IN this issue of Anesthesiology, Bregeon et al.  1report their clinical investigation to determine whether ventilator-associated pneumonia (VAP) is an independent risk factor for death. They matched 108 nonsurvivors of mechanical ventilation with 108 survivors for their underlying diagnoses, age, gender, admission date, severity of illness, and duration of mechanical ventilation. VAP developed in the same number of patients in both groups (39 patients in each group). The authors concluded that VAP is not an important risk factor for hospital mortality. This finding is in contrast to other investigations, which have identified the occurrence of VAP as an independent determinant of hospital mortality. 2,3This discrepancy may be caused by the relatively small number of patients examined in the study by Bregeon et al.  1Additionally, other factors beyond the simple development of VAP may be more important determinants of outcome for patients in whom VAP as well as other nosocomial infections develop.

Ventilator-associated pneumonia is the most common hospital-acquired infection among patients with acute respiratory failure. 4In general, VAP can be categorized according to its onset in relation to the start of mechanical ventilation. Early onset VAP (i.e. , occurring within 96 h of the onset of ventilatory support) usually is attributed to antibiotic-sensitive bacteria, including oxacillin-sensitive Staphylococcus aureus , Haemophilus influenzae , and Streptococcus pneumoniae.  5Late-onset VAP refers to infection occurring more than 96 h after the start of mechanical ventilation and usually is caused by antibiotic-resistant bacteria, including oxacillin-resistant S. aureus , Pseudomonas aeruginosa , and Acinetobacter  species. Prolonged hospital stay and exposure to antibiotics before the onset of infection seem to be important risk factors for VAP attributed to antibiotic-resistant bacteria. 6,7 

In a larger case–control study that compared patients who had VAP with those who did not have VAP, the occurrence of VAP was found to be an independent risk factor for hospital mortality. 8More importantly, it seemed that VAP caused by antibiotic-resistant bacteria was associated more closely with excess hospital mortality. Our own group has demonstrated that VAP is an independent risk factor for hospital mortality and multiorgan dysfunction. 7,9Again, it seemed that most of the pathogens associated with VAP in these studies were high-risk antibiotic-resistant bacteria. This may explain the increased mortality observed in these studies. Inadequate initial antibiotic therapy is more likely to occur in patients infected with antibiotic-resistant bacteria. Several studies have shown that patients with VAP, as well as other nosocomial infections, who receive inadequate initial antibiotic therapy are more likely to die compared with patients treated with initial adequate antibiotic treatment. 10–13Inadequate antibiotic treatment of infection is usually defined as (1) the microbiological documentation of an infection (i.e. , a positive culture result) that was not being effectively treated at the time of its identification, (2) the absence of antimicrobial agents directed against a specific class of microorganisms (e.g. , absence of therapy for fungemia due to Candida albicans ), or (3) the administration of an antimicrobial agent to which the microorganism responsible for the infection was resistant (e.g. , empiric treatment with oxacillin for VAP subsequently attributed to methicillin-resistant S. aureus  based on appropriate culture results).

Even if VAP always was treated effectively and did not contribute to excess mortality, the prevention of this hospital-acquired infection would presumably result in shorter intensive care unit stays and less medical care costs. 14Therefore, systematically applied interventions have been developed for VAP prevention and have been shown to be successful at the local hospital level. 15,16Drakulovic et al.  17demonstrated that semi-recumbent positioning decreased the occurrence of VAP and decreased hospital mortality. Similarly, oral intubation has been shown to decrease the incidence of VAP and hospital mortality compared with nasal intubation. 18,19Reducing the duration of tracheal intubation also has been associated with lower rates of VAP. 20–22Finally, new techniques are undergoing development to prevent biofilm formation on endotracheal tubes, which have been implicated in the pathogenesis of VAP. 23 

Establishing an accurate diagnosis of VAP is controversial because of the nonspecific clinical and microbiologic markers associated with this infection (e.g. , fever, leukocytosis, radiographic infiltrates, tracheal secretions, and tracheal cultures). Nevertheless, several clinical definitions have been proposed for VAP. 24,25Other diagnostic markers, including quantitative lower airway cultures and endotoxin measurements from bronchoalveolar lavage fluid, also have been used to diagnose VAP. 26–28Three studies have found no improvement in survival for patients with VAP diagnoses clinically compared with the use of bronchoscopically obtained lower airway cultures using bronchoalveolar lavage or protected specimen brush samples. 29–31These results differ from a recent multicenter study that showed statistically lower hospital mortality and less antibiotic use with the application of bronchoscopic methods to diagnose VAP. 32However, more patients in the clinical diagnosis part of this study (11.5%) compared with the bronchoscopic diagnosis part (0.5%) were treated initially with inadequate antimicrobial therapy, confounding the mortality analysis. 11,33 

