BackgroundDescription and comparison of bacterial characteristics of ventilator-associated pneumonia (VAP) between critically ill intensive care unit (ICU) patients with COVID-19-positive, COVID + ; and non-COVID-19, COVID-.MethodsRetrospective, observational, multicenter study that focused on French patients during the first wave of the pandemic (March–April 2020).Results935 patients with identification of at least one bacteriologically proven VAP were included (including 802 COVID +). Among Gram-positive bacteria,S. aureusaccounted for more than two-thirds of the bacteria involved, followed byStreptococcaceaeandenterococciwithout difference between clinical groups regarding antibiotic resistance. Among Gram-negative bacteria,Klebsiellaspp. was the most frequently observed bacterial genus in both groups, withK. oxytocaoverrepresented in the COVID- group (14.3%vs. 5.3%; p < 0.05). Cotrimoxazole-resistant bacteria were over-observed in the COVID + group (18.5%vs. 6.1%; p <0.05), and after stratification forK. pneumoniae(39.6%vs. 0%; p <0.05). In contrast, overrepresentation of aminoglycoside-resistant strains was observed in the COVID- group (20%vs. 13.9%; p < 0.01).Pseudomonassp. was more frequently isolated from COVID + VAPs (23.9%vs. 16.7%; p <0.01) but in COVID- showed more carbapenem resistance (11.1%vs. 0.8%; p <0.05) and greater resistance to at least two aminoglycosides (11.8%vs. 1.4%; p < 0.05) and to quinolones (53.6%vs. 7.0%; p <0.05). These patients were more frequently infected with multidrug-resistant bacteria than COVID + (40.1%vs. 13.8%; p < 0.01).ConclusionsThe present study demonstrated that the bacterial epidemiology and antibiotic resistance of VAP in COVID + is different from that of COVID- patients. These features call for further study to tailor antibiotic therapies in VAP patients.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12941-023-00603-0.