Objective To investigate the value of bronchial mucosa biopsy and quantitative culture in the differential diagnosis of lower airway bacterial colonization and infection. Methods A prospective observational cohort survey onMDR Pseudomonas aeruginosa and Acinetobacter baumannii was carried out in intubed or tracheotomized patients with invasive ventilation in respiratory intensive care unite ( RICU) . A total of 50 ICU patients were followed for the detection of MDR pathogen colonization or infection from June 2008 to October 2009. All subjects were divided into an infection group and a colonization group according to the outcome of patients discharged fromthe RICU. Baseline information, APACHEⅡ scores, and CPIS scores were recorded on individual forms for each patient untill discharge or death. Bronchial mucosa biopsy was conducted on appropriate time to identify whether the patient was comfirmed as infection. Microbiological diagnosis was performed with quantitative culture. Results Fifty patients were enrolled in this study, of which infected in 23 cases and colonized in 27 cases. The time of invasive mechanical ventilation, length ofICU stay, catheter indwelling time, and the kinds of disease were significantly different between the two groups( P lt; 0. 05) . The kinds of using antibiotics before onset of multi-drug resistance of bacteria showed that cefoxitin/ cefmetazole and mezlocillin also had significant difference between the infection group and the colonization group. The results of dynamic CPIS score of the infection group showed that scores at each timepoint were higher than those in the colonization group. However, the results of t-test showed that there was higher score in the infection group than that in the colonization group on 14 days after intubation ( P lt;0. 05) . The bronchial mucosa biopsy showed that airway inflammation was detected in 19 cases in the infection group and 9 cases in colonization group. The positive rate in the infection and the colonization group were 55. 6% and 25. 0% , respectively assessed by traditional threshold of 103 cfu/mL for PSB in quantitative bacterial culture. In addition, there was more inflammatory cells in the patients with drug-resistant pathogens infection than that in the patients without nosocomial infection. The combination of bronchial mucosa biopsy and microorganism quantitative cultures had the highest sensitivity and specificity and the highest diagnostic accuracy. Conclusions Bronchial mucosa biopsy combining microorganism quantitative culture is feasible in identifying colonized or infected bacteria. Invasive mechanical ventilation time, length of ICU stay and the catheter indwelling time extending are risk factors for bacterial colonization.