter calcoaceticus var. anitratus in an intensive care unit. Am J Med. 1991;91479- 483Article
121.
Hartstein  AIRashad  ALLiebler  JM  et al.  Multiple intensive care unit outbreak of Acinetobacter calcoaceticus subspecies anitratus respiratory infection and colonization associated with contaminated, reusable ventilator circuits and resuscitation bags. Am J Med. 1988;85624- 631Article
122.
Mulin  BRouget  CClement  C  et al.  Association of private isolation rooms with ventilator-associated Acinetobacter baumanii pneumonia in a surgical intensive-care unit. Infect Control Hosp Epidemiol. 1997;18499- 503Article
123.
Johanson  WG  JrSeidenfeld  JJde los Santos  RCoalson  JJGomez  P Prevention of nosocomial pneumonia using topical and parenteral antimicrobial agents. Am Rev Respir Dis. 1988;137265- 272Article
124.
Sanchez Garcia  MCambronero Galache  JALopez Diaz  J  et al.  Effectiveness and cost of selective decontamination of the digestive tract in critically ill intubated patients: a randomized, double-blind, placebo-controlled, multicenter trial. Am J Respir Crit Care Med. 1998;158908- 916Article
125.
Pugin  JAuckenthaler  RLew  DPSuter  PM Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia: a randomized, placebo-controlled, double-blind clinical trial. JAMA. 1991;2652704- 2710Article
126.
Cockerill  FR  IIIMuller  SRAnhalt  JP  et al.  Prevention of infection in critically ill patients by selective decontamination of the digestive tract. Ann Intern Med. 1992;117545- 553Article
127.
Kollef  MH The role of selective digestive tract decontamination on mortality and respiratory tract infections: a meta-analysis. Chest. 1994;1051101- 1108Article
128.
Not Available, Meta-analysis of randomised controlled trials of selective decontamination of the digestive tract: Selective Decontamination of the Digestive Tract Trialists' Collaborative Group. BMJ. 1993;307525- 532Article
129.
Heyland  DKCook  DJJaeschke  RGriffith  LLee  HNGuyatt  GH Selective decontamination of the digestive tract: an overview. Chest. 1994;1051221- 1229Article
130.
Quinio  BAlbanese  JBues-Charbit  MViviand  XMartin  C Selective decontamination of the digestive tract in multiple trauma patients: a prospective double-blind, randomized, placebo-controlled study. Chest. 1996;109765- 772Article
131.
Verwaest  CVerhaegen  JFerdinande  P  et al.  Randomized, controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multidisciplinary intensive care unit. Crit Care Med. 1997;2563- 71Article
132.
Sun  XWagner  DPKnaus  WA Does selective decontamination of the digestive tract reduce mortality for severely ill patients? Crit Care Med. 1996;24753- 755Article
133.
Donowitz  LGPage  MCMileur  BLGuenthner  SH Alteration of normal gastric flora in critical care patients receiving antacid and cimetidine therapy. Infect Control. 1986;723- 26
134.
Daschner  FKappstein  IEngels  I  et al.  Stress ulcer prophylaxis and ventilation pneumonia: prevention by antibacterial cytoprotective agents? Infect Control Hosp Epidemiol. 1988;959- 65Article
135.
Garvey  BMMcCambley  JATuxen  DV Effects of gastric alkalization on bacterial colonization in critically ill patients. Crit Care Med. 1989;17211- 216Article
136.
Thomason  MHPayseur  ESHakenewerth  AM  et al.  Nosocomial pneumonia in ventilated trauma patients during stress ulcer prophylaxis with sucralfate, antacid, and ranitidine. J Trauma. 1996;41503- 508Article
137.
Prod'hom  GLeuenberger  PKoerfer  J  et al.  Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or sucrulfate as prophylaxis for stress ulcer: a randomized controlled trial. Ann Intern Med. 1994;120653- 662Article
138.
Driks  MRCraven  DECelli  BR  et al.  Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers: the role of gastric colonization. N Engl J Med. 1987;3171376- 1382Article
139.
Cook  DJLaine  LAGuyatt  GHRaffin  TA Nosocomial pneumonia and the role of gastric pH: a meta-analysis. Chest. 1991;1007- 13Article
140.
Cook  DJReeve  BKGuyatt  GH  et al.  Stress ulcer prophylaxis in critically ill patients: resolving discordant meta-analyses. JAMA. 1996;275308- 314Article
141.
Cook  DGuyatt  GMarshall  J  et al.  A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation: Canadian Critical Care Trials Group. N Engl J Med. 1998;338791- 797Article
142.
Bonten  MGaillard  CVan der Geest  S  et al.  The role of intragastric acidity and stress ulcer prophylaxis on colonization and infection in mechanically ventilated patients. Am J Respir Crit Care Med. 1995;1521825- 1834Article
143.
Garrouste-Orgeas  MChevret  SArlet  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;1561647- 1655Article
144.
de Latorre  FJPont  TFerrer  ARossello  JPalomar  MPlanas  M Pattern of tracheal colonization during mechanical ventilation. Am J Respir Crit Care Med. 1995;1521028- 1033Article
145.
Niederman  MSMantovani  RSchoch  PPapas  JFein  AM Patterns and routes of tracheobronchial colonization in mechanically ventilated patients: the role of nutritional status in colonization of the lower airway by Pseudomonas species. Chest. 1989;95155- 161Article
146.
Montecalvo  MASteger  KAFarber  HW  et al.  Nutritional outcome and pneumonia in critical care patients randomized to gastric versus jejunal tube feedings: The Critical Care Research Team. Crit Care Med. 1992;201377- 1387Article
147.
Heyland  DBradley  CMandell  LA Effect of acidified enteral feedings on gastric colonization in the critically ill patient. Crit Care Med. 1992;201388- 1394Article
148.
Bonten  MJGaillard  CAvan der Hulst  R  et al.  Intermittent enteral feeding: the influence on respiratory and digestive tract colonization in mechanically ventilated intensive-care-unit patients. Am J Respir Crit Care Med. 1996;154394- 399Article
149.
Cook  DDe Jonghe  BBrochard  LBrun-Buisson  C Influence of airway management on ventilator-associated pneumonia: evidence from randomized trials. JAMA. 1998;279781- 787Article
150.
Valles  JArtigas  ARello  J  et al.  Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. Ann Intern Med. 1995;122179- 186Article
151.
Mahul  PAuboyer  CJospe  R  et al.  Prevention of nosocomial pneumonia in intubated patients: respective role of mechanical subglottic secretions drainage and stress ulcer prophylaxis. Intensive Care Med. 1992;1820- 25Article
152.
Rouby  JLaurent  PGosnach  M  et al.  Risk factors and clinical relevance of nosocomial maxillary sinusitis in the critically ill. Am J Respir Crit Care Med. 1994;150776- 783Article
153.
Holzapfel  LChevret  SMadinier  G  et al.  Influence of long-term oro- or nasotracheal intubation on nosocomial maxillary sinusitis and pneumonia: results of a prospective, randomized, clinical trial. Crit Care Med. 1993;211132- 1138Article
154.
Holzapfel  LChastang  CDemingeon  GBohe  JPiralla  BCoupry  A A randomized study assessing the systematic search for maxillary sinusitis in nasotracheally mechanically ventilated patients: influence of nosocomial maxillary sinusitis on the occurrence of ventilator-associated pneumonia. Am J Respir Crit Care Med. 1999;159695- 701Article
155.
Torres  ASerra-Batlles  JRos  E  et al.  Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med. 1992;116540- 543Article
156.
Orozco-Levi  MTorres  AFerrer  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;1521387- 1390Article
157.
Nourdine  KCombes  PCarton  MJBeuret  PCannamela  ADucreux  JC Does noninvasive ventilation reduce the ICU nosocomial infection risk? a prospective clinical survey. Intensive Care Med. 1999;25567- 573Article
158.
Antonelli  MConti  GRocco  M  et al.  A comparison of noninvasive positive-pressure ventilation and conventional ventilation in patients with acute respiratory failure. N Engl J Med. 1998;339429- 435Article
159.
Nava  SAmbrosino  NClini  E  et al.  Noninvasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease: a randomized, controlled trial. Ann Intern Med. 1998;128721- 728Article
160.
Guerin  CGirard  RChemorin  CDe Varax  RFournier  G Facial mask noninvasive mechanical ventilation reduces the incidence of nosocomial pneumonia: a prospective epidemiological survey from a single ICU. Intensive Care Med. 1997;231024- 1032Article
161.
Torres  AGatell  JMAznar  E  et al.  Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation. Am J Respir Crit Care Med. 1995;152137- 141Article
162.
Stamm  AM Ventilator-associated pneumonia and frequency of circuit changes. Am J Infect Control. 1998;2671- 73Article
163.
Deppe  SAKelly  JWThoi  LL  et al.  Incidence of colonization, nosocomial pneumonia, and mortality in critically ill patients using a Trach Care closed-suction system versus an open-suction system: prospective, randomized study. Crit Care Med. 1990;181389- 1393Article
164.
Johnson  KKearney  PJohnson  SNiblett  JMacMillan  NMcClain  R Closed versus open endotracheal suctioning: costs and physiologic consequences. Crit Care Med. 1994;22658- 666Article
Review Article
July 10, 2000

Ventilator-Associated Pneumonia

Author Affiliations

From the Division of Pulmonary and Critical Care Medicine, University of Kentucky School of Medicine, and the Department of Medicine, Veterans Affairs Medical Center, Lexington, Ky (Dr Morehead). Dr Pinto is in private practice in Orlando, Fla.

