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Presentation and antibiotic prescribing for common infectious disease episodes decreased substantially during the first COVID-19 pandemic wave in Dutch general practice. We set out to determine the course of these variables during the first pandemic year. We conducted a retrospective observational cohort study using routine health care data from the Julius General Practitioners' Network. All patients registered in the pre-pandemic year (n = 425,129) and/or during the first pandemic year (n = 432,122) were included. Relative risks for the number of infectious disease episodes (respiratory tract/ear, urinary tract, gastrointestinal, and skin), in total and those treated with antibiotics, and proportions of episodes treated with antibiotics (prescription rates) were calculated. Compared to the pre-pandemic year, primary care presentation for common infections remained lower during the full first pandemic year (RR, 0.77; CI, 0.76–0.78), mainly attributed to a sustained decline in respiratory tract/ear and gastrointestinal infection episodes. Presentation for urinary tract and skin infection episodes declined during the first wave, but returned to pre-pandemic levels during the second and start of the third wave. Antibiotic prescription rates were lower during the full first pandemic year (24%) as compared to the pre-pandemic year (28%), mainly attributed to a 10% lower prescription rate for respiratory tract/ear infections; the latter was not accompanied by an increase in complications. The decline in primary care presentation for common infections during the full first COVID-19 pandemic year, together with lower prescription rates for respiratory tract/ear infections, resulted in a substantial reduction in antibiotic prescribing in Dutch primary care. [ABSTRACT FROM AUTHOR]

Antibiotic overprescribing is one of the main drivers of the global and growing problem of antibiotic resistance, especially in primary care and for respiratory tract infections (RTIs). RTIs are the most common reason for patients to consult out-of-hours (OOH) primary care. The COVID-19 pandemic has changed the way general practitioners (GPs) work, both during office hours and OOH. In Belgian OOH primary care, remote consultations with the possibility of issuing prescriptions and telephone triage were implemented. We aimed to describe the impact of COVID-19 on GPs' antibiotic prescribing during OOH primary care. In an observational study, using routinely collected health data from GP cooperatives (GPCs) in Flanders, we analyzed GPs' antibiotic prescriptions in 2019 (10 GPCs) and 2020 (20 GPCs) during OOH consultations (telephone and face-to-face). We used autoregressive integrated moving average (ARIMA) modeling to identify any changes after lockdowns were implemented. In total, 388,293 contacts and 268,430 prescriptions were analyzed in detail. The number of antibiotic prescriptions per weekend, per 100,000 population was 11.47 (95% CI: 9.08–13.87) or 42.9% lower after compared to before the implementation of lockdown among all contacts. For antibiotic prescribing per contact, we found a decrease of 12.2 percentage points (95% CI: 10.6–13.7) or 56.5% among all contacts and of 5.3 percentage points (95% CI: 3.7–6.9) or 23.2% for face-to-face contacts only. The decrease in the number of prescriptions was more pronounced for cases with respiratory symptoms that corresponded with symptoms of COVID-19 and for antibiotics that are frequently prescribed for RTIs, such as amoxicillin (a decrease of 64.9%) and amoxicillin/clavulanate (a decrease of 38.1%) but did not appear for others such as nitrofurantoin. The implementation of COVID-19 lockdown measures coincided with an unprecedented drop in the number of antibiotic prescriptions, which can be explained by a decrease in face-to-face patient contacts, as well as a lower number of antibiotics prescriptions per face-to-face patient contact. The decrease was seen for antibiotics used for RTIs but not for nitrofurantoin, the first-choice antibiotic for urinary tract infections. [ABSTRACT FROM AUTHOR]

Uptake was facilitated by the motivation experienced by GPs belonging to primary care networks. Thus, decreasing the inappropriate use of antibiotics in primary care is crucial not only to slow down the spread and development of antibiotic resistance, but also to deliver high quality health care to patients. 10.1002/14651858.CD011825.pub2 2 Costelloe C., Metcalfe C., Lovering A., Mant D., Hay A.D. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: Systematic review and meta-analysis. Primary care accounts for more than 80% of antibiotic use worldwide. [Extracted from the article]

