Importance, morbidity, and mortality of pneumonia in the surgical intensive care unit

Importance, Morbidity, and Mortality of Pneumonia in the Surgical Intensive Care Unit Philip S. Barie, MD, FCCM, FACS, New York, New York

Surgical patients are at high risk to develop nosocomial pneumonia, although an accurate diagnosis is difficult to make. Staphylococcus aureus and Pseudomonas aeruginosa are the most common pathogens, but Acinetobacter is emerging as an important pathogen. Because affected patients are often critically ill with multisystem pathology, it can be difficult to ascribe morbidity or mortality directly to the infection. Am J Surg. 2000;179(Suppl 2A):2S–7S. © 2000 by Excerpta Medica, Inc.

From the Department of Surgery, New York-Presbyterian Hospital, Weill Medical College of Cornell University, New York, New York, USA. Requests for reprints should be addressed to Philip S. Barie, MD, FCCM, FACS, Department of Surgery, P-713A, New YorkPresbyterian Hospital, Weill Medical College of Cornell University, 525 East 68th Street, New York, New York 10021.

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arge-scale longitudinal outcome studies indicate that pneumonia is not only the most common infectious complication in surgical patients, but that it is the most common complication of any kind after surgery.1 In a Department of Veterans Affairs cooperative study, pneumonia developed in 3.6% of patients.1 Considering that most of those patients underwent elective surgery, the percentage understates the magnitude of the problem in critically ill or injured patients. Pneumonia is now more common than surgical-site (wound) infection in surgical patients and should be of concern to every practicing surgeon, regardless of specialty. Surgical patients appear to be at particular risk of developing pneumonia for several reasons. Surgical patients are often at increased risk of infection by virtue of their illness (eg, trauma, burns, neoplastic disease) or treatment (eg, disruption of natural epithelial barriers by incision or percutaneous catheterization, emergency endotracheal intubation).2 Disruption of gut bacterial homeostasis by antibiotic therapy or prophylaxis, therapeutic immunosuppression of solid organ transplant recipients, or environmental exposure can place patients at increased risk. As examples, endemic or epidemic outbreaks of multi-drug–resistant bacteria can afflict inpatient units, and nursing home patients who undergo surgery are likely to be colonized or infected with nosocomial flora. Surgical patients at particular risk include those with multiple trauma or burns (especially with inhalation injury),3 cardiac and thoracic surgical patients,4 neurosurgical patients, and those who have undergone gastroesophageal surgery (Table).4a However, there is still debate as to whether pneumonia is diagnosed accurately, especially in mechanically ventilated patients. If pneumonia is overdiagnosed (which is the current bias), it certainly would be overtreated, and its impact on outcome could therefore be overestimated. Moreover, pneumonia in surgical patients is almost invariably a complicating factor of some other major medical problem. Therefore, it can be a challenge to attribute an adverse outcome to any specific factor. Stated simply, do surgical patients die of pneumonia, or with it? The evidence is conflicting as to whether pneumonia has an independent adverse effect on surgical outcomes; some carefully done studies suggest not. Several microbiologic factors may also influence outcome. Among these factors are the identity of the infecting organism, whether the pneumonia is complicated by bacteremia, and whether effective antibiotic therapy is administered on a timely basis. Although this analysis focuses on bacterial pathogens, it must be remembered that not all nosocomial pneumonias are caused by bacteria. Herpes virus pneumonia is recognized increasingly as a dangerous entity,5 and fungal pneumonia caused by organisms such as Aspergillus can plague transplant patients, or cause out0002-9610/00/$–see front matter PII S0002-9610(00)00316-0

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TABLE Centers for Disease Control and Prevention National Nosocomial Infection Surveillance System: Nosocomial Infection Rates, 1992–1998 Type of Infection Type of ICU Cardiothoracic Medical Neurosurgical Surgical Burn Trauma

Urinary Catheter 3.3 (2.1) 7.8 (7.0) 8.5 (7.8) 5.7 (4.9) 10.0 (NA) 7.9 (NA)