Arch Intern Med. 2000;160(13):1926-1936. doi:10.1001/archinte.160.13.1926
Abstract

Ventilator-associated pneumonia is a common complication in intensive care units, occurring in 9% to 24% of patients intubated for longer than 48 hours. Because of this large disease burden and the resultant attributable morbidity and mortality, there is great interest in accurately diagnosing, treating, and preventing this complication. More severely ill patients tend to develop ventilator-associated pneumonia, and identified risk factors include prolonged mechanical ventilation, reintubation after failed extubation, and a few other clinical variables. The efficacy of diagnostic and preventive strategies is somewhat controversial. Diagnosis by invasive methods requires a considerable commitment of resources but can potentially reduce cost of care; however, mortality benefit from this approach has not been demonstrated. As such, in most institutions, ventilator-associated pneumonia is best diagnosed using traditional clinical criteria. Prompt administration of appropriate antibiotics seems to be the only intervention that alters outcome once the diagnosis is established. Several strategies seem to reduce pneumonia incidence; however, mortality and cost benefits have yet to be convincingly shown.

Ventilator-associated pneumonia is defined as parenchymal lung infection occurring more than 48 hours after initiation of mechanical ventilation. This serves to differentiate this disorder from community-acquired pneumonia and highlights pathogenic features peculiar to mechanically ventilated patients. A recent multicenter European study1 has shown that pneumonia is now the most common infection acquired in the intensive care unit (ICU), and when acquired during mechanical ventilation it has an associated mortality of 24% to 71%.210 A vast literature has accumulated concerning all facets of this disease, especially regarding the efficacy of available diagnostic methods and putative preventive measures. This article reviews the current state of the art with emphasis on diagnosis, treatment, and prevention strategies.

METHODS

We searched the English-language literature using the MEDLINE database from 1966 to 1998 using search terms ventilator-associated pneumonia and nosocomial pneumonia. Additional articles were identified by reviewing the reference lists of retrieved articles. We selected articles containing information about the epidemiology, pathogenesis, diagnosis, management, and prevention of ventilator-associated pneumonia in adults. In evaluating this literature, meta-analyses, prospective cohort studies, and randomized controlled trials were given preference for inclusion; studies with less rigorous methods were excluded unless no data from preferred sources were found. Concerning interventions designed to prevent ventilator-associated pneumonia, final recommendations incorporate well-established guidelines for grading scientific evidence for medical practice,11 adapted as follows: grade A, recommendation based on 1 or more randomized controlled trials or meta-analysis in which the lower limit of the confidence interval for the treatment effect exceeds the minimally important clinical benefit; grade B, recommendation based on 1 or more randomized controlled trials or meta-analysis in which the lower limit of the confidence interval for the treatment effect overlaps the minimally important clinical benefit; and grade C, recommendation based on evidence from nonrandomized trials, case series, or expert opinion.

EPIDEMIOLOGY

Gram-negative bacillus pneumonia became recognized as a significant cause of morbidity and mortality in hospitalized patients during the 1950s,12,13 coinciding with increasing use of mechanical ventilation and antibiotic drugs. Contaminated respiratory care equipment was initially implicated as the source of these pathogens; however, despite implementation of infection control measures, pneumonia has remained the most common ICU-acquired infection,1 with an incidence of 9% to 24% in patients mechanically ventilated for longer than 48 hours.3,69

The risk of developing ventilator-associated pneumonia relates to host factors and to the duration and intensity of exposure to potential pathogens. Single-center multivariate analyses68,14,15 have implicated prolonged mechanical ventilation and reintubation as risk factors; however, not all studies have agreed, and 2 studies7,15 reached discordant conclusions regarding previous antibiotic use. A recent multicenter Canadian study16 evaluated 1014 mechanically ventilated patients and found the following independent predictors of ventilator-associated pneumonia: a primary diagnosis of burns, trauma, central nervous system disease, respiratory tract disease, or cardiac disease; witnessed aspiration; mechanical ventilation within the previous 24 hours; and use of paralytic agents. Two other important findings of this analysis are (1) a rising daily risk for pneumonia until the fifth day of mechanical ventilation, with subsequent decline, and (2) a protective effect of systemic antibiotic therapy. Factors not assessed in this study but found to be predictive in other analyses include low endotracheal tube cuff pressure,15 transport outside the ICU,14 and supine body position.7 Although authors17 have identified recent surgery and altered sensorium as factors predisposing to pneumonia in mixed populations of ventilated and nonventilated ICU patients, studies68,16 excluding spontaneously breathing patients have consistently been unable to demonstrate this relationship, suggesting that intubation and mechanical ventilation obviate these risks.

APPROACH TO DIAGNOSIS

Respiratory failure combined with critical illness frequently culminates in pneumonia, but accurately determining whether pneumonia is present can be difficult, especially in the setting of acute respiratory distress syndrome. Standard clinical methods are insensitive in unequivocally diagnosing ventilator-associated pneumonia; positive pleural fluid culture or radiographic cavitation is present in only a minority of patients,1821 and blood cultures in this setting are positive in 10% or less.6,8,9,18 Studies22,23 using pulmonary histological patterns as a gold standard comparison reveal that clinical acumen is incorrect in determining the presence or absence of ventilator-associated pneumonia in up to one third of patients; alternative pathological diagnoses in this situation include atelectasis, infarction, hemorrhage, and fibrosis.22 These data suggest the need for improved diagnostic methods, and, in the pursuit of more accurate diagnosis, specific features of ventilator-associated pneumonia pathogenesis become important.

Pathogenesis

Events important in the progression to pneumonia in intubated patients begin with oropharyngeal colonization by potentially pathogenic bacteria.24,25 In this setting, endotracheal tube placement creates an abnormal continuum between the upper airway and the trachea and establishes a subglottic reservoir of secretions rich in bacterial pathogens. Secretions in this subglottic pool are aspirated into the trachea26,27 and become part of the biofilm lining the endotracheal tube.28 This biofilm can then be disseminated into the lung by the ventilator.29 In addition, organisms within the stomach can also contaminate the subglottic secretions. These events are summarized in Figure 1.

Although bacterial colonization of the lower respiratory tract is an essential step in pneumonia development, tracheal aspirate cultures unreliably predict infection, even if a quantitative culture threshold of greater than 103 colony-forming units (CFUs)/mL is stipulated as significant.3032 Given this problem, investigators have sought to correlate pneumonia with the presence of a "significant" level of bacterial growth from the distal airways and lung parenchyma. Autopsies performed on patients dying after prolonged mechanical ventilation reveal 3 distinct lung histological patterns: tracheobronchitis, bronchopneumonia, or bronchiolitis (inflammation of small airways without pneumonia).33 In the absence of antibiotic treatment, histological pneumonia is associated with a bacterial burden greater than 103 CFU per gram of lung tissue,34,35 suggesting a quantitative threshold to diagnose pneumonia. However, studies22,33,34,3638 including patients receiving antibiotic medications reveal a highly variable ability to predict pneumonia for quantitative cultures above threshold: sensitivity, 11% to 100%; specificity, 45% to 100%. Thus, the assumption that quantitative bacteriologic study accurately predicts histological patterns may be incorrect in certain clinical settings.

Diagnostic Methods

Given the limitations of standard clinical methods and the fact that lung biopsy is often not feasible or definitive in this setting,38 an easily applicable diagnostic method has been sought. The bronchoscopically deployed, double-sheathed protected specimen brush catheter is the best-studied invasive technique, and a quantitative bacterial count of 103 CFU/mL or greater is an accepted threshold to diagnose pneumonia.22,34,36 Bronchoalveolar lavage is used by a comparable number of investigators,22,33,34,3942 and the most common reported bacterial colony count indicative of pneumonia is 104 CFU/mL or greater. The attraction of this latter technique rests on the ability to immediately examine Gram stains of retrieved lung cells in which the finding of intracellular bacteria is predictive of pneumonia; 2 recent studies43,44 evaluating this technique report diagnostic specificity approaching 90%.

