Nosocomial and Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) is an infection frequently caused by Pseudomonas aeruginosa, Haemophilus spp. and Klebsiella spp. or by Staphylococcus aureus. Anaerobes are a rare cause of VAP. Virus or fungi are extremely infrequent in immunocompetent patients.

The physical placement of the endotracheal tube is the most important risk factor for the colonisation of oropharyngeal secretions and establishment of VAP. Aspiration of oropharyngeal secretions or leakage of bacteria around the endotracheal cuff is the major route of access by bacteria to the lower respiratory tract. Infected biofilms on the endotracheal tube can work as a reservoir of pathogens that can eventually trigger an episode of VAP.

Patients with late onset of VAP and prior exposure to antibiotics have a greater risk of being infected by a multidrug- resistant pathogen, such as P. aeruginosa, methicillin-resistant S. aureus or Acinetobacter baumanii.

Although the reaction to the infection is not homogeneous, in critically ill patients the mechanical, humoral and cellular responses are suboptimum, which means another challenge in the research and treatment of this disease.

Several biomarkers have been studied as diagnostic tools in patients with ventilator-associated pneumonia (VAP) to assess prognosis, antimicrobial treatment response and duration.

Promising results for the diagnosis of VAP have been reported. However, these results need further validation by independent cohorts. Procalcitonin (PCT) appears to be of limited value, although most data have not been sufficiently controlled for potential confounders. Soluble triggering receptor, expressed on myeloid cells-1, could not be confirmed as a useful diagnostic tool. Overall, diagnostic data for biomarkers are impaired by the same limitations as all data on quantitative cultures of respiratory samples are, i.e. the lack of a gold standard for validation.

All investigated biomarkers differentiated survivors and nonsurvivors; however, predictions were limited by restricted patient numbers and unvalidated results.

Intervention studies using biomarker-based algorithms (particularly PCT) have been shown to safely and effectively reduce the duration of antimicrobial treatment. However, data are affected by obvious overtreatment practices in the control groups. Thus, the role of biomarkers, within simple and inexpensive clinical rules and algorithms, to shorten antimicrobial treatment needs defining.

Several new antibiotics with activity for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) have recently become clinically available. All are variations of existing compounds. Doripenem is probably equivalent to the already available meropenem and is slightly more active than imipenem. Its stability in solution allows use in prolonged infusions. Ceftaroline has been approved by the US Food and Drug Administration for the treatment of community-acquired pneumonia, and may be appropriate for HAP/VAP without multidrug-resistance risk factors. Unfortunately, although active against methicillin-resistant Staphylococcus aureus (MRSA) in vitro, no patients in the ceftaroline clinical trial had MRSA pneumonia so this advantage remains theoretical. Televancin appears to be roughly equivalent to vancomycin, with potentially greater efficacy in MRSA isolates with high mean inhibitory concentrations, but with an equal to greater risk of nephrotoxicity. Tigecycline should not be used as front-line therapy for HAP/VAP but as salvage therapy only in patients infected with extremely drug-resistant pathogens. Colistin finds its greatest use in this same niche, although aerosolised colistin demonstrates trends toward improved outcomes. New antibiotics are clearly needed for nosocomial pneumonia.

Validation of guidelines for the management of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) is important to confirm the reliability of such guidelines in clinical practice and to ascertain their impact on patient-outcome parameters. In order to improve outcomes, guidelines need to be adapted to the local microbiology, accurately predict pathogens, and help physicians to administer the most appropriate empiric antimicrobial therapy. Overall, the implementation of guidelines is followed by an increase in the initially adequate antibiotic treatment. Rather than the onset with time, a proper identification of risk factors for specific pathogens is crucial in choosing an appropriate empiric treatment and needs to be addressed in future guidelines. However, only a few studies have demonstrated that the prediction of microorganisms by HAP and VAP guidelines is reliable. Guideline validation studies are not easy and have to take into account different variables, potentially related with the outcome of patients.

Ventilator-associated pneumonia (VAP) is one of the most common infections in the intensive care unit (ICU) and is associated with high morbidity, mortality and costs. As a result, prevention of VAP is highly relevant in critical care settings. Pulmonary aspiration of colonised oropharyngeal secretions across the tracheal tube cuff is the main pathogenic mechanism for development of VAP. Recently, several strategies have been applied to improve the design of tracheal tubes and reduce the likelihood of aspiration of pathogen-laden secretions across the cuff. The use of endotracheal tubes that allow aspiration of subglottic secretions have demonstrated a decrease in the rate of VAP. In critically ill patients, following tracheal intubation oral flora frequently shifts into a predominance of aerobic Gram-negative pathogens. Extensive efforts have been devoted to reducing the risks of oropharyngeal colonisation with pathogens, including selective digestive decontamination (SDD). Although SDD is a controversial measure, it reduces the incidence of VAP and respiratory infections. The long-term effects of SDD on the emergence of bacterial resistance and risk of superinfections are still controversial.

Viral ventilator-associated pneumonia (VAP) has recently been recognised as a true disease in non-immunosuppressed patients. Viral VAP is typically due to latent viruses that are reactivated in critically ill individuals. Herpes simplex virus (HSV)-1 and cytomegalovirus (CMV) are the main viruses responsible for viral VAP. HSV-1 is frequently recovered from the upper and lower respiratory tract of intensive care unit (ICU) patients. In some patients, true VAP (HSV bronchopneumonitis) can occur. The clinical diagnosis is not specific, but patients frequently have herpes labialis or gingivostomatitis. If HSV bronchopneumonitis is suspected, bronchoalveolar lavage (BAL) can be performed to detect HSV and HSV-specific inclusions in cells recovered in BAL fluid. Whether or not a specific treatment is useful in this setting remains to be determined.

CMV is less frequently recovered from the lower respiratory tract of ICU patients, but can be classed as true CMV pneumonia in some cases. Diagnosis is not easy and often requires lung biopsy. Whether or not noninvasive testing (CMV in BAL or blood) is useful in the diagnosis of CMV pneumonia, remains to be seen. To date, a specific treatment cannot be recommended.

Hospital-acquired pneumonia (HAP) is an important cause of nosocomial infection. Most studies have been carried out in intensive care units (ICUs) where patients requiring mechanical ventilation are at high risk of developing HAP. However, the epidemiological differences between intubated patients and those admitted to general hospitalisation wards suggest that the aetiology and therapeutic approach differ between these two groups. The present article reviews the epidemiology, diagnosis, treatment and prevention of HAP occurring outside ICUs.