Abstract

Aminoglycosides are important options for treating life-threatening infections. However, high levels of aminoglycoside resistance (HLAR) among Klebsiella pneumoniae isolates have been observed to be increasing frequently. In this study, a total of 292 isolates of the K. pneumoniae complex from a teaching hospital in China were analyzed. Among these isolates, the percentage of HLAR strains was 13.7% (40/292), and 15 aminoglycoside resistance genes were identified among the HLAR strains, with rmtB being the most dominant resistance gene (70%, 28/40). We also described an armA-carrying Klebsiella variicola strain KP2757 that exhibited a high-level resistance to all aminoglycosides tested. Whole-genome sequencing of KP2757 demonstrated that the strain contained one chromosome and three plasmids, with all the aminoglycoside resistance genes (including two copies of armA and six AME genes) being located on a conjugative plasmid, p2757-346, belonging to type IncHI5. Comparative genomic analysis of eight IncHI5 plasmids showed that six of them carried two copies of the intact armA gene in the complete or truncated Tn1548 transposon. To the best of our knowledge, for the first time, we observed that two copies of armA together with six AME genes coexisted on the same plasmid in a strain of K. variicola with HLAR. Comparative genomic analysis of eight armA-carrying IncHI5 plasmids isolated from humans and sediment was performed, suggesting the potential for dissemination of these plasmids among bacteria from different sources. These results demonstrated the necessity of monitoring the prevalence of IncHI5 plasmids to restrict their worldwide dissemination.

Highlights

  • Klebsiella pneumoniae (K. pneumoniae) is one of the most common pathogens responsible for human infections

  • minimum inhibitory concentrations (MICs) of six aminoglycosides against 292 K. pneumonia complex isolates showed that the resistance rates for gentamicin, kanamycin, tobramycin, netilmicin, amikacin, and streptomycin were 14.73% (43/292), 14.38% (42/292), 12.33% (36/292), 11.3% (33/292), 9.93% (29/292), and 9.59% (28/292), respectively

  • Thirty of the 137 aminoglycoside-resistant E. coli collected from nine hospitals in France showed high-level resistance (MIC ≥ 256 mg/L) to gentamicin, amikacin, and tobramycin (Caméléna et al, 2020)

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Summary

Introduction

Klebsiella pneumoniae (K. pneumoniae) is one of the most common pathogens responsible for human infections. The emergence of highly antibiotic-resistant K. pneumoniae has become a major challenge facing clinical management and global public health (Kathryn et al, 2015). Aminoglycosides are important options for treating lifethreatening infections and are generally administered in combination with β-lactam agents (Becker and Cooper, 2013). Increasing rates of aminoglycoside resistance in K. pneumoniae have been reported in recent years (Nasiri et al, 2018). An increase in the aminoglycoside resistance rate in Escherichia coli isolates has been reported in France, leading to global concerns (Caméléna et al, 2020). Studies of aminoglycoside resistance in different species or populations have subsequently been conducted. A high level of aminoglycoside resistance in Acinetobacter baumannii and Pseudomonas aeruginosa isolated from a hospital in Brazil was observed (Ballaben et al, 2018), and an alarmingly high resistance to aminoglycosides has been reported in diseased animals and clinical isolates of Enterobacterales from China (Fang-you et al, 2010; Yu-Ting et al, 2013)

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