Antibiotic and antimicrobial resistance

Carbapenemase-producing Enterobacterales (CPE) cause infections, particularly nosocomially, with limited treatment options. NDM-1-producing Klebsiella pneumoniae cases have substantially increased since 2022, associated with the Ukraine war.

We aimed to investigate transmission patterns using Germany’s Integrated Genomic Surveillance (IGS), combining notifications and sequence data.

We selected NDM-1-producing K. pneumoniae cases, confirmed by isolates between 1 January 2022 and 28 February 2023. Isolates were Illumina whole genome-sequenced and linked to notifications. Clusters were defined as ≤ 12 allelic differences in core genome-wide single nucleotide variant-based genotyping. Cluster categories were: ‘no exposure abroad’, ‘exposure in Ukraine’ or ‘other exposure abroad’ if ≥ one case stayed in Ukraine or elsewhere. Follow-up of 13 clusters examined further exposure information.

Among 424 cases of most frequent sequence types, 326 (77%) belonged to 61 clusters. Seventeen (28%) clusters were associated with no exposure abroad, 33 (54%) with exposure in Ukraine, seven (11%) with other exposure abroad, and four (7%) had insufficient data. Cases in clusters with exposure in Ukraine were more dispersed, younger, and more often wound-infected than in other exposure location categories (p < 0.01). Cluster follow-up revealed one cluster with all cases from Ukraine or Russia, another with nosocomial transmission following case importation, and a third with all cases from one German hospital without exposure abroad.

Most cases were in clusters, suggesting preventable chains of transmission. Three patterns emerged: transmission abroad, transmission in German hospitals from imported cases or local outbreaks. IGS can identify where transmission could be interrupted. International cooperation needs strengthening to prevent CPE spread.

To enhance antibiotic stewardship and effectively address antimicrobial resistance (AMR), better understanding of subnational antibiotic consumption patterns is essential.

We aimed to assess antibiotic consumption in Germany using data from 2022 and integrated from two surveillance systems, focusing on regional differences by examining non-university acute care hospitals.

We used pharmacy dispensing data from 525 regional or local hospitals and 35 university hospitals, covering 46.5 million patient days (PD), nearly half of all occupied bed days nationwide, to calculate antibiotic use densities (AUD) for systemic antibiotics, expressed as World Health Organization (WHO) ATC/DDD (Anatomical Therapeutic Chemical/Defined Daily Dose) per 100 patient days (DDD/100 PD). The analysis primarily focused on consumption patterns in non-university hospitals, assessing key antibiotic groups through mixed-effects regression. For sensitivity analyses, we employed hospital-adapted daily dose definitions.

Pooled AUD for participating non-university hospitals was 51.8 DDD/100 PD, with aminopenicillins/beta-lactamase inhibitors being the most prescribed group. Regression analyses, adjusted for hospital size and ward type/admitting specialty, indicated notable regional variation. We identified statistically significant differences in antibiotic consumption, particularly for beta-lactam antibiotics, fluoroquinolones and tetracyclines. For example, several regions exhibited up to 1.4-fold higher use of first- and second-generation cephalosporins compared with the western reference region.

This study highlights substantial regional variation in antibiotic use in German acute care hospitals, underlining the importance of further investigation into influencing factors such as regional guidelines and resistance rates. The methodological approach applied here may serve as a model for other countries interested in analysing regional differences in antibiotic consumption.

Fifteen- and 20-valent pneumococcal conjugate vaccines (PCVs) offer broader protection against invasive pneumococcal disease (IPD) than PCV13. Adopting these vaccines may result in decreasing IPD incidence, antibiotic use and antimicrobial resistance (AMR) rates. If the additional serotypes in PCV15 and PCV20 are associated with AMR, AMR rate reduction could be greater than expected from reduced antibiotic consumption alone.

This retrospective analysis assessed the association between AMR and non-PCV13 serotypes in PCV15 and PCV20.

