Polymyxin heteroresistance in Klebsiella oxytoca

Introduction. Antibiotic heteroresistance presents a growing public health concern, as the phenotype is associated with treatment failure and is hard to detect using conventional diagnostic testing. Gap Statement. Heteroresistance in Klebsiella oxytoca , an opportunistic pathogen associated with hospital-acquired infections, has not been characterized. Aim. In this study, we characterized polymyxin B heteroresistance in a collection of six clinical and environmental isolates of K. oxytoca . Methodology. We assessed heteroresistance using population analysis profile assays and LPS modifications using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). Results. All six isolates tested exhibited heteroresistance, indicated by an 8–16-fold difference between the MIC of the bulk population and the MIC of the resistant sub-population, as determined using population analysis profiling. Heteroresistance was found to be due to the presence of a stable sub-population of resistant bacteria, the size of which was unaffected by growth phase or the presence of host antimicrobial factors present in human serum. MALDI-TOF analysis revealed 4-amino- l -arabinose modifications of the lipid A of resistant sub-populations. Conclusion. This pilot study identifies that polymyxin heteroresistance in K. oxytoca may complicate the treatment of infections caused by this organism.