Antibiotic and antimicrobial resistance

Community-associated Clostridioides difficile infections (CA-CDI) have increased worldwide. Patients with CDI-related symptoms occurring < 48 hours after hospitalisation and no inpatient stay 12 weeks prior are classified as CA-CDI, regardless of hospital day attendances 3 months before CDI onset. Healthcare-associated (HA) CDIs include those with symptom onset ≥ 48 hours post hospitalisation.

To consider an incubation period more reflective of CDI, and changing healthcare utilisation, we measured how varying surveillance specifications to categorise patients according to their CDI origin resulted in changes in patients’ distribution among CDI origin categories.

New CDI cases between 2012–2021 from our hospital were reviewed. For patients with CA-CDI, hospital day attendances in the 3 months prior were recorded. CA-CDI patients with hospital day attendances and recently discharged CDI patients (RD-CDI; CDI onset 4–12 weeks after discharge) were combined into a new ‘healthcare-exposure’ category (HE-CDI). Time from hospitalisation to disease onset was varied and the midpoint between optimal and balanced cut-offs was used instead of 48 hours to categorise HA-CDI.

Of 1,047 patients, 801 (76%) were HA-CDI, 205 (20%) CA-CDI and 41 (4%) were RD-CDI. Of the CA-CDI cohort, 45 (22%) met recent HE-CDI criteria and, when reassigned, reduced CA-CDI to 15%. Sensitivity analysis indicated a day 4 cut-off for assigning HA-CDI. Applying this led to 46 HA-CDI reassigned as CA-CDI. Applying both HE and day 4 criteria led to 72% HA-CDI, 20% CA-CDI, and 8% HE-CDI (previously RD-CDI).

CDI surveillance specifications reflecting healthcare exposure and an incubation period more characteristic of C. difficile may improve targeted CDI prevention interventions.

Previous United Kingdom campaigns targeting antimicrobial resistance (AMR) recommended running multimedia campaigns over an increased timeframe. The 3-year-long Keep Antibiotics Working (KAW) campaign was a mass media campaign in England targeting the public and general practitioners (GPs).

Every year, pre- and post-campaign questionnaire data were collected from the public, whereas post-campaign interview data were obtained from GPs. Data were weighted to allow pre- and post-campaign comparisons between independent samples. Significant changes in nominal and ordinal data were determined using Pearson’s chi-squared (X²) and Mann–Whitney U tests, respectively.

Prompted campaign recognition was high, increasing by 6% from 2018 to 2019 (2017: data unavailable; 2018: 68% (680/1,000); 2019: 74% (740/1,000); X² = 8.742, p = 0.003). Knowledge regarding declining antibiotic effectiveness when taken inappropriately improved following the campaign (net true: pre-2017 = 69.1% (691/1,000); post-2019 = 77.6%; (776/1,000); X² = 5.753, p = 0.016). The proportion of individuals reporting concern for themselves or for children (≤ 16 years) about AMR increased by 11.2% (Z = −5.091, p < 0.001) and 6.0% (Z = −3.616, p < 0.001) respectively, pre- to post-campaign. Finally, in 2017, reported confidence to say no to patients requesting antibiotics differed significantly between GPs who were and were not aware of the campaign (net agree: 98.9% (182/184) vs 92.4% (97/105) respectively; X² = 4.000, p = 0.045).

A high level of prompted campaign recognition was achieved. The KAW campaign improved aspects of AMR knowledge and certain attitudes towards appropriate antimicrobial use. It increased awareness of and concern about AMR, supporting GP confidence to appropriately prescribe antibiotics. Future determination of measurable behaviour changes resulting from AMR campaigns is important.

Escherichia coli is the leading cause of urinary tract infections (UTI) and bloodstream infections (BSI), and the emergence of antimicrobial resistance (AMR) in E. coli causes concern.

To investigate changes in the proportion of extended-spectrum β-lactamase (ESBL) producing isolates among E. coli isolated from urine and blood in Finland during 2008–2019.

Susceptibility testing of 1,568,488 urine (90% female, 10% male) and 47,927 blood E. coli isolates (61% female, 39% male) from all Finnish clinical microbiology laboratories during 2008–2019 was performed according to guidelines from the Clinical and Laboratory Standard Institute during 2008–2010 and the European Committee on Antimicrobial Susceptibility Testing during 2011–2019. A binomial regression model with log link compared observed trends over time and by age group and sex.