Invasive testing is subject to confounding variables. Quantitative bacteriologic study in patients with positive, but subthreshold, culture are often not reproducible on repeated testing,4547 and Gram staining of retrieved lung cells is insensitive in the setting of concurrent antimicrobial therapy.4851 As such, decisions to withhold antibiotic drugs based on subthreshold, positive quantitative culture should be made carefully. Notwithstanding, there are data37,40 supporting the validity of invasive testing in the presence of antimicrobial drugs, provided therapy is not changed within 48 to 72 hours of testing.

Attempting to avoid the high cost and logistic difficulty of bronchoscopy, the protected specimen brush catheter and bronchoalveolar lavage (the latter by a specially designed catheter) have been applied by inserting catheters directly through the endotracheal tube. Several studies34,49,5254 have reported operating characteristics similar to bronchoscopically based procedures, with one study54 demonstrating safety in a series of 72 procedures performed by trained respiratory therapists. In addition to these modifications, quantitative culture of suctioned sputum obtained without use of a specialized catheter has been shown3032,55 to identify pathogens with an equal or greater sensitivity compared with invasive methods, but lower specificity attends its use.

Despite claims of greater accuracy for invasive testing and a published decision analysis56 suggesting mortality benefit using an invasive method–based management algorithm, no conclusive evidence of improved mortality exists. Mechanically ventilated patients with a constellation of clinical findings suggestive of pneumonia will have this diagnosis confirmed by invasive testing in about half of the episodes.5,43,57,58 However, clinical suggestion alone seems to confer higher mortality to patients, even if results of invasive testing are negative.5,57,58 The study protocols of most investigations of invasive pneumonia diagnosis stipulate that patients suspected of having pneumonia receive empirical antibiotic therapy while awaiting invasive test results. As such, negative invasive test results ostensibly identify patients who can have antibiotic drug therapy safely discontinued, whereas positive test results indicate a requirement for continued treatment. Despite the lack of demonstrable mortality benefit, this approach seems to reduce antimicrobial use5961 and might lead to reduced total cost of care and less antibiotic resistance. Two studies60,61 analyzing total cost of care of invasive diagnosis reached discordant conclusions principally on the basis of antimicrobial cost difference; both used bronchoscopy, adding substantially to the cost of diagnosis. An interesting finding in these studies is that physicians often do not discontinue antibiotic drug therapy in the setting of negative or subthreshold quantitative cultures.59,61,62 Heyland and coworkers59 found that invasive testing led to reduced antibiotic use and greater confidence in doing so; however, as suggested by other studies,61,62 physicians use these tests as part of a general clinical gestalt in making decisions to stop or change antibiotic use. This variability in physician practice makes the cost outcome resulting from invasive testing protocols difficult to predict.

In the final analysis, the diagnosis of ventilator-associated pneumonia involves 2 steps: (1) deciding whether pneumonia is present and (2) identifying a microbiologic agent to target antibiotic therapy. In that invasive diagnosis requires a substantial institutional commitment in resources, this approach is beyond the abilities of many institutions. The traditional method of clinical diagnosis continues to be the standard of care in the United States, and support for this "usual care" approach derives from the demonstrated diagnostic accuracy of published clinical scoring systems compared with invasive methods.22,33,38,63 Although not proven, these data suggest that experienced clinicians might perform as well as invasive methods. After pneumonia is diagnosed clinically, refinements in antibiotic selection should rely on the culture of endotracheal aspirate because this method identifies potential pathogens at least as well as invasive methods.3032,35,38,49,64

THERAPEUTIC CONSIDERATIONS

There are no placebo-controlled trials of the treatment of ventilator-associated pneumonia; presumption of benefit is based on the underpinning principles of antibiotic therapy, data demonstrating attributable morbidity and mortality,4,6568 and the poor outcome of patients given antibiotic drugs that do not cover causative bacteria (Table 1).4,8,9,57,62,72,73

Concept of Attributable Morbidity and Mortality

Although it is clear that the presence of ventilatory-associated pneumonia adversely affects outcome, results of investigations24,6567 attempting to document this excess morbidity and mortality as attributable to the pneumonia alone have been somewhat divided. In an effort to clarify this issue, Heyland and colleagues68 used a prospective case-matching scheme that included factors such as duration of ventilator assistance, initial illness severity, and primary diagnosis used in other studies, but they also matched patients by organ dysfunction index the day before pneumonia development to further ensure that both groups were similar at pneumonia onset. In this multicenter study, mortality was higher for the pneumonia group (23.7%) than for the control group (17.9%), but the attributable mortality, 5.8% (95% confidence interval, −2.4% to 14.0%), and relative risk increase for death, 32.3% (95% confidence interval, −20.6% to 85.1%), were not statistically significant. Nevertheless, ventilator-associated pneumonia was associated with significantly greater ICU length of stay (mean difference, 4.3 days; 95% confidence interval, 1.5-7.0 days; P<.001), and this was seen in both survivors and nonsurvivors. In addition, only the medical patients had excess morbidity and mortality. Taken together, the evidence clearly points to ventilator-associated pneumonia as an independent predictor of adverse outcome for patients as a whole; however, this effect is not equal in all populations, as medical patients seem disproportionately affected.

Microbiology

The microbiologic isolates of ventilator-associated pneumonia reflect a broad array of bacteria that vary with the particular hospital and ICU studied. Published series using invasive methods reveal gram-negative bacilli as the most common isolates found above predefined diagnostic thresholds (Table 2). Polymicrobial episodes are also common.3,9,33,72,7476 Anaerobic bacteria were previously thought to be important in the pathogenesis of ventilator-associated pneumonia, but this has been recently questioned. Using invasive testing, Dore and colleagues76 isolated anaerobes in only 23% of patients with confirmed ventilator-associated pneumonia (13% as the sole pathogen), and Marik and Careau77 were unable to identify pathogenic anaerobes in 143 suspected cases. These data, combined with the rare isolation of anaerobes in postmortem lung biopsy specimens,22,34,36 point toward a minor role in most instances. In addition, nosocomial pneumonia caused by Legionella species can occur in institutions with contaminated water sources; ventilated patients can then be exposed if tap water is used for respiratory care procedures.7881

Antibiotic Selection

Appropriate antibiotic therapy for ventilator-associated pneumonia can be defined as treatment with antimicrobial drugs that cover all likely pathogens isolated from respiratory tract secretions. Caveats to this statement include that (1) samples sent for culture should reflect lower respiratory tract secretions, ie, more than 25 granulocytes and less than 10 epithelial cells per low-power field and (2) less virulent organisms such as vancomycin-resistant enterococci and coagulase-negative staphylococci might not be pathogenic; this is especially germane when more virulent bacteria are concurrently isolated (the more likely culprit) and risk factors for invasive disease are absent.

Given these caveats, one important lesson from recent studies is that antibiotic coverage should be given early after infection is suspected, and the spectrum of this agent(s) should address all reasonably suspected pathogens. Several studies57,69,71 have demonstrated that the need to change antibiotic drugs after culture data becomes available identifies a subgroup of patients with higher mortality. Moreover, Luna and colleagues58 noted that the mortality benefit of appropriate antibiotic coverage pertained only to that treatment present before invasive diagnostic testing, suggesting that an important time window exists after which antibiotic treatment, regardless of activity, is less effective. As such, the single most important management decision after a clinical diagnosis of pneumonia is whether antimicrobial activity against potentially resistant organisms such as Pseudomonas aeruginosa, Acinetobacter species, and Stenotrophomonas maltophilia is warranted. These organisms occur later in the course of mechanical ventilation,82 usually in the presence of previous antibiotic therapy,69,83,84 and are independently associated with poor outcome.4,8,9,57,62,72,73 Trouillet and coworkers75 prospectively studied 135 patients with ventilator-associated pneumonia, comparing episodes caused by these high-risk bacteria (including methicillin-resistant Staphylococcus aureus) with those secondary to other pathogens. By multivariate analysis, duration of ventilation before pneumonia onset and previous broad spectrum antibiotic drug use were the only factors associated with high-risk organisms. Moreover, in 84 patients ventilated for 7 days or longer with previous antibiotic exposure, an empirical triple-drug regimen including vancomycin was required to obtain acceptable antimicrobial activity in 88% of episodes. With this sort of data in mind, the American Thoracic Society guidelines85 recommend expanded coverage for these organisms in the presence of 5 days or more of hospitalization before pneumonia onset, previous antibiotic treatment, corticosteroid use, structural lung disease, and immunosuppression.