Central Line Bacteremia 2.8 (1.8) 6.1 (5.3) 5.4 (4.4) 5.7 (4.9) 12.8 (NA) 7.0 (NA)

Ventilator-Associated Pneumonia 11.7 (11.3) 8.5 (7.6) 17.3 (13.8) 14.9 (12.7) 21.1 (NA) 17.0 (NA)

ICU ⫽ intensive care unit; NA ⫽ not available. Number of occurrences ⫻ 1,000. Data are expressed as mean (median), except Number of patient-days with device indwelling where not available owing to the small number of units sampled. Adapted from National Nosocomial Infection Surveillance System.4a

breaks in units where construction is nearby in the environment.

INCIDENCE AND MORTALITY OF PNEUMONIA IN SURGICAL PATIENTS Although an occasional patient will present with concurrent surgical pathology and a community-acquired pneumonia, most surgical patients are affected by nosocomial pneumonia. Standard definitions exist for nosocomial pneumonia, including an onset after the first 72 hours of hospitalization. According to the Centers for Disease Control and Prevention,6 the patient with nosocomial pneumonia has fever, purulent sputum, leukocytosis, and a new or changed lung infiltrate by chest radiography. This convention is widely accepted and promulgated, but it leaves much to be desired, because it does not specify that a pathogenic organism must be isolated. The diagnosis of pneumonia can be challenging, especially of patients receiving mechanical ventilation (ventilator-associated pneumonia, or VAP). The oropharynx is colonized rapidly by potential pathogens shortly after hospitalization, which then may be introduced into the lower respiratory tract by such events as routine nasotracheal suctioning, emergency endotracheal intubation, or ubiquitous episodes of smallvolume aspiraton of gastric contents into the tracheobronchial tree. Microbial isolates may therefore be colonizing rather than infecting organisms, and an uncritical analysis may lead to the overdiagnosis of pneumonia. If pneumonia is diagnosed inaccurately, then estimates of mortality and especially relative risk could be rendered inaccurate. If there is a true difference in mortality, ascribing pneumonia-related mortality to patients who do not have it would tend to decrease the differences in outcome between groups. Methods to increase diagnostic accuracy are available, but controversial. Establishment of the diagnosis of pneumonia by clinical criteria (fever, leukocytosis, purulent sputum, radiographic infiltrate) and sputum collection by routine airway suctioning appears to overestimate the incidence by a factor of two or more. Alternatively, sputum can be collected and examined by several

different techniques (bronchoalveolar lavage versus protected-brush catheters, with or without bronchoscopy, qualitative microbiology or not); on balance, diagnostic accuracy is increased. Whether one technique will prove superior, and whether the use of any such methodology will have a favorable impact on outcome remain to be determined. One important aspect of the use of these technologies for the diagnosis of pneumonia is that the high specificity and negative predictive value increases the confidence of clinicians that the patient in fact does not have pneumonia and that antibiotics can be withheld or withdrawn.7 Cost savings can be substantial,8 and the microbial ecology of the patient and the unit may be improved by decreasing the incidence of multi-drug–resistant bacteria and the chance of superinfections. Incidence The incidence of pneumonia can be described in several ways, including the percentage of patients affected in the total population or a subset thereof. The incidence can be indexed to some particular relevant risk factor, such as the incidence per 1,000 patient-days or ventilator-days. For example, a recent prospective observational study that used protected bronchoscopic sputum collection techniques in critically ill medical patients identified a cumulative incidence of 7.8%, and incidence rates of 12.5 cases per 1,000 patient-days and 20.5 cases per 1,000 ventilator-days.9 Most preferably, the incidence can be described in terms of likelihood or odds ratios,9 or in terms of the relative risk in one population compared with another. The latter estimates can be adjusted to account for covariates and can be tested statistically for the validity of each observation by calculation of confidence intervals. This methodology should come into more widespread use. The incidence of nosocomial infection in surgical patients overall is approximately 5% to 8%,1 but it is much higher in critically ill patients. The incidence of pneumonia reported from surgical intensive care units (ICUs) is 15% to 20%, and occasionally higher.10 Most cases of pneumonia in critically ill patients develop while patients

