Methods of determining whether a target bacteria is susceptible to an antimicrobial compound are provided. In some embodiments the methods comprise providing a sample comprising the target bacteria maintaining the sample in the presence of an antimicrobial compound to provide an antimicrobial compound-exposed target bacterial sample exposing the antimicrobial compound-exposed target bacterial sample to a cell-wall disruption condition and determining the level of lysis and/or the level of remaining intact cells present in the antimicrobial compound-exposed target bacterial sample whether the cell-wall disruption condition lyses target bacterial cells present in the antimicrobial compound-exposed target bacterial sample wherein the method is performed such that the level of lysis and/or remaining intact cells is determined without determining lysis or non-lysis on a cell-by-cell basis. In some embodiments target bacteria are not immobilized during the exposure to cell-wall disruption conditions. In some embodiments the methods further comprise comparing the level of lysis and/or the level of remaining intact cells present in the antimicrobial compound-exposed target bacterial sample to a reference level to score the sample as sensitive or resistant to the at least one antimicrobial compound. In some embodiments the method does not comprise detecting the presence or absence of at least one target bacteria protein and/or at least one target bacteria nucleic acid. Methods of treating a bacterial infection in a subject are also provided. Kits and systems that may be used to, for example, practice the methods are also provided.
