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Nosocomial pneumonia: Problems and progress
Nosocomial pneumonia: Problems and progress Helen M. Crowe, MD, Waterbury, Conn.
N
osocomial pneumonia is one of the most formidable complications to which the hospitalized patient is prey, with a mortality rate estimated at between 30% and 70%.1 Although not uncommon on general medical and surgical wards, pneumonia is primarily a disease of the intensive care unit (ICU), where it is the most common nosocomial infection. Patients for whom mechanical-ventilation is required have an incidence of pneumonia nearly 20 times that of nonintubated patients. Crude incidence ratios suggest that some 25% of intubated patients may develop pneumonia according to clinical criteria with rates differing according to the type of ICU. 1 Recent estimates by the Centers for Disease Control put nosocomial pneumonia responsible for an average of 5.9 days of increased length of stay and nearly $6000 in hospital charges. 2 In the n o n i n t u b a t e d patient, pneumonia occurs primarily because of aspiration of oropharyngeal-colonizing bacteria into the lungs, which sedatives and neurologic deficits can facilitate. For the patient receiving mechanical ventilation, however, airway defenses are bypassed by numerous tubes such as endotracheal, nasotracheal, and nasogastric tubes. Although the cuffed endotracheal tube is commonly thought to block the aspiration of bacteria-laden, upper airway secretions into the lower respiratory tree, it is an
From the Section of Infectious Diseases,Waterbury Hospital, Waterbury Reprint requests: Brian W. Cooper, MD, Chief, Division of InfectiousDiseases,Hartford Hospital,80 SeymourSt., Hartford, CT06102-5037. Heart Lung| 1996;25:418-2l Copyright@ 1996by Mosby-YearBook, inc. 0147~9563/96/$5.00+ 0 2/1/73269
418
imperfect barrier--secretions may flow around it, and the condensate that accumulates inside the tube contains large numbers of bacteria that may reflux into the lungs, if care is not taken to pre* vent this. 3 Additionally, the presence of tubes in the stomach renders the lower esophageal sphincter incompetent, which allows gastric contents to flow retrograde and potentially leak around the endotracheal tube, particularly in the recumbent position. 4 The primary bacteria that cause nosocomial pneumonia are gram-negative, although the specific species thought to be responsible has changed because of newer diagnostic techniques. Enteric gram-negative bacilli formerly were thought to cause two thirds of these incidences of pneumonia, whereas they are now felt to be responsible for 20% or less. ~ Pseudomonas aeruginosa and Acinetobacter spp. now account for one third to one half of ventilator-associated pneumonia, whereas gram-positive organisms such as Staphylococcus aureus and Streptococus pneumoniae cause 25% to 30%. Gram*negative bacteria are the predominant etiologic agents because colonization of the oropharynx by gram-negative organisms occurs in hospitalized patients, virtually all of whom exist under conditions of physio* logic stress. It is believed that stress facilitates the secretion of salivary proteases, which degrade a substance known as fibronectin, a glycopeptide that normally coats the surface of oral mucosal cells. Gram-positive organisms adhere to fibronectin and constitute the indigenous flora of the mouth, but when fibronectin is degraded, gram-negative bacteria become capable of attaching to the cells of the mouth, which changes the resident flora. 1 If these organisms are aspirated in sufficient numbers into the lungs, pneumonia can result.
