**2. Risk factors for VAP**

The use of mechanical ventilation is a significant risk factor for hospital-acquired pneumonia associated with aspiration, lowering of consciousness level, excessive management and patient transport, and chronic lung disease. The risk of VAP increases by 3% in the first 5 days of ventilation, 2% in 5–10 days, and 1% in 10 days of ventilation [11].

without the syndrome [14]. Cigarette smoking, inhibition of mucociliary function, and reduction of cough reflex due to obstruction of airflow make chronic obstructive pulmonary disease

Microbiology of Ventilator-Associated Pneumonia http://dx.doi.org/10.5772/intechopen.69430 107

The exogenous risk factors are due to the interventions undergone by the patient in intensive care units (ICUs) (**Figure 1**). Mechanical ventilation equipment is a primary source of infection, in which respiratory circuit condensations can be sources of microorganisms [8]. The endotracheal tube, as well as other invasive devices, promotes bacterial colonization of the trachea. Bacteria may have access to the lower respiratory tract through a partial blockage

Prolonged intubation may promote the formation of a layer of microorganisms adhered to the inner surface of the endotracheal tube. This formation, known as biofilm, represents an important virulence mechanism and contributes to pathogen persistence as well as therapeutic failures, since microorganisms in the biofilm state are more resistant to host defenses and also metabolically less active, therefore, are more resistant to antibiotics [8, 15]. To inhibit the biofilm formation on the surface of polymeric medical devices, many studies have focused on the development of new biomaterials with modifications that alter the biophysical interactions of the cell surface or impede biofilm growth. A wide range of new coatings with antimicrobials, cationic antimicrobial peptides, or metal nanoparticles (e.g., copper, gold, iron,

(COPD) patients more susceptible to ventilation-associated infections [5].

around the cuff or through the lumen of the endotracheal tube.

**Figure 1.** Main endogenous and exogenous risk factors for VAP.

Although other routes may lead to VAP, such as hematogenous spread, inhalation of contaminated air, and also by extension of an infection of the pleural space, the main entry of pathogens into the lower respiratory tract occurs by aspiration of secretions containing microorganisms (from oropharynx or reflux of the stomach). Pathogens that cause VAP may be part of the upper airway microbiota or are acquired exogenously after hospital admission [8].

**Figure 1** shows the different risk factors that are associated with VAP. Among risk factors inherent to the host (endogenous), it was observed that patients with advanced age, immunosuppressed individuals or pulmonary diseases have an increased risk for the development of VAP [4, 12, 13]. In a multicenter cohort study that analyzed the frequency of VAP among middle-aged, elderly, and very elderly patients, it was concluded that the highest frequency of VAP was in elderly patients (16.6%), associated to increased mortality among the elderly and very elderly (51%) when compared to middle-aged patients (35%) [4].

Long-term mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) increases the risk of VAP [5]. Evaluation of the association between ARDS and VAP found that 55% of patients with ARDS developed nosocomial infection compared to 28%

**Figure 1.** Main endogenous and exogenous risk factors for VAP.

Hospital-acquired infections usually have a high mortality rate (approx. 20%) when compared to the community acquisition (10%), this rate increases even more when it is associated with

According to the guidelines of the American Thoracic Society, hospital pneumonia is divided into ventilator-associated pneumonia (VAP), which develops after 48–72 h of endotracheal intubation and the one that occurs in nonhospitalized patients, but that have constant contact with health services [3]. VAP is the infection of the pulmonary parenchyma with onset after 48–72 h of endotracheal intubation. Early-onset VAP occurs during the first 4 days of mechanical ventilation, whereas late-onset VAP occurs on 5 or more days of mechanical ventilation [4–7]. VAP corresponds to 70–80% of cases of hospital-acquired pneumonia in intensive care units [1]. VAP is characterized by the presence of new or progressive pulmonary infiltrates, systemic alterations such as fever and leukocyte alterations, altered sputum, and diagnosis of an infectious agent [8]. Mortality due to VAP is high, principally because of the association with multidrug-resistance (MDR) bacteria [9]. In pediatrics and neonatology, the frequency of VAP