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are in the ICU, but the likelihood of requiring transfer to the ICU or mechanical ventilation has been reported to be 28% and 22%, respectively, among patients who develop pneumonia while on a general ward.11 Nosocomial infection rates are not higher generally in surgical patients than in medical patients, with the notable exception of pneumonia (Table). Recent surgery, especially of the chest or abdomen/pelvis, is itself a risk factor for the development of pneumonia.12 In some high-risk patients, such as those with the acute respiratory distress syndrome (ARDS), the incidence of pneumonia has been very difficult to define. Plain radiography yields a diagnostic accuracy that is no better than a random event,13 and even computed tomography (CT) has its limitations, with most of its success deriving from the ability of CT to exclude pneumonia in those who do not have it.14 In cases of ARDS, estimates of the incidence of pneumonia vary widely. At the low end is the 15% incidence of positive bronchoscopically collected quantitative cultures in ARDS patients who underwent serial surveillance bronchoscopies at Harborview Medical Center.15 In contrast, the incidence of pneumonia complicating ARDS was 55% to 60% in two French studies, one in which surveillance cultures for quantitative microbiology were taken using the blind insertion of a plugged telescopic catheter,16 and one that used bronchoscopic bronchoalveolar lavage and quantitative microbiology when pneumonia was suspected clinically.17 The incidence of pneumonia in surgical ICUs is approximately twice as high as that reported from medical ICUs.10,12 However, it can be problematic to compare results from one ICU with those from another because of a multiplicity of confounding variables, including case mix and severity of illness. Although the issue of illness severity scoring remains controversial in surgical critical care, it is increasingly apparent that severity scoring with the Acute Physiology and Chronic Health Evaluation (APACHE) II score and especially APACHE III can predict mortality of infectious diseases with reasonable accuracy. In several studies, severity of illness has been the most important predictor of mortality of patients with nosocomial pneumonia.18,19 If severity of illness is not accounted for in outcome studies, flawed conclusions may be reached.20 Because of this variability, the mortality rates of nosocomial pneumonia in individual studies have ranged from 20% to 70%. When matched for severity of illness, nosocomial pneumonia increases the relative risk of death by three- to fourfold. Although generalizations are of limited value, nosocomial gram-positive and gram-negative infections are associated with mortality in about one third of patients. Pneumonias caused by resistant pathogens are more dangerous, but the highest mortality rates are reported consistently for Pseudomonas pneumonia. Attributable Mortality Considering the multiplicity of factors involved, it is difficult to attribute death in critically ill patients to a specific cause. This is especially true for nosocomial pneumonia, given the strong relationship between mortality and severity of illness. Estimates of mortality attributable to nosocomial pneumonia are variable and may be specialty specific. Estimates of attributable mortality in medical ICU 4S

populations range up to 65% of total mortality,21,22 whereas several studies have failed to demonstrate attributable mortality in surgical patient populations.21,23,24 It has been argued that, if mortality is not increased, expensive and sophisticated diagnostic measures are superfluous.23 However, given that no treatment and ineffective treatment each are associated with increased mortality,25,26 and that it is worthwhile to try to withhold antibiotics from patients proved not to have pneumonia, it remains reasonable to continue to try to obtain the best possible evidence in every patient. There are several potential reasons why surgical patients may not have excess mortality resulting from pneumonia. Accuracy of diagnosis is a critical issue. If pneumonia is overdiagnosed, and therefore not present, then excess mortality would be implausible. Alternatively, accurate diagnosis and rapid, accurate antibiotic therapy could produce optimal outcomes. Another possible explanation may relate to the severity of illness and the causative pathogen. Many recent surgical studies have reported relatively low crude mortality rates of 20% to 25%. Such patients may have early infections (ie, within 5 to 7 days) with more sensitive pathogens (see below), and may not require mechanical ventilation. Also, in low-risk populations a large sample size would ordinarily be necessary to detect statistical differences; considering that the incidence and mortality rate of nosocomial pneumonia is dependent on case mix, severity of illness, microbiology, and a host of other factors, power analysis of studies of pneumonia can be complex.