The annual proportion of ESBL-producing E. coli isolates among E. coli from blood cultures increased from 2.4% (23/966) to 8.6% (190/2,197) among males (average annual increase 7.7%; 95% CI: 4.4–11.0%, p < 0.01) and from 1.6% (28/1,806) to 6.4% (207/3,218) among females (9.3%; 95% CI: 4.8–14.0%, p < 0.01). In urine cultures, the proportion of ESBL-producing E. coli isolates increased from 2.2% (239/10,806) to 7.2% (1,098/15,297) among males (8.8%; 95% CI: 6.5–11.3%, p < 0.01) and from 1.0% (1,045/108,390) to 3.1% (3,717/120,671) among females (8.6%; 95% CI: 6.3–11.0%, p < 0.01). A significant increase was observed within most age groups.

Considering the ageing population and their risk of E. coli BSI and UTI, the increase in the annual proportions of ESBL-producing E. coli is concerning, and these increasing trends should be carefully monitored.

In China, the blaNDM gene has been recovered from human bacterial isolates since 2011. After 2014, detections of this gene in animal and food bacterial isolates have increasingly been reported.

We aimed to understand how blaNDM-bearing bacteria could spread between humans, animals, and animal-derived food.

A total of 288 non-duplicate Escherichia coli strains, including 130 blaNDM-carrying and 158 blaNDM-negative strains were collected from clinical (humans), food-producing animals (pigs) and food (retail pork) sources between 2015 and 2017. The strains were whole genome sequenced. Core-genome-multilocus-sequence-typing was conducted. To investigate if sequence types (STs) found in human, animal or food samples could have a prior origin in a clinical, animal or food-borne animal reservoir, discriminant analysis of principal components (DAPC) was used. Plasmids bearing blaNDM were characterised.

The 130 blaNDM-carrying E. coli strains comprised a total of 60 STs, with ST167 (10/51), ST77 (6/33) and ST48 (6/46) being most prevalent in clinical, animal and food sources, respectively. Some ST10 and ST167 strains were respectively found among all three sources sampled, suggesting they might enable transfer of blaNDM between sources. DAPC analysis indicated possible transmissions of ST167 from humans to animals and ST10 from animals to human. In 114 of 130 blaNDM-carrying isolates, blaNDM was located on an IncX3 plasmid.

This study in a Chinese context suggests that cross-species transmission of certain STs of E. coli harbouring blaNDM on mobile elements, may facilitate the spread of carbapenem-resistant Enterobacteriaceae. Stringent monitoring of blaNDM-bearing E. coli in ecosystems is important.

National and regional carbapenemase-producing Enterobacterales (CPE) surveillance is essential to understand the burden of antimicrobial resistance, elucidate outbreaks, and develop infection-control or antimicrobial-treatment recommendations.

This study aimed to describe CPE and their epidemiology in Norway from 2015 to 2021.

A nationwide, population-based observational study of all verified clinical and carriage CPE isolates submitted to the national reference laboratory was conducted. Isolates were characterised by antimicrobial susceptibility testing, whole genome sequencing (WGS) and basic metadata. Annual CPE incidences were also estimated.

A total of 389 CPE isolates were identified from 332 patients of 63 years median age (range: 0–98). These corresponded to 341 cases, 184 (54%) being male. Between 2015 and 2021, the annual incidence of CPE cases increased from 0.6 to 1.1 per 100,000 person-years. For CPE-isolates with available data on colonisation/infection, 58% (226/389) were associated with colonisation and 38% (149/389) with clinical infections. WGS revealed a predominance of OXA-48-like (51%; 198/389) and NDM (34%; 134/389) carbapenemases in a diversified population of Escherichia coli and Klebsiella pneumoniae, including high-risk clones also detected globally. Most CPE isolates were travel-related (63%; 245/389). Although local outbreaks and healthcare-associated transmission occurred, no interregional spread was detected. Nevertheless, 18% (70/389) of isolates not directly related to import points towards potentially unidentified transmission routes. A decline in travel-associated cases was observed during the COVID-19 pandemic.

The close-to-doubling of CPE case incidence between 2015 and 2021 was associated with foreign travel and genomic diversity. To limit further transmission and outbreaks, continued screening and monitoring is essential.

Cassini et al. (2019) estimated that, in 2015, infections with 16 different antibiotic-resistant bacteria resulted in ca 170 disability-adjusted life-years (DALYs) per 100,000 population in the European Union and European Economic area (EU/EEA). The corresponding estimate for Switzerland was about half of this (87.8 DALYs per 100,000 population) but still higher than that of several EU/EEA countries (e.g. neighbouring Austria (77.2)).

In this study, the burden caused by the same infections due to antibiotic-resistant bacteria (‘AMR burden’) in Switzerland from 2010 to 2019 was estimated and the effect of the factors ‘linguistic region’ and ‘hospital type’ on this estimate was examined.