SEPTEMBER/OCTOBER | 996 H E A R T & L U N G
There has been considerable interest in recent years in the stomach as a reservoir of gram-negative organisms. Although gram-negative organisms may reach the stomach and multiply there in large numbers, particularly when gastric acidification is impaired, the so-called "gastropulmonary route" of infection does not appear to be the major mode of pneumonia developing in most patients. ~ Which groups of patients in the ICU are at par~ ticular risk of developing pneumonia? A compila~ tion of risk factors from multiple studies identified the following characteristicsl: duration of mechanical ventilatio n , advanced age, severity of illness, chronic lung diseases, head trauma, reintubation or self-extubation, upper abdominal or thoracic surgery, ventilator circuit changes at less than 48 hour intervals, supine head position, trauma, stress ulcer with macroscopic bleeding, fall or winter season, prior antibiotic therapy, use of a nasogastric tube, bronchoscopy, shock, trauma with emergency intubation, gross aspiration of gastric contents, and gastric acid inhibitor therapy. Poor nutritional state and immunosuppression may also adversely affect the development of pneumonia. The use of antacids and histamine type 2 receptor (H 2) blockers has been identified in a multivariate analysis as a risk factor for the development of nosocomial pneumonia. 6 A subsequent study suggested that the use of sucralfate as gastritis prophylaxis in ICU patients resulted in a lower incidence of nosocomial pneumonia than in a group of patients receiving H 2 blockers or antacids; however, and indeed, in this study, the group receiving H 2 blockers alone had the lowest incidence of pneumonia. 7 The question of which stress-ulcer prophylaxis regimen results in the lowest incidence of nosocomial pneumonia remains open, although the use of sucralfate should be considered. a,9 The past decade also has seen considerable controversy regarding the best method to use to diagnose ventilator-associated pneumonia. Traditional clinical criteria--fever, sputum purulence, new infiltrates on chest radiograph, isolation of a pathogen from respiratory secretions-are at best imprecise indicators of lower respiratory tract infection, with an accuracy of only 62% in a recent study that compared clinical criteria to a protected specimen brush (PSB) technique. 1~ Many noninfectious conditions, such as pulmonary embolism, adult respiratory distress syndrome, and chemical pneumonitis can cause
HEART & L U N G VOL. 25, NO. 5
fever and pulmonary infiltrates on a chest radiograph but not require antimicrobial therapy. The new techniques attempt to circumvent the problem of contamination of secretions obtained through the endotracheal tube. Two techniques, PSB and protected bronchoalveolar lavage, with quantitative culture, have been reviewed recently. ~,12 Briefly, PSB involves bronchoscopy in which a sterile brush is protected inside the bronchoscope by an absorbable plug that can be displaced on entry into a lung segment. The sterile brush is then advanced to obtain a specimen. The brush is withdrawn into the bronchoscope, which is removed and material from the brush is cultured quantitatively. Protected bronchoalveolar lavage involves wedging a bronchoscope into a lung segment before admitting lavage fluid, which is then withdrawn and quantitatively cultured. Whether these techniques should be applied to every patient is controversial. Many patients may respond promptly to empiric antimicrobial therapy for suspected pneumonia without the necessity of an invasive procedure. Both techniques involve bronchoscopy and quantitative cultures, which are labor intensive and expensive. Proponents argue that by improving the accuracy of diagnosis for pneumonia, overuse of antibiotics and s u b s e q u e n t d e v e l o p m e n t of resistant microorganisms will be avoided. 12 Unfortunately, the newer techniques also have problems, which cause difficulty in making the correct diagnosis in patients receiving antimicrobial therapy. 13,14Additionally, clinicians, knowing the risk of death in patients with ventilator-associated pneumonia, may not be willing to withhold antibiotics despite a negative culture result. Until further studies define the clinical utility and cost-effectiveness of these methods, they cannot be recommended for all hospitals at present. However, refinements in the techniques and greater willingness to withhold antibiotics may change this in the future. There are several pathogens that, if present at all in a sample of lower respiratory secretions, signify they are the etiologic agents of the disease. These include Legionella pneumophila and respiratory syncytial and influenza viruses. These organisms are uncommon causes of nosocomial pneumonia at most hospitals, but should be looked for occasionally, particularly during seasonal community outbreaks of respiratory illness or in perplexing cases of pneumonia.
