Investigation of healthcare-associated COVID-19 in a large French hospital group by whole-genome sequencing.

OBJECTIVES: Despite the quick implementation of infection prevention and control procedures and the use of personal protective equipment within healthcare facilities, many cases of nosocomial COVID-19 transmission have been reported. We aimed to estimate the frequency and impact of healthcare-associated COVID-19 (HA-COVID-19) and evaluate the contribution of whole-genome sequencing (WGS) in cluster investigation. METHODS: We estimated the frequency and mortality of HA-COVID-19 infections from September 1 to November 30, 2020, with a focus on the evolution of hospitalized community-associated COVID-19 (CA-COVID-19) cases and cases detected among healthcare workers (HCWs) within the Sorbonne University Hospital Group (Paris, France). We thoroughly examined 12 clusters through epidemiological investigations and WGS. RESULTS: Overall, 209 cases of HA-COVID-19 were reported. Evolution of HA-COVID-19 incidence closely correlated with the incidence of CA-COVID-19 and COVID-19 among HCWs. During the study period, 13.9 % of hospitalized patients with COVID-19 were infected in the hospital and the 30-day mortality rate of HA-COVID-19 was 31.5 %. Nosocomial transmission of SARS-CoV-2 led to clusters involving both patients and HCWs. WGS allowed the exclusion of one-third of cases initially assigned to a cluster. CONCLUSIONS: WGS analysis combined with comprehensive epidemiological investigations is essential to understand transmission routes and adapt the IPC response to protect both patients and HCWs.

Economic impact of an outbreak of carbapenemase producing-Enterobacteriaceae in a surgical intensive care unit.

BACKGROUND: A 15-month outbreak of carbapenemase-producing Enterobacterales (CPE) occurred in the surgical intensive care unit (SICU) of our institution. We aimed to estimate the financial impact of this outbreak from the perspective of the French public health insurance system. METHODS: The characteristics of the colonised/infected CPE patients and outbreak management according to French national guidelines were prospectively collected. Loss of productivity was assessed in terms of the reduction in total number of admissions (TNA) and discharges and in ICU length of stay (LoS). The additional financial burden associated with this outbreak was estimated by the accounting department of the hospital, including the impact of the extended LoS and restricted admissions. RESULTS: Sixteen CPE patients (19 stays) were hospitalised in the SICU (10/2016-01/2018). The median ICU LoS for the CPE cases was 17 [8-36] days versus 6.5 and 6.1 days in 2016 and 2017, respectively, for the whole SICU population. The total number of lost bed days during the outbreak was 452. The TNA dropped dramatically in 2017 (decrease of 20.6%). The estimated costs were 768,386 EUR for bed days lost; 297,176 EUR and 63,675 EUR for the extended LoS for the CPE cases and the patients on contact precautions, respectively; 34,045 EUR for staff reinforcements; 85,764 EUR for bacteriological screening tests; and 42,857 EUR for antimicrobial treatment. The total financial burden of the outbreak was 1,291,903 EUR. CONCLUSION: Management of a CPE outbreak in the SICU is associated with a huge financial burden for the unit and for the institution.

Simultaneous Hospital Outbreaks of New Delhi Metallo-ß-Lactamase-Producing Enterobacterales Unraveled Using Whole-Genome Sequencing.

