Project description:Antibiotic consumption is considered to be a main driver of antibiotic resistant bacteria. Mink breeding follows a distinctive seasonal reproduction cycle, and all of the mink produced in the northern hemisphere are bred, born, and pelted around the same time of year. Some of the diseases are age-related, which is reflected in the seasonal variation of antibiotic consumption. The seasonality makes mink a good model for the investigation of the association between antibiotic consumption and resistance. The objectives of this study were (1) to monitor the farm level of antibiotic resistance during one production cycle and (2) to assess the potential associations between antibiotic consumption and resistance. Twenty-four farms were included in this study (Denmark n = 20, Iceland n = 2, and The Netherlands n = 2), following a cohort of animals born in 2018. Staphylococcus delphini and Escherichia coli were isolated from samples of the carcasses and faeces and were collected randomly. The isolates were susceptibility tested and subsequently divided into the sensitive wildtype (WT) and the resistant non-wildtype (NWT) populations. The antibiotic consumption relative to the sampling periods was assessed as having a short-term or a long-term impact, i.e., in two explanatory factors. For both S. delphini and E. coli, a large between-farm variation of NWT profiles was detected. In the final multivariable, generalized linear mixed models, significant associations between NWT isolates and the consumption of specific antibiotics were found: the short-term use of tetracyclines in the growth period was associated with the occurrence of tetracycline NWT E. coli in the growth period (OR: 11.94 [1.78; 89.28]), and the long-term use of macrolide and tetracyclines was associated with the occurrence of erythromycin NWT S. delphini in the weaning period (OR: 18.2 [2.26; 321.36]) and tetracycline NWT S. delphini in the growth period (OR: 8.2 [1.27; 63.31]), respectively. Farms with zero consumption in the study years prior to sampling also had a substantial proportion of NWT isolates, indicating that NWT isolates are persistent and/or widely spread in the environment. Generally, a high occurrence of tetracycline NWTs was observed. NWT isolates with resistance against the most commonly used antibiotics were found on all the farms, stressing the need for routine surveillance and the prudent use of antibiotics. The results offer a preview of the complex relationship between consumption and resistance, demonstrating some significant associations between use and resistance. Moreover, antibiotic-resistant bacteria are present even on farms with no antibiotic consumption over extended periods, and theoretical explanations supported by the data are offered.
Project description:BackgroundIn antibiotic naïve populations, there is a strong association between the use of an antimicrobial and resistance to this antimicrobial. Less evidence is available as to whether this relationship is weakened in populations highly exposed to antimicrobials. Individuals taking HIV preexposure prophylaxis (PrEP) have a high intake of antimicrobials. We previously found that there was no difference in the prevalence of pheno- and genotypic antimicrobial resistance between two groups of PrEP clients who had, and had not, taken antimicrobials in the prior 6 months. Both groups did, however, have a higher prevalence of resistance than a sample of the general population.MethodsIn the current study, we used zero-inflated negative binomial regression models to evaluate if there was an individual level association between the consumption of antimicrobials and 1. the minimum inhibitory susceptibilities of oral Neisseria subflava and 2. the abundance of antimicrobial resistance genes in the oropharynges of these individuals.ResultsWe found no evidence of an association between the consumption of antimicrobials and the minimum inhibitory susceptibilities of oral Neisseria subflava or the abundance of antimicrobial resistance genes in these individuals.ConclusionsWe conclude that in high-antimicrobial-consumption populations, the association between antimicrobial consumption and resistance may be attenuated. This conclusion would not apply to lower-consumption populations.
Project description:BackgroundIntensive care units (ICU) constitute a high-risk setting for antimicrobial resistance (AMR).AimWe aimed to describe secular AMR trends including meticillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci (GRE), extended-spectrum cephalosporin-resistant Escherichia coli (ESCR-EC) and Klebsiella pneumoniae (ESCR-KP), carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) from Swiss ICU. We assessed time trends of antibiotic consumption and identified factors associated with CRE and CRPA.MethodsWe analysed patient isolate and antibiotic consumption data of Swiss ICU sent to the Swiss Centre for Antibiotic Resistance (2009-2018). Time trends were assessed using linear logistic regression; a mixed-effects logistic regression was used to identify factors associated with CRE and CRPA.ResultsAmong 52 ICU, MRSA decreased from 14% to 6% (p = 0.005; n = 6,465); GRE increased from 1% to 3% (p = 0.011; n = 4,776). ESCR-EC and ESCR-KP increased from 7% to 15% (p < 0.001, n = 10,648) and 5% to 11% (p = 0.002; n = 4,052), respectively. CRE, mostly Enterobacter spp., increased from 1% to 5% (p = 0.008; n = 17,987); CRPA remained stable at 27% (p = 0.759; n = 4,185). Antibiotic consumption in 58 ICU increased from 2009 to 2013 (82.5 to 97.4 defined daily doses (DDD)/100 bed-days) and declined until 2018 (78.3 DDD/100 bed-days). Total institutional antibiotic consumption was associated with detection of CRE in multivariable analysis (odds ratio per DDD: 1.01; 95% confidence interval: 1.0-1.02; p = 0.004).DiscussionIn Swiss ICU, antibiotic-resistant Enterobacterales have been steadily increasing over the last decade. The emergence of CRE, associated with institutional antibiotic consumption, is of particular concern and calls for reinforced surveillance and antibiotic stewardship in this setting.