Number of infections, DALYs and deaths were estimated according to Cassini et al. (2019) whereas separate models were built for each linguistic region/hospital type combination.

DALYs increased significantly from 3,995 (95% uncertainty interval (UI): 3;327–4,805) in 2010 to 6,805 (95% UI: 5,820–7,949) in 2019. Linguistic region and hospital type stratifications significantly affected the absolute values and the slope of the total AMR burden estimates. DALYs per population were higher in the Latin part of Switzerland (98 DALYs per 100,000 population; 95% UI: 83–115) compared with the German part (57 DALYs per 100,000 population; 95% UI: 49–66) and in university hospitals (165 DALYs per 100,000 hospitalisation days; 95% UI: 140–194) compared with non-university hospitals (62 DALYs per 100,000 hospitalisation days; 95% UI: 53–72).

The AMR burden estimate in Switzerland has increased significantly between 2010 and 2019. Considerable differences depending on the linguistic region and the hospital type were identified – a finding which affects the nationwide burden estimation.

Carbapenemase-producing Enterobacterales (CPE) are rapidly increasing worldwide, also in Europe. Although prevalence of CPE in Germany is comparatively low, the National Reference Centre for Multidrug-resistant Gram-negative Bacteria noted annually increasing numbers of NDM-5-producing Escherichia coli isolates.

As part of our ongoing surveillance programme, we characterised NDM-5-producing E. coli isolates received between 2013 and 2019 using whole genome sequencing (WGS).

From 329 identified NDM-5-producing E. coli, 224 isolates from known geographical locations were subjected to Illumina WGS. Analyses of 222 sequenced isolates included multilocus sequence typing (MLST), core genome (cg)MLST and single-nucleotide polymorphism (SNP)-based analyses.

Results of cgMLST revealed genetically distinct clusters for many of the 43 detected sequence types (ST), of which ST167, ST410, ST405 and ST361 predominated. The SNP-based phylogenetic analyses combined with geographical information identified sporadic cases of nosocomial transmission on a small spatial scale. However, we identified large clusters corresponding to clonal dissemination of ST167, ST410, ST405 and ST361 strains in consecutive years in different regions in Germany.

Occurrence of NDM-5-producing E. coli rose in Germany, which was to a large extent due to the increased prevalence of isolates belonging to the international high-risk clones ST167, ST410, ST405 and ST361. Of particular concern is the supra-regional dissemination of these epidemic clones. Available information suggest community spread of NDM-5-producing E. coli in Germany, highlighting the importance of epidemiological investigation and an integrated surveillance system in the One Health framework.

The emergence of colistin resistance is a One Health antimicrobial resistance challenge worldwide. The close contact between companion animals and humans creates opportunities for transmission and dissemination of colistin-resistant bacteria.

To detect potential animal reservoirs of colistin-resistant Escherichia coli and investigate the possible sharing of these bacteria between dogs, cats and their cohabiting humans in the community in Lisbon, Portugal.

A prospective longitudinal study was performed from 2018 to 2020. Faecal samples from dogs and cats either healthy or diagnosed with a skin and soft tissue or urinary tract infection, and their cohabiting humans were screened for the presence of colistin-resistant E. coli. All isolates were tested by broth microdilution against colistin and 12 other antimicrobials. Colistin-resistant isolates were screened for 30 resistance genes, including plasmid-mediated colistin resistance genes (mcr-1 to mcr-9), and typed by multilocus sequence typing. Genetic relatedness between animal and human isolates was analysed by whole genome sequencing.

Colistin-resistant E. coli strains harbouring the mcr-1 gene were recovered from faecal samples of companion animals (8/102; 7.8%) and humans (4/125; 3.2%). No difference between control and infection group was detected. Indistinguishable multidrug-resistant E. coli ST744 strains harbouring the mcr-1 gene were found in humans and their dogs in two households.

The identification of identical E. coli strains containing the plasmid-mediated mcr-1 gene in companion animals and humans in daily close contact is of concern. These results demonstrate the importance of the animal–human unit as possible disseminators of clinically important resistance genes in the community setting.

In 2019, the World Health Organization published the 21^st Model list of Essential Medicines and updated the Access, Watch Reserve (AWaRe) antibiotics classification to improve metrics and indicators for antibiotic stewardship activities. Reserve antibiotics are regarded as last-resort treatment options.

We investigated hospital-sector consumption quantities and trends of Reserve group antibiotics in European Union/European Economic Area countries and the United Kingdom (EU/EEA/UK).