Many microorganisms can be involved in VAP. In this chapter, data on microbiology of VAP are reviewed, including risk factors, etiology, virulence features of main pathogens contribut-

The use of mechanical ventilation is a significant risk factor for hospital-acquired pneumonia associated with aspiration, lowering of consciousness level, excessive management and patient transport, and chronic lung disease. The risk of VAP increases by 3% in the first 5 days

Although other routes may lead to VAP, such as hematogenous spread, inhalation of contaminated air, and also by extension of an infection of the pleural space, the main entry of pathogens into the lower respiratory tract occurs by aspiration of secretions containing microorganisms (from oropharynx or reflux of the stomach). Pathogens that cause VAP may be part of the upper airway microbiota or are acquired exogenously after hospital admission [8].

**Figure 1** shows the different risk factors that are associated with VAP. Among risk factors inherent to the host (endogenous), it was observed that patients with advanced age, immunosuppressed individuals or pulmonary diseases have an increased risk for the development of VAP [4, 12, 13]. In a multicenter cohort study that analyzed the frequency of VAP among middle-aged, elderly, and very elderly patients, it was concluded that the highest frequency of VAP was in elderly patients (16.6%), associated to increased mortality among the elderly

Long-term mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) increases the risk of VAP [5]. Evaluation of the association between ARDS and VAP found that 55% of patients with ARDS developed nosocomial infection compared to 28%

is 3–19%, with a mortality rate ranging from 10 to 20% of patients [10].

ing to VAP severity, antimicrobial susceptibility, and laboratory diagnosis.

of ventilation, 2% in 5–10 days, and 1% in 10 days of ventilation [11].

and very elderly (51%) when compared to middle-aged patients (35%) [4].

mechanical ventilation [2].

106 Contemporary Topics of Pneumonia

**2. Risk factors for VAP**

without the syndrome [14]. Cigarette smoking, inhibition of mucociliary function, and reduction of cough reflex due to obstruction of airflow make chronic obstructive pulmonary disease (COPD) patients more susceptible to ventilation-associated infections [5].

The exogenous risk factors are due to the interventions undergone by the patient in intensive care units (ICUs) (**Figure 1**). Mechanical ventilation equipment is a primary source of infection, in which respiratory circuit condensations can be sources of microorganisms [8]. The endotracheal tube, as well as other invasive devices, promotes bacterial colonization of the trachea. Bacteria may have access to the lower respiratory tract through a partial blockage around the cuff or through the lumen of the endotracheal tube.

Prolonged intubation may promote the formation of a layer of microorganisms adhered to the inner surface of the endotracheal tube. This formation, known as biofilm, represents an important virulence mechanism and contributes to pathogen persistence as well as therapeutic failures, since microorganisms in the biofilm state are more resistant to host defenses and also metabolically less active, therefore, are more resistant to antibiotics [8, 15]. To inhibit the biofilm formation on the surface of polymeric medical devices, many studies have focused on the development of new biomaterials with modifications that alter the biophysical interactions of the cell surface or impede biofilm growth. A wide range of new coatings with antimicrobials, cationic antimicrobial peptides, or metal nanoparticles (e.g., copper, gold, iron, magnesium, silver, titanium, or zinc) have been applied to medical devices such as endotracheal tubes [16, 17]. Other approach consists in the use of polymers that exhibit antimicrobial activity by themselves, with positively charged active groups (biguanide, cyclic *N*-halamine, quaternary ammonium, pyridinium or phosphonium salts, and polyionenes) or other polymers, such as synthetic poly(phenylene ethynylenes), polynorbornenes, and polymethacrylates that display similar antimicrobial activities of human peptides [17]. Both types of devices display advantages and disadvantages, but in the near future one expects to have nontoxic and biocompatible products available, which display broad-spectrum antibiofilm activities for the prevention of biofilm formation on endotracheal tubes [18].

