used in VAP patients, with sensitivities obtained by the usual procedure. The six antibiotics
included in the rapid test were oxacilin, cefepime, imipenem, piperacillin-tazobactam,
amikacin, and ciprofloxacin. Sensitivity data were comparable to those obtained by the
standard procedure in 98% of cases. We have already demonstrated the impact of this method
in improving and reducing the use of antimicrobials in patients with VAP (235). Patients with
information provided by the direct E-test differed significantly from the second group in terms
of the following factors: more days of adequate antibiotic treatment, smaller defined daily
doses (DDD) of antibiotics, fewer days of fever, fewer episodes of diarrhea associated with
Clostridium difficile,and less money spent on antibiotics.
Assessing the Patient Response
Along with the findings of semiquantitative EA, the patient response should be assessed on
day 3 of therapy (236). By this time, fever has resolved, the PaO 2 /FiO 2 is >250 mm Hg, and a
normal white blood cell count is found in 73.3%, 74.7%, and 53.3% of patients, respectively
(56). Other authors report that infection variables resolve after antimicrobial therapy in
patients with VAP by day 6 (237). Resolution of radiologic opacities and clearance of secretions
occur at a median time of 14 days and 6 days, respectively (56). However, failure to improve
after 48 hours of therapy occurs in 65% of ARDS patients (56). Thus, ARDS significantly delays
the clinical response to treatment in critically ill patients with VAP, although temperature is
still the earliest resolved factor in this group of patients. Reassessment is necessary in patients
who show no clinical improvement by day 3—especially those in whom the PaO 2 /FiO 2 ratio
and fever fail to improve—while for those showing a good response, it may be possible to
design an abbreviated course of therapy (238,239).
Prompt empirical therapy for all patients suspected of having VAP should be balanced
with the need to limit antimicrobial misuse in ICU’s. The reassessment of the patient’s
situation based on culture results is another major principle. In patients with positive cultures,
therapy can be tailored in terms of quality and duration. Patients with positive cultures who
have not improved probably have VAP, but may be receiving inappropriate antimicrobial
therapy; suffer a complication of VAP; have a second source of infection; or have a second
diagnosis. The antimicrobial regimen should be adjusted, and, then, complications, other sites
of infection, and other pathogens should be sought. In patients with negative cultures, the need
to continue treatment with antimicrobial drugs should be promptly reassessed. Discontinua-
tion of antimicrobial agents is presently recommended in patients with a stable condition,
although in deteriorating or critically ill patients, it is difficult to make this decision.
Value of Surveillance
Several research teams have addressed the issue of whether routine systematic surveillance of
EA cultures may serve as a predictive diagnostic tool for VAP, although results have been
contradictory (5,240–245). In a study performed at our center, the pathogens present in
surveillance cultures taken prospectively on a twice-weekly basis did not correlate well with
cultures obtained on diagnosis of VAP (5).
Table 5 summarizes the performance of the different culture methods for the diagnosis of
VAP.
ANTIMICROBIAL TREATMENT
Selecting an Empirical Regimen
When trying to overcome severe infection, cardiovascular support and measures to improve
hemodynamics and oxygenation are critical (56). The most important lesson learned in the last
decade on the management of VAP is probably that delaying effective antimicrobial therapy in
these patients increases mortality (65,122,125,260), length of stay, and costs (261).
As soon as there is clinical suspicion of VAP, adequate antibiotics should be
administered to increase the likelihood of an early reduction in the bacterial load.
The first step is to decide whether a patient carries a low or high risk of having an MDR
pathogen. The main risk factors for an MDR pathogen are (i)fiveormoredaysofprior
hospitalization or mechanical ventilation, (ii) exposure to antibiotics in the preceding 90 days, (iii)a
high incidence of antimicrobial resistance in the specific hospital unit, and (iv) comorbidities
190 Bouza and Burillo