Nitrofurantoin is an antimicrobial agent obtained through the addition of a nitro group and a side chain containing hydantoin to a furan ring. The interactions of the antibiotic with human serum albumin (HSA) have been investigated by fluorescence, UV-VIS, Fourier transform infrared spectroscopy (FTIR) spectroscopy, and protein-ligand docking studies. The fluorescence studies indicate that the binding site of the additive involves modifications of the environment around Trp214 at the level of subdomain IIA. Fluorescence and UV-VIS spectroscopy, displacement studies, and FTIR experiments show the association mode of nitrofurantoin to HSA, suggesting that the primary binding site of the antibiotic is located in Sudlow's site I. Molecular modeling suggests that nitrofurantoin is involved in the formation of hydrogen bonds with Trp214, Arg218, and Ser454, and is located in the hydrophobic cavity of subdomain IIA. Moreover, the curve-fitting results of the infrared Amide I' band indicate that the binding of nitrofurantoin induces little change in the protein secondary structure. Overall, these data clarify the blood transportation process of nitrofurantoin and its rapid transfer to the kidney for its elimination, hence leading to a better understanding of its biological effects and being able to design other molecules, based on nitrofurantoin, with a higher biological potential. [ABSTRACT FROM AUTHOR]

Background. The use of antibiotics in food production selects for resistant bacteria and may cause a threat to human and animal health. Belgium and the Netherlands have one of the highest densities of broilers and pigs in Europe, making active monitoring of antibiotic use and resistance in this region vital. Objectives. This study aimed to quantify ESBL-producing (ESBL-E. coli), carbapenem- and ciprofloxacin-resistant (CiproR) Escherichia coli in animal feces on broiler and pig farms with a history of high antibiotic use in Belgium and the Netherlands. Methods. A total of 779 broiler and 817 pig fecal samples, collected from 29 conventional broiler and 31 multiplier pig farms in the cross-border region of Belgium and the Netherlands, were screened for the presence of antibiotic-resistant E. coli using selective culturing. Results. Carbapenem-resistant E. coli were not detected. ESBL-E. coli were remarkably more prevalent in samples from Belgian than Dutch farms. However, CiproR-E. coli were highly prevalent in broilers of both countries. The percentage of samples with ESBL- and CiproR-E. coli was lower in pig compared to poultry farms and varied between farms. No clear association with the on-farm antibiotic use in the year preceding sampling was observed. Multidrug resistance was frequently observed in samples from both countries, but ESBL-production in combination with ciprofloxacin resistance was higher in samples from Belgium. Conclusions. This study demonstrated marked differences in antibiotic resistance between countries, farms and within farms. The observed variation cannot be explained straightforward by prior quantity of antibiotic use suggesting that it results from more complex interactions that warrant further investigation. [ABSTRACT FROM AUTHOR]

