For polymicrobial infections, AtbFinder utilizes a novel paradigm of the population response to antibiotics, enabling bacterial growth in the form of a mixed microbial community and selecting the antibiotics targeting not only the principal pathogen, but also those bacteria that support their growth. TGV medium allowed culturing a more diverse set of bacteria from polymicrobial biospecimens, compared with that achieved with the standard media and enabled, already within 4h, accurate selection of the antibiotics that completely eliminated all cultivatable bacteria from clinical samples. In conclusion, AtbFinder system may be a valuable tool in improving antibiotic selection, enabling targeted empirical therapy and accurate antibiotic replacement, which is especially important in high-risk patients.