Empirical antibiotic medication selection should take into account risk factors, as outlined above, especially time of pneumonia onset. Patients with late-onset pneumonia (≥5 days of hospitalization) or risk factors should be covered with antibiotic drugs with acceptable antipseudomonal activity (Figure 2), including select fluoroquinolones, aminoglycosides, β-lactams with or without β-lactamase inhibitors, and third-generation cephalosporins, as well as imipenem, meropenem, and aztreonam. Monotherapy with these agents (excluding aminoglycosides) is associated with clinical failure in 15% to 29% of patients8689; however, because of exclusion of the most severely ill patients in some of these trials, the failure rate experienced in clinical practice might be higher. High-risk organisms constitute most clinical failures, as evidenced by the ability to eradicate P aeruginosa in only 34% of pneumonic episodes in one study.90 Multicenter randomized trials have compared imipenem with ciprofloxacin,90 piperacillin-tazobactam,86 and ceftazidime87 as single-agent therapy but did not demonstrate clear-cut superiority of any one agent; however, use of piperacillin-tazobactam seemed to be more efficacious against P aeruginosa.86 To minimize clinical failure associated with high-risk pathogens, 2 antimicrobial agents of different action mechanisms are recommended until culture results are available. A traditional choice in this regard has been an extended spectrum β-lactam plus an aminoglycoside; however, newer agents also have excellent activity (Figure 2). Limited information suggests that piperacillin-tazobactam may be the preferred agent against high-risk organisms; one recent multicenter study91 comparing a combination of piperacillin-tazobactam plus amikacin with ceftazidime plus amikacin revealed a 2-fold higher rate of clinical and microbiologic failure with the ceftazidime-containing regimen (26% vs 46%; P=.023). The reasons for this failure were a 2-fold higher rate of both superinfection and persistence and relapse of the initial infecting organism. Given that failure to eradicate high-risk organisms might be responsible for most recurrent ventilator-associated pneumonia,92 and the risk of inducing resistance during cephalosporin monotherapy,93 it seems most reasonable to use noncephalosporin antibiotics for high-risk organisms (ie, P aeruginosa, Acinetobacter species, Enterobacter species, and S maltophilia) or a second agent to prevent this occurrence.

Empirical antibiotic selection should also be cognizant of local bacterial resistance patterns and the heightened risk of inadequate therapy in more severely ill patients. A recent study94 demonstrated significant variability in pathogens in 3 institutions such that in 1, inadequate empirical therapy would have been prescribed for almost 20% of patients if standard guidelines had been followed without regard to local bacterial patterns. In addition, methicillin-resistant S aureus is prevalent in certain institutions with risk factors similar to high-risk gram-negative bacilli95; in these institutions, the addition of vancomycin to the empirical regimen should be considered in patients at risk for early death. Intravenous administration should be the rule during the initial treatment phase in all but the most stable patients to avoid irregular gastrointestinal tract absorption that might accompany critical illness.

Antibiotic resistance is a serious emerging problem, and data from the National Nosocomial Infectious Surveillance System96 document higher levels of antibiotic resistance in patients treated in ICUs compared with non-ICU hospitalized and ambulatory patients. Because this problem is largely related to antimicrobial exposure, judicious antimicrobial use in the ICU should be a major concern in all management decisions. Extended spectrum lactam agents are particular likely to induce bacterial resistance to antibiotic drugs. Induction of β-lactamases after β-lactam use9799 and alterations in bacterial membrane permeability after imipenem use100,101 have received considerable attention; however, no antibiotic class is immune to this phenomenon. Given these facts, antibiotic resistance should be minimized by using agents with the narrowest activity spectrum after culture and sensitivity data become available and by stopping antimicrobial therapy when infection is reasonably excluded. Other strategies to potentially prevent resistance include antibiotic class restriction100 and scheduled changes in antibiotic class used for empirical therapy in ICUs.102

PREVENTION

Given the considerable attributable morbidity of ventilator-associated pneumonia and the fiscal loss to hospitals caring for these patients,103,104 prevention has become a major focus. Published guidelines105107 emphasize the importance of infection control and surveillance, and implementation of a nosocomial pneumonia prevention policy has been shown to decrease disease incidence.108,109 Bacterial colonization of the lower respiratory tract of mechanically ventilated patients is the targeted event of most preventive strategies. Several of the more controversial topics are discussed in the following subsections (Table 3); the reader is directed to a recent comprehensive review for further information.110

Prevention of Bacterial Colonization

Depending on primary disease and previous patient locale, bacterial colonization of the trachea is recognized in up to three quarters of patients on initial sampling after ICU admission.111113 Studies are somewhat divided as to the source of these microbes: some data112 support between-patient transmission and others114118 suggest that most pathogens are endogenous flora. Nevertheless, simple infection control measures such as hand washing are important,119 and an outbreak should prompt policy reevaluation.120122

Selective decontamination of the aerodigestive tract with topically applied antibiotic drugs reduces the gastric bacterial burden and prevents tracheobronchial colonization and ventilator-associated pneumonia.123128 Factors against routine use are the marginal mortality benefit for ventilated patients as a whole,127129 cost of application, and risk of inducing antibiotic resistance.127,130,131 Moreover, studies reporting these finding have variously decontaminated the stomach alone, stomach and oropharynx, or both with the addition of a parenteral antibiotic drug, making the most appropriate approach unclear. Nevertheless, a subset of severely ill patients seem to derive benefit, as suggested by a reanalysis132 of previously performed studies and a recent study124 demonstrating reduced total cost of care. At present, despite reduced pneumonia incidence, more cost-benefit data are needed before selective decontamination is widely recommended.

High gastric pH is associated with increased numbers of gastric bacteria,133135 and pH-altering drugs (antacids and histamine2 antagonists) are frequently administered to mechanically ventilated patients, potentially increasing the gastric bacterial burden. The association between treatment with pH-altering agents and nosocomial pneumonia, especially events occurring after 4 days of ventilation, has been suggested.136138 However, meta-analyses139,140 reveal only a trend toward pneumonia reduction with non–pH-altering therapy, and a recent multicenter study141 of 1200 mechanically ventilated patients did not show a statistical difference. The poor correlation between pH-altering therapy and pneumonia is likely due to the intrinsically high gastric pH present in many critically ill patients137,142 and the fact that the stomach is the source of pathogens in only a few patients.143 Bacteria isolated from the trachea of mechanically ventilated patients arrive by different routes.111,112,142,144Pseudomonas aeruginosa, eg, most commonly appears de novo in the trachea and therefore is unlikely to be affected by gastric pH, in contrast to the Enterobacteriaceae, which are often first found in the stomach.111,145 Consistent with these findings, the delivery site and method of enteral feeding have not convincingly altered the incidence of nosocomial pneumonia,146148 although postpyloric feeding could theoretically reduce colonization by gastric bacteria.

Airway Management and Respiratory Care

Airway management strategies have been studied in relation to pneumonia prevention and are the subject of a recent review.149 Two studies150,151 evaluating an endotracheal tube allowing removal of subglottic secretions demonstrated reduced incidence of pneumonia. Nasal endotracheal tubes have a higher incidence of radiographic sinusitis152 and may predispose to pneumonia. Holzapfel and colleagues153 reported a nonsignificant trend toward lower pneumonia incidence in orotracheally (6%) than nasotracheally (11%) intubated patients (P=.11) and in a subsequent study154 demonstrated a reduction in ventilator-associated pneumonia in nasotracheally intubated patients by using an aggressive diagnostic and treatment protocol for nosocomial sinusitis. In addition, supine position has been significantly associated with the occurrence of ventilator-associated pneumonia,7 probably because of increased aspiration into the respiratory tract, a preventable phenomenon if patients are treated upright at 45°.155,156

There is an increasing emphasis on noninvasive ventilation in the management of acute respiratory failure of diverse etiologies. Emerging data157160 suggest that patients who tolerate noninvasive ventilation might have a lesser incidence of nosocomial pneumonia than those tracheally intubated. Moreover, because it seems that failed extubation and reintubation are also associated with an increased risk of pneumonia,8,161 management of respiratory failure without tracheal intubation holds promise regarding pneumonia prevention.

Several respiratory care practices have been the subject of study. Two recent reviews149,162 of ventilator circuit change frequency confirm that changes more often than every 7 days are unnecessary and may increase the risk of pneumonia. Despite the lack of definitive trials, heat and moisture exchangers and kinetic bed therapy also seem to reduce the incidence of pneumonia,149 but closed endotracheal tube suctioning systems do not demonstrably alter this occurrence.163,164 Larger, prospective trials are still needed to identify which of these interventions are cost-effective and which patient subgroups are most likely to benefit.