The gastrointestinal tract is an important reservoir of extended spectrum beta-lactamase (ESBL)/carbapenemase-producing Enterobacterales isolates. This study included patients from two Bulgarian hospitals. Overall, 98 ESBL producers (including 68 Escherichia coli and 20 Klebsiella pneumoniae isolates) were detected among 99 hospitalized patients, 212 patients at admission, and 92 hospital staff in 42.4%, 24.5%, and 4%, respectively. We observed blaCTX-M-15 in 47% of isolates, blaCTX-M-3 in 39% and blaCTX-M-14 in 11%. Three blaCTX-M-15 positive isolates were also blaKPC-2 positive. High transferability was detected for blaCTX-M-3 carrying plasmids (55%) with L/M and I1 replicon plasmids, followed by CTX-M-14 (36.4%) and CTX-M-15 (27.9%) with IncF plasmids. BlaKPC-2 was carried by FIIAs plasmids. Epidemiology typing revealed 8 K. pneumoniae ST types—ST15(8/20), ST17(4/20), ST37(2/20) and 9 E. coli ST types—ST131 (30.9%, 21/68), ST38 (8/68), ST95(7/68) and ST316(7/68). All ST131 isolates but one was from the highly virulent epidemic clone O25bST131. This is the first report in Bulgaria about ESBL/carbapenemase faecal carriage. We observed high ESBL/carbapenemases prevalence. A predominant number of isolates were members of highly epidemic and virulent PanEuropean clones ST15 K. pneumoniae and O25bST131 E. coli. High antibiotics usage during the COVID pandemic will worsen the situation. Routine screenings and strict infection control measures should be widely implemented. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has impacted on public access to health services. This study aimed to investigate the impact of COVID-19 pandemic on commonly prescribed first-line antibiotics in English primary care. A secondary analysis of publicly available government data pertaining to primary care prescribing was conducted. A list of twenty first-line antibiotics used to treat common infections was developed following the National Institute of Clinical Excellence (NICE) guidelines. All primary care prescription and cost data pertaining to commonly prescribed first-line antibiotics in England between March and September of 2018–2020 were extracted and adjusted for inflation. Analysis suggests prescribing of antibiotics significantly reduced by 15.99% (p = 0.018) and 13.5% (p = 0.002) between March and September 2020 compared with same time period for 2018 and 2019, respectively. The most noticeable decrease in 2020 was noticed for prescribing for meningitis (−62.3%; p = 0.002) followed by respiratory tract infections (−39.13%; p = 0.035), in terms of indications. These results are suggestive of reduced transmission of infections in the community due to national lockdowns, social distancing and hygiene practices. In addition, the impact of reduced face-to-face consultations in general practices needs to be investigated as a potential reason for reduced prescribing. The pandemic also offers an opportunity to rationalize antibiotics use in the community. [ABSTRACT FROM AUTHOR]

Poultry represents a common source of bacteria with resistance to antibiotics including the critically important ones. Selective cultivation using colistin, cefotaxime and meropenem was performed for 66 chicken samples coming from 12 farms in Paraguay while two breeding companies supplied the farms. A total of 62 Escherichia coli and 22 Klebsiella pneumoniae isolates were obtained and representative isolates were subjected to whole-genome sequencing. Relatively high prevalence of phylogenetic group D and F was observed in E. coli isolates and several zoonotic sequence types (STs) including ST457 (14 isolates), ST38 (5), ST10 (2), ST117 (2) or ST93 (4) were detected. Isolates from three farms, which purchased chicken from a Paraguayan hatchery showed higher prevalence of mcr-5.1 and blaCTX-M-8 compared to the other nine farms, which purchased chickens from a Brazilian hatchery. Moreover, none of the K. pneumoniae isolates were linked to the Paraguayan hatchery. ESBL/AmpC and mcr-5-carrying multi-drug resistant (MDR) plasmids were characterized, and complete sequences were obtained for eight plasmids. The study shed light on Paraguayan poultry farms as a reservoir of antibiotic resistance commonly conferred via MDR plasmids and showed linkage between resistance and origin of the chickens at the hatcheries level. [ABSTRACT FROM AUTHOR]

