Co-occurrence of aminoglycoside and β-lactam resistance mechanisms in aminoglycoside- non-susceptible Escherichia coli isolated in the Zurich area, Switzerland

Elias Bodendoerfer,Martina Marchesi,Frank Imkamp,Patrice Courvalin,Erik C Böttger,Stefano Mancini

doi:10.1016/j.ijantimicag.2020.106019

Elias Bodendoerfer, Martina Marchesi + Show 4 more

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https://doi.org/10.1016/j.ijantimicag.2020.106019

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Abstract

The co-occurrence of aminoglycoside and β-lactam resistance was assessed in 3358 consecutive Escherichia coli clinical isolates collected in 2014 in the greater Zurich area, Switzerland. Non-susceptibility to at least one of the tested aminoglycosides was observed in 470/3358 E. coli strains (14%). In strains categorized as broad-spectrum β-lactamase (BSBL)-producers (1241/3358 isolates), extended-spectrum β-lactamase (ESBL)-producers (262/3358) and AmpC-producers (66/3358), resistance to aminoglycoside was found in 23%, 52% and 20% of the isolates, respectively. In contrast, aminoglycoside-susceptible strains were rarely resistant to β-lactams (33/1777, 1.9%). The genomes of 439 aminoglycoside-resistant E. coli were sequenced and aminoglycoside and β-lactam genotypes were analysed. The most prevalent aminoglycoside resistance genes were aph(3’)-Ia (133 strains, 30.3%), aac(3)-IId (100 strains, 22.8%), and aac(6’)-Ib-cr (52 strains, 11.8%). The most frequent associations with β-lactam resistance genes were aph(3’)-Ia or aac(3)-IId with blaTEM-1 (94 and 72 strains, respectively), and aac(3)-IIa/aac(6’)-Ib-cr with blaCTX-M-15/blaOXA-1 (23 strains). These results indicate a frequent association of aac(3) and aph(3’) genotypes with BSBL production, and a frequent co-occurrence of aac(6’) genes with ESBL production. The high rate of co-occurrence of aminoglycoside resistance and β-lactamase production must be considered in combination therapy.

Highlights

Aminoglycosides are an important class of bactericidal antibiotics that are frequently used, mostly in combination with β-lactams, to treat severe infections caused by Gram-negative bacteria [1]
ECOFFs were used to screen for aminoglycoside-non-susceptible E. coli as ECOFFS separate wild-type from non-wild-type populations more accurately than clinical breakpoints (CBPs) [6,8,26]
The ANRESIS report includes strains isolated from hospitalized patients and outpatients, whereas most of the E. coli analysed in the current study were collected from the University Hospital of Zurich, a Gentamicin, tobramycin and kanamycin inhibition zone diameters [mm] of 3358 unique E. coli grouped by β-lactam resistance mechanism

Summary

Introduction

Aminoglycosides are an important class of bactericidal antibiotics that are frequently used, mostly in combination with β-lactams, to treat severe infections caused by Gram-negative bacteria [1]. Resistance to aminoglycosides has been increasingly reported, including, most worryingly, in association with that to other antibiotic classes, such as β-lactams and fluoroquinolones [2,3,4,5]. Resistance to aminoglycosides in Gram-negative bacteria is mainly due to the production of aminoglycoside-modifying enzymes (AMEs) [1,6] or modification of the ribosome by acquired 16S rRNA methyltransferases (RMTases) [6,7]. AMEs can modify aminoglycosides at various sites of the drug scaffold and the enzymes are classified into subclasses and types according to different substrate profiles. AMEs frequently modify more than one aminoglycoside and the same aminoglycoside can be affected by several enzymes. Aminoglycoside modification may not always result in recognizable phenotypic resistance as determined in vitro by assessment of minimal inhibitory concentrations (MICs) [1 , 8]

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