Epidemiological Study on Prevalence, Serovar Diversity, Multidrug Resistance, and CTX-M-Type Extended-Spectrum β-Lactamases of Salmonella spp. from Patients with Diarrhea, Food of Animal Origin, and Pets in Several Provinces of China

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ABSTRACT

A total of 2,283 Salmonella isolates were recovered from 18,334 samples, including samples from patients with diarrhea, food of animal origin, and pets, across 5 provinces of China. The highest prevalence of Salmonella spp. was detected in chicken meats (39.3%, 486/1,237). Fifteen serogroups and 66 serovars were identified, with Salmonella enterica serovars Typhimurium and Enteritidis being the most dominant. Most (85.5%, 1,952/2,283) isolates exhibited resistance to ≥1 antimicrobial, and 56.4% were multidrug resistant (MDR). A total of 222 isolates harbored extended-spectrum β-lactamases (ESBLs), and 200 of these were of the CTX-M type and were mostly detected in isolates from chicken meat and turtle fecal samples. Overall, eight bla _CTX-M genes were identified, with bla _CTX-M-65, bla _CTX-M-123, bla _CTX-M-14, bla _CTX-M-79, and bla _CTX-M-130 being the most prevalent. In total, 166 of the 222 ESBL-producing isolates had amino acid substitutions in GyrA (S83Y, S83F, D87G, D87N, and D87Y) and ParC (S80I), while the plasmid-mediated quinolone resistance (PMQR)-encoding genes oqxA, oqxB, qepA, qnrB, and qnrS were detected in almost all isolates. Of the 15 sequence types (STs) identified in the 222 ESBLs, ST17, ST11, ST34, and ST26 ranked among the top 5 in number of isolates. Our study revealed considerable serovar diversity and a high prevalence of the co-occurrence of MDR determinants, including CTX-M-type ESBLs, quinolone resistance-determining region (QRDR) mutations, and PMQR genes. This is the first report of CTX-M-130 Salmonella spp. from patients with diarrhea and QRDR mutations from turtle fecal samples. Our study emphasizes the importance of actions, both in health care settings and in the veterinary medicine sector, to control the dissemination of MDR, especially the CTX-M-type ESBL-harboring Salmonella isolates.

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Global trends in antimicrobial use in food animals.

Thomas Van Boeckel, Charles Brower, Marius Gilbert … (2015)

Demand for animal protein for human consumption is rising globally at an unprecedented rate. Modern animal production practices are associated with regular use of antimicrobials, potentially increasing selection pressure on bacteria to become resistant. Despite the significant potential consequences for antimicrobial resistance, there has been no quantitative measurement of global antimicrobial consumption by livestock. We address this gap by using Bayesian statistical models combining maps of livestock densities, economic projections of demand for meat products, and current estimates of antimicrobial consumption in high-income countries to map antimicrobial use in food animals for 2010 and 2030. We estimate that the global average annual consumption of antimicrobials per kilogram of animal produced was 45 mg⋅kg(-1), 148 mg⋅kg(-1), and 172 mg⋅kg(-1) for cattle, chicken, and pigs, respectively. Starting from this baseline, we estimate that between 2010 and 2030, the global consumption of antimicrobials will increase by 67%, from 63,151 ± 1,560 tons to 105,596 ± 3,605 tons. Up to a third of the increase in consumption in livestock between 2010 and 2030 is imputable to shifting production practices in middle-income countries where extensive farming systems will be replaced by large-scale intensive farming operations that routinely use antimicrobials in subtherapeutic doses. For Brazil, Russia, India, China, and South Africa, the increase in antimicrobial consumption will be 99%, up to seven times the projected population growth in this group of countries. Better understanding of the consequences of the uninhibited growth in veterinary antimicrobial consumption is needed to assess its potential effects on animal and human health.