Multidrug-resistant Enterobacterales, including carbapenemase producers, are currently spreading in health care facilities and the community. The Bichat Claude Bernard hospital in Paris faced a prolonged NDM-producing Enterobacterales (NDM-CPE) outbreak. Whole-genome sequencing (WGS) was performed on all isolated NDM-CPE to evaluate its benefits for outbreak surveillance and comprehension. All NDM-CPE isolates collected during the outbreak period (August 2016 to January 2018) were sequenced using the Illumina NextSeq platform. Gene content and core genomes were compared. Genomics results underwent epidemiological analysis which classified NDM-CPE cases as imported (positive sample during the 48 h after admission), hospital acquired, or uncertain. Over the epidemic period, 61 patients were colonized or infected with 81 distinct NDM-CPE isolates. Klebsiella pneumoniae was the most common species (n = 52, 64%), followed by Escherichia coli (13.5%) and other species (22.5%). In all, 43/52 (83%) K. pneumoniae isolates were clonal (≤18 single nucleotide polymorphisms [SNPs] except for three isolates) and belonged to ST307. The IncFIIK [K2:A-/B-] plasmid carrying blaNDM-1 present in all ST307 K. pneumoniae isolates was also detected in 18 other NDM-CPE isolates. Additionally, eight clonal ST144 Klebsiella oxytoca (≤18 SNPs) isolates lacking the epidemic plasmid were observed. The WGS analyses confirmed the acquired and imported cases except for two patients and resolved uncertain cases, which all turned out to be hospital acquisitions. WGS coupled with epidemiological analysis unraveled three epidemic phenomena: mainly the spread of a clonal ST307 K. pneumoniae strain and its conjugative plasmid carrying blaNDM-1 but also the unexpected clonal spread of an ST144 K. oxytoca strain. IMPORTANCE Carbapenemase-producing Enterobacterales (CPE) can spread and cause outbreaks in health care facilities, resulting in increased lengths of stay and morbidity. Control of outbreaks requires epidemiological surveillance, usually based on microbiological screening and patient follow-up. These data are sometimes insufficient to identify the routes of dissemination. There is therefore a need for more accurate tools such as whole-genome sequencing (WGS), which allows comparison of isolates but also plasmids carrying resistance with a high definition. In this work, we retrospectively sequenced the genomes of all NDM-producing Enterobacterales isolated during a prolonged NDM outbreak in our hospital. We demonstrated the value of combining WGS with epidemiological data that unveiled the multiple mechanisms of dissemination involved in the outbreak and confirmed transmission cases. This work reinforces the potential of WGS in outbreak surveillance and suggests that it could improve outbreak control if used in real time by confirming transmission cases more rapidly.

Nosocomial transmission clusters and lineage diversity characterized by SARS-CoV-2 genomes from two large hospitals in Paris, France, in 2020.

France went through three deadly epidemic waves due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing major public health and socioeconomic issues. We proposed to study the course of the pandemic along 2020 from the outlook of two major Parisian hospitals earliest involved in the fight against COVID-19. Genome sequencing and phylogenetic analysis were performed on samples from patients and health care workers (HCWs) from Bichat (BCB) and Pitié-Salpêtrière (PSL) hospitals. A tree-based phylogenetic clustering method and epidemiological data were used to investigate suspected nosocomial transmission clusters. Clades 20A, 20B and 20C were prevalent during the spring wave and, following summer, clades 20A.EU2 and 20E.EU1 emerged and took over. Phylogenetic clustering identified 57 potential transmission clusters. Epidemiological connections between participants were found for 17 of these, with a higher proportion of HCWs. The joint presence of HCWs and patients suggest viral contaminations between these two groups. We provide an enhanced overview of SARS-CoV-2 phylogenetic changes over 2020 in the Paris area, one of the regions with highest incidence in France. Despite the low genetic diversity displayed by the SARS-CoV-2, we showed that phylogenetic analysis, along with comprehensive epidemiological data, helps to identify and investigate healthcare associated clusters.

Factors responsible for Ixodes ricinus nymph abundance: Are soil features indicators of tick abundance in a French region where Lyme borreliosis is endemic?

In Europe, the hard tick Ixodes ricinus (Acari: Ixodidae) is the main vector of Lyme borreliosis spirochetes (Borrelia burgdorferi sensu lato group). A field study was conducted to evaluate the abundance of Ixodes nymphs in the French region of Alsace, where Lyme borreliosis is endemic, and to determine whether environmental factors such as soil moisture and composition may be associated with nymph abundance. In the ten sites studied, ticks were collected by drag sampling from March to October in 2013 and 2014. Temperature, relative humidity, saturation deficit, soil pH, humus composition and type of vegetation were recorded at each site. The abundance of I. ricinus was highly variable from one site to another. Inter-annual variations were also observed, since the nymph abundance were higher in 2013 than in 2014. This study shows that humus type can be indicative of nymph abundance. Three types of humus were observed: (1) moder, (2) mull, and (3) mull-moder humus. One of them, moder humus, which is characterized by a thick layer of fragmented leaves, was found in multivariate analyses to be strongly associated with the nymph abundance. This study demonstrates that factors such as saturation deficit do not suffice to explain the differences in nymph abundance among sites. The composition of the soil and especially the type of humus should also be taken into consideration when assessing acarological risk.