SUMMARY

Ventilator-associated pneumonia is common in mechanically ventilated, critically ill patients, and higher severity of illness, prolonged mechanical ventilation, and intrinsic lung disease increase the risk of this complication. Invasive study of the lower respiratory tract in these patients has led to a better understanding of the pathogenic events leading to pneumonia but has not convincingly altered mortality or cost of care. Because inappropriate antibiotic drug therapy and the presence of high-risk organisms correlate with mortality secondary to ventilator-associated pneumonia, empirical antibiotic coverage should include agents with activity against P aeruginosa and related bacteria in the presence of prolonged mechanical ventilation and/or other risk factors. Efforts targeted at prevention have identified several respiratory care and airway management practices that seem to be efficacious. Selective decontamination of the aerodigestive tract also reduces pneumonia incidence but has not yet convincingly been shown to alter mortality or cost of care. Future investigations should include more outcomes assessments of newer diagnostic and preventive methods.

Back to top
Article Information

Accepted for publication January 10, 2000.

We thank Rolando Berger, MD, and Eric Bensadoun, MD, for review of the manuscript and helpful suggestions and Martha Cooper for the illustrations.

Reprints not available from the authors.

References
1.
Vincent  JLBihari  DJSuter  PM  et al.  The prevalence of nosocomial infection in intensive care units in Europe: results of the European Prevalence of Infection in Intensive Care (EPIC) Study: EPIC International Advisory Committee. JAMA. 1995;274639- 644Article
2.
Baker  AMMeredith  JWHaponik  EF Pneumonia in intubated trauma patients: microbiology and outcomes. Am J Respir Crit Care Med. 1996;153343- 349Article
3.
Papazian  LBregeon  FThirion  X  et al.  Effect of ventilator-associated pneumonia on mortality and morbidity. Am J Respir Crit Care Med. 1996;15491- 97Article
4.
Fagon  JYChastre  JHance  AJMontravers  PNovara  AGibert  C Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay. Am J Med. 1993;94281- 288Article
5.
Timsit  JFChevret  SValcke  J  et al.  Mortality of nosocomial pneumonia in ventilated patients: influence of diagnostic tools. Am J Respir Crit Care Med. 1996;154116- 123Article
6.
Craven  DEKunches  LMKilinsky  VLichtenberg  DAMake  BJMcCabe  WR Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation. Am Rev Respir Dis. 1986;133792- 796
7.
Kollef  MH Ventilator-associated pneumonia: a multivariate analysis. JAMA. 1993;2701965- 1970Article
8.
Torres  AAznar  RGatell  JM  et al.  Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis. 1990;142523- 528Article
9.
Fagon  JYChastre  JDomart  Y  et al.  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 Dis. 1989;139877- 884Article
10.
Fagon  JYChastre  JVuagnat  ATrouillet  JLNovara  AGibert  C Nosocomial pneumonia and mortality among patients in intensive care units. JAMA. 1996;275866- 869Article
11.
Cook  DGuyatt  GLaupacis  ASackett  DGoldberg  R Clinical recommendations using levels of evidence for antithrombotic agents. Chest. 1995;108(suppl 4)S227- S230Article
12.
Rogers  D The changing patterns of life-threatening microbial disease. N Engl J Med. 1959;261677- 683Article
13.
Kneeland  YPrice  K Antibiotics and terminal pneumonia: a postmortem microbiologic study. Am J Med. 1960;29967- 979Article
14.
Kollef  MHVon Harz  BPrentice  D  et al.  Patient transport from intensive care increases the risk of developing ventilator-associated pneumonia. Chest. 1997;112765- 773Article
15.
Rello  JSonora  RJubert  PArtigas  ARue  MValles  J Pneumonia in intubated patients: role of respiratory airway care. Am J Respir Crit Care Med. 1996;154111- 115Article
16.
Cook  DJWalter  SDCook  RJ  et al.  Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med. 1998;129433- 440Article
17.
Joshi  NLocalio  ARHamory  BH A predictive risk index for nosocomial pneumonia in the intensive care unit. Am J Med. 1992;93135- 142Article
18.
Rello  JMirelis  BAlonso  CPrats  G Lack of usefulness of blood cultures to diagnose ventilator-associated pneumonia. Eur Respir J. 1991;41020
19.
Chendrasekhar  A Are routine blood cultures effective in the evaluation of patients clinically diagnosed to have nosocomial pneumonia? Am Surg. 1996;62373- 376
20.
Pham  LHBrun-Buisson  CLegrand  P  et al.  Diagnosis of nosocomial pneumonia in mechanically ventilated patients: comparison of a plugged telescoping catheter with the protected specimen brush. Am Rev Respir Dis. 1991;1431055- 1061Article
21.
Fagon  JYChastre  JHance  AJ  et al.  Detection of nosocomial lung infection in ventilated patients: use of a protected specimen brush and quantitative culture techniques in 147 patients. Am Rev Respir Dis. 1988;138110- 116Article
22.
Torres  Ael-Ebiary  MPadro  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;149324- 331Article
23.
Andrews  CPCoalson  JJSmith  JDJohanson  WG  Jr Diagnosis of nosocomial bacterial pneumonia in acute, diffuse lung injury. Chest. 1981;80254- 258Article
24.
Johanson  WPierce  ASanford  JThomas  G Nosocomial respiratory infections with gram-negative bacilli: the significance of colonization of the respiratory tract. Ann Intern Med. 1972;77701- 706Article
25.
Johanson  WPierce  ASanford  J Changing oropharyngeal bacterial flora of hospitalized patients. N Engl J Med. 1969;2811137- 1140Article
26.
Petring  OAdelhoj  BJensen  BPedersen  NLomholt  N Prevention of silent aspiration due to leaks around cuffs of endotracheal tubes. Anesth Analg. 1986;65777- 780Article
27.
Spray  SZuidema  GCameron  J Aspiration pneumonia. Am J Surg. 1976;131701- 703Article
28.
Feldman  CKassel  MCantrell  J  et al.  The presence and sequence of endotracheal tube colonization in patients undergoing mechanical ventilation. Eur Respir J. 1999;13546- 551Article
29.
Inglis  TMillar  MJones  JJones  JRobinson  D Tracheal tube biofilm as a source of bacterial colonization of the lung. J Clin Microbiol. 1989;272014- 2018
30.
Jourdain  BNovara  AJoly-Guillou  ML  et al.  Role of quantitative cultures of endotracheal aspirates in the diagnosis of nosocomial pneumonia. Am J Respir Crit Care Med. 1995;152241- 246Article
31.
Marquette  CHGeorges  HWallet  F  et al.  Diagnostic efficiency of endotracheal aspirates with quantitative bacterial cultures in intubated patients with suspected pneumonia: comparison with the protected specimen brush. Am Rev Respir Dis. 1993;148138- 144Article
32.
el-Ebiary  MTorres  AGonzalez  J  et al.  Quantitative cultures of endotracheal aspirates for the diagnosis of ventilator-associated pneumonia. Am Rev Respir Dis. 1993;1481552- 1557Article
33.
Rouby  JDeLassale  EPoete  P  et al.  Nosocomial bronchopneumonia in the critically ill: histologic and bacteriologic aspects. Am Rev Respir Dis. 1992;1461059- 1066Article
34.
Papazion  LThomas  PGarbe  L  et al.  Bronchoscopic or blind sampling techniques for the diagnosis of ventilator-associated pneumonia. Am J Respir Crit Care Med. 1995;1521982- 1991Article
35.
Johanson  WG  JrSeidenfeld  JJGomez  Pde los Santos  RCoalson  JJ Bacteriologic diagnosis of nosocomial pneumonia following prolonged mechanical ventilation. Am Rev Respir Dis. 1988;137259- 264Article
36.
Chastre  JViau  FBrun  P  et al.  Prospective evaluation of the protected specimen brush for the diagnosis of pulmonary infections in ventilated patients. Am Rev Respir Dis. 1984;130924- 929
37.
Chastre  JFagon  JYBornet-Lecso  M  et al.  Evaluation of bronchoscopic techniques for the diagnosis of nosocomial pneumonia. Am J Respir Crit Care Med. 1995;152231- 240Article
38.
Kirtland  SHCorley  DEWinterbauer  RH  et al.  The diagnosis of ventilator-associated pneumonia: a comparison of histologic, microbiologic, and clinical criteria. Chest. 1997;112445- 457Article
39.