MICROBIOLOGY Several lines of evidence indicate that the microbiology of nosocomial infection can be influenced by many factors, which in turn can clearly influence outcome. Overall, the most common pathogen in nosocomial pneumonia is Staphylococcus aureus, with Pseudomonas aeruginosa a close second. Polymicrobial infection is uncommon.27 The microbiology is different depending on whether the pneumonia is “early” onset or “late” onset (usually defined by a cut point of 7 days after some discrete risk factor, such as the date of operation or injury). Early pneumonias tend to be caused by bacteria, such as Haemophilus influenzae28 and methicillin-sensitive S. aureus,29 whereas late pneumonias are caused by methicillin-resistant S. aureus (MRSA), Pseudomonas, Acinetobacter, and other enteric gram-negative bacilli. Sicker patients may be predisposed to these “high-risk” organisms by known risk factors for pneumonia, such as the severity of illness and attendant immunosuppression, and prolonged ventilator dependence, which would translate directly into an increased susceptibility to pneumonia extending into the putative high-risk period. Nonetheless, mortality rates are clearly higher for Pseudomonas pneumonia,30 –33 and MRSA as opposed to methicillin-sensitive S. aureus pneumonia, and possibly higher for infections caused by other gram-negative bacilli. Acinetobacter is increasingly isolated as a pathogen and appears to be associated with an increased mortality rate also.34,35 Bacteremic Pneumonia Nosocomial pneumonias can sometimes be associated with bacteremia. Common pathogens, including S. aureus

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and P. aeruginosa, are known to cause pneumonia on a hematogenous basis, but conversely the bacteremia may be a secondary event. In either case, the incidence is relatively low (approximately 10%),11 but the stakes are high. The mortality rate of bacteremic nosocomial pneumonia is reported to be 45% to 48%.36,37 Bacteremia resulting from pneumonia may have higher mortality than nonpneumonic bacteremias,38 and Pseudomonas carries especially high risk. Data also demonstrate that a reduced incidence of bacteremia can be a consequence of appropriate empiric therapy.39 Impact of Antibiotics on Risk and Outcome The “high-risk” pathogens may pose their increased risk because they are commonly resistant to multiple antibiotics, leading to the failure of inappropriate empiric antibiotic regimens that directly increases mortality.25,40 Conversely, several studies indicate that previous antibiotic therapy increases the risk of developing pneumonia,41 as well as other nosocomial infections. Some specific antibiotics used as empiric therapy, notably ceftazidime, have been associated with increased likelihood of empiric therapeutic failure and increased mortality.34,39,41,42 Careful selection of empiric treatment regimens, so as to cover the likely pathogens and the possibility of antibiotic resistance, can reduce the risk of death.39,43 Accurate therapy is a critical issue, but so may be timing. Administration of an initially inappropriate regimen has been associated with increased mortality that is not reduced by the subsequent correction of the regimen based on microbiologic data,25 but rapid empiric therapy will inevitably have the undesirable result of patients being treated who do not have pneumonia. Two studies in surgical patients suggest that waiting to start antibiotics until after bronchoscopic specimen collection,25 or that delays in therapy of as much as 24 hours after the diagnosis is established,44 do not have an adverse effect on outcome. For many years, a complex multipart hypothesis of the pathogenesis of pneumonia has evolved. It has been hypothesized that the gastrointestinal tract is an endogenous reservoir of potential pneumonia pathogens. Overgrowth of pathogens is promoted by the gastric cytoprotective actions of a therapeutic reduction of gastric acidity. Considering that aspiration of gastric contents into the tracheobronchial tree is ubiquitous in critically ill patients, and that airway colonization follows aspiration and precedes the development of invasive pathogens, the incidence of pneumonia has been hypothesized to increase as a result. The evidence in favor of the hypothesis is conflicting. On the one hand, the use of antacids and H2-receptor antagonists for prophylaxis of stress-related gastric mucosal hemorrhage does not increase the risk of nosocomial pneumonia.45 On the other hand, selective digestive decontamination (SDD) by the topical administration of antibacterial and antifungal agents to the oropharynx and gastric lumen appears to have favorable effects on mortality, the incidence of pneumonia, and the incidence of bacteremia in critically ill surgical patients.46 However, in critically ill medical patients the effect is observed only for pneumonia. Confounding the interpretation, and perhaps accounting for the limited acceptance that SDD has enjoyed in clinical practice, is the fact that the salutary effects are most

