Reference
Year
VAP criterion
n
Incidence
Per 1,000 ventilator days
Fayon et al.
Consensus
439
2.5 %; 6.9 % of those ventilated ≥3 days
–
Richards et al.
CDC criteria
110,709
2.8 %
6 (median 5, 90th percentile 12)
Raymond et al.
Modified CDC
710
12.7 %
–
Fischer et al.
Modified CDC
272
9.6 %
–
NNIS
CDC criteria
75 PICUs
–
4.9 (median 4.6, 90th percentile 11.1)
Grobskopf et al.
CDC criteria
256
6.6 %
–
Elward et al.
CDC criteria
595
5.1 %
11.6
NNIS
CDC criteria
52 PICUs
–
2.9 (median 2.3, 90th percentile 8.1)
Almuneef et al.
Modified CDC
361
10.3 %
8.9
NHSN
CDC criteria
50 PICUs
–
2.1 (median 0.7, 90th percentile 4.1)
INICC
CDC criteria
1,808
7.9 %
6.1 (90th percentile 15.5)
Srinivasan et al.
Consensus
58
32 %
–
35.1.1.3 Outcomes of VAP in Adult and Pediatric Intensive Care
Most of the data on outcomes of VAP come from the adult intensive care literature. Reviews suggest that an episode of VAP is associated with an increase in hospital length of stay of approximately 4–9 days and an increase in hospital costs of over $15–40,000 per patient (ATS 2005; Chastre and Fagon 2002). The attributable mortality has been controversial as some studies have found no increase in attributable mortality from an episode of VAP. Nevertheless, systematic reviews of VAP in adults suggest there is an attributable mortality in the range of 20–50 % for an episode (Safdar et al. 2005). This attributable mortality is higher in patients with associated bacteremia, VAP due to Pseudomonas aeruginosa or Acinetobacter sp., medical patients, VAP of late onset, and for patients treated initially with ineffective antibiotics (ATS 2005; Chastre and Fagon 2002).
There is comparatively little data on outcomes of VAP in children. Fayon et al. (1997) found that multiple organ system failure “attributable” to VAP occurred in 1/12 (8 %) patients and death attributable to VAP in another 1/12 (8 %) patients. Grobskopf et al. (2002) found that those children with any pediatric intensive care unit-acquired infection, of which VAP accounted for 28 %, had a longer length of hospital stay (9.5 vs 4 days), length of intensive care stay (8 vs 2 days), and a higher age-adjusted risk of death within 4 weeks (RR 3.4, 95 % CI 1.7–6.5). Elward et al. (2002) found in a univariate analysis that children with VAP had a longer intensive care length of stay (27 vs 6 days), longer hospital length of stay (52 vs 15 days), and a higher mortality (20 % vs 7 %, p = 0.065). Fischer et al. (2000) found that in children after cardiac surgery, VAP led to an attributable median delay of extubation of 3.7 days. Finally, Bigham et al. (2009) found that VAP was associated with PICU length of stay (19.5 vs 7.5 days), mortality (19 % vs 7 %), and ventilator days (16.3 vs 5.3 days) on univariate analysis. These studies were limited by small sample sizes, lack of multiple variable analyses, and lack of control groups; however, taken together, they do suggest that VAP in children is most likely associated with morbidity and mortality similar to the adult literature. Specifically, it is likely that an episode of VAP in children contributes to a prolonged length of stay and hospital costs and may also increase mortality.
35.1.2 Predisposing Factors for VAP
35.1.2.1 Nonmodifiable Predisposing Factors for VAP in Adult Intensive Care
Once again, most of the data for predisposing factors for VAP comes from the adult literature. It is useful to consider these risk factors for VAP in terms of modifiable and nonmodifiable risks. In the adult literature, many host and intervention factors have been identified in different studies (Table 35.2) (Chastre and Fagon 2002). Many of these risk factors are not easily modifiable and therefore are not reasonable targets for prevention strategies for VAP (see later in this chapter).