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CTX-M Enzymes: Origin and Diffusion

Rafael Cantón, José-María González-Alba, Juan Carlos Galán … (2012)

CTX-M β-lactamases are considered a paradigm in the evolution of a resistance mechanism. Incorporation of different chromosomal bla CTX-M related genes from different species of Kluyvera has derived in different CTX-M clusters. In silico analyses have shown that this event has occurred at least nine times; in CTX-M-1 cluster (3), CTX-M-2 and CTX-M-9 clusters (2 each), and CTX-M-8 and CTX-M-25 clusters (1 each). This has been mainly produced by the participation of genetic mobilization units such as insertion sequences (ISEcp1 or ISCR1) and the later incorporation in hierarchical structures associated with multifaceted genetic structures including complex class 1 integrons and transposons. The capture of these bla CTX-M genes from the environment by highly mobilizable structures could have been a random event. Moreover, after incorporation within these structures, β-lactam selective force such as that exerted by cefotaxime and ceftazidime has fueled mutational events underscoring diversification of different clusters. Nevertheless, more variants of CTX-M enzymes, including those not inhibited by β-lactamase inhibitors such as clavulanic acid (IR-CTX-M variants), only obtained under in in vitro experiments, are still waiting to emerge in the clinical setting. Penetration and the later global spread of CTX-M producing organisms have been produced with the participation of the so-called “epidemic resistance plasmids” often carried in multi-drug resistant and virulent high-risk clones. All these facts but also the incorporation and co-selection of emerging resistance determinants within CTX-M producing bacteria, such as those encoding carbapenemases, depict the currently complex pandemic scenario of multi-drug resistant isolates.

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World Health Organization Estimates of the Global and Regional Disease Burden of 22 Foodborne Bacterial, Protozoal, and Viral Diseases, 2010: A Data Synthesis

Martyn D. Kirk, Sara M. Pires, Robert E Black … (2015)

Background Foodborne diseases are important worldwide, resulting in considerable morbidity and mortality. To our knowledge, we present the first global and regional estimates of the disease burden of the most important foodborne bacterial, protozoal, and viral diseases. Methods and Findings We synthesized data on the number of foodborne illnesses, sequelae, deaths, and Disability Adjusted Life Years (DALYs), for all diseases with sufficient data to support global and regional estimates, by age and region. The data sources included varied by pathogen and included systematic reviews, cohort studies, surveillance studies and other burden of disease assessments. We sought relevant data circa 2010, and included sources from 1990–2012. The number of studies per pathogen ranged from as few as 5 studies for bacterial intoxications through to 494 studies for diarrheal pathogens. To estimate mortality for Mycobacterium bovis infections and morbidity and mortality for invasive non-typhoidal Salmonella enterica infections, we excluded cases attributed to HIV infection. We excluded stillbirths in our estimates. We estimate that the 22 diseases included in our study resulted in two billion (95% uncertainty interval [UI] 1.5–2.9 billion) cases, over one million (95% UI 0.89–1.4 million) deaths, and 78.7 million (95% UI 65.0–97.7 million) DALYs in 2010. To estimate the burden due to contaminated food, we then applied proportions of infections that were estimated to be foodborne from a global expert elicitation. Waterborne transmission of disease was not included. We estimate that 29% (95% UI 23–36%) of cases caused by diseases in our study, or 582 million (95% UI 401–922 million), were transmitted by contaminated food, resulting in 25.2 million (95% UI 17.5–37.0 million) DALYs. Norovirus was the leading cause of foodborne illness causing 125 million (95% UI 70–251 million) cases, while Campylobacter spp. caused 96 million (95% UI 52–177 million) foodborne illnesses. Of all foodborne diseases, diarrheal and invasive infections due to non-typhoidal S. enterica infections resulted in the highest burden, causing 4.07 million (95% UI 2.49–6.27 million) DALYs. Regionally, DALYs per 100,000 population were highest in the African region followed by the South East Asian region. Considerable burden of foodborne disease is borne by children less than five years of age. Major limitations of our study include data gaps, particularly in middle- and high-mortality countries, and uncertainty around the proportion of diseases that were foodborne. Conclusions Foodborne diseases result in a large disease burden, particularly in children. Although it is known that diarrheal diseases are a major burden in children, we have demonstrated for the first time the importance of contaminated food as a cause. There is a need to focus food safety interventions on preventing foodborne diseases, particularly in low- and middle-income settings.