Molecular epidemiology of antibiotic resistant ESKAPE pathogens isolated from public sector hospitals in uMgungundlovu District, KwaZulu-Natal, South Africa.

Doctor of Philosophy in Medical Microbiology. University of KwaZulu-Natal. Durban, 2017.Multi-drug resistant Enterococcus faecium, staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp termed ESKAPE pathogens are commonly implicated in difficult-to-treat infectious diseases in developed and developing countries. The prevalence, risk factors, phenotypic and genotypic profiles including but not limited to clonal relatedness, genetic diversity, resistance and virulence associated with ESKAPE bacteria were investigated in carriage and clinical isolates from patients in a rural, district and an urban tertiary hospital in the public health sector in uMgungundlovu District, Kwazulu- Natal, South Africa. The overall carriage of MDR ESKAPE Gram-negative bacteria in both hospitals was 37.21%, 42.31% and 57.14% at admission, after 48 hours and at discharge, respectively. The prevalence of MDR ESKAPE Gram-negative bacteria in faecal carriage (46%) was higher than clinical samples (28%) and colonization was mainly associated with referral from the district to the 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. Similarly, the overall prevalence of faecal VRE carriage was 53% with patients at the district hospital being more likely to be colonized by VRE at admission (44%), after 48 hours (64%) and discharge (100%) than those of the tertiary level. Fifteen (39%) E. faecium and 23 (61%) E. faecalis, were detected and displayed high level of antibiotic resistance. Extensive genetic diversity of E. faecalis and E. faecium and clonal dissemination of various lineages were observed across wards and within hospitals. The high levels of resistance in S. aureus were attributed to the multi-drug resistant efflux pumps mepA, mexE, AcrB, MATE, qac and qacA. Whole genome analysis revealed that the circulating S. aureus isolates belonged to the extremely virulent ST121 clone that harboured a total of 18 virulence genes. The high prevalence, genetic diversity and virulence of antibiotic-resistant ESKAPE bacteria elucidated in this study necessitates routine screening and surveillance in communities and hospitals, stringent infection prevention and control measures and antibiotic stewardship to monitor epidemiological changes, to contain their spread and inform appropriate antibiotic treatment options respectively

Antibiotic resistance in the food chain: A developing country-perspective

Antibiotics are now endangered species facing extinction due to the worldwide emergence of antibiotic resistance (ABR). Food animals are considered as key reservoirs of antibiotic-resistant bacteria with the use of antibiotics in the food production industry having contributed to the actual global challenge of ABR. There are no geographic boundaries to impede the worldwide spread of ABR. If preventive and containment measures are not applied locally, nationally and regionally, the limited interventions in one country, continent and for instance, in the developing world, could compromise the efficacy and endanger ABR containment policies implemented in other parts of the world, the best-managed high-resource countries included. Multifaceted, comprehensive and integrated measures complying with the One Health approach are imperative to ensure food safety and security, effectively combat infectious diseases, curb the emergence and spread of ABR, and preserve the efficacy of antibiotics for future generations. Countries should follow the World Health Organization, World Organization for Animal Health, and the Food and Agriculture Organization of the United Nations recommendations to implement national action plans encompassing human, (food) animal, and environmental sectors to improve policies, interventions and activities that address the prevention and containment of ABR from farm-to-fork. This review covers (i) the origin of antibiotic resistance, (ii) pathways by which bacteria spread to humans from farm-to-fork, (iii) differences in levels of antibiotic resistance between developed and developing countries, and (iv) prevention and containment measures of antibiotic resistance in the food chain

Clinical and economic impact of antibiotic resistance in developing countries: A systematic review and meta-analysis.

Despite evidence of the high prevalence of antibiotic resistant infections in developing countries, studies on the clinical and economic impact of antibiotic resistance (ABR) to inform interventions to contain its emergence and spread are limited. The aim of this study was to analyze the published literature on the clinical and economic implications of ABR in developing countries.A systematic search was carried out in Medline via PubMed and Web of Sciences and included studies published from January 01, 2000 to December 09, 2016. All papers were considered and a quality assessment was performed using the Newcastle-Ottawa quality assessment scale (NOS).Of 27 033 papers identified, 40 studies met the strict inclusion and exclusion criteria and were finally included in the qualitative and quantitative analysis. Mortality was associated with resistant bacteria, and statistical significance was evident with an odds ratio (OR) 2.828 (95%CI, 2.231-3.584; p = 0.000). ESKAPE pathogens was associated with the highest risk of mortality and with high statistical significance (OR 3.217; 95%CIs; 2.395-4.321; p = 0.001). Eight studies showed that ABR, and especially antibiotic-resistant ESKAPE bacteria significantly increased health care costs.ABR is associated with a high mortality risk and increased economic costs with ESKAPE pathogens implicated as the main cause of increased mortality. Patients with non-communicable disease co-morbidities were identified as high-risk populations

Extended spectrum beta-lactamase mediated resistance in carriage and clinical gram-negative ESKAPE bacteria: a comparative study between a district and tertiary hospital in South Africa

Abstract Background 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. Objectives To 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. Methods This 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 bla CTX-M group-1-2-9, bla CTX-M group 8/25, bla SHV, bla TEM, bla OXA-1-like, bla KPC, bla VIM, bla IMP, bla GES 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. Results Overall 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). bla CTX-M-group-9, bla CTX-M-group-1 and bla SHV 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. Conclusion The 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

Eligibility criteria.

<p>Eligibility criteria.</p

Genome Analysis of ESBL-Producing <i>Escherichia coli</i> Isolated from Pigs

The resistome, virulome and mobilome of extended spectrum ß-lactamase (ESBL)-producing Escherichia coli (ESBL-Ec) isolated from pigs in Cameroon and South Africa were assessed using whole genome sequencing (WGS). Eleven clonally related phenotypic ESBL-Ec isolates were subjected to WGS. The prediction of antibiotic resistance genes, virulence factors (VFs) and plasmids was performed using ResFinder, VirulenceFinder and PlasmidFinder, respectively. Diverse sequence types (STs) were detected with ST2144 and ST88 being predominant and blaCTX-M-15 (55%) being the principal ESBL gene. All except two isolates harboured various aminoglycoside resistance genes, including aph(3″)-Ib (6/11, 55%) and aph(6)-1d (6/11, 55%), while the qnrS1 gene was identified in four of the isolates. The ESBL-Ec isolates showed a 93.6% score of being human pathogens. The fim, ehaB, ibeB/C were the leading virulence factors detected. All isolates harboured at least three extraintestinal pathogenic E. coli (ExPEC) VFs, with one isolate harbouring up to 18 ExPEC VFs. Five isolates (45.45%) harboured the plasmid incompatibility group IncF (FII, FIB, FIC, FIA). The study revealed that there is an urgent need to implement effective strategies to contain the dissemination of resistant and virulent ESBL-Ec through the food chain in Cameroon and South Africa

Studies describing mortality rate associated with resistant and MDR ESKAPE bacteria.

<p>Studies describing mortality rate associated with resistant and MDR ESKAPE bacteria.</p

Summary of data on health care costs associated with resistant infections.

<p>Summary of data on health care costs associated with resistant infections.</p

Graphical representation of AMR in developing countries included in the study.

<p>Graphical representation of AMR in developing countries included in the study.</p