The optimal antibiotic treatment for VAP is unknown. In general, when a decision is made to treat VAP, antibiotics with demonstrable in vitro  activity against the causative bacteria should be used. Additionally, unnecessary antibiotic treatment should be avoided to limit the emergence of resistance. Singh et al.  34used a simple clinical scoring system to identify patients at lower risk of having VAP. They found that 3 days of antibiotic treatment in these patients was as effective as 10–21 days of treatment and was associated with less emergence of subsequent bacterial resistance. Similarly, in a before–after trial, we have demonstrated that 7 days of antibiotic treatment is as effective as 14 days of treatment in patients with VAP. 35Additionally, several clinical studies have found that anaerobic bacteria are uncommon in the lower airways of patients with VAP or aspiration pneumonia occurring in the hospital setting. 36,37This may explain the lack of greater efficacy among antibiotic regimens with intrinsic anaerobic activity for patients with VAP. 38 

In summary, VAP is an important nosocomial infection because of increased patient morbidity, greater hospital costs, and longer lengths of hospital stay. 14,39Clinicians practicing in the intensive care unit should support the development and routine implementation of interventions aimed at preventing VAP and encouraging rational use of antibiotic therapy.

Bregeon F, Ciais V, Carret V, Gregoire R, Saux P, Drancourt M, Auffray J-P, Papazian L: Is ventilator-associated pneumonia an independent risk factor for death? A nesthesiology 2001; 94: 554–60
Fagon JY, Chastre J, Hance AJ, Montravers P, Novara A, Gibert C: Nosocomial pneumonia in ventilated patients: A cohort study evaluating attributable mortality and hospital stay. Am J Med 1993; 94: 281–8
Craven DE: Epidemiology of ventilator-associated pneumonia. Chest 2000; 117: 186s–7s
Richards MJ, Edwards JR, Culver DH, Gaynes RP: Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med 1999; 27: 887–92
Kollef MH: Epidemiology and risk factors for nosocomial pneumonia. Clin Chest Med 1999; 20: 653–70
Trouillet JL, Chastre J, Vuagnat A, Joly-Guillou ML, Combaux D, Dombret MC, Gilbert C: Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. Am J Respir Crit Care Med 1998; 157: 531–9
Kollef MH, Sharpless L, Vlasnik J, Plasque C, Murphy D, Fraser VJ: The impact of nosocomial infections on patient outcomes following cardiac surgery. Chest 1997; 112: 666–75
Bercault N, Boulain T: Mortality associated with ventilator-associated pneumonia in an adult intensive care unit: A prospective 135 matched-pairs cohort study. Crit Care Med 2001; (in press)
Ibrahim EH, Ward S, Sherman G, Kollef MH: A comparative analysis of patients with early-onset versus late-onset nosocomial pneumonia (NP) in the ICU setting. Chest 2000; 117: 1434–42
Ibrahim EH, Sherman G, Ward S, J FV, Kollef MH: The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 2000; 118:146–55
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; 22: 387–94
Luna CM, Vujacich P, Niederman MS, Vay C, Gherardi C, Matera J, Jolly EC: Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest 1997; 111: 676–85
Rello J, Gallego M, Mariscal D, Sonora R, Valles J: The impact of routine microbial investigation in ventilator-associated pneumonia. Am J Respir Crit Care Med 1997; 156: 196–200
Markowicz P, Wolff M, Djedaini K, Cohen Y, Chastre J, Delclaux C, Merrer J, Herman B, Veber B, Fontaine A, Dreyfus D: Multicenter prospective study of ventilator-associated pneumonia during acute respiratory distress syndrome-incidence, prognosis, and risk factors. Am J Respir Crit Care Med 2000; 161: 1942–8
Joiner GA, Salisbury D, Bollin GE: Utilizing quality assurance as a tool for reducing the risk of nosocomial ventilator-associated pneumonia. Am J Medical Quality 1996; 11: 100–3
Kelleghan SI, Salemi C, Padilla S, McCord M, Mermilliod G, Canola T, Becker L: An effective continuous quality improvement approach to the prevention of ventilator-associated pneumonia. Am J Infect Control 1993; 21: 322–330
Drakulovic MB, Torres A, Bauer TT, Nicolas JM, Nogue S, Ferrer M: Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: A randomized trial. Lancet 1999; 354: 1851–8
Holzapfel L, Chastang C, Demingeon G, Bohe J, Piralla B, Coupry 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; 159: 695–701