Project description:Antimicrobial resistance (AMR), a central health challenge of the twenty first century, poses substantial population health risks, with deaths currently estimated to be around 700,000 per year globally. The international community has signaled its commitment to exploring and implementing effective policy responses to AMR, with a Global Action Plan on AMR approved by the World Health Assembly in 2015. Major governance challenges could thwart collective efforts to address AMR, along with limited knowledge about how to design effective global governance mechanisms. To identify common ground for more coordinated global actions we conducted a narrative review to map dominant ideas and academic debates about AMR governance. We found two categories of global governance mechanisms: binding and non-binding and discuss advantages and drawbacks of each. We suggest that a combination of non-binding and binding governance mechanisms supported by leading antimicrobial use countries and important AMR stakeholders, and informed by One Health principles, may be best suited to tackle AMR.
Project description:For the first time since 2015, the World Health Organization's (WHO) global Antimicrobial Resistance and Use Surveillance (GLASS) featured both global reports for antimicrobial resistance (AMR) and antimicrobial consumption (AMC) data in its annual reports. In this study we investigated the relationship of AMR with AMC within participating countries reported in the GLASS 2022 report. Our analysis found a statistically significant correlation between beta-lactam/cephalosporin and fluoroquinolones consumption and AMR to these antimicrobials associated with bloodstream E. coli and Klebsiella pneumoniae among the participating countries (P<0.05). We observed that for every 1 unit increase in defined daily dose DDD of beta-lactam/cephalosporins and quinolone consumptions among the countries, increased the recoveries of bloodstream-associated beta-lactam/cephalosporins-resistant E. coli/Klebsiella spp. by 11-22% and quinolone-resistant E. coli/Klebsiella spp. by 31-40%. When we compared the antimicrobial consumptions between the antimicrobial ATC (Alphanumeric codes developed by WHO) groups and countries, we observed a statistically significant higher daily consumption of beta-lactam-penicillins (J01C, DDD difference range: 5.23-8.13) and cephalosporins (J01D, DDD difference range: 2.57-5.13) compared to other antimicrobial groups among the countries (adjusted for multiple comparisons using Tukey's method). Between the participating countries, we observed a statistically significant higher daily consumption of antimicrobial groups in Iran (DDD difference range: 3.63-4.84) and Uganda (DDD difference range: 3.79-5.01) compared to other participating countries (adjusted for multiple comparisons using Tukey's method). Understanding AMC and how it relates to AMR at the global scale is critical in the global AMR policy development and implementation of global antimicrobial stewardship.
Project description:Antimicrobial resistance (AMR) is one of the key threats to global health and requires sustainable and effective actions to reduce its consequences in the near future worldwide. There are several well-documented and epidemiologically supported examples that both bacterial and viral vaccines might have an impact on AMR. Here, we conducted an ecological analysis of Italian data to evaluate the relationship between influenza vaccination coverage and AMR proportions over the last two decades. We found significant negative correlations between influenza vaccination coverage in the population over 64 years and AMR in Escherichia coli and Klebsiella pneumoniae isolates. The observed inverse relationships were confirmed by linear regression analysis. Similar results were obtained for the vaccination coverage in the overall population. Despite the main limitations of our study, its findings suggested an inverse relationship between influenza vaccination coverage and AMR proportions over the years, which was in accordance with previous theories illustrating how influenza vaccination reduced antibiotic prescriptions. However, since our study did not allow for us to elucidate the mechanisms underpinning the observed relationship, more and better data on confounding and mediating factors should be considered in future research.