Jourdain  BJoly-Guillou  MLDombret  MC  et al.  Usefulness of quantitative cultures of BAL fluid for diagnosing nosocomial pneumonia in ventilated patients. Chest. 1997;111411- 418Article
40.
Souweine  BVeber  BBedos  JP  et al.  Diagnostic accuracy of protected specimen brush and bronchoalveolar lavage in nosocomial pneumonia: impact of previous antimicrobial treatments. Crit Care Med. 1998;26236- 244Article
41.
Meduri  GUBeals  DHMaijub  AGBaselski  V Protected bronchoalveolar lavage: a new bronchoscopic technique to retrieve uncontaminated distal airway secretions. Am Rev Respir Dis. 1991;143855- 864Article
42.
Cantral  DETape  TGReed  ECSpurzem  JRRennard  SIThompson  AB Quantitative culture of bronchoalveolar lavage fluid for the diagnosis of bacterial pneumonia. Am J Med. 1993;95601- 607Article
43.
Meduri  GUReddy  RCStanley  TEl-Zeky  F Pneumonia in acute respiratory distress syndrome: a prospective evaluation of bilateral bronchoscopic sampling. Am J Respir Crit Care Med. 1998;158870- 875Article
44.
Prekates  ANanas  SArgyropoulou  A  et al.  The diagnostic value of Gram stain of bronchoalveolar lavage samples. Scand J Infect Dis. 1998;3043- 47Article
45.
Gerbeaux  PLedoray  VBoussuges  AMolenat  FJean  PSainty  J Diagnosis of nosocomial pneumonia in mechanically ventilated patients: repeatability of the bronchoalveolar lavage. Am J Respir Crit Care Med. 1998;15776- 80Article
46.
Timsit  JFMisset  BFrancoual  SGoldstein  FWVaury  PCarlet  J Is protected specimen brush a reproducible method to diagnose ICU-acquired pneumonia? Chest. 1993;104104- 108Article
47.
Marquette  CHHerengt  FMathieu  DSaulnier  FCourcol  RRamon  P Diagnosis of pneumonia in mechanically ventilated patients: repeatability of the protected specimen brush. Am Rev Respir Dis. 1993;147211- 214Article
48.
Sole-Violan  JRodriguez de Castro  FRey  AMartin-Gonzalez  JCCabrera-Navarro  P Usefulness of microscopic examination of intracellular organisms in lavage fluid in ventilator-associated pneumonia. Chest. 1994;106889- 894
49.
Papazian  LMartin  CMeric  BDumon  JFGouin  F A reappraisal of blind bronchial sampling in the microbiologic diagnosis of nosocomial bronchopneumonia: a comparative study in ventilated patients. Chest. 1993;103236- 242Article
50.
Dotson  RGPingleton  SK The effect of antibiotic therapy on recovery of intracellular bacteria from bronchoalveolar lavage in suspected ventilator-associated nosocomial pneumonia. Chest. 1993;103541- 546Article
51.
Papazian  LAutillo-Touati  AThomas  P  et al.  Diagnosis of ventilator-associated pneumonia: an evaluation of direct examination and presence of intracellular organisms. Anesthesiology. 1997;87268- 276Article
52.
Marquette  CHHerengt  FSaulnier  F  et al.  Protected specimen brush in the assessment of ventilator-associated pneumonia: selection of a certain lung segment for bronchoscopic sampling is unnecessary. Chest. 1993;103243- 247Article
53.
Marik  PEBrown  WJ A comparison of bronchoscopic vs blind protected specimen brush sampling in patients with suspected ventilator-associated pneumonia. Chest. 1995;108203- 207Article
54.
Kollef  MHBock  KRRichards  RDHearns  ML The safety and diagnostic accuracy of minibronchoalveolar lavage in patients with suspected ventilator-associated pneumonia. Ann Intern Med. 1995;122743- 748Article
55.
Torres  AMartos  APuig 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;147952- 957Article
56.
Sterling  TRHo  EJBrehm  WTKirkpatrick  MB Diagnosis and treatment of ventilator-associated pneumonia—impact on survival: a decision analysis. Chest. 1996;1101025- 1034Article
57.
Kollef  MHWard  S The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia. Chest. 1998;113412- 420Article
58.
Luna  CMVujacich  PNiederman  MS  et al.  Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest. 1997;111676- 685Article
59.
Heyland  DCook  DMarshall  J  et al.  The clinical utility of invasive diagnostic techniques in the setting of ventilator-associated pneumonia. Chest. 1999;1151076- 1084Article
60.
Croce  MAFabian  TCShaw  B  et al.  Analysis of charges associated with diagnosis of nosocomial pneumonia: can routine bronchoscopy be justified? J Trauma. 1994;37721- 727Article
61.
Bonten  MJBergmans  DCStobberingh  EE  et al.  Implementation of bronchoscopic techniques in the diagnosis of ventilator-associated pneumonia to reduce antibiotic use. Am J Respir Crit Care Med. 1997;1561820- 1824Article
62.
Sanchez-Nieto  JMTorres  AGarcia-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;157371- 376Article
63.
Pugin  JAuckenthaler  RMili  NJanssens  JPLew  PDSuter  PM Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am Rev Respir Dis. 1991;1431121- 1129Article
64.
Rumbak  MJBass  RL Tracheal aspirate correlates with protected specimen brush in long-term ventilated patients who have clinical pneumonia. Chest. 1994;106531- 534Article
65.
Cunnion  KMWeber  DJBroadhead  WEHanson  LCPieper  CFRutala  WA Risk factors for nosocomial pneumonia: comparing adult critical-care populations. Am J Respir Crit Care Med. 1996;153158- 162Article
66.
Kappstein  ISchulgen  GBeyer  UGeiger  KSchumacher  MDaschner  FD Prolongation of hospital stay and extra costs due to ventilator-associated pneumonia in an intensive care unit. Eur J Clin Microbiol Infect Dis. 1992;11504- 508Article
67.
Craig  CConnelly  S Effect of intensive care unit nosocomial pneumonia on duration of stay and mortality. Am J Infect Control. 1984;12233- 238Article
68.
Heyland  DCook  DGriffith  LKeenan  SBrun-Buisson  C The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. Am J Respir Crit Care Med. 1999;1591249- 1256Article
69.
Alvarez-Lerma  F Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit: ICU-Acquired Pneumonia Study Group. Intensive Care Med. 1996;22387- 394Article
70.
Celis  RTorres  AGatell  JMAlmela  MRodriguez-Roisin  RAgusti-Vidal  A Nosocomial pneumonia: a multivariate analysis of risk and prognosis. Chest. 1988;93318- 324Article
71.
Rello  JGallego  MMariscal  DSonora  RValles  J The value of routine microbial investigation in ventilator-associated pneumonia. Am J Respir Crit Care Med. 1997;156196- 200Article
72.
Crouch Brewer  SWunderink  RGJones  CBLeeper  KV  Jr Ventilator-associated pneumonia due to Pseudomonas aeruginosa. Chest. 1996;1091019- 1029Article
73.
Kollef  MHSilver  PMurphy  DMTrovillion  E The effect of late-onset ventilator-associated pneumonia in determining patient mortality. Chest. 1995;1081655- 1662Article
74.
Jimenez  PTorres  ARodriguez-Roisin  R  et al.  Incidence and etiology of pneumonia acquired during mechanical ventilation. Crit Care Med. 1989;17882- 885Article
75.
Trouillet  JLChastre  JVuagnat  A  et al.  Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. Am J Respir Crit Care Med. 1998;157531- 539Article
76.
Dore  PRobert  RGrollier  G  et al.  Incidence of anaerobes in ventilator-associated pneumonia with use of a protected specimen brush. Am J Respir Crit Care Med. 1996;1531292- 1298Article
77.
Marik  PCareau  P The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: a prospective study. Chest. 1999;115178- 183Article
78.
Mastro  TDFields  BSBreiman  RFCampbell  JPlikaytis  BDSpika  JS Nosocomial Legionnaires' disease and use of medication nebulizers. J Infect Dis. 1991;163667- 671Article
79.
Muder  RRYu  VLWoo  AH Mode of transmission of Legionella pneumophila: a critical review. Arch Intern Med. 1986;1461607- 1612Article
80.
Roig  JAguilar  XRuiz  J  et al.  Comparative study of Legionella pneumophila and other nosocomial-acquired pneumonias. Chest. 1991;99344- 350Article
81.
Goetz  AMStout  JEJacobs  SL  et al.  Nosocomial Legionnaires' disease discovered in community hospitals. Am J Infect Control. 1998;268- 11Article
82.
Bregeon  FPapazian  LVisconti  AGregoire  RThirion  XGouin  F Relationship of microbiologic diagnostic criteria to morbidity and mortality in patients with ventilator-associated pneumonia. JAMA. 1997;277655- 662Article
83.
Talon  DMulin  BRouget  CBailly  PThouverez  MViel  JF Risks and routes for ventilator-associated pneumonia with Pseudomonas aeruginosa. Am J Respir Crit Care Med. 1998;157978- 984Article
