OBJECTIVE: To study the changes in the expression of rat beta-defensin-2 (RBD-2) gene in the lung tissue with P. aeruginosa (PA) pneumonia following tracheal mechanical ventilation (MV), and to evaluate the pathogenesis of ventilator-associated pneumonia (VAP). METHODS: A total of 58 normal healthy Sprague-Dawley rats, weighing between 280 and 320 g, were randomly divided into the control group and the conventional MV group (CMV). A tracheal catheter was inserted via mouth in every rat under urethane anesthesia. PA (1 MIC, 0.2 ml) was instilled into the tracheal in the control group. Rats of CMV group received MV (V(T)=12 ml/kg) through tracheal tube for 24 hours, and then were challenged intra-tracheally with PA (1 MIC, 0.2 ml). Fluid loss was replenished through intravenous infusion. The arterial catheter was used for hemodynamics, parameters were monitored, and arterial blood gases were determined. Samples of lung were harvested at 0 hours, 15 hours, 3 hours, 6 hours, 12 hours, 1 day, 3 days and 5 days, respectively, after bacterial challenge. The mRNA of RBD-2 was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the protein levels were analyzed by Western blotting. RESULTS: Expression of RBD-2 mRNA and protein was lower in CMV group compared with the control 3 hours before instillation of bacteria. RBD-2 mRNA increased 3 hours after bacteria instillation, reaching the peak at 12-24 hours. No significant difference in RBD-2 expression between the control group and the CMV group within 3 hours, but it was significantly higher at 3 hours, 6 hours, 12 hours, 1 day, 3 days and 5 days in the control group than in the CMV group. The number of inflammatory cells infiltrating the bronchial submucous layer was significantly higher in the control group than in the CMV group (P<0.05). There was milder interstitial pulmonary edema and less red blood cells in the alveoli in the control group than in the CMV group. The mortality rate of the CMV group was 60%, which was significantly higher than that of the control group (20%, P<0.05). The positive rates of blood culture and bronchoalveolar lavage fluid (BALF) bacterial culture were also higher in the CMV group (P<0.05). The survival rate in CMV group (40%) was lower than that of the control group (P<0.05). CONCLUSION: The lowering of BD-2 gene and protein expression in the CMV group 3 hours after bacteria challenge might be one of the contributory factors in causing VAP.
Disease Models, Animal ; Lung/metabolism ; Lung/pathology ; Pneumonia, Ventilator-Associated/*metabolism ; Pneumonia, Ventilator-Associated/pathology ; RNA, Messenger/metabolism ; Random Allocation ; Rats, Sprague-Dawley ; beta-Defensins/genetics ; beta-Defensins/*metabolism

BackgroundAntimicrobial de-escalation refers to starting the antimicrobial treatment with broad-spectrum antibiotics, followed by narrowing the drug spectrum according to culture results. The present study evaluated the effect of de-escalation on ventilator-associated pneumonia (VAP) in trauma patients.

MethodsThis retrospective study was conducted on trauma patients with VAP, who received de-escalation therapy (de-escalation group) or non-de-escalation therapy (non-de-escalation group). Propensity score matching method was used to balance the baseline characteristics between both groups. The 28-day mortality, length of hospitalization and Intensive Care Unit stay, and expense of antibiotics and hospitalization between both groups were compared. Multivariable analysis explored the factors that influenced the 28-day mortality and implementation of de-escalation.

ResultsAmong the 156 patients, 62 patients received de-escalation therapy and 94 patients received non-de-escalation therapy. No significant difference was observed in 28-day mortality between both groups (28.6% vs. 23.8%, P = 0.620). The duration of antibiotics treatment in the de-escalation group was shorter than that in the non-de-escalation group (11 [8-13] vs. 14 [8-19] days, P = 0.045). The expenses of antibiotics and hospitalization in de-escalation group were significantly lower than that in the non-de-escalation group (6430 ± 2730 vs. 7618 ± 2568 RMB Yuan, P = 0.043 and 19,173 ± 16,861 vs. 24,184 ± 12,039 RMB Yuan, P = 0.024, respectively). Multivariate analysis showed that high Acute Physiology and Chronic Health Evaluation II (APACHE II) score, high injury severity score, multi-drug resistant (MDR) infection, and inappropriate initial antibiotics were associated with patients' 28-day mortality, while high APACHE II score, MDR infection and inappropriate initial antibiotics were independent factors that prevented the implementation of de-escalation.

ConclusionsDe-escalation strategy in the treatment of trauma patients with VAP could reduce the duration of antibiotics treatments and expense of hospitalization, without increasing the 28-day mortality and MDR infection.

APACHE ; Anti-Bacterial Agents ; therapeutic use ; Female ; Humans ; Intensive Care Units ; Male ; Pneumonia, Ventilator-Associated ; drug therapy ; pathology ; Propensity Score ; Retrospective Studies