**4. Virulence of major pathogens and VAP severity**

Clinical outcomes of VAP depend on a variety of factors, which are inherent to the patient, the hospital assistance, and also the microorganism, including host immune system status, underlying diseases associated, appropriate antibiotic therapy, accurate and rapid clinical and laboratory diagnosis, antimicrobial susceptibility, and virulence of the pathogen. Antimicrobial susceptibility is discussed in Section 5. Here, we present significance of major virulence factors associated with VAP severity of four selected pathogens: *Acinetobacter baumannii*, *K. pneumoniae*, *P. aeruginosa*, and *S. aureus*.

#### **4.1.** *Acinetobacter baumannii*

There are more than 20 *Acinetobacter* species, with *A. baumannii* being the most commonly isolated in clinical settings, in which it represents important emerging nosocomial pathogen. *A. baumannii* is a Gram-negative bacterium, strictly aerobic, nonfermentative coccobacillus, nonmotile, nonpigmented, and catalase-positive. It is ubiquitous in nature and has been recovered from soil, water, and animals and found as part of the normal skin, throat, and rectal flora of human. Although a frequent colonizer, *A. baumannii* can be the cause of severe and sometimes lethal infections, frequently of nosocomial origin, principally VAP. A survey in U.S. hospitals showed that the majority of the isolates (57.6%) were from the respiratory tract, and *Acinetobacter* species ranked fifth as the causative organism of VAP (6.6%) [28–30].

In recent years, it has been designated a "red alert" human pathogen and has caused considerable concern in the medical community. This pathogen can adhere to surfaces, and it specifically targets moist tissues such as mucous membranes or skin that has been exposed due to accident or injury, and can cause a wide variety of infections. Most of the cases involve the respiratory tract, but bacteremia, meningitis, and wound infection may also occur. A recent systematic review and meta-analysis showed that some invasive procedures frequently used in the ICU increase the risk of *A. baumannii* bacteremia: mechanical ventilation, central venous or urinary catheterization, and nasogastric tube use [31, 32].

The virulence of *A. baumannii* can be attributed to several factors: capacity to form biofilms; its ability to adhere, to colonize, and invade human epithelial cells; its antibiotic resistance mechanisms; and its ability to acquire foreign genetic material to promote its own survival under antibiotic and host selection pressures. Approximately 30% of *Acinetobacter* strains also produce an exopolysaccharide, which is a major virulence factor protecting bacteria from host defenses [28, 31].