Table 35.2
Risk factors for VAP in adult intensive care units
Nonmodifiable risk factors | Potentially modifiable risk factors | |
|---|---|---|
Protective | Risk | |
Season | Infection control | |
Fall and winter | Use of alcohol-based hand sanitizers, adequate nurse staffing | Poor practice of infection control |
Host factors | Intubation factors | |
Age over 60 years | Orotracheal endotracheal tube (vs nasotracheal tube), sedation protocols, ventilator weaning protocols, noninvasive ventilation | Pharmacologic paralysis, reintubation |
Comorbidities | Aspiration of microorganisms | |
Chronic obstructive lung disease | Semirecumbent position, post-pyloric enteral feeds, continuous aspiration of subglottic secretions, endotracheal tube cuff pressures at least 20 cm H2O | Inadvertent flushing of ventilator tubing condensate down the endotracheal tube (e.g., during hospital transports, lifting of bed rails, patient repositioning) |
Underlying disease | Other factors | |
Acute respiratory distress syndrome, coma or impaired consciousness, burns, trauma, severity of illness, and organ dysfunctions | Stress ulcer prophylaxis with H2 blockers? sinusitis | |
35.1.2.2 Modifiable Predisposing Factors for VAP in Adult Intensive Care
Many studies have identified modifiable risk factors for VAP in adults. Some of the studies have obtained conflicting results, and therefore, only risk factors that have been generally accepted in the literature will be presented here. The risk factors seem to be inclusive of infection control, intubation, aspiration, colonization, and other factors (Table 35.2) (ATS 2005; Bonten et al. 2004; CDC 2004; Chastre and Fagon 2002; Collard et al. 2003; Dodek et al. 2004; Muscedere et al. 2008b).
35.1.2.3 Predisposing Factors for VAP in Pediatric Intensive Care
The applicability of the risk factors identified in adults for pediatric VAP is unclear, as there are a limited number of studies examining risk factors for VAP. Identified risk factors in the few studies include immunodeficiency, immunosuppression, and neuromuscular blockade (Fayon et al. 1997); a genetic syndrome, reintubation, and transport out of the pediatric intensive care unit (Elward et al. 2002); female gender, postsurgical diagnosis, any narcotic use, enteral predominantly gastric feeds, and lack of any blood product administration (Srinivasan et al. 2009); enteral nasogastric feeds, prior antibiotic therapy, and bronchoscopy (Almuneef et al. 2004); and subglottic or tracheal stenosis, trauma, and tracheostomy (Bigham et al. 2009).
Some risk factors identified in adults may be difficult to extrapolate to children, such as the usefulness of noninvasive ventilation, sedation protocols, ventilator weaning protocols, continuous aspiration of subglottic secretions, and maintenance of cuff pressures at least 20 cm H2O (which may be dangerous in smaller children due to the risk of ischemia with lower mean arterial pressures). Some risk factors in adults can likely be extrapolated to children despite the absence of good pediatric studies, including poor infection control, lower nurse staffing, poor ventilator tubing condensate management, lack of semirecumbent positioning, and lack of post-pyloric feeds. What can be said is that in children, available evidence suggests that some risk factors in adults also are true for children, including use of neuromuscular blockade, reintubation, and transports out of the pediatric intensive care unit.
Knowing the true modifiable risk factors is very important for designing practical VAP prevention strategies and studies in children. Whether some of these risk factors are indeed causative or merely associations with VAP is important. These identified risk factors need to be subjected to study to determine whether interventions to modify the risk factor prevent VAP. This question will be addressed in a later section of this chapter.
35.1.3 Pathogenesis of VAP
35.1.3.1 Colonization of the Oropharynx, Tracheobronchial Tree, and Stomach
The pathogenesis of VAP is somewhat unclear. VAP is a result of microorganisms invading the lung parenchyma. These microorganisms are thought to be micro-aspirated into the lung prior to this invasion of the lung parenchyma.