84.
Rello  JAusina  VRicart  MCastella  JPrats  G Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. Chest. 1993;1041230- 1235Article
85.
Not Available, Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventative strategies: a consensus statement, American Thoracic Society, November 1995. Am J Respir Crit Care Med. 1996;1531711- 1725Article
86.
Jaccard  CTroillet  NHarbarth  S  et al.  Prospective randomized comparison of imipenem-cilastatin and piperacillin-tazobactam in nosocomial pneumonia or peritonitis. Antimicrob Agents Chemother. 1998;422966- 2972
87.
Cometta  ABaumgartner  JDLew  D  et al.  Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in nonneutropenic patients. Antimicrob Agents Chemother. 1994;381309- 1313Article
88.
Norrby  SRFinch  RGGlauser  M Monotherapy in serious hospital-acquired infections: a clinical trial. J Antimicrob Chemother. 1993;31927- 937Article
89.
Rubinstein  ELode  HGrassi  C Ceftazidime monotherapy vs. ceftriaxone/tobramycin for serious hospital-acquired gram-negative infections: Antibiotic Study Group. Clin Infect Dis. 1995;201217- 1228Article
90.
Fink  MPSnydman  DRNiederman  MS  et al.  Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. Antimicrob Agents Chemother. 1994;38547- 557Article
91.
Brun-Buisson  CSollet  JPSchweich  HBriere  SPetit  C Treatment of ventilator-associated pneumonia with piperacillin-tazobactam/amikacin versus ceftazidime/amikacin: a multicenter, randomized controlled trial: VAP Study Group. Clin Infect Dis. 1998;26346- 354Article
92.
Rello  JMariscal  DMarch  F  et al.  Recurrent Pseudomonas aeruginosa pneumonia in ventilated patients: relapse or reinfection? Am J Respir Crit Care Med. 1998;157912- 916Article
93.
Chow  JFine  MShlaes  D  et al.  Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy. Ann Intern Med. 1991;115585- 590Article
94.
Rello  JSa-Borges  MCorrea  HLeal  SRBaraibar  J Variations in etiology of ventilator-associated pneumonia across four treatment sites: implications for antimicrobial prescribing practices. Am J Respir Crit Care Med. 1999;160608- 613Article
95.
Rello  JTorres  ARicart  M  et al.  Ventilator-associated pneumonia by Staphylococcus aureus: comparison of methicillin-resistant and methicillin-sensitive episodes. Am J Respir Crit Care Med. 1994;1501545- 1549Article
96.
Archibald  LPhillips  LMonnet  DMcGowan  JTenover  FGaynes  R Antimicrobial resistance in isolates from inpatients and outpatients in the United States: increasing importance of the intensive care unit. Clin Infect Dis. 1997;24211- 215Article
97.
Cailleaux  VMulin  BCapellier  GJulliot  MThouverez  MTalon  D Epidemiological study of variations in β-lactam antibiotic susceptibility of Pseudomonas aeruginosa in two intensive care units. J Hosp Infect. 1997;37217- 224Article
98.
Lee  SFung  CLiu  P  et al.  Nosocomial infections with ceftazidime-resistant Pseudomonas aeruginosa: risk factors and outcome. Infect Control Hosp Epidemiol. 1999;20205- 207Article
99.
D'Agata  EVenkataraman  LDeGirolami  P  et al.  Colonization with broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units during a nonoutbreak period: prevalence, risk factors, and rate of infection. Crit Care Med. 1999;271090- 1095Article
100.
Rajal  JUrban  CHorn  D  et al.  Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella. JAMA. 1998;2801233- 1237Article
101.
Troillet  NSamore  MCarmeli  Y Imipenem-resistant Pseudomonas aeruginosa: risk fac tors and antibiotic susceptibility patterns. Clin Infect Dis. 1997;251094- 1098Article
102.
Kollef  MHVlasnik  JSharpless  LPasque  CMurphy  DFraser  V Scheduled change of antibiotic classes: a strategy to decrease the incidence of ventilator-associated pneumonia. Am J Respir Crit Care Med. 1997;1561040- 1048Article
103.
Boyce  JMPotter-Bynoe  GDziobek  LSolomon  SL Nosocomial pneumonia in Medicare patients: hospital costs and reimbursement patterns under the prospective payment system. Arch Intern Med. 1991;1511109- 1114Article
104.
Haley  RWWhite  JWCulver  DHHughes  JM The financial incentive for hospitals to prevent nosocomial infections under the prospective payment system: an empirical determination from a nationally representative sample. JAMA. 1987;2571611- 1614Article
105.
Boyce  JMWhite  RLSpruill  EYWall  M Cost-effective application of the Centers for Disease Control Guideline for Prevention of Nosocomial Pneumonia. Am J Infect Control. 1985;13228- 232Article
106.
Craven  DESteger  KA Hospital-acquired pneumonia: perspectives for the healthcare epidemiologist. Infect Control Hosp Epidemiol. 1997;18783- 795Article
107.
Gaynes  RPSolomon  S Improving hospital-acquired infection rates: the CDC experience. Jt Comm J Qual Improv. 1996;22457- 467
108.
Kelleghan  SISalemi  CPadilla  S  et al.  An effective continuous quality improvement approach to the prevention of ventilator-associated pneumonia. Am J Infect Control. 1993;21322- 330Article
109.
Joiner  GASalisbury  DBollin  GE Utilizing quality assurance as a tool for reducing the risk of nosocomial ventilator-associated pneumonia. Am J Med Qual. 1996;11100- 103Article
110.
Kollef  M The prevention of ventilator-associated pneumonia. N Engl J Med. 1999;340627- 634Article
111.
Bonten  MJGaillard  CAvan Tiel  FHSmeets  HGvan der Geest  SStobberingh  EE The stomach is not a source for colonization of the upper respiratory tract and pneumonia in ICU patients. Chest. 1994;105878- 884Article
112.
Bonten  MGaillard  CJohanson  W  et al.  Colonization in patients receiving and not receiving topical antibiotic prophylaxis. Am J Respir Crit Care Med. 1994;1501332- 1340Article
113.
Pingleton  SKHinthorn  DRLiu  C Enteral nutrition in patients receiving mechanical ventilation: multiple sources of tracheal colonization include the stomach. Am J Med. 1986;80827- 832Article
114.
Flynn  DMWeinstein  RANathan  CGaston  MAKabins  SA Patients' endogenous flora as the source of "nosocomial" Enterobacter in cardiac surgery. J Infect Dis. 1987;156363- 368Article
115.
Weber  DWilson  MRutala  WThomann  C Manual ventilation bags as a source for bacterial colonization of intubated patients. Am Rev Respir Dis. 1990;142892- 894Article
116.
Craven  DGoularte  TMake  B Contaminated condensate in mechanical ventilator circuits: a risk factor for nosocomial pneumonia? Am Rev Respir Dis. 1984;129625- 628
117.
Cross  ARoup  B Role of respiratory assistance devices in endemic nosocomial pneumonia. Am J Med. 1981;70681- 685Article
118.
Craven  DLichtenberg  DGoularte  TMake  BMcCabe  W Contaminated medication nebulizers in mechanical ventilator circuits: source of bacterial aerosols. Am J Med. 1984;77834- 838Article
119.
Doebbeling  BNStanley  GLSheetz  CT  et al.  Comparative efficacy of alternative hand-washing agents in reducing nosocomial infections in intensive care units. N Engl J Med. 1992;32788- 93Article
120.
Patterson  JEVecchio  JPantelick  EL  et al.  Association of contaminated gloves with transmission of Acinetobacter calcoaceticus var. anitratus in an intensive care unit. Am J Med. 1991;91479- 483Article
121.
Hartstein  AIRashad  ALLiebler  JM  et al.  Multiple intensive care unit outbreak of Acinetobacter calcoaceticus subspecies anitratus respiratory infection and colonization associated with contaminated, reusable ventilator circuits and resuscitation bags. Am J Med. 1988;85624- 631Article
122.
Mulin  BRouget  CClement  C  et al.  Association of private isolation rooms with ventilator-associated Acinetobacter baumanii pneumonia in a surgical intensive-care unit. Infect Control Hosp Epidemiol. 1997;18499- 503Article
123.
Johanson  WG  JrSeidenfeld  JJde los Santos  RCoalson  JJGomez  P Prevention of nosocomial pneumonia using topical and parenteral antimicrobial agents. Am Rev Respir Dis. 1988;137265- 272Article
124.