419
The therapy of nosocomial pneumonia is complex and depends on many factors, including the timing of the development of pneumonia in the patient's hospital course, prior antibiotic therapy, and the indigenous flora of the specific ICU. Suffice it to say that single-drug, ~-lactam therapy is sufficient for most gram~positive types of pneumonia and those caused by common Enterobacteriaceae (Escherichia coli, Klebsiella); but for significant types of pneumonia with resistant gram-negative pathogens, especially P. aerugi, nosa, dual therapy with an aminoglycoside combined with a [3qactam should be used to improve efficacy and discourage the development of resistant microorganisms. 15 The duration of therapy depends on the patient's clinical course and the microorganism responsible, but some patients may be candidates for early oral therapy, which may expedite their transfer from the ICU or hospital discharge. Finally, how can those caring for critically ill patients prevent them from developing nosocomial pneumonia? Several simple techniques are recommended, such as elevating the patient's head whenever possible, avoiding reflux of condensate down the endotracheal tube, and good hand washing between care of each patient. 8,9 Ventilator tubing should b e changed no more than every 48 hours, and respiratory equipment should be disinfected between patients. More sophisticated techniques have been proposed, such as administration of sucralfate instead of antacids as prophylaxis against stressqnduced gastrointestinal bleeding, which, as noted, requires more study. The routine administration of topical and systemic antibiotics to prevent infection--known as selective digestive decontamination-was popular at some centers several years ago, but has not been shown to benefit the general population of ICU patients ~6 and cannot be recommended for general use. A recent study suggested that continuous aspiration of subglottic secretions could prevent the development of subsequent pneumonia17; such a Conceptually simple and easily implemented technique deserves more extensive evaluation. Other commonly used practices to prevent pneumonia should be continued. Patients should be counseled before surgery regarding the need to cough and in deep breathing and incentive inspirometry. Postoperative pain should be adequately controlled, with use of parenteral analgesics and nerve blocks or epidural analgesia, or bothl Staff should be educated
420
regarding risk factors for nosocomial pneumonia, potential severity for the patient, and preventive measures. In the future, pneumonia should continue to be recognized as a major hurdle for the hospitalized patient in terms of both morbidity and mortality rates and medical costs. Funding, research efforts, and the development of new technology should be directed at preventing ventilator-associated pneumonia, the most significant nosocomial infectionof ICUs.
REFERENCES 1. George DL. Epidemiology of pneumonia in intensive care unit patients. Clin Chest Med 1995;16:29-44. 2. CDC. Public health focus: surveillance, prevention and control of nosocomial infections. MMWR Morb Mortal Wkly Rep 1992;41:783-7. 3. Craven DE, Goularte TA, Make BJ. Contaminated condensate in mechanical ventilator circuits: a risk factor for nosocomial pneumonia? Am Rev Respir Dis 1984;129: 625-8. 4. Tortes A, Serra-Batlles J, Ros E, Piera C, Puig de la Bellacasa J, Cobos A, et al. Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med 1992;116:540-3. 5. Bonten MJM, Gaillard CA, van Tiel FH, Smeets HG, Van der Geest S 5tobberingh EE. The stomach is not a source for colonization of the upper respiratory tract and pneumonia in ICU patients Chest 1994 105:878~84. 6. Craven DE. Kunches LM. Kilinsky V, Lichtenberg DA Make BI McCabe WR.. Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation Am Rev Respir Dis 1986-133:792-6. 7. Driks MR. Craven DE Celli BR Manning M Burke RA. Garvin GM et al. Nosocomial pneumoma in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. New Engl I Med 1987:317:137682 8. Craven DE. Prevention of hospital-acquired pneumonia: measuring effect in ounces, pounds and tons. Ann Intern Med 1995 122:229-31. 9 Tablan OC Anderson LJ, Arden NH Breiman RE Butler JC McNeil MN et al. Guidelines for the prevention of nosocomial pneumonia Infect Control Hosp Epidemiol 1994 15:587-90 10. Fagon IY Chastre I HanceAI Domart Y Trouillet IL. Gibert C. Evaluation of clinical judgment in the identification and treatment of nosocomial pneumonia in ventilated patients. Chest 1993 102:547-53. 11 Griffen II Meduri GU. New approaches in the diagnosis of nosocomial pneumoma Med Clin North Am 1994 78:1091 122. 12 Chastre 1. Fagon JY Trouillet IL. Diagnosis and treatment of nosocomial pneumonia in patients in intensive care units. Clin Infect Dis 1995 21(suppl 31:$226~37 13. Torres A El~Eb~ary M. Padro L Gonzalez J de la Bellasca JP, Ramirez I e t al. Validation of different techniques for the diagnosis of ventilator-associated pneumonia: comparison with immediate postmortem pulmonary biopsy. Am J Respir Crit Care Med 1994;149:324~31. 14. Bouten MJ, Gaillard CA, Wouters EF, van Tiel FH, $tobberingh EE, van der Geest S. Problems in diagnosing nosocomial pneumonia in mechanically ventilated patients: a review. Crit Care Med 1994;22:1683~91.