Exactly where these aspirated microorganisms first colonize has been a matter of debate. It is known that over time, in hospitalized patients, and in particular ventilated patients, bacteria colonize the oropharynx, tracheobronchial tree, and stomach (Chastre and Fagon 2002). The sequence of colonization of these sites has been suggested to be stomach first, then oropharynx, and then tracheobronchial tree (Torres et al. 1996). However, some studies have not confirmed this, with airway colonization being preceded by oropharyngeal and not gastric colonization (Bonten et al. 1996; Cendrero et al. 1999; Ewig et al. 1999; Garrouste-Orgeas et al. 1997) or preceded by neither (Berdal et al. 2007). It is likely that the sequence of colonization is variable, and can be direct to tracheobronchial tree, or preceded by oropharyngeal and sometimes gastric colonization. Indeed, tracheobronchial colonization with potentially pathogenic bacteria occurs in ventilated patients, and when there is no lung parenchyma invasion, there is no associated VAP.
35.1.3.2 Microbiologic Epidemiology of VAP in Adult and Pediatric Intensive Care
In adults with VAP, the microbiologic organisms causing the infection are varied. In fact, VAP is often polymicrobial, in up to 50 % in some series (Chastre and Fagon 2002; Rouby et al. 1992). The organisms causing VAP are different in early-onset and late-onset VAP. Early-onset VAP is more often associated with organisms that colonize the patient’s oropharynx from the community, including Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, and occasionally enteric gram-negative bacilli. These organisms are said to have less resistance than the typical nosocomial bacteria that cause later-onset VAP (ATS 2005; Rotstein et al. 2008). Nevertheless, resistance in these community-acquired organisms is increasing to very high levels in some geographic regions. For example, community-associated methicillin-resistant Staphylococcus aureus (MRSA) is becoming common in parts of the United States and Europe, and penicillin-resistant Streptococcus pneumoniae is already common in many countries (Gerber et al. 2009).
Late-onset VAP, occurring at least 5 days after hospital admission, is more often associated with nosocomial bacteria that are often multiresistant to antibiotics. These organisms include Pseudomonas aeruginosa; Acinetobacter sp.; Stenotrophomonas maltophilia; enteric gram-negative bacilli including Enterobacter sp., Klebsiella sp., and Citrobacter sp.; and also MRSA (ATS 2005; Rotstein et al. 2008). Although Candida sp. are often isolated from secretions, this fungus is only very rarely the cause of VAP (Meersseman et al. 2009).
Although there is less data in children, the microbiology of VAP seems to be similar to that in adults. As shown in Table 35.3, there is a predominance of gram-negative bacilli including Pseudomonas aeruginosa and enteric gram-negative bacilli in children with VAP. Staphylococcus aureus and other gram-positive cocci (including Streptococcus pneumoniae) are also common.
Table 35.3
Etiologic organisms in VAP in children
Reference | Year | GNB (%) | Pseudomonas (%) | Enteric GNB (%) | GPC (%) | S. aureus (%) |
|---|---|---|---|---|---|---|
Fayon et al. | 92 | 25 | 33 | 25 | 17 | |
Richards et al. | 67 | 22 | 25 | 22 | 17 | |
Raymond et al. | 51 | 36 | 16 | 26 | 19 | |
Grobskopf et al. | 60 | 10 | 30 | 35 | 30 | |
Elward et al. | 67 | 29 | 29 | 24 | 12 | |
Almuneef et al. | 80 | 57 | 14 | 22 | 19 | |
Srinivasan et al. | 55 | 3 | 23 | 50 | 23 | |
Bigham et al. | 52 | 19 | 21 | 29 | 24 |
35.1.4 Diagnosis of VAP
The diagnosis of VAP has been the most controversial aspect of the illness. There is little data in children. The problem has been that there is absolutely no well-accepted “gold standard” for diagnosis to use for studies of diagnostic tests. The goal of a diagnostic algorithm for VAP should be to define whether a patient has pneumonia and to determine the etiologic pathogen(s). Unfortunately, no test can reliably provide this information.
35.1.4.1 Diagnosis of VAP in Adult Intensive Care
Since VAP is associated with morbidity, mortality, and cost, a clinician needs to know the sensitivity and specificity of diagnostic tests for VAP. An evidence-based assessment of the diagnostic tests for VAP is shown in Table 35.4 (Grossman et al. 2000).