*aureus*. On the other hand, late-onset VAP is usually caused by antibiotic-resistant bacteria, such as *Pseudomonas aeruginosa*, *Acinetobacter* spp., methicillin-resistant *S. aureus* (MRSA), and extended-spectrum β-lactamase producing Enterobacteriaceae, such as *Klebsiella pneumoniae*, *Escherichia coli*, *Enterobacter* spp., among others [5–7]. However, some studies have reported that both susceptible and antibiotic-resistant microorganisms can have similar frequencies in

Microbiology of Ventilator-Associated Pneumonia http://dx.doi.org/10.5772/intechopen.69430 109

In many cases, VAP can be caused by more than one pathogen (polymicrobial infection). This fact can be ignored sometimes when isolates are reported only as a percentage of the total number of isolates. In a recent study, performed in medical and surgical ICUs of a hospital in Spain, of 147 VAP patients, 32 (21%) had more than one pathogen associated. Interestingly, the clinical outcomes were not influenced by the polymicrobial etiology, when appropriate

The etiology of VAP varies in different countries and even between ICUs of the same city, distinct patients groups (like the ARDS patients, immunocompromised, and so on), or settings of the same hospital [25]. However, among Gram-negative bacteria, a high frequency is generally reported for *P. aeruginosa*, *Acinetobacter* spp., and Enterobacteriaceae members. Among Gram-positive isolates, *S. aureus* and *Streptococcus* spp. are considered as important pathogens [3, 5, 14, 25–27]. **Table 1** shows a list of the most frequently and also some uncom-

early and late-onset VAP [22, 23].

antibiotic therapy was administered [24].

mon microorganisms detected in VAP patients.

(1) Gram-positive bacteria

(2) Gram-negative bacteria

Anaerobes

*Corynebacterium* spp.

**Microorganisms Frequency (%)**

*Staphylococcus aureus* 20–32 *Streptococcus* spp. 2–8 Coagulase-negative staphylococci 1–2

*Pseudomonas aeruginosa* 20–28 *Acinetobacter* spp. 4–13 *Klebsiella pneumoniae* 8–12 *Escherichia coli* 4–10 *Haemophilus influenzae* 4–8 *Enterobacter* spp. 6–7 *Serratia* spp. 2–4 *Neisseria* spp. 2–3 *Stenotrophomonas maltophilia* 2–3 (3) Other bacteria <1 each

The aspiration technique of endotracheal secretions also plays an important role as a risk factor for the establishment of VAP. The open method where a sterile aspiration probe is introduced has disadvantages such as loss of oxygenation, since the patient is temporarily disconnected from the ventilator and the system is opened with exposure of the patient, and the maximum duration of use of each circuit is not known [5].

Tracheostomy is an indicated procedure after 2 weeks of translaryngeal intubation of critically ill patients. Apparently, early tracheostomy may be associated with a lower incidence of pneumonia when compared to the late procedure or nonprocedure [19]. Frequent reintubations are also associated with VAP because of the risk of aspiration of gastric contents through the use of the nasogastric tube, subglottic dysfunction, and lowering of the level of consciousness [5].

The VAP prevention guidelines recommend the placement of the patient in the bed between 30 and 45° semi-reclined [20]. The supine position to which the patient is subjected may lead to lesions such as atelectasis in the dorsal lung region, barotrauma in the ventral lung region [5]. Experiments performed on rats proved the advantage of lateral decubitus in improving gas exchange, reducing gastroesophageal reflux, and avoiding pulmonary infection by gastric aspiration due to gravity [21]. Recently, the semi-decubitus position (30–60°) was shown to reduce the risk of VAP compared to supine positioning (0–10°) [20].

Nasal feeding by nasogastric tube increases gastric secretions and pH, leading to colonization by Gram-negative bacilli. Aspiration of this gastric content increases the risk of VAP. The use of sedative medications used in therapeutic procedures can cause prolonged relaxation of the muscles, increasing the risk of aspiration [5].

In addition, in the neonatal intensive care unit (NICU), some risk factors are associated with characteristics peculiar to this age group, including: length of stay in the NICU, enteral and parenteral feeding, blood transfusion, low birth weight, prematurity, and bronchopulmonary dysplasia [10, 13].
