Abstract
BackgroundGram-negative ESKAPE bacteria are increasingly implicated in several difficult-to-treat infections in developed and developing countries. They are listed by the World Health Organization as resistant bacteria of critical priority in research.ObjectivesTo determine the risk factors, prevalence, phenotypic profiles, genetic diversity and clonal relatedness of extended-spectrum β-lactamase (ESBL)-producing multi-drug resistant (MDR) Gram-negative ESKAPE bacteria in the faecal carriage and clinical samples from patients in an urban, tertiary and a rural, district hospital in uMgungundlovu District, KwaZulu-Natal, South Africa.MethodsThis study took place in a district and tertiary hospital during a two-months period from May to June 2017 in uMgungundlovu district, South Africa. Rectal swabs collected from hospitalized patients, at admission, after 48 h and at discharge (whenever possible) formed the carriage sample while clinical isolates routinely processed in the microbiological laboratory during the sampling period were also collected and formed the clinical sample. Gram-negative ESKAPE bacteria were screened for ESBL production on selective MacConkey agar and confirmed using ROSCO kits. Minimum inhibitory concentrations were determined, and real-time and multiplex polymerase chain reaction were used to ascertain the presence of blaCTX-M group-1-2-9, blaCTX-M group 8/25, blaSHV, blaTEM, blaOXA-1-like, blaKPC, blaVIM, blaIMP, blaGES and AmpC genes. Genomic fingerprinting was also performed using ERIC-PCR. Risk factors for ESBL-mediating MDR Gram-negative ESKAPE colonization were ascertained by univariate and multivariate logistic regression analyses.ResultsOverall prevalence of carriage of ESBL-mediating MDR Gram-negative ESKAPE was 37.21% (16/43), 42.31% (11/26) and 57.14% (4/7) at admission, after 48 h and at discharge respectively. The prevalence of ESBL-mediating MDR Gram-negative ESKAPE bacteria in faecal carriage (46%) was higher than clinical samples (28%). Colonization was mainly associated with the referral from district to tertiary hospital with high statistical significance (OR: 14.40, 95% CI 0.98–210.84). blaCTX-M-group-9, blaCTX-M-group-1 and blaSHV were the main resistance genes identified. Several patients carried more than two different isolates. A Klebsiella pneumoniae (K1) clone was circulating within wards and between hospitals.ConclusionThe study highlights the high prevalence of ESBL-mediating MDR Gram-negative ESKAPE bacteria in carriage and clinical samples among hospitalized patients in uMgungundlovu, South Africa. The wide dissemination of these resistant ESKAPE bacteria in hospitals necessitates improvements in routine screening and reinforcement of infection, prevention and control measures.
Highlights
The selective pressure exerted using antibiotics and aggravated by the dearth of new active substances in the current therapeutic pipeline has led to a considerable increase in antibiotic resistance (ABR) worldwide [1, 2]
Colonization was mainly associated with the referral from district to tertiary hospital with high statistical significance (OR: 14.40, 95% CI 0.98–210.84). blaCTX-M-group-9, blaCTX-M-group-1 and blaSHV were the main resistance genes identified
Patients in the tertiary hospital were more likely to be colonized by multi-drug resistance (MDR) ESKAPE bacteria at admission (50%) and discharge (66.66%) than those of the district hospital (Table 1)
Summary
The selective pressure exerted using antibiotics and aggravated by the dearth of new active substances in the current therapeutic pipeline has led to a considerable increase in antibiotic resistance (ABR) worldwide [1, 2]. Of the six infamous ESKAPE pathogens, the four Gram-negative bacteria, i.e., K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp., have been associated with four major types of multi-drug resistance (MDR), namely extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae and Enterobacter spp., carbapenemase-producing A. baumannii and metallo-β-lactamase producing P. aeruginosa (MBL-PA) which limit therapeutic options and negatively affect clinical outcomes [3,4,5,6]. Several resistance genes have been associated with the emergence of ESBL-mediating MDR Gram-negative ESKAPE bacteria globally. Gram-negative ESKAPE bacteria are increasingly implicated in several difficult-to-treat infections in developed and developing countries. They are listed by the World Health Organization as resistant bacteria of critical priority in research
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