Pneumonia is the second most common nosocomial infection, following urinary tract infection, and is the leading cause of nosocomial-related mortality.1-3 Nosocomial pneumonia is defined as an infection that is caused by bacterial, viral, or fungal pathogens and occurs 48 hours or more after hospital admission.3

Significant risk factors for developing nosocomial pneumonia include surgery (particularly high abdominal or thoracic), chronic lung disease, advanced age, and immunosuppressive chemotherapy.1 Patients who require mechanical ventilator support are at substantially higher risk of developing pneumonia.4 Ventilator-associated pneumonia (VAP) is a particular type of nosocomial pneumonia that develops 48 hours or more after tracheal intubation or tracheostomy and the initiation of mechanical ventilation.3,5

Consequences of VAP
Approximately 300,000 cases of nosocomial pneumonia and VAP occur annually in the United States. VAP is especially prevalent in intensive care units (ICUs). The reported incidence of VAP among ICU patients varies substantially, but recent data suggest that 9 to 27 percent of intubated patients develop VAP. The risk of developing VAP is highest during the first 5 days of ventilation, and approximately half of all cases develop within 4 days of ventilation.3

Patients who develop VAP are at significantly increased risk of morbidity and mortality. Development of secondary bacteremia is not uncommon and consequently results in more antibiotic use, longer hospital stays and increased costs. A recent study was conducted to determine the specific costs of care associated with VAP. From January 2002 through September 2003, ICU patients and charts were evaluated by an infection control practitioner to identify cases of VAP, as defined by the National Nosocomial Infection Surveillance (NNIS) guidelines. All patients who required more than one day of mechanical ventilation were evaluated. A total of 70 patients with VAP and 70 patients without VAP were matched and compared. Total ICU costs of care between the two patient groups were significant, as shown in Figure 1 (P=0.05). A substantial percentage of the increased costs of VAP was due to longer hospital stays and was estimated at $1,861 per day. Figure 2 presents the difference in length of hospital stay between the two groups. Patients with VAP required mechanical ventilation for an average of 17.7 days compared to 5.8 days for patients without VAP (P<0.05).6

Patients who develop VAP are at significantly higher risk of dying. The reported mortality rate among patients with VAP also varies substantially, ranging from 15 to 50 percent or higher among severely ill patients.3,4,7 The wide variation in mortality rates due to VAP is based on several factors including differences in the way crude mortality data are gathered and the effects of underlying illness on mortality.

Pathogenesis of VAP
Patients develop VAP when microorganisms enter the normally sterile lower respiratory tract and produce a sustained infection. This happens through several processes: aspiration of contaminated secretions either directly from the oropharynx or secondarily from gastric reflux into the oropharynx; extension of a contiguous infection such as pleural space infection; inhalation of contaminated air; or by systemic circulation of microorganisms from other infections, such as urinary tract infections or bloodstream infections.4

Normal host defenses are compromised by several factors in patients who are mechanically ventilated, but suppression of the cough reflex is a primary contributor to susceptibility to VAP. When the cough reflex is impaired, the patient’s ability to clear mucociliary areas is compromised. Importantly, the endotracheal tube provides a conduit for microorganisms to enter the lower respiratory tract.3,4

Resistant bacteria and VAP
Antibiotic-resistant microorganisms are commonly found in VAP.3,8 Staphylococcus aureus, Pseudomonas aeruginosa, and Haemophilus influenzae were the most common causes of nosocomial pneumonia in the late 1990s.8 The presence of methicillin-resistant strains of S. aureus, vancomycin-resistant Enterobacter species, and b-lactam-resistant streptococci also increased significantly during this period and are now commonly associated with VAP.3,8 The presence of resistant P. aeruginosa is significantly associated with mortality.3 Antibiotic resistance and improper antimicrobial therapy contribute to mortality in patients with VAP.

Prevention and treatment
Avoiding intubation and mechanical ventilation is obviously the best way to prevent VAP. Noninvasive ventilation may be used effectively in some patients and is associated with much lower mortality than mechanical ventilation. Avoiding mechanical ventilation may not be possible for all patients, however. In patients who are at risk of developing VAP, preventive measures include the use of aerosolized antimicrobials, which settle deep into the areas where infection is likely to occur. Higher concentrations of aerosolized antimicrobials may be achieved compared to systemic antimicrobials. Selective digestive decontamination (SDD) also has been studied for prevention of VAP. Topically-applied nonabsorbable oral antibiotics with a short course of parenteral antimicrobials has been evaluated for prevention of VAP. This approach to SDD appears to reduce the incidence of VAP but has not been shown to reduce ICU mortality. Any prophylactic use of antimicrobials raises concerns about the development of resistance over time. Elimination of biofilms on endotracheal tubes (ETTs) is also a focus of VAP prevention. ETTs impregnated with chlorhexidine and silver carbonate have been shown to significantly reduce colony counts compared to control tubes. Additional studies of antimicrobial-impregnated ETTs is underway. Extending the time before circuit changes in ventilator equipment also has been recommended to reduce exposure to microorganisms, although additional study is needed to determine whether this reduces the incidence of VAP. Other areas of study include the presence of upper respiratory infections and the potential for contamination through hospital water and air systems.4

Conclusion
VAP is the most common cause of nosocomial-associated mortality. Avoidance of mechanical ventilation, although effective in reducing VAP, is not always possible. The prophylactic use of aerosolized antimicrobials and avoidance of biofilms on ETTs have each been shown to decrease the incidence of VAP. Other methods, such as SDD and extended periods between mechanical ventilator circuit changes are under study.

In addition to mortality, VAP is associated with significant morbidity and substantial costs of care. Growing antibiotic resistance and the increased population of elderly patients suggest that VAP might become a growing problem. HPN

References

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2.Wenzel RP, Edmond MB. The impact of hospital-acquired bloodstream infections. Emerging Infect Dis. 2001;7(2):174-177.

3.Kollef MH. What is ventilator-associated pneumonia and why is it important? Respir Care. 2005;50(6):714-717.

4.Safdar N, Crnich CJ, Maki DG. The pathogenesis of ventilator-associated pneumonia: its relevance to developing effective strategies for prevention. Respir Care. 2005;50(6):725-741.

5.Mayhall CG. Ventilator-associated pneumonia or not? Contemporary diagnosis. Emerg Infect Dis. 2001;7(2):200-204.

6.Cocanour CS, Ostrosky-Zeichner L, Peninger M, et al. Cost of a ventilator-associated pneumonia in a shock trauma intensive care unit. Surg Infect (Larchmt). 2005;6(1):65-72.

7.Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002;165(7):867-903.

8.Jones RN. Resistance patterns among nosocomial pathogens: trends over the past few years. Chest. 2001;119(2 Suppl):397S-404S.