BACKGROUND: Lower respiratory tract infection (LRTI) remains the leading infectious cause of morbidity and mortality globally. Key bacterial pathogens include Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus and Streptococcus pneumoniae. This study examined the prevalence and antimicrobial resistance patterns of major bacterial pathogens from community- and hospital-acquired LRTIs across six major hospitals in Vietnam. METHODS: Between January 2022 and May 2023, 1000 bacterial isolates were collected through an isolate-based surveillance. Species identification and antimicrobial susceptibility testing were performed by VITEK-2/Phoenix M50, with MICs determined by E-test or broth microdilution. Multiplex PCRs were used to detect common AMR genes. RESULTS: A. baumannii (49.6%), P. aeruginosa (21%), K. pneumoniae (18.6%) were predominant, followed by S. aureus (6.7%), E. coli (3.9%) and S. pneumoniae (0.2%). Most isolates (94.4%) were identified from hospital-acquired cases. High prevalence of MDR and carbapenem resistance were identified in A. baumannii (96% and 95%), P. aeruginosa (56.7% and 57.1%), and K. pneumoniae (78% and 69.2%), respectively. Notably, resistance to ceftazidime-avibactam was detected in K. pneumoniae (34.3%), P. aeruginosa (29%), and E. coli (7.7%), while colistin resistance was found in K. pneumoniae (18.2%) and A. baumannii (2.8%). MRSA prevalence was 79.1%, though S. aureus remained susceptible to vancomycin, linezolid and ceftaroline. Most bla-positive K. pneumoniae (62/71, 87.3%), E. coli (2/2, 100%), and P. aeruginosa (23/25, 85.2%) showed resistance to ceftazidime-avibactam. Whole genome sequencing revealed that the bla-positive but ceftazidime-avibactam susceptible isolates (9 K. pneumoniae and 2 P. aeruginosa) carried truncated bla. Overall, ceftazidime-avibactam was effective against K. pneumoniae, E. coli, and P. aeruginosa isolates carrying ESBL, ESBL and bla, or ESBL and bla. Alternatively, no detectable AMR genes were found in 35 ceftazidime-avibactam resistant P. aeruginosa isolates. CONCLUSIONS: Carbapenem-resistant Gram-negative pathogens were predominant among hospital-acquired LRTIs in Vietnam, with notable resistance to ceftazidime-avibactam and colistin. The lack of effective treatment for A. baumannii remains a major concern. We found a strong correlation between AMR phenotype and genotype among K. pneumoniae and E. coli, supporting gene-based therapy to guide ceftazidime-avibactam use. However, the presence of disrupted bla underscores the need to re-evaluate commercial PCR assays for carbapenemase detection.