Molecular Epidemiology of Extended-Spectrum Beta-Lactamase and AmpC Producing Enterobacteriaceae among Sepsis Patients in Ethiopia: A Prospective Multicenter Study.

Melese Legese,Badrul Hasan,Abraham Aseffa,Daniel Asrat,Göte Swedberg,Adane Mihret

doi:10.3390/antibiotics11020131

Abstract

Extended-spectrum beta-lactamases (ESBLs) and AmpC producing Enterobacteriaceae are public health threats. This study aims to characterize ESBL and AmpC producing Enterobacteriaceae isolated from sepsis patients. A multicenter study was conducted at four hospitals located in central (Tikur Anbessa and Yekatit 12), southern (Hawassa) and northern (Dessie) parts of Ethiopia. Blood culture was performed among 1416 sepsis patients. Enterobacteriaceae (n = 301) were confirmed using MALDI-TOF and subjected for whole genome sequencing using the Illumina (HiSeq 2500) system. The overall genotypic frequencies of ESBL and AmpC producing Enterobacteriaceae were 75.5% and 14%, respectively. The detection of ESBL producing Enterobacteriaceae at Hawassa, Yekatit 12, Tikur Anbessa and Dessie was 95%, 90%, 82% and 55.8%, respectively. The detection frequency of blaCTX-M, blaTEM and blaSHV genes was 73%, 63% and 33%, respectively. The most frequently detected ESBL gene was blaCTX-M-15 (70.4%). The common AmpC genes were blaACT (n = 22) and blaCMY (n = 13). Of Enterobacteriaceae that harbored AmpC (n = 42), 71% were ESBL co-producers. Both blaTEM-1B (61.5%) and blaSHV-187 (27.6%) were the most frequently detected variants of blaTEM and blaSHV, respectively. The molecular epidemiology of ESBL producing Enterobacteriaceae showed high frequencies and several variants of ESBL and AmpC genes. Good antimicrobial stewardship and standard bacteriological laboratory services are necessary for the effective treatment of ESBL producing Enterobacteriaceae.

Highlights

Introduction published maps and institutional affilGlobally, Enterobacteriaceae that harbor extended-spectrum beta-lactamase (ESBL)genes are spreading and causing serious infections, such as sepsis [1]
Antibiotic options for the management of septic patients caused by ESBL producing Enterobacteriaceae (ESBL-pE) is narrow, which can lead to longer hospital stays, increased hospital costs and increased mortality [4]
A p-value < 0.05 was considered as statistically significant. This is the first multicenter study that reported the molecular epidemiology of ESBL and AmpC producing Enterobacteriaceae among sepsis patients at four Ethiopian hospitals located in the northern, central and southern parts of the country

Summary

Introduction

Genes are spreading and causing serious infections, such as sepsis [1]. Sepsis is a lifethreatening condition resulting from a dysregulated immune response to the infection, which results in organ dysfunction [2,3]. Antibiotic options for the management of septic patients caused by ESBL producing Enterobacteriaceae (ESBL-pE) is narrow, which can lead to longer hospital stays, increased hospital costs and increased mortality [4]. ESBL-pE has become a global health problem [5] because ESBL can make a diverse range of β-lactam antibiotics ineffective, including penicillins, cephalosporins and monobactams [6]. Enterobacteriaceae acquire and disseminate these ESBL-encoding genes horizontally, mainly through plasmids [7]. In addition to Escherichia coli, various species of Klebsiella, Enterobacter, Serratia and Salmonella are major ESBL producers in the family Enterobacteriaceae [8,9,10]

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