Table 35.4
Evidence-based diagnosis of VAP in studies in adult intensive care
Diagnostic technique | Sensitivity for VAP | Specificity for VAP |
|---|---|---|
Clinical criteria | High | Low |
Chest roentgenogram | 50–78 % | Unknown. Likely <60 % |
EA qualitative | High | Low |
EA quantitative at 106 CFU/ml | 76 ± 9 % (range 38–82 %) | 75 ± 28 % (range 72–85 %) |
BAL at 104 CFU/ml | 73 ± 18 % (range 42–93 %) | 82 ± 19 % (range 45–100 %) |
BAL with ICO | 69 ± 20 % | 75 ± 28 % |
PSB at 103 CFU/ml | 66 ± 19 % (range 33–100 %) | 90 ± 15 % (range 50–100 %) |
Blinded procedure (PSB or BAL) | Range 58–100 % | Range 66–100 % |
Clinical diagnosis is usually based on the presence of two or more of temperature >38 °C or <36 °C, leukopenia or leukocytosis, purulent tracheal secretions, and decreased oxygenation. A higher index of suspicion is required in the setting of ARDS, unexplained hemodynamic instability, or deterioration of blood gases (ATS 2005; Horan et al. 2008; Chastre and Fagon 2002; Rotstein et al. 2008). If the clinical diagnosis is suspected, a chest roentgenogram (CXR) is indicated. If the CXR shows new, worsening, or persistent alveolar infiltrates or air bronchograms, then a microbiologic diagnostic test is done (ATS 2005; Rotstein et al. 2008). The microbiologic tests can include a qualitative or quantitative endotracheal tube aspirate (EA) for gram stain and culture, a bronchoalveolar lavage (BAL) for gram stain and quantitative culture, a protected specimen brush (PSB) for quantitative culture, or a blind BAL or PSB for culture (ATS 2005; Muscedere et al. 2008a; Rotstein et al. 2008). As shown in Table 35.4, each of these tests has far from perfect sensitivity and specificity (Grossman et al. 2000). The studies used to make this table had variable gold standards for VAP and often had poor documentation of antibiotic administration prior to the microbiologic test. In addition, inflammatory cells in the BAL and bacteria on gram stains of BAL have had variable sensitivity and specificity (Albert et al. 2008; Oudhuis et al. 2009; Rea-Neto et al. 2008). Blood culture also has poor sensitivity and is positive in only 8–20 % of cases of VAP (Chastre and Fagon 2002).
35.1.4.1.1 Histologic Diagnosis of VAP
By histology, VAP is often multifocal and patchy, involving both lungs, usually in the posterior and lower segments, and in different phases of evolution at different sites in the lung, often sparing peripheral lung (Chastre and Fagon 2002; Fabregas et al. 1996; Rouby et al. 1992; Torres et al. 1994, 2000). In addition, in the lungs with VAP, the microbiology is multifocal and nonhomogeneous, with different organisms not uncommon in different areas of the lung (Chastre and Fagon 2002; Fabregas et al. 1996; Pugin et al. 1991; Rouby et al. 1992; Torres et al. 1994, 2000). This suggests that culture techniques cannot be expected to have high sensitivity or specificity for VAP.
Animal data for diagnosis of VAP have the advantage of avoiding patient comorbidities, heterogeneity of underlying disease, and antibiotic exposure, each of which could complicate the histologic diagnosis. In a ventilated piglet model (weight 22 ± 2 kg ventilated for 4 days), histologic VAP had poor correlation with quantitative lung culture or with invasive microbiologic culture techniques (PSB and BAL), as shown in Table 35.5 (Wermert et al. 1998). Again, this suggests limitations to current invasive culture techniques for diagnosis of VAP.
Table 35.5
Diagnosis of VAP in piglets (weight of 22 ± 2 kg) ventilated for 4 days
Gold standard for VAP | Diagnostic technique | Sensitivity for VAP (%) | Specificity for VAP (%) |
|---|---|---|---|
Histology of the lungs | PSB | 74 | 36 |
BAL | 82 | 33 | |
BAL with ICO | 52 | 83 | |
Lung culture at 104 CFU/g | PSB | 35 | – |
BAL | 50 | – | |
EA | 94 | – |
There have been several postmortem studies examining the diagnosis of VAP in adults. Table 35.6 shows results of diagnostic tests compared to lung histology as the gold standard for VAP, and Table 35.7 shows results of diagnostic tests compared to lung culture as the gold standard for VAP. In general, the sensitivity and specificity of the tests are often disappointing (Rea-Neto et al. 2008).
