Abstract & Commentary

Treating VAP: The Importance of Getting Initial Antibiotic Coverage Right

By David J. Pierson, MD, Professor Emeritus, Pulmonary and Critical Care Medicine, University of Washington, Seattle.

This story ran previously in the March 2012 issue of Critical Care Alert and was peer reviewed by William Thompson, MD. Dr. Pierson reports no financial relationships relevant to this field of study.

Synopsis: In this study in which all patients with clinically suspected ventilator-associated pneumonia were given prompt empiric antibiotic therapy, wh ether that therapy turned out to be appropriate for the organisms recovered turned out to be an important determinant of patient outcomes.

Source: Muscedere JG, et al for the Canadian Critical Care Trials Group. The adequacy of timely empiric antibiotic therapy for ventilator-associated pneumonia: An important determinant of outcome. J Crit Care 2011;Nov 30. [Epub ahead of print.]

This study was a secondary analysis of data from an earlier randomized clinical trial comparing one antibiotic vs two (meropenem alone or meropenem plus ciprofloxacin) as early empiric therapy for ventilator-associated pneumonia (VAP). In that study, once the clinical suspicion of VAP (CSVAP) had been established, lower-airway culture specimens were obtained (by endotracheal suction in half the patients and bronchoalveolar lavage in half, via a stratified design) and empiric antibiotics begun within a median of 9 hours. Here, the authors examined outcomes in that study (ICU and hospital mortality, days of mechanical ventilation, and ICU and hospital lengths of stay) among the 47% of the originally enrolled patients who were proven microbiologically to have VAP, according to whether the recovered organisms were sensitive to the antibiotics used. Bacteriologic results from the two diagnostic procedure groups were combined for the purposes of this study, and all patients determined in the earlier trial to have had VAP were adjudicated by the authors to confirm this diagnosis clinically and microbiologically.

Thus, this was a retrospective analysis of outcomes in the 350 patients with positive cultures from among 739 with CSVAP who were begun promptly on empiric broad-spectrum antibiotic therapy. The 37 patients (10.6%) with one or more organisms that were not susceptible to the initially administered antibiotics (inadequate therapy, IT) were compared to the 313 patients (89.4%) whose infecting organisms were sensitive to what they received (appropriate therapy, AT).

The IT group had statistically higher mortality, both in the ICU (35.1% vs 11.8%; P = 0.0001) and in the hospital (48.7% vs 19.5%; P = 0.02). They also spent more days on mechanical ventilation (15.8 vs 16.8 days; P = 0.0005), in the ICU (13.5 vs 8.4 days; P = 0.02), and in the hospital (42.2 vs 27.9 days; P = 0.04), than those in the AT group. In a separate 3:1 case-control analysis, the odds ratio of in-hospital mortality with IT was 3.00 (95% confidence interval, 1.24-7.24; P = 0.01).

Commentary

In previous studies of CSVAP in which empiric broad-spectrum antibiotic treatment has been given initially and then tailored to the results of microbiologic studies among patients who prove to actually have VAP, worse outcomes have been documented in those who do not initially receive AT. However, in those studies empiric therapy in patients with initial IT has often been both microbiologically inappropriate and delayed. This is the first study to look specifically at the issue of appropriate empiric antibiotics in the context of all patients having received antibiotics promptly once CSVAP was identified. Thus, the authors were able to take the confounding variable of the timing of initial antibiotic therapy out of the equation. They demonstrate that the microbiologic appropriateness of the initial antibiotic(s) given is a significant determinant of patient outcome.

The selection of an appropriate initial empiric antibiotic regimen, once a critically ill ventilated patient is clinically suspected of having VAP, remains a complicated and controversial task. The original clinical trial from which this secondary analysis was performed found no differences in outcomes among patients who had Pseudomonas as the causative organism with the two antibiotic regimens used. However, the number and choice of antibiotics in patients with CSVAP cannot be approached as a "one-size-fits-all" proposition. Local practice patterns and preferences enter into it, as do the patient's immune status and recent antibiotic history, plus local VAP organism prevalence, resistance patterns, and the institution's current "antibiogram." This study's findings, though, support the concept that initial empiric antibiotic therapy for CSVAP needs to be begun promptly and be broad enough to cover the likely causative organism(s), in that context and for that patient. Once culture results are available, coverage can be narrowed appropriately.