Hospital-acquired pneumonia and ventilator-associated pneumonia

Nosocomial pneumonia including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the second most frequent nosocomial infections and the first in terms of morbidity, mortality, and costs.

In recent years two different sets of guidelines for the management of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) and (2017) Guidelines of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT).

Nosocomial pneumonia are generally classified into hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP).

Hospital-acquired pneumonia (HAP) is defined as pneumonia occurring at least 48 hours after hospital admission, excluding any infection incubating at the time of admission.

Ventilator-associated pneumonia (VAP) is defined as a pneumonia occurring in patients under mechanical ventilation for at least 48 hours. It is a frequent issue in intensive care units, with a great impact on morbidity, mortality and cost of care. Treating VAP is a difficult task, as initial antibiotics have to be appropriate and prompt.

The term healthcare-associated pneumonia (HCAP) was included in the previous guidelines to identify patients coming from community settings at risk for multidrug-resistant (MDR) bacteria. HCAP referred to pneumonia acquired in healthcare facilities including nursing homes, hemodialysis centers and outpatient clinics or acquired in patients with previous hospitalization within the past 90 days. However HCAP was not included in recent guidelines because there is increasing evidence that aetiology in HCAP patients is similar to that of community-acquired pneumonia and that many patients with HCAP are not at high risk for MDR bacteria.

The pathogenesis of nosocomial pneumonia is multifactorial. The concomitant illnesses of hospitalized patients is a risk for nosocomial infections. in hospitalized patients alterations in immune function make patients more susceptible to invasive infections that would not occur in healthy individuals. Many hospitalized patients are in poor nutritional status, increasing their risk of infection. Severe illness and hemodynamic compromise are associated with increased rates of nosocomial pneumonia. Aspiration of oropharyngeal secretions may play a significant role in the development of nosocomial pneumonia. In hospitalized patients the combination of alterated immune function, impaired mucocilliary clearance of the respiratory tract and oropharynx colonization by enteric Gram-negative pathogens make aspiration an important contributor to pneumonia. Moreover supine positioning contributes greatly to the aspiration risk.

Risk factors are also prolonged hospital length of stay, cigarette smoking, increasing age, uremia, prior antibiotic exposure, alcohol consumption, endotracheal intubation, coma, major surgery, malnutrition, multiple organ-system failure, and neutropenia. Importantly, the use of stress ulcer prophylaxis, such as proton pump inhibitors commonly used in critically ill patients, is associated with risk of nosocomial pneumonia. Finally, foreign bodies, such as endotracheal and nasogastric tubes, may provide a source for further colonization allowing migration of pathogens to the lower respiratory.

The guidelines recommend obtaining cultures of respiratory secretions and blood cultures from all patients with suspected HAP or VAP in order to guide antibiotic treatment. Noninvasive techniques such as endotracheal aspiration can be done more rapidly than invasive sampling, with fewer complications and resources, however may led to an over-identification of bacteria by initial direct examination of samples. Invasive bronchoscopic techniques such as bronchoalveolar lavage (BAL) or protected specimen brush (PSB) require the participation of qualified clinicians, may compromise gas exchange during the procedure and may be associated with higher direct costs.

Microbiology can be confirmed by both semiquantitative culture results (with growth of microorganism(s) reported as light/few, moderate, or abundant/many) and quantitative culture results (growth thresholds considered significant at 103 colony-forming units [CFU]/mL for PSB or 104 CFU/mL for BAL). However, there is no still consensus in the clinical microbiology community as to whether these specimens should be cultured quantitatively, using the aforementioned designated bacterial cell count to designate infection, or by a semiquantitative approach.

Once HAP or VAP is suspected clinically, antibiotic therapy should be started. In patients with sepsis or septic shock, antibiotics should be started as soon as possible (within 1 hour).

Delaying empiric antibiotic treatment and failing to give an appropriate regimen are both associated with higher mortality rates.

Choice of a specific regimen for empiric therapy should be based on:

·         patient’s clinical conditions,

·         knowledge of the prevailing pathogens within the healthcare setting

·         the individual patient’s risk factors for multidrug resistance.

Knowledge of the predominant bacteria, and particularly their susceptibility patterns, should greatly impact the choice of empiric therapy. Awareness and knowledge of local resistance patterns is critical to decide empiric antibiotic therapy for HAP and VAP.

According to the European guidelines, a narrow-spectrum empiric antibiotic therapy with activity against non-resistant Gram-negative and methicillin-sensitive S. aureus (MSSA) is suggested in low risk patients and early-onset HAP/VAP. Low risk patients are those who present HAP/VAP without septic shock, with no other risk factors for MDR bacteria and those who are not in hospitals with a high background rate of resistant pathogens.

Conversely, broader-spectrum initial empiric therapy covering Gram-negative bacteria and include antibiotic coverage for MRSA is suggested in high-risk patients. High-risk patients are those with septic shock and/or who have the following risk factors for potentially resistant bacteria including hospital settings with high rates of MDR bacteria, previous antibiotic use, recent prolonged hospital stay and previous colonization with MDR bacteria.

The traditional intermittent dosing of each agent for VAP may be replaced with prolonged infusions of certain beta-lactam antibiotics to optimize pharmacokinetic/pharmacodynamic principles, especially in critically ill patients with infections caused by Gram-negative bacilli and overall for those patients with infections caused by Gram-negative bacilli that have elevated but susceptible MICs to the chosen agent.

Longer treatment corse increases the risks of both Clostridium difficile infections and antimicrobial resistance. A 7–8 day course of antibiotic therapy in patients with HAP/VAP without immunodeficiency, cystic fibrosis, empyema, lung abscess, cavitation or necrotising pneumonia and with a good clinical response to therapy is generally suggested. In these patients prolonged regimens do not improve patients outcome.


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