Project description:Bacterial antimicrobial resistance (AMR) in pigs is an important public health concern due to its possible transfer to humans. We aimed at quantifying the relationship between the lifetime exposure of antimicrobials and seven antimicrobial resistance genes in Danish slaughter pig farms. AMR gene levels were quantified by qPCR of total-community DNA in faecal samples obtained from 681 batches of slaughter pigs. The lifetime exposure to antimicrobials was estimated at batch level for the piglet, weaner, and finisher periods individually for the sampled batches. We showed that the effect of antimicrobial exposure on the levels of AMR genes was complex and unique for each individual gene. Several antimicrobial classes had both negative and positive correlations with the AMR genes. From 10-42% of the variation in AMR gene levels could be explained in the final regression models, indicating that antimicrobial exposure is not the only important determinant of the AMR gene levels.
Project description:Antibiotics are commonly prescribed in community and hospital care. Overuse and misuse favors emergence and spread of resistant bacteria. The ATC/DDD methodology is commonly used for presenting the drug utilization data. In primary care, the consumption is usually expressed in DDD per 1,000 inhabitants per day, in hospital, preferably in DDD per 100 bed days and DDD per 100 admissions. The alternative metric is days of therapy (DOT), which needs IT support. Antibiotics have ecological adverse effects at individual and population level. Antibiotics select resistant bacteria among pathogens and normal flora. Broad-spectrum antibiotics, low dosage and prolonged antibiotic therapy favor the development of resistance. Although total use of antibiotics in hospital is much less than in the community, the intensity of use magnified by cross infection ensures a multitude of resistant bacteria in today's hospitals. Reversal of resistance is complex and might persist for many years despite the introduction of antimicrobial containment and stewardship programs.
Project description:Virulent strains of Pseudomonas aeruginosa are often associated with an acquired cytotoxic protein, exoenzyme U (ExoU) that rapidly destroys the cell membranes of host cells by its phospholipase activity. Strains possessing the exoU gene are predominant in eye infections and are more resistant to antibiotics. Thus, it is essential to understand treatment options for these strains. Here, we have investigated the resistance profiles and genes associated with resistance for fluoroquinolone and beta-lactams. A total of 22 strains of P. aeruginosa from anterior eye infections, microbial keratitis (MK), and the lungs of cystic fibrosis (CF) patients were used. Based on whole genome sequencing, the prevalence of the exoU gene was 61.5% in MK isolates whereas none of the CF isolates possessed this gene. Overall, higher antibiotic resistance was observed in the isolates possessing exoU. Of the exoU strains, all except one were resistant to fluoroquinolones, 100% were resistant to beta-lactams. 75% had mutations in quinolone resistance determining regions (T81I gyrA and/or S87L parC) which correlated with fluoroquinolone resistance. In addition, exoU strains had mutations at K76Q, A110T, and V126E in ampC, Q155I and V356I in ampR and E114A, G283E, and M288R in mexR genes that are associated with higher beta-lactamase and efflux pump activities. In contrast, such mutations were not observed in the strains lacking exoU. The expression of the ampC gene increased by up to nine-fold in all eight exoU strains and the ampR was upregulated in seven exoU strains compared to PAO1. The expression of mexR gene was 1.4 to 3.6 fold lower in 75% of exoU strains. This study highlights the association between virulence traits and antibiotic resistance in pathogenic P. aeruginosa.
Project description:IntroductionAntimicrobial resistance (AMR) is a global public health crisis. This study assessed the general public's consumption of antibiotics and associated factors in the Lusaka district of Zambia.MethodsThis cross-sectional study was conducted among 2038 participants between December 2022 and January 2023. Data were analysed using Stata 13.0. Multivariable regression techniques were used to determine the factors that influenced antibiotic consumption.ResultsOf the 2038 participants, 53.4% were female, and 51.5% had attended at least secondary school. Antibiotic use was 99.2%, of which 40.9% were appropriately used. Overall, 79.1% of antibiotics were prescribed in hospitals, while 20.9% were used from leftovers and accessed without prescriptions. This study found that the appropriate use of antibiotics was associated with being female, being aged 35 years and above, attaining secondary school or tertiary education, having a monthly expenditure of 195 USD and above, being aware that antibiotics were not the same as painkillers, and being confident that when someone was hospitalized, they would get well.ConclusionsThis study found that the appropriate use of antibiotics was low, and this is an urgent public health issue requiring community engagement in tackling AMR and adherence to treatment guidelines in healthcare facilities. Additionally, there is a need to implement and strengthen antimicrobial stewardship programmes in healthcare facilities to promote the rational use of antibiotics in Zambia. There is also a need to heighten community awareness campaigns and educational activities on the appropriate use of antibiotics.