SEPTEMBER/OCTOBER 1996 HEART & L U N G
15. Niederman MS. An approach to empiric therapy of nosocomial pneumonia. Med Clin North Amer 1994;78:1123-41. 16. Gastinne H, Wolff M, Delatour F, Faurisson F, Chevret S. A controlled trial in intensive care units of selective decontamination of the digestive tract with nonabsorbable antibiotics. N Engl J Med 1992;326:54-9.
17. Valles J, Artigas A, Rello J, Bonsoms N, Fontanals D, Blanch L, et al. Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. Ann Intern Med 1995; 122:179~86.
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HEART & LUNG VOL.25, NO. 5
OR FAX TO:
OR PHONE:
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421
N
osocomial pneumonia is one of the most formidable complications to which the hospitalized patient is prey, with a mortality rate estimated at between 30% and 70%.1 Although not uncommon on general medical and surgical wards, pneumonia is primarily a disease of the intensive care unit (ICU), where it is the most common nosocomial infection. Patients for whom mechanical-ventilation is required have an incidence of pneumonia nearly 20 times that of nonintubated patients. Crude incidence ratios suggest that some 25% of intubated patients may develop pneumonia according to clinical criteria with rates differing according to the type of ICU. 1 Recent estimates by the Centers for Disease Control put nosocomial pneumonia responsible for an average of 5.9 days of increased length of stay and nearly $6000 in hospital charges. 2 In the n o n i n t u b a t e d patient, pneumonia occurs primarily because of aspiration of oropharyngeal-colonizing bacteria into the lungs, which sedatives and neurologic deficits can facilitate. For the patient receiving mechanical ventilation, however, airway defenses are bypassed by numerous tubes such as endotracheal, nasotracheal, and nasogastric tubes. Although the cuffed endotracheal tube is commonly thought to block the aspiration of bacteria-laden, upper airway secretions into the lower respiratory tree, it is an
From the Section of Infectious Diseases,Waterbury Hospital, Waterbury Reprint requests: Brian W. Cooper, MD, Chief, Division of InfectiousDiseases,Hartford Hospital,80 SeymourSt., Hartford, CT06102-5037. Heart Lung| 1996;25:418-2l Copyright@ 1996by Mosby-YearBook, inc. 0147~9563/96/$5.00+ 0 2/1/73269
418
imperfect barrier--secretions may flow around it, and the condensate that accumulates inside the tube contains large numbers of bacteria that may reflux into the lungs, if care is not taken to pre* vent this. 3 Additionally, the presence of tubes in the stomach renders the lower esophageal sphincter incompetent, which allows gastric contents to flow retrograde and potentially leak around the endotracheal tube, particularly in the recumbent position. 4 The primary bacteria that cause nosocomial pneumonia are gram-negative, although the specific species thought to be responsible has changed because of newer diagnostic techniques. Enteric gram-negative bacilli formerly were thought to cause two thirds of these incidences of pneumonia, whereas they are now felt to be responsible for 20% or less. ~ Pseudomonas aeruginosa and Acinetobacter spp. now account for one third to one half of ventilator-associated pneumonia, whereas gram-positive organisms such as Staphylococcus aureus and Streptococus pneumoniae cause 25% to 30%. Gram*negative bacteria are the predominant etiologic agents because colonization of the oropharynx by gram-negative organisms occurs in hospitalized patients, virtually all of whom exist under conditions of physio* logic stress. It is believed that stress facilitates the secretion of salivary proteases, which degrade a substance known as fibronectin, a glycopeptide that normally coats the surface of oral mucosal cells. Gram-positive organisms adhere to fibronectin and constitute the indigenous flora of the mouth, but when fibronectin is degraded, gram-negative bacteria become capable of attaching to the cells of the mouth, which changes the resident flora. 1 If these organisms are aspirated in sufficient numbers into the lungs, pneumonia can result.
