Rapid resistance detection is reliable for prompt adaptation of isoniazid resistant tuberculosis management.

Objectives: Appropriate tuberculosis (TB) management requires anti-TB drugs resistance detection. We assessed the performance of rapid resistance detection assays and their impact on treatment adaptation, focusing on isoniazid resistant (Hr) TB. Methods: From 2016 to 2022, all TB cases enrolled in 3 hospitals were reviewed for phenotypic drug susceptibility testing (p-DST) and genotypic DST (g-DST) performed by rapid molecular testing, and next generation sequencing (NGS). Clinical characteristics, treatment and outcome were collected for Hr-TB patients. The concordance between g-DST and p-DST results, and delay between treatment initiation and results of g-DST and p-DST were respectively recorded to assess the contribution of DST results on Hr-TB management. Results: Among 654 TB cases enrolled, 29 were Hr-TB. Concordance between g-DST by rapid molecular methods and p-DST was 76.9 %, whilst concordance between NGS-based g-DST and p-DST was 98.7 %. Rapid resistance detection significantly fastened Hr-TB treatment adaptation (median delay between g-DST results and treatment modification was 6 days). It consisted in fluoroquinolone implementation for 17/23 patients; outcome was favourable except for 2 patients who died before DST reporting. Conclusion: Rapid resistance detection fastened treatment adaptation. Also, NGS-based g-DST showed almost perfect concordance with p-DST, thus providing rapid and safe culture-free DST alternative.

Opti-4TB: A protocol for a prospective cohort study evaluating the performance of new biomarkers for active tuberculosis outcome prediction.

Introduction: Tuberculosis (TB) treatment requires the combination of multiple anti-TB drugs during 6 months or more depending on strain drug susceptibility profile. Optimizing the monitoring of anti-TB therapy efficacy is required to provide adequate care and prevent drug resistance emergence. Moreover, accurate monitoring tools are needed for the development of strategies aiming at reducing treatment duration. Opti-4TB is a "proof of concept" study aiming at developing a blood-based monitoring of TB outcome by deciphering host immune signatures associated with latency or disease activity through the combination of "omic" methods. The primary objective is to assess the performances of new biomarkers for TB outcome prediction and to determine specific profiles associated with the outcome of treated TB patients. Methods and analysis: Opti-4TB is a prospective, single center study including adult patients hospitalized for pulmonary TB. A workflow will be set up to study the immune status of 40 TB patients and 20 controls with latent TB infection. Blood samples will be collected at four timepoints: before treatment initiation (V1), at day 15 (V2), at 2 months (V3) and at 6 months (V4). Mtb-specific immune responses will be assessed at each timepoint with three different assays: (1) A whole blood transcriptomic signature assessing the "RISK-6" score; (2) A proteomic signature based on 27 cytokines and chemokines measured in plasma; (3) An immunophenotypic monitoring of circulating T-cell subpopulations using spectral flow cytometry. This in depth characterization of Mtb-specific immune response throughout the treatment, correlated with clinical outcomes, will lay the basis for the elaboration of the most basic and universal stage-specific immune signatures associated with latency, active disease and cure. Ethics and dissemination: Ethical approval has been obtained from the institutional review board (n°69HCL18_0757). Results will be communicated at scientific meetings and submitted for publication in peer-reviewed journals. Trial registration number: NCT04271397.

Host Immunity and Francisella tularensis: A Review of Tularemia in Immunocompromised Patients.

Tularemia, caused by the bacterium Francisella tularensis, is an infrequent zoonotic infection, well known in immunocompetent (but poorly described in immunocompromised) patients. Although there is no clear literature data about the specific characteristics of this disease in immunocompromised patients, clinical reports seem to describe a different presentation of tularemia in these patients. Moreover, atypical clinical presentations added to the fastidiousness of pathogen identification seem to be responsible for a delayed diagnosis, leading to a" loss of chance" for immunocompromised patients. In this article, we first provide an overview of the host immune responses to Francisella infections and discuss how immunosuppressive therapies or diseases can lead to a higher susceptibility to tularemia. Then, we describe the particular clinical patterns of tularemia in immunocompromised patients from the literature. We also provide hints of an alternative diagnostic strategy regarding these patients. In conclusion, tularemia should be considered in immunocompromised patients presenting pulmonary symptoms or unexplained fever. Molecular techniques on pathological tissues might improve diagnosis with faster results.

Seven Years Leptospirosis Follow-Up in a Critical Care Unit of a French Metropolitan Hospital; Role of Real Time PCR for a Quick and Acute Diagnosis.

(1) Background: Leptospirosis infection can lead to multiple organ failure, requiring hospitalization in an intensive care unit for supportive care, along with initiation of an adapted antibiotic therapy. Achieving a quick diagnosis is decisive in the management of these patients. (2) Methods: We present here a review of leptospirosis cases diagnosed in the intensive care unit of our hospital over seven years. Clinical and biological data were gathered, and we compared the differences in terms of diagnostic method. (3) Results: Molecular biology method by Polymerase Chain Reaction (PCR) allowed quick and reliable diagnosis when performed in the first days after the symptoms began. Moreover, we identified that sampling blood and urine for PCR was more efficient than performing PCR on only one type of biological sample. (4) Conclusions: Our results confirm the efficiency of PCR for the quick diagnosis of leptospirosis and suggest that testing both blood and urine early in the disease might improve diagnosis.

Severe infections due to Francisella tularensis ssp. holarctica in solid organ transplant recipient: report of two cases and review of literature.

BACKGROUND: Tularemia is a rare zoonotic infection caused by bacterium Francisella tularensis. It has been well described in immunocompetent patients but poorly described in immunocompromised patients notably in solid organ transplant recipients. CASE PRESENTATIONS: We report here two cases of tularemia in solid organ transplant recipients including first case after heart transplant. We also carried out an exhaustive review of literature describing characteristics of this infection in solid organ transplant recipients.

Acute Tibial osteomyelitis caused by intraosseous access during initial resuscitation: a case report and literature review.

BACKGROUND: Intra-osseous (IO) access is recommended in cases of pre-hospital emergency or resuscitation when intravascular (IV) route is difficult or impossible. Despite recent improvement in IO devices and increasing indications, it remains rarely used in practice. Various complications have been reported but are uncommon. CASE PRESENTATION: We report a case of massive acute tibial osteomyelitis in an adult male three months after an IO catheter insertion for emergency drug infusion. We review the literature on association between IO access and acute osteomyelitis in children and adults. CONCLUSIONS: Emergency-care givers and radiologists should be informed about this infrequent complication in order to make early diagnosis and initiate adequate antibiotic therapy.