Laboratory-based surveillance data on 8,123 IPD isolates were obtained retrospectively from the Belgian Reference Centre for invasive Streptococcus pneumoniae. Isolates (n = 8,088) were serotyped and tested for AMR. Associations between vaccine serotype groups and AMR were evaluated by multinomial logistic regression. Where associations varied with patients’ age, ranges of odds ratios (ORs) are presented.

PCV15-non-PCV13 and PCV20-non-PCV13 serotypes accounted for 7.4% (n = 597) and 37% (n = 2,992) of IPD isolates respectively. Of non-PCV20 serotypes, 24% (508/2,125) were penicillin resistant. Compared with non-PCV20 serotypes, PCV15-non-PCV13 serotypes were more often associated with erythromycin (ORs: 3.59–9.43) and tetracycline (OR: 2.00) resistance, and with trimethoprim/sulfamethoxazole (OR: 0.11) susceptibility. PCV20-non-PCV15 serotypes were more often associated with amoxicillin (OR: 9.45) and cefotaxime (ORs: 5.06–82.38) resistance, and with erythromycin (ORs: 0.13–0.18), tetracycline (OR: 0.71) and penicillin (ORs: 0.05–0.46) susceptibility.

PCV20 may lead to a larger decrease in overall IPD incidence than PCV15. Although the PCV20 vaccination impact on AMR may be limited, some resistant or difficult to treat infections could be avoided. Serotype replacement might lead to infections with low level penicillin resistance increasing, but most of these should remain treatable.

Mandatory reporting of healthcare-associated infections (HCAI) in England is conducted locally by acute hospital groups and can be a large burden on healthcare staff.

We aimed to determine the case ascertainment of a potential centrally-implemented, automated HCAI surveillance system in England using preexisting data feeds at the UK Health Security Agency.

We compared monthly case numbers submitted between 1 April 2016 and 31 March 2023 by acute hospital groups (locally-implemented surveillance) to routinely-collected laboratory and hospital encounter records (centrally-implemented surveillance) for all infections under mandatory surveillance in England. Since laboratories can serve multiple hospitals, we compared several methods of assigning laboratory-confirmed cases to hospital groups.

Locally-implemented vs centrally-implemented surveillance identified: meticillin-resistant Staphylococcus aureus bacteraemias 5,453 vs 5,859 (ratio 1.07), meticillin-susceptible S. aureus bacteraemias 84,680 vs 83,326 (0.98), Escherichia coli bacteraemias 281,100 vs 275,133 (0.98), Klebsiella species bacteraemias 65,877 vs 67,301 (1.02), Pseudomonas aeruginosa bacteraemias 25,862 vs 25,715 (0.99), Clostridioides difficile infections (CDI) 94,054 v 90,942 (0. 97) respectively. Assigning hospital groups by linking laboratory records to hospital encounters produced lower monthly mean absolute difference (MAD) vs locally-implemented surveillance than using laboratory records alone. MAD was 0.65 cases/month for bacteraemias, 2.99 for CDI; differences occurred in both directions. MAD decreased over time for bacteraemias but increased from April 2021 onwards for CDI.

Centrally-implemented surveillance could be feasible for bacteraemias in England due to comparable case numbers with local surveillance. However, more research is needed around understanding and managing data quality of automated feeds, particularly for CDI.

Data for healthcare-associated infections (HAI) and antibiotic use in long-term care facilities (LTCF) in Switzerland are lacking but are necessary to take actions.

We aimed to estimate HAI prevalence and antibiotic use and to record existing structure and process indicators in the area of infection prevention/antibiotic use in Swiss LTCF.

We invited all Swiss LTCF for this PPS in September 2024 using the adapted Healthcare-Associated Infections in European Long-Term Care Facilities (HALT)-4 protocol. The proportion of residents with HAI and systemic antibiotic treatment was calculated for a representative sample, stratified by language region and size. We assessed resident-level and institutional risk factors for HAI in all participating institutions, using random-effects logistic regression.

