Abstract

This study investigated the characteristics and mechanisms of eravacycline resistance and heteroresistance in clinical Klebsiella pneumoniae isolates. A total of 393 clinical K. pneumoniae isolates were collected and subjected to eravacycline and tigecycline MIC determinations using the agar dilution method. Eravacycline heteroresistance was assessed by a population analysis profile (PAP). The expression levels of efflux pumps and their regulators were determined by quantitative reverse-transcription PCR (qRT-PCR). This study identified 67 eravacycline-nonsusceptible isolates; among the extended-spectrum β-lactamase (ESBL)-positive isolates, eravacycline-nonsusceptible isolates were detected more frequently than tigecycline-nonsusceptible isolates (21.7% vs. 9.4%, p = 0.001). The study sample was observed to include 20 K. pneumoniae isolates with eravacycline heteroresistance. Compared to the reference strain, oqxA or oqxB overexpression was observed in nine eravacycline-nonsusceptible isolates (range, 35.64–309.02-fold) and 13 eravacycline-heteroresistant isolates (8.42–296.34-fold). The overexpression of macA or macB was detected in 12 eravacycline-heteroresistant isolates (3.23–28.35-fold). Overexpression of the efflux pump regulator gene ramA was observed in 11 eravacycline-nonsusceptible isolates (3.33–94.05-fold) and 18 eravacycline-heteroresistant isolates (3.89–571.70-fold). The eravacycline MICs were increased by one–fourfold by overexpression of oqxAB or macAB in three eravacycline-sensitive isolates. In conclusion, the overexpression of OqxAB and MacAB efflux pumps and the transcriptional regulator RamA were suggested to be involved in K. pneumoniae eravacycline resistance and heteroresistance.

Highlights

  • Introduction Concerns regarding theGram-negative pathogen Klebsiella pneumoniae, a member of the EnterobacteriaceaeEnterobacteriaceae are an emergent global health threat because carbapenems had previously been effective for eliminating multidrug-resistant Gram-negative bacterial infections[2]

  • Tigecycline and eravacycline susceptibilities among clinical K. pneumoniae isolates

  • Among the ESBL-positive isolates, eravacycline nonsusceptibility was more common than tigecycline nonsusceptibility (21.7% vs. 9.4%, P = 0.001)

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Summary

Introduction

Gram-negative pathogen Klebsiella pneumoniae, a member of the Enterobacteriaceae. Enterobacteriaceae are an emergent global health threat because carbapenems had previously been effective for eliminating multidrug-resistant Gram-negative bacterial infections[2]. Increases in carbapenemresistant K. pneumoniae (CR-Kp) frequencies worldwide are resulting in K. pneumoniae infections that are very difficult to treat and are associated with higher mortality rates[3]. Zheng et al Emerging Microbes & Infections (2018)7:139 Characteristic. ESBLa Positive (n = 203) Negative (n = 145). CR-Kp Positive (n = 45) Negative (n = 348) Total (n = 393)

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