Table 35.6
Diagnosis of VAP in adults using postmortem lung histology as the gold standard
Reference | Year | Antibiotics | Diagnostic technique | Sensitivity for VAP (%) | Specificity for VAP (%) |
|---|---|---|---|---|---|
Rouby et al. | 55/69 on antibiotics | NB-BAL | 70 | 69 | |
NB-BAL at 103 CFU/ml | 45 | – | |||
Torres et al. | 8/30 on recent antibiotics for 3 ± 1 days | Lung biopsy 103 CFU/g | 40 | 45 | |
PSB 103 CFU/ml | 36 | 50 | |||
BAL 104 CFU/ml | 50 | 45 | |||
CXR with 2 clinical criteria | 70 | 45 | |||
Marquette et al. | 13/28 recent antibiotics for <48 h | EA 106 CFU/ml | 55 | 85 | |
PSB 103 CFU/ml | 58 | 88 | |||
BAL 104 CFU/ml | 47 | 100 | |||
EA gram stain | 50 | 75 | |||
BAL with ICO | 37 | 100 | |||
Kirtland et al. | 33/39 on antibiotics | Lung tissue 104 CFU/g | 11 | 93 | |
PSB 103 CFU/ml | 33 | 63 | |||
BAL 104 CFU/ml | 11 | 80 | |||
CXR with progression | 55 | 50 | |||
Bregeon et al. | 1/27 recent antibiotics | Clinical judgment | 100 | 61 | |
CPIS score | 100 | 69 | |||
Mini-BAL 103 CFU/ml | 50 | 86 | |||
Torres et al. | 17/25 on antibiotics for 9.5 ± 7.9 days | EA 105 CFU/ml | 35 | 50 | |
PSB 103 CFU/ml | 28 | 50 | |||
BAL 104 CFU/ml | 37 | 50 | |||
Guided lung biopsy | 32 | 50 |
Table 35.7
Diagnosis of VAP in adults using postmortem lung culture as the gold standard
Reference | Year | Antibiotics | Gold standard | Diagnostic technique | Sensitivity for VAP (%) | Specificity for VAP (%) |
|---|---|---|---|---|---|---|
Chastre et al. | 0/20 on new antibiotics | Lung culture 104 CFU/g | PSB 103 CFU/ml | 82 | 89 | |
BAL 104 CFU/ml | 91 | 78 | ||||
BAL with ICO | 91 | 89 | ||||
PSB or BAL with ICO | 91 | 89 | ||||
Papazian et al. | 8/38 on new antibiotics | Histology and lung culture | CPIS | 72 | 85 | |
PSB 103 CFU/ml | 42 | 95 | ||||
BAL 104 CFU/ml | 58 | 95 | ||||
BBS 104 CFU/ml | 83 | 80 | ||||
Kirtland et al. | 33/39 on antibiotics | Lung culture | EA qualitative | 87 | 31 | |
PSB 103 CFU/ml | 44 | 81 | ||||
BAL 104 CFU/ml | 65 | 63 | ||||
Fabregas et al. | 17/25 on antibiotics for 9.5 ± 7.9 days | Histology and lung culture | CXR | 92 | 33 | |
CXR with 2 clinical | 69 | 75 | ||||
CPIS | 77 | 42 | ||||
EA 105CFUL/ml | 69 | 92 | ||||
BAL 104 CFU/ml | 77 | 58 | ||||
PBAL 104 CFU/ml | 39 | 100 | ||||
PSB 103 CFU/ml | 62 | 75 | ||||
Bregeon et al. | 1/27 recent antibiotics | Lung culture | Mini-BAL 103 CFU/ml | 78 | 86 | |
Torres et al. | 17/25 on antibiotics for 9.5 ± 7.9 days
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