prominent in patients who also received intravenous antibiotic prophylaxis, usually cefotaxime (a third-generation cephalosporin).

COMPLICATIONS The morbidity of nosocomial pneumonia is substantial but less well quantified than mortality. A fundamental issue is the differentiation of the morbidity of the disease from that of the treatment. Mechanical ventilation may be prolonged as a result of pneumonia,47 but prolonged intubation and ventilation beforehand is a known risk factor for pneumonia. Moreover, tracheostomy is intimately related to the duration of mechanical ventilation. Tracheostomy has been reported to reduce the incidence of pneumonia,48 but also to increase the risk. The duration of mechanical ventilation and the length of the ICU stay or the entire hospitalization thus become difficult to quantify as risks. Likewise, nonpulmonary organ dysfunction appears to be a risk factor for the development of pneumonia, as well as a major adverse outcome that is directly related to increased mortality. Copious airway secretions or bleeding from necrotizing pneumonia or tracheobronchitis can lead to airway obstruction, hypoventilation, aggravated hypoxemia, and the possibility of tissue ischemia/infarction. Airway bleeding could be related to the infection, or a tracheostomy-related complication. Empyema is rare, and in selected patients, such as multiple trauma patients who undergo emergency tube thoracostomy for blunt thoracic trauma, pneumonia could result from the injury, whereas empyema might relate to poor infection-control practices during insertion of the catheter. Adverse drug interactions related to antibiotic use are common49 and must not be discounted even though their interpretation is problematic. For example, it may be impossible to ascribe thrombocytopenia to the antibiotic as opposed to the infection.

NOSOCOMIAL PNEUMONIA: ARE SURGICAL PATIENTS DIFFERENT? Although not invariably the case, surgical and medical patients do appear to be different with respect to nosocomial pneumonia in several aspects. The risk of developing pneumonia is higher in surgical patients. The microbiology and the overall mortality rate appear to be similar, but the mortality attributable to pneumonia appears to be less in surgical patients. Perhaps these same risk factors (such as severity of illness) lead to pneumonia, exerting independent effects on mortality that overwhelm any apparent contribution of pneumonia. There is no evidence that surgical patients require antibiotic therapy that is inherently different. There are aspects of antibiotic administration that may highlight differences. Brief delays in antibiotic therapy may not be harmful in surgical patients, and SDD appears to be more effective in critically ill surgical patients. The reasons for these putative differences remain inapparent and portend an active future for clinical research in critically ill surgical patients afflicted with nosocomial pneumonia.