Hospital-sector antimicrobial consumption data for 2010–2018 were obtained from the European Centre for Disease Prevention and Control. Antibacterials’ consumption for systemic use (Anatomical Therapeutic Chemical classification (ATC) group J01) were included in the analysis and expressed as defined daily doses (DDD) per 1,000 inhabitants per day. We defined reserve antibiotics as per AWaRe classification and applied linear regression to analyse trends in consumption of reserve antibiotics throughout the study period.

EU/EEA/UK average hospital-sector reserve-antibiotic consumption increased from 0.017 to 0.050 DDD per 1,000 inhabitants per day over the study period (p = 0.002). This significant increase concerned 15 countries. In 2018, four antibiotics (tigecycline, colistin, linezolid and daptomycin) constituted 91% of the consumption. Both absolute and relative (% of total hospital sector) consumption of reserve antibiotics varied considerably (up to 42-fold) between countries (from 0.004 to 0.155 DDD per 1,000 inhabitants per day and from 0.2% to 9.3%, respectively).

An increasing trend in reserve antibiotic consumption was found in Europe. The substantial variation between countries may reflect the burden of infection with multidrug-resistant bacteria. Our results could guide national actions or optimisation of reserve antibiotic use.

Gonococcal antimicrobial resistance is emerging worldwide and is monitored in the Netherlands in 18 of 24 Sexual Health Centres (SHC).

To report trends, predictors and regional variation of gonococcal azithromycin resistance (AZI-R, minimum inhibitory concentration (MIC) > 1 mg/L) and ceftriaxone decreased susceptibility (CEF-DS, MIC > 0.032 mg/L) in 2013–2019.

SHC reported data on individual characteristics, sexually transmitted infection diagnoses, and susceptibility testing (MIC, measured by Etest). We used multilevel logistic regression analysis to identify AZI-R/CEF-DS predictors, correcting for SHC region. Population differences’ effect on regional variance of AZI-R and CEF-DS was assessed with a separate multilevel model.

The study included 13,172 isolates, predominantly (n = 9,751; 74%) from men who have sex with men (MSM). Between 2013 and 2019, annual proportions of AZI-R isolates appeared to increase from 2.8% (37/1,304) to 9.3% (210/2,264), while those of CEF-DS seemed to decrease from 7.0% (91/1,306) to 2.9% (65/2,276). Among SHC regions, 0.0‒16.9% isolates were AZI-R and 0.0−7.0% CEF-DS; population characteristics could not explain regional variance. Pharyngeal strain origin and consultation year were significantly associated with AZI-R and CEF-DS for MSM, women, and heterosexual men. Among women and heterosexual men ≥ 4 partners was associated with CEF-DS, and ≥ 10 with AZI-R.

No resistance or decreasing susceptibility was found for CEF, the first line gonorrhoea treatment in the Netherlands. Similar to trends worldwide, AZI-R appeared to increase. Regional differences between SHC support nationwide surveillance with regional-level reporting. The increased risk of resistance/decreased susceptibility in pharyngeal strains underlines the importance of including extragenital infections in gonococcal resistance surveillance.

Effective surveillance of antimicrobial resistance (AMR) in Neisseria gonorrhoeae is required for the early detection of resistant strains and to ensure that treatment guidelines are appropriate for the setting in which they are implemented. AMR in N. gonorrhoeae has been identified as a global health threat.

We performed a systematic review to identify and describe surveillance systems targeting AMR in N. gonorrhoeae.

We searched Medline, PubMed, Global Health, EMBASE, CINAHL, Web of Science and ProQuest databases and grey literature between 1 January 2012 and 27 September 2020. Surveillance systems were defined as the continuous, systematic collection, analysis and interpretation of N. gonorrhoeae resistance data. The key components of surveillance systems were extracted, categorised, described and summarised.

We found 40 publications reporting on N. gonorrhoeae AMR surveillance systems in 27 countries and 10 multi-country or global surveillance reports. The proportion of countries with surveillance systems in each of the WHO's six regions ranged from one of 22 countries in the Eastern Mediterranean and five of 54 in Africa, to three of 11 countries in South East Asia. Only four countries report systems which are both comprehensive and national. We found no evidence of a current surveillance system in at least 148 countries. Coverage, representativeness, volume, clinical specimen source, type and epidemiological information vary substantially and limit interpretability and comparability of surveillance data for public health action.

Globally, surveillance for N. gonorrhoeae AMR is inadequate and leaves large populations vulnerable to a major public health threat.

Antimicrobial resistance poses a risk for healthcare, both in the community and hospitals. The spread of multidrug-resistant organisms (MDROs) occurs mostly on a local and regional level, following movement of patients, but also occurs across national borders.

