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The genomic comparison of two Klebsiella michiganensis clinical isolates recovered from the same patient, one resistant to piperacillin-tazobactam and intermediate to cefotaxime, the other resistant to ceftazidime but susceptible to piperacillin-tazobactam, revealed one mutation in the bla OXY-1-24 gene accounting for a L169M substitution in the Ω loop. Cloning experiment in Escherichia coli demonstrated the contribution of this mutation to the hydrolysis spectrum extension towards ceftazidime and cefepime, whereas the resistance to piperacillin-tazobactam was reduced. To the best of our knowledge, this study shows for the first time that ceftazidime resistance can occur in vivo from OXY-1 precursor by structural alteration., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Group B Streptococcus (GBS) is the leading cause of invasive infections in newborns. The prevention of GBS neonatal disease relies on the administration of an intrapartum antibiotic prophylaxis to GBS-colonized women. In recent years, rapid intrapartum detection of GBS vaginal colonization using real-time nucleic acid amplification tests (NAATs) emerged as an alternative to antenatal culture screening methods., Methods: We compared the performances of two loop-mediated isothermal amplification (LAMP) tests, the Ampliflash® GBS and the PlusLife® GBS tests, to standard culture for GBS detection in vaginal specimens from pregnant women. The study was conducted from April to July 2023 in a French hospital of the Paris area., Results: A total of 303 samples were analyzed, including 85 culture-positive samples (28.1%). The Ampliflash® GBS test and the PlusLife® GBS tests gave a result for 100% and 96.3% tests, respectively. The performances of the tests were as follows: sensitivity 87.1% (95% confidence interval (CI) 78.3-92.6) and 98.7% (95% CI 93.0-99.8), specificity 99.1% (95% CI 96.7-99.8), and 91.9% (95% CI 87.3-95.0), respectively. False negative results of the Ampliflash® GBS test correlated with low-density GBS cultures. Time-to-results correlated with GBS culture density only for the PlusLife® GBS test (p < 0.001)., Conclusion: Both techniques provide excellent analytical performances with high sensitivity and specificity together with a short turnaround time and results available in 10 to 35 min. Their potential to further reduce the burden of GBS neonatal disease compared with antenatal culture screening needs to be assessed in future clinical studies., (© 2024. The Author(s).)

Introduction: Tacrolimus, exhibits interindividual pharmacokinetic variability and a narrow therapeutic index. The influence of the CYP3A5 6986A>G single nucleotide polymorphism (SNP) on this variability remains a topic of debate., Aim: To assess the impact of the aforementioned SNP on tacrolimus area under curve (AUC0-12h), adverse drug reactions (ADRs), and kidney graft outcomes., Methods: Blood samples were collected from Tunisian kidney transplants over a five-year period during either the early (<3 months) or late (>3 months) post-transplant phases. Through blood concentration (C0) and AUC0-12h of tacrolimus were measured. Patients were prospectively followed to assess graft outcomes. Polymerase chain reaction of restriction fragment length polymorphism was used for CYP3A5 6986A>G genotyping., Results: Fifty Tunisian kidney recipients receiving tacrolimus were enrolled in the study. Acute and chronic graft rejections were observed in eight and three patients, respectively. Twenty-one patients (42%) reported ADRs. C0 and AUC0-12h, showed a significant difference between CYP3A5*1 carriers (mean C0=4 ng.mL-1 and AUC0-12h=94.37 ng.h.mL-1) and CYP3A5*3/3 or poor metabolizers carriers (mean C0=7.45 ng.mL-1; AUC0-12h=151.27 ng.h.mL-1) (p=0.0001; p=0.003, respectively). Supratherapeutic tacrolimus levels were significantly more common in poor metabolizers (p=0.046; Odds-ratio =1.3; confidence interval 95% [1.12-1.66]). The impact of SNP was significant on C0, AUC0-12h, C0/Dose and AUC0-12h/Dose, only in the late phase (p=0.01, 0.002, 0.012, 0.003 respectively)., Conclusion: CYP3A5*3 variant was significantly associated with tacrolimus pharmacokinetics but had no impact on graft outcomes.

