Antibiotic and antimicrobial resistance

Vancomycin-resistant Enterococcus faecium (VREfm) isolates of sequence type (ST)1299 were described recently in south-eastern German hospitals and rapidly expanded from local to cross-border level.

We describe the spread of the novel VREfm strain ST1299/vanA on a genetic, geographical and temporal level during the first 5 years after its detection.

At University Hospital Regensburg (UHoR), routine VREfm surveillance is whole genome sequencing-based (≥ 1 VREfm per van-genotype, patient and year). In this observational cohort study, we analysed one VREfm ST1299 isolate from our database (2016–2022) per patient and year. Isolates were added from the Hospital of the Merciful Brothers Regensburg (MBR), the National Reference Centre for Staphylococci and Enterococci (NRC), and clinical isolates from Austria.

We identified 635 VREfm ST1299 isolates (100% vanA), including 504 from Regensburg, and 113 blood cultures. ST1299 isolates were first detected in 2018 simultaneously in Regensburg (n = 2) and southern Bavaria (n = 2), with local (UHoR) and regional numbers increasing rapidly from 2020, shifting to national scale in the same year. Genome data, analysed by cgMLST, showed a predominance of ST1299/CT1903 (315/504 isolates, 62.5%) and ST1299/CT3109 (127/504 isolates, 25.2%) isolates from Regensburg. By 2021, ST1299/CT1903 reached Upper Austria causing hospital outbreaks (n = 5). Phylogeny analysis suggests common ancestors with VREfm ST80, ST18 and ST17.

Since their emergence in 2018, two highly transmissible subtypes of ST1299/vanA reached national, then cross-border scale. The observed outbreak tendency may explain the rapid and successful spread and the high clonality in our collection.

In Europe and other high-income countries, antibiotics are mainly prescribed in the outpatient setting, which consists of primary, specialist and hospital-affiliated outpatient care. Established surveillance platforms report antimicrobial consumption (AMC) on aggregated levels and the contribution of the different prescriber groups is unknown.

To determine the contribution of different prescribers to the overall outpatient AMC in Switzerland.

We conducted a retrospective observational study using claims data from one large Swiss health insurance company, covering the period from 2015 to 2022. We analysed antibiotic prescriptions (ATC code J01) prescribed in the Swiss outpatient setting. Results were reported as defined daily doses per 1,000 inhabitants per day (DID) and weighted according to the total population of Switzerland based on census data.

We analysed 3,663,590 antibiotic prescriptions from 49 prescriber groups. Overall, AMC ranged from 9.12 DID (2015) to 7.99 DID (2022). General internal medicine (40.1% of all prescribed DID in 2022), hospital-affiliated outpatient care (20.6%), group practices (17.3%), paediatrics (5.4%) and gynaecology (3.7%) were the largest prescriber groups. Primary care accounted for two-thirds of the prescribed DID. Quantity and type of antibiotics prescribed varied between the prescriber groups. Broad-spectrum penicillins, tetracyclines and macrolides were the most prescribed antibiotic classes.

Primary care contributed considerably less to AMC than anticipated, and hospital-affiliated outpatient care emerged as an important prescriber. Surveillance at the prescriber level enables the identification of prescribing patterns within all prescriber groups, offering unprecedented visibility and allowing a more targeted antibiotic stewardship according to prescriber groups.

Antimicrobial resistance (AMR) of Mycoplasma genitalium (MG) is a growing concern worldwide and surveillance is needed. In Belgium, samples are sent to the National Reference Centre of Sexually Transmitted Infections (NRC-STI) on a voluntary basis and representative or robust national AMR data are lacking.

We aimed to estimate the occurrence of resistant MG in Belgium.

Between July and November 2022, frozen remnants of MG-positive samples from 21 Belgian laboratories were analysed at the NRC-STI. Macrolide and fluoroquinolone resistance-associated mutations (RAMs) were assessed using Sanger sequencing of the 23SrRNA and parC gene. Differences in resistance patterns were correlated with surveillance methodology, socio-demographic and behavioural variables via Fisher’s exact test and logistic regression analysis.

Of the 244 MG-positive samples received, 232 could be sequenced for macrolide and fluoroquinolone RAMs. Over half of the sequenced samples (55.2%) were resistant to macrolides. All sequenced samples from men who have sex with men (MSM) (24/24) were macrolide-resistant. Fluoroquinolone RAMs were found in 25.9% of the samples and occurrence did not differ between socio-demographic and sexual behaviour characteristics.

Although limited in sample size, our data suggest no additional benefit of testing MG retrieved from MSM for macrolide resistance in Belgium, when making treatment decisions. The lower occurrence of macrolide resistance in other population groups, combined with emergence of fluoroquinolone RAMs support macrolide-resistance testing in these groups. Continued surveillance of resistance in MG in different population groups will be crucial to confirm our findings and to guide national testing and treatment strategies.

The COVID-19 pandemic resulted in adaptation in infection control measures, increased patient transfer, high occupancy of intensive cares, downscaling of non-urgent medical procedures and decreased travelling.

To gain insight in the influence of these changes on antimicrobial resistance (AMR) prevalence in the Netherlands, a country with a low AMR prevalence, we estimated changes in demographics and prevalence of six highly resistant microorganisms (HRMO) in hospitalised patients in the Netherlands during COVID-19 waves (March–June 2020, October 2020–June 2021, October 2021–May 2022 and June–August 2022) and interwaves (July–September 2020 and July–September 2021) compared with pre-COVID-19 (March 2019–February 2020).

We investigated data on routine bacteriology cultures of hospitalised patients, obtained from 37 clinical microbiological laboratories participating in the national AMR surveillance. Demographic characteristics and HRMO prevalence were calculated as proportions and rates per 10,000 hospital admissions.