Sanchez Garcia  MCambronero Galache  JALopez Diaz  J  et al.  Effectiveness and cost of selective decontamination of the digestive tract in critically ill intubated patients: a randomized, double-blind, placebo-controlled, multicenter trial. Am J Respir Crit Care Med. 1998;158908- 916Article
125.
Pugin  JAuckenthaler  RLew  DPSuter  PM Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia: a randomized, placebo-controlled, double-blind clinical trial. JAMA. 1991;2652704- 2710Article
126.
Cockerill  FR  IIIMuller  SRAnhalt  JP  et al.  Prevention of infection in critically ill patients by selective decontamination of the digestive tract. Ann Intern Med. 1992;117545- 553Article
127.
Kollef  MH The role of selective digestive tract decontamination on mortality and respiratory tract infections: a meta-analysis. Chest. 1994;1051101- 1108Article
128.
Not Available, Meta-analysis of randomised controlled trials of selective decontamination of the digestive tract: Selective Decontamination of the Digestive Tract Trialists' Collaborative Group. BMJ. 1993;307525- 532Article
129.
Heyland  DKCook  DJJaeschke  RGriffith  LLee  HNGuyatt  GH Selective decontamination of the digestive tract: an overview. Chest. 1994;1051221- 1229Article
130.
Quinio  BAlbanese  JBues-Charbit  MViviand  XMartin  C Selective decontamination of the digestive tract in multiple trauma patients: a prospective double-blind, randomized, placebo-controlled study. Chest. 1996;109765- 772Article
131.
Verwaest  CVerhaegen  JFerdinande  P  et al.  Randomized, controlled trial of selective digestive decontamination in 600 mechanically ventilated patients in a multidisciplinary intensive care unit. Crit Care Med. 1997;2563- 71Article
132.
Sun  XWagner  DPKnaus  WA Does selective decontamination of the digestive tract reduce mortality for severely ill patients? Crit Care Med. 1996;24753- 755Article
133.
Donowitz  LGPage  MCMileur  BLGuenthner  SH Alteration of normal gastric flora in critical care patients receiving antacid and cimetidine therapy. Infect Control. 1986;723- 26
134.
Daschner  FKappstein  IEngels  I  et al.  Stress ulcer prophylaxis and ventilation pneumonia: prevention by antibacterial cytoprotective agents? Infect Control Hosp Epidemiol. 1988;959- 65Article
135.
Garvey  BMMcCambley  JATuxen  DV Effects of gastric alkalization on bacterial colonization in critically ill patients. Crit Care Med. 1989;17211- 216Article
136.
Thomason  MHPayseur  ESHakenewerth  AM  et al.  Nosocomial pneumonia in ventilated trauma patients during stress ulcer prophylaxis with sucralfate, antacid, and ranitidine. J Trauma. 1996;41503- 508Article
137.
Prod'hom  GLeuenberger  PKoerfer  J  et al.  Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or sucrulfate as prophylaxis for stress ulcer: a randomized controlled trial. Ann Intern Med. 1994;120653- 662Article
138.
Driks  MRCraven  DECelli  BR  et al.  Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers: the role of gastric colonization. N Engl J Med. 1987;3171376- 1382Article
139.
Cook  DJLaine  LAGuyatt  GHRaffin  TA Nosocomial pneumonia and the role of gastric pH: a meta-analysis. Chest. 1991;1007- 13Article
140.
Cook  DJReeve  BKGuyatt  GH  et al.  Stress ulcer prophylaxis in critically ill patients: resolving discordant meta-analyses. JAMA. 1996;275308- 314Article
141.
Cook  DGuyatt  GMarshall  J  et al.  A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation: Canadian Critical Care Trials Group. N Engl J Med. 1998;338791- 797Article
142.
Bonten  MGaillard  CVan der Geest  S  et al.  The role of intragastric acidity and stress ulcer prophylaxis on colonization and infection in mechanically ventilated patients. Am J Respir Crit Care Med. 1995;1521825- 1834Article
143.
Garrouste-Orgeas  MChevret  SArlet  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;1561647- 1655Article
144.
de Latorre  FJPont  TFerrer  ARossello  JPalomar  MPlanas  M Pattern of tracheal colonization during mechanical ventilation. Am J Respir Crit Care Med. 1995;1521028- 1033Article
145.
Niederman  MSMantovani  RSchoch  PPapas  JFein  AM Patterns and routes of tracheobronchial colonization in mechanically ventilated patients: the role of nutritional status in colonization of the lower airway by Pseudomonas species. Chest. 1989;95155- 161Article
146.
Montecalvo  MASteger  KAFarber  HW  et al.  Nutritional outcome and pneumonia in critical care patients randomized to gastric versus jejunal tube feedings: The Critical Care Research Team. Crit Care Med. 1992;201377- 1387Article
147.
Heyland  DBradley  CMandell  LA Effect of acidified enteral feedings on gastric colonization in the critically ill patient. Crit Care Med. 1992;201388- 1394Article
148.
Bonten  MJGaillard  CAvan der Hulst  R  et al.  Intermittent enteral feeding: the influence on respiratory and digestive tract colonization in mechanically ventilated intensive-care-unit patients. Am J Respir Crit Care Med. 1996;154394- 399Article
149.
Cook  DDe Jonghe  BBrochard  LBrun-Buisson  C Influence of airway management on ventilator-associated pneumonia: evidence from randomized trials. JAMA. 1998;279781- 787Article
150.
Valles  JArtigas  ARello  J  et al.  Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. Ann Intern Med. 1995;122179- 186Article
151.
Mahul  PAuboyer  CJospe  R  et al.  Prevention of nosocomial pneumonia in intubated patients: respective role of mechanical subglottic secretions drainage and stress ulcer prophylaxis. Intensive Care Med. 1992;1820- 25Article
152.
Rouby  JLaurent  PGosnach  M  et al.  Risk factors and clinical relevance of nosocomial maxillary sinusitis in the critically ill. Am J Respir Crit Care Med. 1994;150776- 783Article
153.
Holzapfel  LChevret  SMadinier  G  et al.  Influence of long-term oro- or nasotracheal intubation on nosocomial maxillary sinusitis and pneumonia: results of a prospective, randomized, clinical trial. Crit Care Med. 1993;211132- 1138Article
154.
Holzapfel  LChastang  CDemingeon  GBohe  JPiralla  BCoupry  A A randomized study assessing the systematic search for maxillary sinusitis in nasotracheally mechanically ventilated patients: influence of nosocomial maxillary sinusitis on the occurrence of ventilator-associated pneumonia. Am J Respir Crit Care Med. 1999;159695- 701Article
155.
Torres  ASerra-Batlles  JRos  E  et al.  Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med. 1992;116540- 543Article
156.
Orozco-Levi  MTorres  AFerrer  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;1521387- 1390Article
157.
Nourdine  KCombes  PCarton  MJBeuret  PCannamela  ADucreux  JC Does noninvasive ventilation reduce the ICU nosocomial infection risk? a prospective clinical survey. Intensive Care Med. 1999;25567- 573Article
158.
Antonelli  MConti  GRocco  M  et al.  A comparison of noninvasive positive-pressure ventilation and conventional ventilation in patients with acute respiratory failure. N Engl J Med. 1998;339429- 435Article
159.
Nava  SAmbrosino  NClini  E  et al.  Noninvasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease: a randomized, controlled trial. Ann Intern Med. 1998;128721- 728Article
160.
Guerin  CGirard  RChemorin  CDe Varax  RFournier  G Facial mask noninvasive mechanical ventilation reduces the incidence of nosocomial pneumonia: a prospective epidemiological survey from a single ICU. Intensive Care Med. 1997;231024- 1032Article
161.
Torres  AGatell  JMAznar  E  et al.  Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation. Am J Respir Crit Care Med. 1995;152137- 141Article
162.
Stamm  AM Ventilator-associated pneumonia and frequency of circuit changes. Am J Infect Control. 1998;2671- 73Article
163.
Deppe  SAKelly  JWThoi  LL  et al.  Incidence of colonization, nosocomial pneumonia, and mortality in critically ill patients using a Trach Care closed-suction system versus an open-suction system: prospective, randomized study. Crit Care Med. 1990;181389- 1393Article
164.
Johnson  KKearney  PJohnson  SNiblett  JMacMillan  NMcClain  R Closed versus open endotracheal suctioning: costs and physiologic consequences. Crit Care Med. 1994;22658- 666Article
×