Escherichia coli is frequently associated with multiple antimicrobial resistances and a major cause of bacterial extraintestinal infections in livestock and humans. However, data on the epidemiology of (i) multidrug-resistant (MDR) and (ii) extraintestinal pathogenic E. coli (ExPEC) in poultry and pig slaughterhouses in Germany is currently lacking. Selected E. coli isolates (n = 71) with phenotypic resistance to cephalosporins from two poultry and two pig slaughterhouses expressing high MDR rates (combined resistance to piperacillin, cefotaxime and/or ceftazidime, and ciprofloxacin) of 51.4% and 58.3%, respectively, were analyzed by whole-genome sequencing. They constituted a reservoir for 53 different antimicrobial resistance determinants and were assigned various sequence types, including high-risk clones involved in human infections worldwide. An ExPEC pathotype was detected in 17.1% and 5.6% of the isolates from poultry and pig slaughterhouses, respectively. Worryingly, they were recovered from scalding water and eviscerators, indicating an increased risk for cross-contaminations. Uropathogenic E. coli (UPEC) were detected in the effluent of an in-house wastewater treatment plant (WWTP) of a poultry slaughterhouse, facilitating their further dissemination into surface waters. Our study provides important information on the molecular characteristics of (i) MDR, as well as (ii) ExPEC and UPEC regarding their clonal structure, antimicrobial resistance and virulence factors. Based on their clinical importance and pathogenic potential, the risk of slaughterhouse employees' exposure cannot be ruled out. Through cross-contamination, these MDR E. coli pathotypes may be introduced into the food chain. Moreover, inadequate wastewater treatment may contribute to the dissemination of UPEC into surface waters, as shown for other WWTPs. [ABSTRACT FROM AUTHOR]

Resistance mediated by β-lactamases is a globally spread menace. The aim of the present study was to determine the occurrence of Escherichia coli producing plasmid-encoded AmpC β-lactamases (pAmpC) in animals. Fecal samples from chickens (n = 159), cattle (n = 104), pigs (n = 214), and various wild bird species (n = 168), collected from different Greek regions during 2018–2020, were screened for the presence of pAmpC-encoding genes. Thirteen E. coli displaying resistance to third-generation cephalosporins and a positive AmpC confirmation test were detected. blaCMY-2 was the sole pAmpC gene identified in 12 chickens' and 1 wild bird (Eurasian magpie) isolates and was in all cases linked to an upstream ISEcp1-like element. The isolates were classified into five different sequence types: ST131, ST117, ST155, ST429, and ST1415. Four chickens' stains were assigned to ST131, while five chickens' strains and the one from the Eurasian magpie belonged to ST117. Seven pAmpC isolates co-harbored genes conferring resistance to tetracyclines (tetM, tetB, tetC, tetD), 3 carried sulfonamide resistance genes (sulI and sulII), and 10 displayed mutations in the quinolone resistance-determining regions of gyrA (S83L+D87N) and parC (S80I+E84V). This report provides evidence of pAmpC dissemination, describing for the first time the presence of CMY-2 in chickens and wild birds from Greece. [ABSTRACT FROM AUTHOR]

Maternal carriage and vertical transmission of extended-spectrum, beta-lactamase-producing Enterobacteriaceae (ESBL-E), such as Escherichia coli, hamper the treatment of infections, resulting in high morbidity. E. coli is the most frequent cause of early-onset neonatal sepsis (EOS) in preterm infants, where ESBL-E are more frequently isolated. In this prospective, case-controlled study, maternal rectovaginal ESBL-E colonization and vertical transmission to preterm infants were assessed in 160 women with preterm premature rupture of membranes (PPROM; 57.4%) or preterm labor (42.6%); additional cultures were obtained from the placenta, amnion, and umbilical cord during preterm labor. Maternal and neonatal ESBL-E-carriage rates were 17.5% and 12.9%, respectively, and the vertical-transmission rate was 50%. Maternal ESBL-E colonization among women with PPROM was 21.3%, and in women with premature labor it was 12.6%. No correlation was observed between maternal ESBL-E-colonization and previous hospitalization or antibiotic administration during pregnancy. However, a correlation was found between placental inflammation and maternal ESBL-E colonization (p = 0.007). ESBL-E-colonized infants were delivered at an earlier gestational age and were more likely to have complications. Thus, the high ESBL-E carriage rate in women with threatened preterm labor, without obvious risk factors for carriage, and a high vertical transmission rate, combined with a correlation between placental inflammation and ESBL-E carriage, support maternal–neonatal ESBL-E-colonization surveillance and active measures to prevent ESBL-E-related EOS. [ABSTRACT FROM AUTHOR]