The aim of this observational study was to determine the prevalence of MDROs in a European cross-border region to understand differences and improve infection prevention based on real-time routine data and workflows.

Between September 2017 and June 2018, 23 hospitals in the Dutch (NL)–German (DE) cross-border region (BR) participated in the study. During 8 consecutive weeks, patients were screened upon admission to intensive care units (ICUs) for nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA) and rectal carriage of vancomycin-resistant Enterococcus faecium/E. faecalis (VRE), third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE) and carbapenem-resistant Enterobacteriaceae (CRE). All samples were processed in the associated laboratories.

A total of 3,365 patients were screened (median age: 68 years (IQR: 57–77); male/female ratio: 59.7/40.3; NL-BR: n = 1,202; DE-BR: n = 2,163). Median screening compliance was 60.4% (NL-BR: 56.9%; DE-BR: 62.9%). MDRO prevalence was higher in DE-BR than in NL-BR, namely 1.7% vs 0.6% for MRSA (p = 0.006), 2.7% vs 0.1% for VRE (p < 0.001) and 6.6% vs 3.6% for 3GCRE (p < 0.001), whereas CRE prevalence was comparable (0.2% in DE-BR vs 0.0% in NL-BR ICUs).

This first prospective multicentre screening study in a European cross-border region shows high heterogenicity in MDRO carriage prevalence in NL-BR and DE-BR ICUs. This indicates that the prevalence is probably influenced by the different healthcare structures.

Intensive care units (ICU) constitute a high-risk setting for antimicrobial resistance (AMR).

We 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.

We 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.

Among 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).

In 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.

Invasive infections caused by Staphylococcus aureus have high clinical and epidemiological relevance. It is therefore important to monitor the S. aureus trends using suitable methods.

The study aimed to describe the trends of bloodstream infections (BSI) caused by meticillin-resistant S. aureus (MRSA) and meticillin-susceptible S. aureus (MSSA) in the European Union (EU) and the European Economic Area (EEA).

Annual data on S. aureus BSI from 2005 to 2018 were obtained from the European Antimicrobial Resistance Surveillance Network (EARS-Net). Trends of BSI were assessed at the EU/EEA level by adjusting for blood culture set rate (number of blood culture sets per 1,000 days of hospitalisation) and stratification by patient characteristics.

Considering a fixed cohort of laboratories consistently reporting data over the entire study period, MRSA percentages among S. aureus BSI decreased from 30.2% in 2005 to 16.3% in 2018. Concurrently, the total number of BSI caused by S. aureus increased by 57%, MSSA BSI increased by 84% and MRSA BSI decreased by 31%. All these trends were statistically significant (p < 0.001).

The results indicate an increasing health burden of MSSA BSI in the EU/EEA despite a significant decrease in the MRSA percentage. These findings highlight the importance of monitoring antimicrobial resistance trends by assessing not only resistance percentages but also the incidence of infections. Further research is needed on the factors associated with the observed trends and on their attributable risk.

Healthcare-associated foodborne outbreaks (HA-FBO) may have severe consequences, especially in vulnerable groups.

The aim was to describe the current state of HA-FBO and propose public health recommendations for prevention.

We searched PubMed, the Outbreak Database (Charité, University Medicine Berlin), and hand-searched reference lists for HA-FBO with outbreak onset between 2001 and 2018 from Organisation for Economic Co-operation and Development (OECD) countries and HA-FBO (2012–2018) from the German surveillance system. Additionally, data from the European Food Safety Authority were analysed.

The literature search retrieved 57 HA-FBO from 16 OECD countries, primarily in the US (n = 11), Germany (n = 11) and the United Kingdom (n = 9). In addition, 28 HA-FBO were retrieved from the German surveillance system. Based on the number of outbreaks, the top three pathogens associated with the overall 85 HA-FBO were Salmonella (n = 24), norovirus (n = 22) and Listeria monocytogenes (n = 19). Based on the number of deaths, L. monocytogenes was the main pathogen causing HA-FBO. Frequently reported implicated foods were ‘mixed foods’ (n = 16), ‘vegetables and fruits’ (n = 15) and ‘meat and meat products’ (n = 10). Consumption of high-risk food by vulnerable patients, inadequate time-temperature control, insufficient kitchen hygiene and food hygiene and carriers of pathogens among food handlers were reported as reasons for HA-FBO.

To prevent HA-FBO, the supply of high-risk food to vulnerable people should be avoided. Well working outbreak surveillance facilitates early detection and requires close interdisciplinary collaboration and exchange of information between hospitals, food safety and public health authorities.