SEPTEMBER/OCTOBER | 996 H E A R T & L U N G
There has been considerable interest in recent years in the stomach as a reservoir of gram-negative organisms. Although gram-negative organisms may reach the stomach and multiply there in large numbers, particularly when gastric acidification is impaired, the so-called "gastropulmonary route" of infection does not appear to be the major mode of pneumonia developing in most patients. ~ Which groups of patients in the ICU are at par~ ticular risk of developing pneumonia? A compila~ tion of risk factors from multiple studies identified the following characteristicsl: duration of mechanical ventilatio n , advanced age, severity of illness, chronic lung diseases, head trauma, reintubation or self-extubation, upper abdominal or thoracic surgery, ventilator circuit changes at less than 48 hour intervals, supine head position, trauma, stress ulcer with macroscopic bleeding, fall or winter season, prior antibiotic therapy, use of a nasogastric tube, bronchoscopy, shock, trauma with emergency intubation, gross aspiration of gastric contents, and gastric acid inhibitor therapy. Poor nutritional state and immunosuppression may also adversely affect the development of pneumonia. The use of antacids and histamine type 2 receptor (H 2) blockers has been identified in a multivariate analysis as a risk factor for the development of nosocomial pneumonia. 6 A subsequent study suggested that the use of sucralfate as gastritis prophylaxis in ICU patients resulted in a lower incidence of nosocomial pneumonia than in a group of patients receiving H 2 blockers or antacids; however, and indeed, in this study, the group receiving H 2 blockers alone had the lowest incidence of pneumonia. 7 The question of which stress-ulcer prophylaxis regimen results in the lowest incidence of nosocomial pneumonia remains open, although the use of sucralfate should be considered. a,9 The past decade also has seen considerable controversy regarding the best method to use to diagnose ventilator-associated pneumonia. Traditional clinical criteria--fever, sputum purulence, new infiltrates on chest radiograph, isolation of a pathogen from respiratory secretions-are at best imprecise indicators of lower respiratory tract infection, with an accuracy of only 62% in a recent study that compared clinical criteria to a protected specimen brush (PSB) technique. 1~ Many noninfectious conditions, such as pulmonary embolism, adult respiratory distress syndrome, and chemical pneumonitis can cause
HEART & L U N G VOL. 25, NO. 5
fever and pulmonary infiltrates on a chest radiograph but not require antimicrobial therapy. The new techniques attempt to circumvent the problem of contamination of secretions obtained through the endotracheal tube. Two techniques, PSB and protected bronchoalveolar lavage, with quantitative culture, have been reviewed recently. ~,12 Briefly, PSB involves bronchoscopy in which a sterile brush is protected inside the bronchoscope by an absorbable plug that can be displaced on entry into a lung segment. The sterile brush is then advanced to obtain a specimen. The brush is withdrawn into the bronchoscope, which is removed and material from the brush is cultured quantitatively. Protected bronchoalveolar lavage involves wedging a bronchoscope into a lung segment before admitting lavage fluid, which is then withdrawn and quantitatively cultured. Whether these techniques should be applied to every patient is controversial. Many patients may respond promptly to empiric antimicrobial therapy for suspected pneumonia without the necessity of an invasive procedure. Both techniques involve bronchoscopy and quantitative cultures, which are labor intensive and expensive. Proponents argue that by improving the accuracy of diagnosis for pneumonia, overuse of antibiotics and s u b s e q u e n t d e v e l o p m e n t of resistant microorganisms will be avoided. 