Although no significant persistent changes in HRMO prevalence were detected, some relevant non-significant patterns were recognised in intensive care units. Compared with pre-COVID-19 we found a tendency towards higher prevalence of meticillin-resistant Staphylococcus aureus during waves and lower prevalence of multidrug-resistant Pseudomonas aeruginosa during interwaves. Additionally, during the first three waves, we observed significantly higher proportions and rates of cultures with Enterococcus faecium (pooled 10% vs 6% and 240 vs 120 per 10,000 admissions) and coagulase-negative Staphylococci (pooled 21% vs 14% and 500 vs 252 per 10,000 admissions) compared with pre-COVID-19.

We observed no substantial changes in HRMO prevalence in hospitalised patients during the COVID-19 pandemic.

Preliminary unpublished results of the survey of carbapenem- and/or colistin-resistant Enterobacterales (CCRE survey) showed the expansion of carbapenemase-producing Klebsiella pneumoniae (CPKP) sequence type (ST) 39 in 12 of 15 participating Greek hospitals in 2019.

We conducted a rapid survey to determine the extent of spread of CPKP high-risk clones in Greek hospitals in 2022 and compare the distribution of circulating CPKP clones in these hospitals since 2013.

We analysed whole genome sequences and epidemiological data of 310 K. pneumoniae isolates that were carbapenem-resistant or ‘susceptible, increased exposure’ from Greek hospitals that participated in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE, 2013–2014), in the CCRE survey (2019) and in a national follow-up survey (2022) including, for the latter, an estimation of transmission events.

Five K. pneumoniae STs including ST258/512 (n = 101 isolates), ST11 (n = 93), ST39 (n = 56), ST147 (n = 21) and ST323 (n = 13) accounted for more than 90% of CPKP isolates in the dataset. While ST11, ST147 and ST258/512 have been detected in participating hospitals since 2013 and 2014, KPC-2-producing ST39 and ST323 emerged in 2019 and 2022, respectively. Based on the defined genetic relatedness cut-off, 44 within-hospital transmission events were identified in the 2022 survey dataset, with 12 of 15 participating hospitals having at least one within-hospital transmission event.

The recent emergence and rapid spread of new high-risk K. pneumoniae clones in the Greek healthcare system related to within-hospital transmission is of concern and highlights the need for molecular surveillance and enhanced infection prevention and control measures.

Since 2021, an emergence of New Delhi metallo-β-lactamase (NDM)-14-producing Klebsiella pneumoniae has been identified in France. This variant with increased carbapenemase activity was not previously detected in Enterobacterales.

We investigated the rapid dissemination of NDM-14 producers among patients in hospitals in France.

All NDM-14-producing non-duplicate clinical isolates identified in France until June 2022 (n = 37) were analysed by whole genome sequencing. The phylogeny of NDM-14-producers among all K. pneumoniae sequence type (ST) 147 reported in France since 2014 (n = 431) was performed. Antimicrobial susceptibility testing, conjugation experiments, clonal relationship and molecular clock analysis were performed.

The 37 NDM-14 producers recovered in France until 2022 belonged to K. pneumoniae ST147. The dissemination of NDM-14-producing K. pneumoniae was linked to a single clone, likely imported from Morocco and responsible for several outbreaks in France. The gene blaNDM-14 was harboured on a 54 kilobase non-conjugative IncFIB plasmid that shared high homology with a known blaNDM-1-carrying plasmid. Using Bayesian analysis, we estimated that the NDM-14-producing K. pneumoniae ST147 clone appeared in 2020. The evolutionary rate of this clone was estimated to 5.61 single nucleotide polymorphisms per genome per year. The NDM-14 producers were highly resistant to all antimicrobials tested except to colistin, cefiderocol (minimum inhibitory concentration 2 mg/L) and the combination of aztreonam/avibactam.

Highly resistant NDM-14 producing K. pneumoniae can rapidly spread in healthcare settings. Surveillance and thorough investigations of hospital outbreaks are critical to evaluate and limit the dissemination of this clone.

Multidrug-resistant (MDR) bacteria are among chief causes of healthcare-associated infections (HAIs). In Spain, studies addressing multidrug resistance based on epidemiological surveillance systems are lacking.

In this observational study, cases of HAIs by MDR bacteria notified to the epidemiological surveillance system of Andalusia, Spain, between 2014−2021, were investigated. Notified cases and their spatiotemporal distribution were described, with a focus on social determinants of health (SDoH).

New cases during the study period of HAIs caused by extended-spectrum β-lactamase (ESBL)-/carbapenemase-producing Enterobacterales, MDR Acinectobacter baumannii, MDR Pseudomonas aeruginosa or meticillin resistant Staphylococcus aureus were considered. Among others, notification variables included sex and age, while socio-economic variables comprised several SDoH. Cases’ spatial distribution across municipalities was assessed. The smooth standardised incidence ratio (sSIR) was obtained using a Bayesian spatial model. Association between municipalities’ sSIR level and SDoH was evaluated by bivariate analysis.

In total, 6,389 cases with a median age of 68 years were notified; 61.4% were men (n = 3,921). The most frequent MDR bacteria were ESBL-producing Enterobacterales (2,812/6,389; 44.0%); the main agent was Klebsiella spp. (2,956/6,389; 46.3%). Between 2014 and 2021 case numbers appeared to increase. Overall, up to 15-fold differences in sSIR between municipalities were observed. In bivariate analysis, there appeared to be an association between municipalities’ sSIR level and deprivation (p = 0.003).

This study indicates that social factors should be considered when investigating HAIs by MDR bacteria. The case incidence heterogeneity between Andalusian municipalities might be explained by SDoH, but also possibly by under-notification. Automatising reporting may address the latter.