We included 94 LTCF (7,244 residents), whereof 49 LTCFs (3,375 residents) belonged to the representative sample. Median age of residents in the representative sample was 87 years (range: 36–107) and 2,334 (69.2%) were female. Prevalence of HAI was 2.2% (95% confidence interval (CI): 1.7–2.7); 2.7% (95% CI: 2.2–3.3) were receiving antibiotic treatment, with highest use in LTCF in French-speaking cantons (5.9%; 95% CI: 4.2–7.5). Urinary tract (46%) and respiratory infections (20%) were most common, aminopenicillins (26%) and nitrofurantoin (19%) the most commonly used antimicrobials. The strongest independent risk factor for HAI was presence of urinary catheters (adjusted odds ratio = 2.65; 95% CI: 1.71–4.11).

Prevalence of HAI and antibiotic use in Swiss LTCFs were comparable to the European average from 2023/24. There are regional differences in antibiotic consumption. Urinary catheterisation, potentially modifiable, was the most important risk factor for HAI.

Carbapenemase-producing Enterobacterales (CPE) frequently cause nosocomial outbreaks. To investigate these, tracing focused on patients with related CPE strains and spatiotemporal contact (e.g. contact with each other in a room or on a ward during overlapping periods) has limitations. Moreover, as widely available molecular typing methods cannot detect plasmid-related transmissions, carbapenemase gene transfer across enteric bacteria through plasmids in hospitals remains poorly understood.

Because whole-genome sequencing (WGS), particularly long-read sequencing, can offer insights into bacterial relationships both at core-genome and plasmid levels, we tested its utility, using VIM-CPE as example, to investigate plasmid and CPE spread in a hospital beyond outbreaks.

We included inpatient episodes from 2018 to 2021 involving blaVIM-bearing CPE isolates. Short- and long-read WGS data were combined with patient movement information to identify genomically related hospital-acquired VIM-CPE and putative transmission routes.

Among 43 included inpatient episodes, 27 isolates were hospital-acquired, with 23 genomically related based on core-genome or plasmid analyses. For 14 of these 23 isolates, patient movement data supported suspected transmission events. Plasmid and core-genome level analyses revealed that most transmission events did not temporally concur, occurring over up to 33 months. Thus, conventional infection tracing methods focusing on concurrent spatiotemporal contact missed a substantial proportion of transmission events.

With our findings, we advocate for broader epidemiological investigations of temporal connections if genomic data suggest relatedness. We emphasise considering plasmid transfer alongside analyses of core-genome relatedness of bacteria beyond patient contact events to study CPE and resistance spread, and guide infection control strategies.

Staphylococcus haemolyticus (SH) is an opportunistic pathogen associated with nosocomial infections, particularly bacteraemia in neonates. Epidemiological trends and genetic diversity of these infections worldwide are largely unknown.

To investigate an increase in SH vascular catheter-related bacteraemia in neonates and describe the molecular epidemiology in France between 2019 and 2023.

We analysed clinical and microbiological surveillance data from the French national surveillance network for central catheter-related (venous and umbilical) infections between 2019 and 2023. We also performed genomic and phylogenetic analyses of 496 strains isolated both inside (n = 383 from neonates, staff and environmental samples) and outside (n = 113 from adults) the neonatal intensive care unit (NICU) settings.

The proportion of SH among the 474 reported cases of nosocomial bacteraemia increased from about 20% to 30% over 5 years, mainly affecting very low birth weight preterm neonates (≤ 1,500 g). The ST29 sequence type (ST) not prevalent in previous studies was predominant, accounting for 74% of NICU strains. ST29 was characterised by phenotypic multidrug resistance to at least six classes of antibiotics (oxacillin, quinolones, gentamicin, cotrimoxazole, clindamycin and rifampicin), which distinguished it with good sensitivity and specificity from other prevalent multidrug-resistant STs identified (ST1 and ST25). ST29 strains more frequently harboured the drfG, vga-LC and mupA genes and a triple point mutation (D471E, I527M and S532N) in the rpoB gene.

The present study highlights the success of a highly resistant ST29 lineage in French NICUs mainly affecting very low birth weight premature neonates.

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.