12 Unfortunately, the newer techniques also have problems, which cause difficulty in making the correct diagnosis in patients receiving antimicrobial therapy. 13,14Additionally, clinicians, knowing the risk of death in patients with ventilator-associated pneumonia, may not be willing to withhold antibiotics despite a negative culture result. Until further studies define the clinical utility and cost-effectiveness of these methods, they cannot be recommended for all hospitals at present. However, refinements in the techniques and greater willingness to withhold antibiotics may change this in the future. There are several pathogens that, if present at all in a sample of lower respiratory secretions, signify they are the etiologic agents of the disease. These include Legionella pneumophila and respiratory syncytial and influenza viruses. These organisms are uncommon causes of nosocomial pneumonia at most hospitals, but should be looked for occasionally, particularly during seasonal community outbreaks of respiratory illness or in perplexing cases of pneumonia.
419
The therapy of nosocomial pneumonia is complex and depends on many factors, including the timing of the development of pneumonia in the patient's hospital course, prior antibiotic therapy, and the indigenous flora of the specific ICU. Suffice it to say that single-drug, ~-lactam therapy is sufficient for most gram~positive types of pneumonia and those caused by common Enterobacteriaceae (Escherichia coli, Klebsiella); but for significant types of pneumonia with resistant gram-negative pathogens, especially P. aerugi, nosa, dual therapy with an aminoglycoside combined with a [3qactam should be used to improve efficacy and discourage the development of resistant microorganisms. 15 The duration of therapy depends on the patient's clinical course and the microorganism responsible, but some patients may be candidates for early oral therapy, which may expedite their transfer from the ICU or hospital discharge. Finally, how can those caring for critically ill patients prevent them from developing nosocomial pneumonia? Several simple techniques are recommended, such as elevating the patient's head whenever possible, avoiding reflux of condensate down the endotracheal tube, and good hand washing between care of each patient. 8,9 Ventilator tubing should b e changed no more than every 48 hours, and respiratory equipment should be disinfected between patients. More sophisticated techniques have been proposed, such as administration of sucralfate instead of antacids as prophylaxis against stressqnduced gastrointestinal bleeding, which, as noted, requires more study. The routine administration of topical and systemic antibiotics to prevent infection--known as selective digestive decontamination-was popular at some centers several years ago, but has not been shown to benefit the general population of ICU patients ~6 and cannot be recommended for general use. A recent study suggested that continuous aspiration of subglottic secretions could prevent the development of subsequent pneumonia17; such a Conceptually simple and easily implemented technique deserves more extensive evaluation. Other commonly used practices to prevent pneumonia should be continued. Patients should be counseled before surgery regarding the need to cough and in deep breathing and incentive inspirometry. Postoperative pain should be adequately controlled, with use of parenteral analgesics and nerve blocks or epidural analgesia, or bothl Staff should be educated
420
regarding risk factors for nosocomial pneumonia, potential severity for the patient, and preventive measures. In the future, pneumonia should continue to be recognized as a major hurdle for the hospitalized patient in terms of both morbidity and mortality rates and medical costs. Funding, research efforts, and the development of new technology should be directed at preventing ventilator-associated pneumonia, the most significant nosocomial infectionof ICUs.