Aims: This study aims to determine whether a modification in Fc-γ receptors' (FcgRs) affinity to Fc portion, caused by single nucleotide polymorphisms such as rs1801274-R131H FcgRIIa, rs396991-F158V FcgRIIIa and NA1/NA2-FcgRIIIb, might impact clearance of therapeutic monoclonal antibodies and thus serum drug levels and the development of anti-drug antibodies., Methods: A cross sectional, multicentral and noninterventional study was conducted in Tunisian RA patients treated with rituximab (RTX), etanercept (ETA), infliximab (IFX) and adalimumab (ADL). Serum drug level (SDL) of the different biologics and ADA against them were measured. All patients were genotyped for the 3 FcgR single nucleotide polymorphisms., Results: A total of 81 patients were included: 47 were under tumour necrosis factor inhibitors (18 ETA, 13 ADL and 16 IFX), and 34 were under RTX. Regardless of the type of biotherapy, SDL was in therapeutic range, in 35 patients (43.2%), of whom only 1 was treated with RTX. Fourteen patients (22.2%) developed ADA, but none of the patients treated with ETA had detectable ADA levels. There was no association between SDL positivity and FcgR polymorphisms. However, the high affinity FcgR2A 131 H/H receptor was statistically more prevalent in patients with detectable ADA treated with ADL, IFX and RTX (P = .018). The same result was obtained in the monoclonal antibody tumour necrosis factor inhibitor subgroup (n = 29, P = .022) as well as in patients treated only with IFX (n = 16, P = .029)., Conclusion: Our work supports the hypothesis of an impact of FcgR single nucleotide polymorphisms on biologics' immunogenicity, particularly FcgR R131H polymorphism, but further studies with larger cohorts need to be undertaken to confirm these results., (© 2023 British Pharmacological Society.)

Background: This trial aimed to assess the efficacy of Atorvastatin reloading on the prevention of Contrast-induced nephropathy (CIN) in patients pre-treated with this statin and undergoing coronary catheterization., Methods: This was a prospective randomized controlled study including patients on chronic atorvastatin therapy. We randomly assigned the population to the Atorvastatin Reloading group (AR group), by reloading patients with 80 mg of atorvastatin one day before and three days after the coronary procedure, and the Non-Reloading group (NR group), including patients who received their usual dose without a reloading dose. The primary endpoints were the incidence of cystatin (Cys)-based CIN and Creatinine (Scr)-based CIN. The secondary endpoints consisted of the changes in renal biomarkers (Δ biomarkers) defined as the difference between the follow-up level and the baseline level., Results: Our population was assigned to the AR group (n = 56 patients) and NR group (n = 54 patients). The baseline characteristics of the 2 groups were similar. Serum creatinine (SCr)-based CIN occurred in 11.1% in the NR group, and in 8.9% in the AR group without any significant difference. Cys-based CIN occurred in 37% in the NR group and 26.8% in the AR group without any significant difference. The subgroup analysis showed that high dose reloading had significantly reduced the CYC-based CIN risk in patients with type 2 diabetes (43.5% vs 18.8%, RR = 0.43. CI 95% [0.18-0.99])). The comparison of "Δ Cystatin" and Δ eGFR between the AR and NR groups didn't show any significant difference. However, cystatin C had significantly increased between baseline and at 24 hours in the NR group (0.96 vs 1.05, p = 0.001), but not in the AR group (0.94 vs 1.03, p = 0.206)., Conclusions: Our study did not find a benefit of systematic atorvastatin reloading in patients on chronic atorvastatin therapy in preventing CIN. However, it suggested that this strategy could reduce the risk of CyC-based CIN in diabetic type 2 patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hammami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Carbamazepine is an anticonvulsant largely used in the treatment of epilepsy. The use of generic antiepileptic drugs (AEDs) is controversial because of the eventual possibility to loss seizures control. The aim of our study was to compare the concentration over dose ratio of two products containing carbamazepine, the innovator (Tégrétol®-NOVARTIS) and the generic (Taver®-MEDOCHEMIE)., Methods: It is a retrospective study (2009-2016) including 32 patients treated with carbamazepine. Patients were treated initially by innovator then switched to generic or vice versa. All patients have at least one level of carbamazepine plasma concentration (C 0 ) with the innovator or the generic formulation. Monitoring of carabamazepine was made using immunoassay method (ARCHITECT-ABOTT®)., Results: The mean age of our patients was 28.4 years and ranged from 2 to 55 years. The sex ratio M/F was 1.46. The mean ratio C 0 /dose for the innovator group was 0.723 (min/max: 0.017/1.73), and the mean ratio C 0 /dose for the generic group was also 0.607 (min/max: 0.064/1.68). There was no statistically significant difference between both groups (P=0.16)., Conclusion: Our results confirm the difference between the innovator and the generic formulation of carbamazepine. So, switching from innovator to generic seems to be safe and exposure to carbamazepine remains the same., (Copyright © 2022 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)