Control of Mycobacterium tuberculosis transmission in high-income healthcare settings and in low tuberculosis (TB) prevalence countries remains a public health priority given the constant changes in M. tuberculosis epidemiology worldwide. Though Europe is a low prevalence area [1], TB burden among precarious and migrant populations contributes to this evolving landscape, as addressed by the action framework towards TB elimination [2]. At the core of the national healthcare system, tertiary care hospitals manage both patients with greater susceptibility to TB, and patients with complex and/or advanced TB disease. Key measures for TB control rely on enabling linkage of cases and identification of transmission chains, often supported by molecular survey tools [3,4]. This is achieved by highlighting matched genotypes through a population-based systematic molecular TB survey in order to uncover outbreaks, even between apparently unrelated cases [5]. On that basis, further investigations can be triggered to understand the circumstances of transmission. In case of healthcare-related transmission, the origin of TB exposure is difficult to track as clinical disease develops months or years after patient discharge [6]. Therefore, understanding nosocomial TB transmission is essential for implementing control measures preventing such events. Herein, we bring evidence of the usefulness of molecular survey programmes to detect unsuspected TB transmission events among highly susceptible populations, and from a multidrug-resistant (MDR)-TB patient to a community-based individual. Subsequent corrective interventions implemented to prevent further nosocomial TB transmission are also described.Since 2008, the laboratory of the Lyon University Hospital has implemented a prospective population-based survey by systematic genotyping of M. tuberculosis isolates from the surrounding geographic districts (ORAM: Observatoire Rhône-Alpes des Mycobactéries), to facilitate the reporting of clinical microbiology results from TB laboratories to an operational network including TB management and control centres, and a centralised regional health agency [7]. In addition to spoligo-and MIRU-VNTR15-typing performed as described [7], from 2016 onwards, whole genome sequencing (WGS) was implemented as previously reported [5]. Sampling and testing were performed upon diagnosis and in accordance with the French bioethics laws. Contact-tracing was conducted as recommended by the French guidelines [8].From 2008 to 2018, 3230 cases of microbiologically proven TB were recorded; 20.5% of these cases were clustered, representing 662 patients distributed in 217 clusters. Among 96 clusters (341 cases) with confirmed transmission ( patients knew each other), four were healthcare-related (transmission occurring in hospital area), representing eight patients, including a single MDR-TB transmission event (figure 1a). Among them, three cases in lung transplant recipients resulted from nosocomial transmission of drug-susceptible TB. All index cases were men aged fro...

Background Early antibiotic discontinuation according to the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations is not systematically applied in high-risk neutropenic patients with haematological malignancies. Methods A retrospective multicentre observational study was conducted over 2 years to evaluate the safety of early antibiotic discontinuation for fever of unknown origin (FUO) during neutropenia after induction chemotherapy or HSCT, in comparison with a historical cohort. We used Cox proportional hazards models, censored on neutropenia resolution, to analyse factors associated with febrile recurrence. Results Among 147 included patients in the ECIL-4 cohort, mainly diagnosed with acute leukaemia (n = 104, 71%), antibiotics were discontinued during 170 post-chemotherapy neutropenic episodes. In comparison with the historical cohort of 178 episodes of neutropenia without antibiotic discontinuation, no significant differences were observed regarding febrile recurrences [71.2% (121/170) versus 71.3% (127/178), P = 0.97], admission in ICUs [6.5% (11/170) versus 11.2% (20/178), P = 0.17], septic shock [0.6% (1/170) versus 3.9% (7/178), P = 0.07] and 30 day mortality [1.4% (2/147) versus 2.7% (4/150), P = 0.084]. In the ECIL-4 cohort, the rate of bacteraemia in case of febrile recurrence was higher [27.1% (46/170) versus 11.8% (21/178), P < 0.01] and antibiotic consumption was significantly lower (15.5 versus 19.9 days, P < 0.001). After early antibiotic discontinuation according to ECIL-4 recommendations, enterocolitis was associated with febrile recurrence [HR = 2.31 (95% CI = 1.4–3.8), P < 0.001] and stage III–IV oral mucositis with bacteraemia [HR = 2.26 (95% CI = 1.22–4.2), P = 0.01]. Conclusions After an FUO episode in high-risk neutropenia, compliance with ECIL-4 recommendations for early antibiotic discontinuation appears to be safe and mucosal damage was associated with febrile recurrence and bacteraemia. Prospective interventional studies are warranted to assess this strategy in high-risk neutropenic patients.

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