REFERENCES 1. George DL. Epidemiology of pneumonia in intensive care unit patients. Clin Chest Med 1995;16:29-44. 2. CDC. Public health focus: surveillance, prevention and control of nosocomial infections. MMWR Morb Mortal Wkly Rep 1992;41:783-7. 3. Craven DE, Goularte TA, Make BJ. Contaminated condensate in mechanical ventilator circuits: a risk factor for nosocomial pneumonia? Am Rev Respir Dis 1984;129: 625-8. 4. Tortes A, Serra-Batlles J, Ros E, Piera C, Puig de la Bellacasa J, Cobos A, et al. Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann Intern Med 1992;116:540-3. 5. Bonten MJM, Gaillard CA, van Tiel FH, Smeets HG, Van der Geest S 5tobberingh EE. The stomach is not a source for colonization of the upper respiratory tract and pneumonia in ICU patients Chest 1994 105:878~84. 6. Craven DE. Kunches LM. Kilinsky V, Lichtenberg DA Make BI McCabe WR.. Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation Am Rev Respir Dis 1986-133:792-6. 7. Driks MR. Craven DE Celli BR Manning M Burke RA. Garvin GM et al. Nosocomial pneumoma in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. New Engl I Med 1987:317:137682 8. Craven DE. Prevention of hospital-acquired pneumonia: measuring effect in ounces, pounds and tons. Ann Intern Med 1995 122:229-31. 9 Tablan OC Anderson LJ, Arden NH Breiman RE Butler JC McNeil MN et al. Guidelines for the prevention of nosocomial pneumonia Infect Control Hosp Epidemiol 1994 15:587-90 10. Fagon IY Chastre I HanceAI Domart Y Trouillet IL. Gibert C. Evaluation of clinical judgment in the identification and treatment of nosocomial pneumonia in ventilated patients. Chest 1993 102:547-53. 11 Griffen II Meduri GU. New approaches in the diagnosis of nosocomial pneumoma Med Clin North Am 1994 78:1091 122. 12 Chastre 1. Fagon JY Trouillet IL. Diagnosis and treatment of nosocomial pneumonia in patients in intensive care units. Clin Infect Dis 1995 21(suppl 31:$226~37 13. Torres A El~Eb~ary M. Padro L Gonzalez J de la Bellasca JP, Ramirez I e t al. Validation of different techniques for the diagnosis of ventilator-associated pneumonia: comparison with immediate postmortem pulmonary biopsy. Am J Respir Crit Care Med 1994;149:324~31. 14. Bouten MJ, Gaillard CA, Wouters EF, van Tiel FH, $tobberingh EE, van der Geest S. Problems in diagnosing nosocomial pneumonia in mechanically ventilated patients: a review. Crit Care Med 1994;22:1683~91.
SEPTEMBER/OCTOBER 1996 HEART & L U N G
15. Niederman MS. An approach to empiric therapy of nosocomial pneumonia. Med Clin North Amer 1994;78:1123-41. 16. Gastinne H, Wolff M, Delatour F, Faurisson F, Chevret S. A controlled trial in intensive care units of selective decontamination of the digestive tract with nonabsorbable antibiotics. N Engl J Med 1992;326:54-9.
17. Valles J, Artigas A, Rello J, Bonsoms N, Fontanals D, Blanch L, et al. Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. Ann Intern Med 1995; 122:179~86.
ION THEMOVE? D o n ' t miss a single issue of the journal! To e n s u r e p r o m p t service w h e n y o u c h a n g e y o u r address, please p h o t o c o p y a n d c o m p l e t e the f o r m below.
Please send your change of address notification at least six weeks before you r move to ensure continued service. We regret we cannot guarantee replacement of issues missed due to late notification. J O U R N A L TITLE:
Fill in the title of the journal here. OLD A D D R E S S :
NEW ADDRESS:
Affix the address label from a recent issue of the journal here.
Clearly print your new address here. Name Address City/State/ZIP
COPY A N D M A I L T H I S F O R M TO: Journal Subscription Services Mosby-Year Book, Inc. 11830 Westline Industrial Dr. St. Louis, M O 63146-3318
HEART & LUNG VOL.25, NO. 5
OR FAX TO:
OR PHONE:
314-432-1158
1-800-453-4351 Outside t h e U . S . , c a l l 314-453-4351
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421