Background: The already high and increasing occurrence of extended-spectrum beta-lactamases (ESBL) producing Escherichia coli in European broiler populations is of concern due to the fact that third and fourth generation cephalosporins are deemed critically important in human medicine. In Sweden 34% of the broilers carry ESBL/ pAmpC producing E. coli in their gut, despite the absence of a known selection pressure such as antimicrobial usages. The aim of the current study was to characterise a selection of E. coli strains carrying the blaCTX-M-1, to determine if the spread was due to a specific clone. Findings: Ten isolates carrying blaCTX-M-1 from Swedish broilers belonged to eight different multi-locus sequence types with three isolates belonging to ST155. The ST155 isolates were identical as assessed by PFGE. The blaCTX-M-1 was in all isolates carried on a plasmid of replicon type incI, which also transferred resistance to tetracycline and sulfamethoxazole. Conclusion: The occurrence of ESBL-producing E. coli in the Swedish broilers is not due to the emergence of a single clone, but rather the spread of a specific incI plasmid carrying blaCTX-M-1. [ABSTRACT FROM AUTHOR]

Animals, humans and food are all interconnected sources of antimicrobial resistance (AMR), allowing extensive and rapid exchange of AMR bacteria and genes. Whole genome sequencing (WGS) was used to characterize 279 Escherichia coli isolates obtained from animals (livestock, companion animals, wildlife), food and humans in Italy. E. coli predominantly belonged to commensal phylogroups B1 (46.6%) and A (29%) using the original Clermont criteria. One hundred and thirty-six sequence types (STs) were observed, including different pandemic (ST69, ST95, ST131) and emerging (ST10, ST23, ST58, ST117, ST405, ST648) extraintestinal pathogenic Escherichia coli (ExPEC) lineages. Eight antimicrobial resistance genes (ARGs) and five chromosomal mutations conferring resistance to highest priority critically important antimicrobials (HP-CIAs) were identified (qnrS1, qnrB19, mcr-1, blaCTX-M1,15,55, blaCMY-2, gyrA/parC/parE, ampC and pmrB). Twenty-two class 1 integron arrangements in 34 strains were characterized and 11 ARGs were designated as intI1 related gene cassettes (aadA1, aadA2, aadA5, aad23, ant2_Ia, dfrA1, dfrA7, dfrA14, dfrA12, dfrA17, cmlA1). Notably, most intI1 positive strains belonged to rabbit (38%) and poultry (24%) sources. Three rabbit samples carried the mcr-1 colistin resistance gene in association with IS6 family insertion elements. Poultry meat harbored some of the most prominent ExPEC STs, including ST131, ST69, ST10, ST23, and ST117. Wildlife showed a high average number of virulence-associated genes (VAGs) (mean = 10), mostly associated with an ExPEC pathotype and some predominant ExPEC lineages (ST23, ST117, ST648) were identified. [ABSTRACT FROM AUTHOR]

The spread of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) has posed a critical health risk to both humans and animals, because resistance to beta-lactam antibiotics makes treatment for commonly infectious diseases more complicated. In this study, we report the prevalence and genetic characteristics of ESBL-ECs isolated from retail meat samples in Korea. A total of 1205 E. coli strains were isolated from 3234 raw meat samples, purchased from nationwide retail stores between 2015 and 2018. Antimicrobial susceptibility testing was performed for all isolates by a broth microdilution method, and the ESBL phenotype was determined according to the Clinical and Laboratory Standards Institute (CLSI) confirmatory method. All ESBL-EC isolates (n = 29) were subjected to whole-genome sequencing (WGS). The antimicrobial resistance genes, plasmid incompatibility types, E. coli phylogroups, and phylogenetic relations were investigated based on the WGS data. The prevalence of ESBL-ECs in chicken was significantly higher than that in other meat samples. The results in this study demonstrate that clonally diverse ESBL-ECs with a multidrug resistance phenotype were distributed nationwide, although their prevalence from retail meat was 0.9%. The dissemination of ESBL-ECs from retail meat poses a potential risk to consumers and food-handlers, suggesting that the continuous surveillance of ESBL-ECs in retail meat should be conducted at the national level. [ABSTRACT FROM AUTHOR]