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in ventilated patients. A cohort study evaluating attributable mortality and hospital stay. Am J Med. 1993;94:281–288. 23. Helling TS, Van Way C III, Krantz S, et al. The value of clinical judgement in the diagnosis of nosocomial pneumonia. Am J Surg. 1996;171:570 –575. 24. Baker AM, Meredith JW, Haponik EF. Pneumonia in intubated trauma patients. Microbiology and outcome. Am J Respir Crit Care Med. 1996;153:343–349. 25. Luna CM, Vujacich P, Niederman MS, et al. Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest. 1997;111:676 – 685. 26. Croce MA, Fabian TC, Schurr MJ, et al. Using bronchoalveolar lavage to distinguish nosocomial pneumonia from systemic inflammatory response syndrome: a prospective analysis. J Trauma. 1995;39:1134 –1139. 27. Rello J, Quintana E, Ausina V, et al. Incidence, etiology, and outcome of nosocomial pneumonia in mechanically ventilated patients. Chest. 1991;100:439 – 444. 28. Singh N, Falesting MN, Rogers P, et al. Pulmonary infiltrates in the surgical ICU: prospective assessment of predictors of etiology and outcome. Chest. 1998;114:1129 –1136. 29. Pujol M, Corbella X, Pena C, et al. Clinical and epidemiological findings in mechanically ventilated patients with methicillinresistant Staphylococcus aureus pneumonia. Eur J Clin Microbiol Infect Dis. 1998;17:622– 628. 30. Almirall J, Mesalles E, Klamburg J, et al. Prognostic factors of pneumonia requiring admission to the intensive care unit. Chest. 1995;107:511–516. 31. Rello J, Rue M, Jubert P, et al. Survival in patients with nosocomial pneumonia: impact of the severity of illness and the etiologic agent. Crit Care Med. 1997;25:1862–1867. 32. Rello J, Jubert P, Valles J, et al. Evaluation of outcome for intubated patients with pneumonia due to Pseudomonas aeruginosa. Clin Infect Dis. 1996;23:973–978. 33. Couch-Brewer S, Wunderink RG, Jones CB, Leeper KV Jr. Ventilator-associated pneumonia due to Pseudomonas aeruginosa. Chest. 1996;109:1019 –1029. 34. Husni RN, Goldstein LS, Arrologa AG, et al. Risk factors for an outbreak of multi-drug-resistant Acinetobacter nosocomial pneumonia among intubated patients. Chest. 1999;115:1378 –1382. 35. Baraibar J, Correa H, Mariscal D, et al. Risk factors for infection by Acinetobacter baumanii in intubated patients with nosocomial pneumonia. Chest. 1997;112:1050 –1054. 36. Taylor GD, Buchanan-Chell M, Kirkland T, et al. Bacteremic nosocomial pneumonia. A 7-year experience in one institution. Chest. 1995;108:786 –788. 37. Bryan CS, Reynolds KL. Bacteremic nosocomial pneumonia. Analysis of 172 episodes from a single metropolitan area. Am Rev Respir Dis. 1984;129:668 – 671. 38. Pittet D, Li N, Woolson RF, Wenzel RP. Microbiological factors influencing the outcome of nosocomial blood stream infections: a 6-year, validated, population-based model. Clin Infect Dis. 1997;24:1068 –1078. 39. Kollef MH, Vlasnik J, Sharpless L, et al. Scheduled change of antibiotic classes: a strategy to decrease the incidence of ventilatorassociated pneumonia. Am J Respir Crit Care Med. 1997;156:1040 – 1048. 40. Kollef MA, Ward S. The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia. Chest. 1998;113:412– 420. 41. Weber DJ, Raasch R, Rutala WA, et al. Nosocomial infections in the ICU: the growing importance of antibiotic-resistant pathogens. Chest. 1999;115(suppl 3):34S– 41S. 42. Joshi M, Bernstein J, Solomkin J, et al. Piperacillin/tazobactom plus tobramycin versus ceftazidime plus tobramycin for the treatment of patients with nosocomial lower respiratory tract infection. Piperacillin/tazobactam Nosocomial Pneumonia Study Group. J Antimicrob Chemother. 1999;43:389 –397. 43. Schentag JJ, Birmingham MC, Paladino JA, et al. In nosoco-

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mial pneumonia, optimizing antibiotics other than aminoglycosides is a more important determinant of successful clinical outcome, and a better means of avoiding resistance. Semin Respir Infect. 1997;12: 278 –293. 44. Pelletier SJ, Crabtree TD, Gleason TG, Sawyer RG. Waiting for microbiologic data to direct therapy against nosocomial infections does not worsen outcome in surgical patients. Seattle, WA: Surgical Infection Society Program Book, 1999:47. 45. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses. JAMA. 1996;275:308 –314.

