Molecular Epidemiological Characterisation of ESBL- and Plasmid-Mediated AmpC-Producing Escherichia coli and Klebsiella pneumoniae at Kamuzu Central Hospital, Lilongwe, Malawi

The global rise in infections caused by multidrug resistant (MDR) Enterobacterales poses a public health problem. We have performed a molecular epidemiological characterisation of representative plasmid-mediated AmpC (pAmpC) and ESBL-positive clinical isolates of Escherichia coli (n = 38) and Klebsiella pneumoniae (n = 17) from a tertiary hospital in Malawi collected in 2017. BlaCTX-M-15 was the most prevalent ESBL-determinant in E. coli (n = 30/38) and K. pneumoniae (n = 17/17), whereas blaCMY-2 was detected in nearly all AmpC-phenotype E. coli (n = 15/17). Whole genome sequencing revealed dominant globally disseminated E. coli sequence types (STs); ST410 (n = 16), ST131 (n = 7), and ST617 (n = 6). The ST distribution in K. pneumoniae was more diverse but included ST101 (n = 2), ST14 (n = 2), and ST340 (n = 2), all considered high-risk MDR clones. The isolates expressed an MDR profile, including resistance against commonly used antibiotics, such as fluoroquinolones, aminoglycosides, and/or trimethoprim-sulfamethoxazole, and harboured corresponding resistance determinants. Clonal analyses of the major STs of E. coli revealed closely related genetic clusters within ST410, ST131, and ST617 supporting within-hospital transmission between patients and/or via a common reservoir. The overall findings add to the limited knowledge on the molecular epidemiology of MDR E. coli and K. pneumoniae in Malawi and may help health policy makers to identify areas to target when addressing this major threat of antibiotic resistance

Genomic analysis of a multidrug-resistant clinical Providencia rettgeri (PR002) strain with the novel integron ln1483 and an A/C plasmid replicon

Please read abstract in the article.Supplementary material: Figure S1. Prophages of P. rettgeri PR002 were identified using the PHAge Search Tool (PHAST). PR002 contained four intact prophages (red color), one incomplete prophage (gray color), and one questionable prophage (green color).Supplementary tables: Table S1. Metadata (biosample data) of all sequenced P. rettgeri isolates from NCBI GenBank database Table S2. Genes associated with general COG functional categories in the genome of P. rettgeri PR002. Table S3. Pathogenicity islands (PAIs) predicted for PR002 from VFDB (http://www.paidb.re.kr/about_paidb.php). Table S5. Diversity of metal resistance gene determinants found in PR002 genome.File S1. Metadata of isolates used in phylogenomics.The National Health Laboratory Services of South Africahttps://nyaspubs.onlinelibrary.wiley.com/journal/17496632hj2021Medical Microbiolog

Effect of rifampicin and efavirenz on moxifloxacin concentrations when co-administered in patients with drug-susceptible TB.

CAPRISA, 2017.Abstract available in pdf

Models for increasing the health workforce

A stable human resource base in the health sector is critical to achieving health-related Millennium Development Goals. There is a severe quantitative and qualitative shortfall of healthcare professionals in South Africa, and the existing and future health workforce production is inadequate for our healthcare needs. The production model must include all healthcare disciplines because the quadruple burden of disease necessitates multi-professional healthcare teams working synergistically to improve health outcomes and life expectancy

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

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

Secondary school factors relating to academic success in first-year Health Science students

Universities in South Africa, experience challenges related to throughput rates, especially in the first year of study. Student dropout in the School of Health Sciences (SHS) negatively affects the enrolment targets with the concomitant loss of student subsidy and fees as well as the number of prospective health care professionals who are required to address the shortage of skilled health care workers in the country. This thus emphasizes the need to determine secondary school factors that relate to success and throughput in the first year of study, viz., area and type of schooling, matriculation point scores and matriculation subject choices. A retrospective design with a quantitative approach was used to collect data from a total of 713 student records over the period 2009-2011. Quantitative data were analysed using descriptive and inferential statistics while the Spearman Rank-order correlation test and the Mann-Whitney test were used to determine differences among variables related to academic success. A p-value of ?0.05 was considered statistically significant. Data was analysed and presented as annual composite results as well as stratified by disciplines. Overall the area of secondary schooling did not statistically significantly correlate with academic success. In contrast, the type of secondary schooling (p=.012), matriculation points (p=.000) and all matriculation subjects investigated (p<.005) were statistically significant variables that correlated with academic success. At discipline-level, Physiotherapy showed to have the most consistent correlations among variables, with a moderate correlation with matriculation subjects as well as the APS. The results of this study yielded evidence-based admissions criteria for students into the SHS at the University of KwaZulu-Natal (UKZN)

Multidrug-resistant gram-negative bacterial infections in a teaching hospital in Ghana

Abstract Background Multidrug-resistant Gram-negative bacteria have emerged as major clinical and therapeutic dilemma in hospitals in Ghana. To describe the prevalence and profile of infections attributable to multidrug-resistant Gram-negative bacteria among patients at the Komfo Anokye Teaching Hospital in the Ashanti region of Ghana. Methods Bacterial cultures were randomly selected from the microbiology laboratory from February to August, 2015. Bacterial identification and minimum inhibitory concentrations were conducted using standard microbiological techniques and the Vitek-2 automated system. Patient information was retrieved from the hospital data. Results Of the 200 isolates, consisting of K. pneumoniae, A. baumannii, P. aeruginosa, Enterobacter spp., E. coli, Yersinia spp., Proteus mirabilis, Pasteurella spp., Chromobacterium violaceum, Salmomella enterica, Vibrio spp., Citrobacter koseri, Pantoea spp., Serratia spp., Providencia rettgeri Burkholderia cepacia, Aeromonas spp., Cadecea lapagei and Sphingomonas paucimobilis, 101 (50.5%) and 99 (49.5%) recovered from male and female patients respectively The largest proportion of patients were from age-group ≥60 years (24.5%) followed by < 10 years (24.0%) and least 10–19 years (9.5%) with a mean patient age of 35.95 ± 27.11 (0.2–91) years. The decreasing order of specimen source was urine 97 (48.5%), wound swabs 47 (23.5%), sputum 22 (11.0%) bronchial lavage, nasal and pleural swabs 1 (0.50%). Urinary tract infection was diagnosed in 34.5% of patients, sepsis in 14.5%, wound infections (surgical and chronic wounds) in 11.0%, pulmonary tuberculosis in 9.0% and appendicitis, bacteremia and cystitis in 0.50%. The isolates showed high resistance to ampicillin (94.4%), trimethoprim/sulfamethoxazole (84.5%), cefuroxime (79.0%) and cefotaxime (71.3%) but low resistance to ertapenem (1.5%), meropenem (3%) and amikacin (11%). The average multi-drug resistance was 89.5%, and ranged from 53.8% in Enterobacter spp. to 100.0% in Acinetobacter spp. and P. aeruginosa. Conclusion Bacterial infections caused by multi-drug resistant (isolates resistant to at least one agent in three or more antibiotic classes) Gram-negative pathogens among patients at Komfo Anokye Teaching Hospital in Kumasi, Ghana are rife and interventions are necessary for their containment

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