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Published on: April 18, 2019
Polymyxin heteroresistance in Klebsiella oxytoca
Eunice A Ayerakwa1,2, Edward J A Douglas3,4, Gerald Larrouy-Maumus3,5
1Department of Biochemistry, West African Centre for Cell Biology of Infectious Pathogens, Cell and Molecular Biology, University of Ghana, Accra, Ghana.
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.
Insights
Antibiotic heteroresistance in Klebsiella oxytoca is a significant public health concern. This study reveals polymyxin B heteroresistance in K. oxytoca, complicating treatment of infections.
Area of Science:
- Microbiology
- Antimicrobial Resistance
- Clinical Diagnostics
Background:
- Antibiotic heteroresistance is a growing public health threat, linked to treatment failures and diagnostic challenges.
- Klebsiella oxytoca, an opportunistic pathogen, is frequently implicated in hospital-acquired infections.
- Characterization of heteroresistance in K. oxytoca is lacking.
Purpose of the Study:
- To characterize polymyxin B heteroresistance in clinical and environmental isolates of K. oxytoca.
- To investigate the underlying mechanisms of this heteroresistance.
Main Methods:
- Population analysis profile (PAP) assays were employed to assess heteroresistance.
- Lipid A modifications were analyzed using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry.
Main Results:
- All six K. oxytoca isolates exhibited polymyxin B heteroresistance, with a 8-16 fold increase in MIC for resistant subpopulations.
- Heteroresistance was attributed to a stable resistant subpopulation, independent of growth phase or human serum factors.
- MALDI-TOF analysis identified 4-amino-l-arabinose modifications in the lipid A of resistant subpopulations.
Conclusions:
- Polymyxin B heteroresistance is present in K. oxytoca.
- This heteroresistance may pose challenges for treating K. oxytoca infections.
- Further research is warranted to understand and manage this phenomenon.
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