Poultry frequently account for the highest prevalence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in livestock. To investigate the impact of direct-fed microbials (DFM) and phytobiotic feed additives on prevalence and conjugation of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, an animal trial was conducted. Lactobacillus agilis LA73 and Lactobacillus salivarius LS1 and two commercial phytogenic feed additives (consisting of carvacrol, cinnamaldehyde, and eugenol) were used as feed additives either alone or as a combination of DFM and phytogenic feed additive. An ESBL-producing E.coli donor and a potentially pathogenic Salmonella Typhimurium recipient were inoculated at 5 × 109 cells/mL in cecal contents from 2-week-old broilers. Conjugation frequencies were determined after 4 h aerobic co-incubation at 37 °C and corrected for the impact of the sample matrix on bacterial growth of donor and recipient. Surprisingly, indigenous Enterobacteriaceae acted as recipients instead of the anticipated Salmonella recipient. The observed increase in conjugation frequency was most obvious in the groups fed the combinations of DFM and phytogenic product, but merely up to 0.6 log units. Further, cecal samples were examined for ESBL-producing Enterobacteriaceae on five consecutive days in broilers aged 27–31 days. All samples derived from animals fed the experimental diet showed lower ESBL-prevalence than the control. It is concluded that Lactobacillus spp. and essential oils may help to reduce the prevalence of ESBL-harboring plasmids in broilers, while the effect on horizontal gene transfer is less obvious. [ABSTRACT FROM AUTHOR]

This paper focusses on biological hazards at the global level and considers the challenges to risk assessment (RA) from a One Health perspective. Two topics – vector‐borne diseases (VBD) and antimicrobial resistance (AMR) – are used to illustrate the challenges ahead and to explore the opportunities that new methodologies such as next‐generation sequencing can offer. Globalisation brings complexity and introduces drivers for infectious diseases. Cooperation and the application of an integrated RA approach – one that takes into consideration food farming and production systems including social and environmental factors – are recommended. Also needed are methodologies to identify emerging risks at a global level and propose prevention strategies. AMR is one of the biggest threats to human health in the infectious disease environment. Whereas new genomic typing techniques such as whole genome sequencing (WGS) provide further insights into the mechanisms of spread of resistance, the role of the environment is not fully elucidated, nor is the role of plants as potential vehicles for spread of resistance. Historical trends and recent experience indicate that (re)‐emergence and/or further spread of VBD within the EU is a matter of when rather than if. Standardised and validated vector monitoring programs are required to be implemented at an international level for continuous surveillance and assessment of potential threats. There are benefits to using WGS – such as a quicker and better response to outbreaks and additional evidence for source attribution. However, significant challenges need to be addressed, including method standardisation and validation to fully realise these benefits; barriers to data sharing; and establishing epidemiological capacity for cluster triage and response. [ABSTRACT FROM AUTHOR]

β-lactam antibiotics are widely used for the treatment of different types of infections worldwide and the resistance to these antibiotics has grown sharply, which is of great concern. Resistance to β-lactams in gram-negative bacteria is mainly due to the production of β-lactamases, which are classified according to their functional activities. The aim of this study was to verify the presence of β-lactamases encoding genes in feces, soil, and water from a Brazilian pig farm. Different β-lactamases encoding genes were found, including blaCTX-M-Gp1, blaCTX-M-Gp9, blaSHV, blaOXA-1-like, blaGES, and blaVEB. The blaSHV and blaCTX-M-Gp1 genes have been detected in all types of samples, indicating the spread of β-lactam resistant bacteria among farm pigs and the environment around them. These results indicate that β-lactamase encoding genes belonging to the cloxacillinase, ESBL, and carbapenemase and they have high potential to spread in different sources, due to the fact that genes are closely related to mobile genetic elements, especially plasmids. [ABSTRACT FROM AUTHOR]