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DISCUSSION

monia. We see a large population of patients whom we are treating early, but for very short periods of time, maybe 5 to 7 days, and I wonder whether the ecology and epidemiology of pneumonia is changing. Perhaps your patients are different from mine. Jorge L. Rodriguez, MD (Minneapolis, Minnesota): It is very clear in young trauma patients without a lot of comorbidity that getting nosocomial pneumonia will increase their ventilator days, ICU days, but it is not going to kill them. Pneumonia may hurt the older surgical patient with significant morbidity who has gone into emergency operation. That is the difference. David A. Spain, MD (Louisville, Kentucky): I think the first half of your statement is true if the pneumonia does not recur or persist. Dr. Rodriguez: As long as you appropriately treat it. Dr. Barie: We also have to postulate here that many of those patients may in fact be dying of multiple organ failure. Even though they still have a pro-inflammatory type response, they may have dead bacteria and dead tissue in there. Dr. Rodriguez: Patient population becomes critical as you start defining some of the problems with these nicely delineated studies that you mentioned. The patient relation is fairly heterogeneous in these large studies. Dr. Barie: One of the studies that claimed no difference in attributable mortality was a trauma study. Dr. Fabian: Let’s be careful with the concept of attributable mortality. When does the patient die from pneumonia? It is not an on-and-off dichotomous switch. There is going to be some bias in assessing attributable mortality. Dr. Malangoni: Otherwise, all attributable mortality would be due to the fact that your heart stopped beating and you stopped breathing. The autopsy study would state the cause of death as cardiorespiratory arrest. That kills everybody. Dr. Barie: It is nearly impossible to categorize these patients with only a single disease entity. You could say they are dying from their underlying disease and their pneumonia has nothing to do with it. Dr. Fabian: There may be two pathways to death with pneumonia. One, pneumonia initiates the multiple organ failure syndrome and the patient dies with sterile lungs. That might not be something that matters, as opposed to the person who goes down the street having a pneumonia attack that kills him.

Philip S. Barie, MD (New York, New York): The most powerful predictor of how a patient is going to do is probably how sick the patient is. With the probable exception of Pseudomonas pneumonia and MRSA, and possibly Acinetobacter, in good studies that have been adjusted for severity of illness you do not see the organism as an independent risk factor predicting mortality. We have to focus on how sick the patients are and make sure the groups we are comparing are fairly comparable in several different respects. Once we do that, we will get a better handle on these outcomes. Timothy C. Fabian, MD (Memphis, Tennessee): It brings us back to the issue of diagnosis. Are in fact these studies saying there is no attributable mortality? Is Cook looking at a group of patients, half of whom are colonized rather than having pneumonia? How were they diagnosed? Dr. Barie: The Cook study is a very high-quality study. You can perhaps quibble about the other two. They were diagnosed prospectively with bronchoscopic alveolar lavage quantitative cultures. Mark A. Malangoni, MD (Cleveland, Ohio): Isn’t it true that what you have shown is that there is no attributable mortality to properly treated ventilator-acquired pneumonia? If you say there is no attributable mortality in pneumonia, you can conclude that you do not have to treat anyone, and I think none of us would do that. Dr. Barie: No. In fact, I included the caveat that I would not do that either. That may be what we are seeing, that if the patient is adequately treated, the outcome will be no different. But that means that there is no attributable mortality if we have maximized appropriate therapy as our desired endpoint. Dr. Malangoni: Do you believe that? Is that your experience? It is not mine. There are people in our ICU who die from pneumonia, and therefore there is an attributable mortality. I agree it is more often from the high-risk organism, but these studies say there is no attributable mortality. Does that work in my unit? No, and that is what I am trying to reconcile. Dr. Barie: There may be such patients, and of course we are all burdened by our own observational biases. That was one of the stumbling blocks to the lack of acceptance of these high-technology–assisted diagnoses of pneumonia that everyone is now beginning to accept. There are data now showing that whatever method you choose is better than clinical assessment alone for the diagnosis of pneu-

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