Attributable mortality of ventilator-associated pneumonia: a meta-analysis.

OBJECTIVE: To investigate whether ventilator-associated pneumonia (VAP) is a true cause of mortality in the intensive care unit setting. METHODS: We performed a meta-analysis of available data without time restrictions. A conservative random effects model was employed to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of 968 retrieved reports, 44 studies fulfilled our inclusion criteria. Presence, as opposed to absence, of VAP was associated with higher mortality in the ICU setting (OR 1.96, 95%CI 1.26-3.04). This result persisted when matched case-control studies (OR 1.73, 95%CI 1.23-2.45) or studies in which VAP was microbiologically confirmed in all patients (OR 2.20, 95%CI 1.01-4.81) were evaluated separately. VAP continued to be associated with higher mortality when the impact of immune suppression was controlled. VAP was not associated with higher mortality in the subgroup analysis of studies including patients who received appropriate initial antimicrobial treatment (OR 1.64, 95%CI 0.68-3.96). CONCLUSION: Presence, compared to absence, of VAP seems to be associated with higher mortality in critically ill patients. Appropriateness of initial antimicrobial treatment in such patients may moderate this association.

Some current issues in the pharmacokinetics/pharmacodynamics of antimicrobials in intensive care.

Infections, particularly those caused by resistant pathogens, are a common cause of morbidity and mortality in critically ill patients. However, the availability of effective antimicrobial agents is limited. Critical illness itself can influence the pharmacokinetic/pharmacodynamic (PK/PD) parameters of antimicrobials by altering their volume of distribution and the rate of their excretion and elimination and by impairing their penetration into tissues. Therefore, when designing a treatment regimen, the intensivist should consider and take advantage of antibiotic PK/PD properties. There is significant but inconclusive evidence that critically ill patients may benefit more when antibiotics with time-dependent action are administered in a continuous/prolonged infusion regimen. On the other hand, aminoglycosides exhibit a concentration-dependent pattern of killing and should be administered at high doses once daily or at extended intervals, and their levels in the plasma should by strictly monitored to avoid both underexposure and toxicity. The problem of antimicrobial resistance now involves agents traditionally considered reliable in that aspect, such as vancomycin. Strict monitoring of vancomycin MIC for methicillin-resistant Staphylococcus aureus and the prudent use of the available alternative agents as well as de-escalation strategies might be reasonable strategies for dealing with this problem.