BackgroundHospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP), particularly cases caused by multidrug-resistant organisms, often require newer antibiotic treatment. The efficacy and safety of newer antibiotics compared with generic antibiotics in randomized controlled trials (RCTs) have not been evaluated before.MethodsIn this systematic review, we searched RCTs in the United States National Library of Medicine (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Ovid MEDLINE, ClinicalTrials.gov, and Google Scholar databases published between 2013 and 2025 (registration no. CRD42023476481). The primary efficacy end point was the 28-day all-cause mortality rate, and the secondary efficacy end points were clinical and microbiological response. The safety end point was nephrotoxicity.ResultsWe identified 8 eligible RCTs involving 2881 patients with HABP/VABP (1450 treated with newer antibiotics and 1431 treated with generic antibiotics). The meta-analysis did not reveal any significant differences between newer and generic antibiotics in the 28-day all-cause mortality rate (risk ratio [RR], 0.97; 95% confidence interval [CI], .72-1.30; I2 = 30%), the clinical response (1.04 [.93-1.17]; I2 = 35%), or the microbiological response (1.05 [.89-1.24]; I2 = 52%). However, newer antibiotics showed significant lower occurrences of nephrotoxicity than regimens with a colistin component (RR, 0.30 [95% CI, .11-.79]; I2 = 0%). In the subgroup analysis, newer antibiotic regimens demonstrated significant improvement in microbiological eradication of carbapenem-resistant gram-negative bacilli (RR, 1.50 [95% CI, 1.18-1.90]; I2 = 0%).ConclusionsNewer antibiotics and generic drugs showed similar efficacy and safety in treating HABP/VABP. The superiority of newer antibiotics in the microbiological eradication of carbapenem-resistant gram-negative bacilli could suggest that future trials should be targeted to those patients to improve understanding of the therapeutic use of these antibiotics and the pathophysiology of these conditions.