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Background Genomic tools permit a detailed analysis of antibiotic resistance determinants in bacteria, or resistome. Here we discuss variations in antibiotic resistance in K. pneumoniae (Kp) not explained by changes in the resistome Methods We compared Kp strains with divergent carbapenem and aminoglycoside susceptibilities. After identification of bacteria, antibiotic susceptibility testing was performed according to CLSI guidelines. Draft genome sequences were generated using Illumina MiSeq (Nextera paired-end library) and assembled using CLC Genomics Workbench (CLC bio, Cambridge, MA). Resistome, plasmid types and MLST were investigated using the CGE platform (http://cge.cbs.dtu.dk), while capsular type and virulence genes were investigated using the Pasteur BIGsDB database (https://bigsdb.pasteur.fr). Results While receiving amoxicillin-clavulanate, a 44-year old man with diabetes mellitus and paraplegia with neurogenic bladder grew Kp resistant to carbapenems and amikacin from urine. He was treated with fosfomycin and amikacin, followed by imipenem and plazomicin, prior to lithotripsy. Three months later, while off antibiotics, urine cultures grew Kp susceptible to carbapenems and amikacin (figure). Genetic comparison between resistant (November 20, 2018) and susceptible (January 30, 2019) strains revealed they were isogenic, only differing by 559 SNPs (table). Both were ST14, presented capsular type 16, and shared cehalosporinase (bla SHV-28, bla CTX-M-15, bla TEM-1B, bla OXA-1) and aminoglycoside modifying enzyme (AME) (aph(3")-Ib, aph(6)-Id, aac(6')-Ib-cr) genes. Although both had mutations in the outer membrane porin OmpK36, these differed (stop AA125 and frameshift AA183, respectively) Conclusion Carbapenem resistance in the initial Kp is likely explained by overexpression of cephalosporinases in combination with changes in membrane permeability, while amikacin resistance is likely due to AMEs. Since no significant gene variation was observed in the susceptible Kp , reversal of resistance was likely due to decreased expression of cephalosporinases and AMEs after antibiotics were stopped. Incorporation of antibiotic history and host factors can explain clinically important changes in antibiotic resistance Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]