# Polymyxin heteroresistance in Klebsiella oxytoca

## TL;DR

This study shows that Klebsiella oxytoca can develop polymyxin heteroresistance, making infections harder to treat due to a stable resistant subpopulation.

## Contribution

The study is the first to characterize polymyxin B heteroresistance in Klebsiella oxytoca using population analysis and MALDI-TOF.

## Key findings

- All six K. oxytoca isolates showed polymyxin B heteroresistance with 8–16-fold MIC differences.
- Heteroresistance was due to a stable resistant subpopulation unaffected by growth phase or human serum factors.
- Resistant subpopulations had 4-amino-l-arabinose modifications in lipid A detected via MALDI-TOF.

## Abstract

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.