Ventilator-associated pneumonia - Understanding epidemiology and pathogenesis to guide prevention and empiric therapy

Abstract

Nosocomial pneumonia is associated with a high rate of mortality, particularly in ventilated patients in the intensive care unit (ICU). There have recently been a number of advances in the diagnosis, prevention and treatment of ventilator-associated pneumonia (VAP), as well as in the understanding of its etiology and pathophysiology. New diagnostic techniques, such as protected specimen brushing (PSB) and bronchoalveolar lavage (BAL) have been developed and assessed. Potential sources of pathogens have been investigated with molecular techniques. Progress in prevention has been made, with new measures, including putting intubated patients in a semi-recumbent position with continuous aspiration of subglottic secretions or selecting stress-ulcer prophylactic regimens which do not modify the gastric pH. Meta-analysis has shown that selective digestive decontamination (SDD) reduces the risk of developing ventilator-associated pneumonia and possibly mortality. Empirical treatment before culture results depends on various factors including the severity of the symptoms and the associated risk factors, but more importantly, the time of onset of pneumonia. Early-onset VAP (less than 4 days after admission) is likely to be caused by pathogens which originate in the oropharyngeal cavity (Staphylococcus aureus. Streptococcus pneumoniae, Haemophilus influenzae), whereas aerobic, multi-resistant. Gram-negative bacilli are less likely unless there are predisposing risk factors. Late-onset VAP is more likely to be caused by Gram-negative bacilli or S. aureus and may involve Pseudomonas aeruginosa and Acinetobacter spp. Diagnostic work-up and antimicrobial treatment adapted to the individual patient with VAP is important and even crucial in patients with late-onset VAP and in patients with early-onset VAP and risk factors. Empirical treatment should be started after having collected adequate samples and should be modified according to microbiological results once they are available. Monotherapy with a β-lactam/β-lactamase-inhibitor or a second- or third-generation cephalosporin is appropriate for empiric treatment of early-onset VAP with no risk factors which may alter the spectrum or susceptibility of microorganisms. A quinolone may be used in combination with clindamycin to ensure optimal coverage of S. aureus and anerobes, which are listed as potential pathogens. A third-generation cephalosporin may be chosen in areas where resistant pneumococci are frequently encountered. In the case of late-onset pneumonia, or early-onset pneumonia with risk factors, the β-lactam should have antipseudomonal activity (broad-spectrum penicillins or third-generation cephalosporins with antipseudomonal activity, fourth-generation cephalosporins, carbapenems). A fluoroquinolone plus clindamycin could be used in patients with penicillin allergy. A fourth-generation cephalosporin or carbapenem would also cover the most probable pathogens, such as Gram-negative bacilli (even those with inducible β-lactamases), and would ensure a better coverage for S. aureus than a third-generation cephalosporin. In hospitals where methicillin-resistant S. aureus is a problem, these agents should be combined with a glycopeptide.