Rouby JJ, Laurent P, Gosnach M, Cambau E, Lamas G, Zouaoui A, Leguillou JL, Bodin L, Khac TD, Marsault C, Poete P, Nicolas MH, Jarlier V, Viars P: Risk factors and clinical relevance of nosocomial maxillary sinusitis in the critically ill. Am J Respir Crit Care Med 1994; 150: 776–83
Antonelli M, Conti G, Rocco M, Bufis M, DeBlasi RA, Vivino G, Gasparetto A, Meduri GV: A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med 1998; 339: 429–35
Nava S, Ambrosino N, Clini E, Prato M, Orlando G, Vitacca M, Brigada P, Fracchia C, Rubini F: 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; 128: 721–8
Marelich GP, Murin S, Battistella F, Inciardi J, Vierra T, Roby M: Protocol weaning of mechanical ventilation in medical and surgical patients by respiratory care practitioners and nurses: Effect on weaning time and incidence of ventilator-associated pneumonia. Chest 2000; 118: 459–67
Adair CG, Gorman SP, Feron BM, Byers LM, Jones DS, Goldsmith CE, Moore JE, Kerr JR, Curran MD, Hogg G, Webb CH, McCarthy GJ, Milligan KR: Implications of endotracheal tube biofilm for ventilator-associated pneumonia. Intensive Care Med 1999; 25: 1072–6
Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM: Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic ‘blind‘ bronchoalveolar lavage fluid. Am Rev Respir Dis 1991; 143: 1121–9
Wunderink RG: Clinical criteria in the diagnosis of ventilator-associated pneumonia. Chest 2000; 117: 191S–4S
Kollef MH, Eisenberg PR, Ohlendorf MF, Wick MR: The accuracy of elevated concentrations of endotoxin in bronchoalveolar lavage fluid for the rapid diagnosis of gram-negative pneumonia. Am J Respir Crit Care Med 1996; 154: 1020–8
Baughman RP: Protected-specimen brush technique in the diagnosis of ventilator-associated pneumonia. Chest 2000; 117: 203S–6S
Torres A, El-Ebiary M: Bronchoscopic BAL in the diagnosis of ventilator-associated pneumonia. Chest 2000; 117: 198S–202S
Sanchez-Nieto JM, Torres A, Garcia-Cordoba F, El-Ebiary M, Carrillo A, Ruiz J, Nunez ML, Niederman M: Impact of invasive and noninvasive quantitative culture sampling on outcome of ventilator-associated pneumonia: A pilot study. Am J Respir Crit Care Med 1998; 157: 371–6
Violan JS, Fernandez JA, Benitez AB, Cendrero JAC, de Castro FR: Impact of quantitative invasive diagnostic techniques in the management and out of mechanically ventilated patients with suspected pneumonia. Crit Care Med 2000; 28: 2737–41
Ruiz M, Torres A, Ewig S, Marcos MA, Alcor A, Lledo R, Asenjo MA, Maldonaldo A: Noninvasive versus invasive microbial investigation ventilator-associated pneumonia: Evaluation of outcome. Am J Respir Crit Care Med 2000; 162: 119–25
Fagon JY, Chastre J, Wolff M, Gervais C, Parer-Aubas S, Stephan F, Similowski T, Mercat A, Diehl JL, Sollet JP, Tenaillon A: Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia: A randomized trial. Ann Intern Med 2000; 132: 621–8
Kollef MH, Sherman G, Ward S, Fraser VJ: Inadequate antimicrobial treatment of infections: A risk factor for hospital mortality among critically ill patients. Chest 1999; 115: 462–74
Singh N, Rogers P, Atwood CW, Yu V: Short course empiric antibiotic therapy for pulmonary infiltrates in the intensive care unit: A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med 2000; 162: 505–11
Ibrahim EH, Kollef MH: Improving antibiotic utilization for the treatment of ventilator-associated pneumonia using a clinical guideline. Chest 2000; 118: 112S
Dore P, Robert R, Grollier G, Rouffineau J, Lanquetot H, Charriere JM, Fauchere JL: Incidence of anaerobes in ventilator-associated pneumonia with use of a protected specimen brush. Am J Respir Crit Care Med 1996; 153: 1292–8
Marik PE, Careau P: The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: A prospective study. Chest 1999; 115: 178–83
Fink MP, Snydman DR, Niederman MS, Leeper KV Jr, Johnson RH, Heard SO, Wunderink RG, Caldwell JW, Schentagg JJ, Siami GA, Zamecks RL, Haverstock DC: Treatment of severe pneumonia in hospitalized patients: Results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenemcilastin. Antimicrobial Agents of Chemotherapy 1994; 38: 547–57
Heyland DK, Cook DJ, Griffith L, Keenan SP, Brun-Buissons C: The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. Am J Respir Crit Care Med 1999; 159: 1249–56