Background and research question In pyogenic spondylodiscitis, infections with coagulase-negative staphylococci must be given increasing importance. Empirical antibiosis is particularly necessary in patients with severe or progressive neurological deficits or hemodynamic instability, as well as in the case of culture-negative spondylodiscitis. It is unclear whether uniform empirical antibiosis standards adapted to the resistance profiles exist in Germany. Study design and methods A survey on the empirical antibiotic therapy for pyogenic spondylodiscitis was conducted at German university and Berufsgenossenschaft clinics, each in the departments of orthopedics and trauma surgery. The survey results were applied to the resistance profiles of pathogens in 45 spondylodiscitis patients treated in our department between 2013 and 2020. Thus, the potential susceptibility and resistance rates were calculated for the indicated antibiotic therapies. Results Of the 71 clinics queried, a total of 44 (62.0%) responded. Sixteen different antibiotic therapies were reported as standard regimes. Among these, 14 different combination therapies were reported. The most commonly reported empirical antibiotics, namely amoxicillin/clavulanic acid or ampicillin/sulbactam (29.5%) and cephalosporins (18.2%) showed high potential resistance rates of 20.0% and 35.6%, respectively, in relation to the previously published resistance profile. The highest potential susceptibility rates were achieved with a combination of vancomycin + ampicillin/sulbactam (91.1% sensitive pathogens), vancomycin + piperacillin/tazobactam (91.1% sensitive pathogens), and ampicillin/sulbactam + teicoplanin (95.6% sensitive pathogens). One out of these combinations was reported as standard regime by three clinics (6.8%). Conclusion The nationwide survey of empiric antibiotic treatment for pyogenic spondylodiscitis revealed a large heterogeneity in the standard of care. A combination of a broad-spectrum-beta-lactam antibiotic with an additional glycopeptide antibiotic may be justified.