Therapeutic Drug Monitoring of Tacrolimus in Tunisian Renal Transplant Patients during the Tuberculosis Infection: A Retrospective, Observational, Single-centre Analysis.

Tuberculosis is a challenge in organ transplantation due to the interaction between Anti- Tuberculosis Treatment (ATT) and immunosuppressive drugs, such as Tacrolimus (TAC). This study aimed to assess this interaction and discuss the guidelines used in this specific case. METHODS: A retrospective, observational, single-center analysis was performed at the Department of Clinical Pharmacology (National Centre of Pharmacovigilance, Tunisia). We analyzed the database of patients who received TAC from 2009 until 2018. We included samples provided from renal transplant patients infected by Mycobacterium tuberculosis after transplantation. Trough blood levels (C0) were determined using an immunoassay analyzer. The Therapeutic Range (TR) of TAC was considered between 5 and 10 ng/mL. Pharmacokinetic parameters were compared between the period of co-administration of TAC/ATT (period A) and the period during which patients received only TAC (period B). RESULTS: Seven renal transplant patients treated by TAC were included. 41 samples were analyzed (16; period A, 25; period B). Only 6 % of C0 values were found within TR during period A, while this rate was 44% during period B. During period A, 88% of TAC C0 was under the lower limit of TR, indicating a high risk of transplant rejection. The mean C0 and C0/D were significantly lower during period A (3.11±1.53 ng/mL vs 7.11 ± 3.37 ng/mL; p = 0.001 and 33.06 ± 24.89 vs 83.14 ± 44.46; p = 0.0006, respectively), without difference in doses between periods. CONCLUSION: Considering the results of this study, clinicians are suggested to monitor TAC closely in this particular circumstance.

Phylogenetic and amino acid signature analysis of the SARS-CoV-2s lineages circulating in Tunisia.

Since the beginning of the Coronavirus disease-2019 pandemic, there has been a growing interest in exploring SARS-CoV-2 genetic variation to understand the origin and spread of the pandemic, improve diagnostic methods and develop the appropriate vaccines. The objective of this study was to identify the SARS-CoV-2s lineages circulating in Tunisia and to explore their amino acid signature in order to follow their genome dynamics. Whole genome sequencing and genetic analyses of fifty-eight SARS-CoV-2 samples collected during one-year between March 2020 and March 2021 from the National Influenza Center were performed using three sampling strategies.. Multiple lineage introductions were noted during the initial phase of the pandemic, including B.4, B.1.1, B.1.428.2, B.1.540 and B.1.1.189. Subsequently, lineages B1.160 (24.2%) and B1.177 (22.4%) were dominant throughout the year. The Alpha variant (B.1.1.7 lineage) was identified in February 2021 and firstly observed in the center of our country. In addition, A clear diversity of lineages was observed in the North of the country. A total of 335 mutations including 10 deletions were found. The SARS-CoV-2 proteins ORF1ab, Spike, ORF3a, and Nucleocapsid were observed as mutation hotspots with a mutation frequency exceeding 20%. The 2 most frequent mutations, D614G in S protein and P314L in Nsp12 appeared simultaneously and are often associated with increased viral infectivity. Interestingly, deletions in coding regions causing consequent deletions of amino acids and frame shifts were identified in NSP3, NSP6, S, E, ORF7a, ORF8 and N proteins. These findings contribute to define the COVID-19 outbreak in Tunisia. Despite the country's limited resources, surveillance of SARS-CoV-2 genomic variation should be continued to control the occurrence of new variants.

[Antiepileptic drugs administration by nasogastric tube in comatose patients]. / Modalités d'administration des antiépileptiques par sonde nasogastrique chez des patients comateux : étude des connaissances, attitudes et pratiques.

AIM: To evaluate the modalities of administration of antiepileptic drugs (AED) with nasogastric tube (NGT) by nurses and to draw up recommendations. METHODS: Our study consisted on investigating the modalities of administration of AED's with NGT by nurses during four months. We prepared 10 questions including demographic information. Participation was voluntary and anonymous. The questionnaire was distributed in seven intensive care departments after authorization of each head of the department. Thus, 45 nurses were included. RESULTS: Nurses sex ratio was 1.5 and mean age was 31 years (25 to 37 years). Among the nurses, 60% mentioned that the NGT were silicone made and 4% that they were PVC made. The mean duration before replacing the NGT was thought to be 5±3 days. Among the nurses, 91% affirmed to clear the NGT after each use. All the nurses had agreed that the solid form is the most commonly used pharmaceutical form in the NGT. AED were associated with the enteral feeding solution in 56%. The AED should be crushed before administration for 98% of the nurses even in case of polymedication. Among them, 62% recommended to crush all of the associated drugs together. Before introducing the AED into the NGT, 93% of the nurses reported mixing with tap water. We have noticed that 62% of nurses felt the need to improve their knowledge AED administration with NGT. CONCLUSION: To optimize AED therapy, modalities of administration by NGT in epileptic comatose patients should be enhanced.