Long-term plasma pharmacokinetics of bedaquiline for multidrug- and extensively drug-resistant tuberculosis.

SETTING: Bedaquiline (BDQ) has been approved for the treatment of multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB). For many patients treatment is prolonged beyond the recommended 6 months. The long-term pharmacokinetics of BDQ have yet to be elucidated. OBJECTIVE: To evaluate plasma concentrations of BDQ during treatment and its elimination after treatment discontinuation. DESIGN: This was a retrospective study conducted in two units in France that provide treatment for MDR/XDR-TB. Sociodemographic, clinical, biological and therapeutic parameters were collected from patients currently or formerly treated with BDQ. Plasma concentrations of BDQ and its active M2 (N-desmethyl) metabolite were determined using ultra-performance liquid chromatography with tandem mass spectrometry. RESULTS: Thirteen patients were recruited (35 samples): 10 (31 samples) during BDQ treatment and 3 (4 samples) after BDQ discontinuation. The median duration of treatment with BDQ was 11 months (interquartile range [IQR] 8-14). During treatment, the median plasma BDQ concentrations and M2 were respectively 1264 ng/ml (IQR 910-2244) and 252 ng/ml (IQR 134-290). In one patient, BDQ was detected in the plasma 200 days after treatment discontinuation (528 ng/ml). CONCLUSION: BDQ and M2 plasma concentrations were consistent with good drug efficacy/safety profiles, suggesting good treatment adherence with no relevant drug interactions. The long-term plasma detectability of BDQ after treatment discontinuation may raise the spectre of the emergence of resistance.

[Diagnostic issues of lymphogranuloma venereum: A case series of 5 patients]. / Diagnostic de la lymphogranulomatose vénérienne : à propos d'une série de 5 cas.

INTRODUCTION: Lymphogranuloma venereum (LG) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis L serovar. METHODS: These five consecutive cases aim to highlight the risk of LG misdiagnosis, in case of initial presentation with isolated inguinal adenitis. RESULTS: Five men (mean age: 30±7 years) were seen in an internal medicine department, for inguinal adenopathy. One patient had clinical signs of urethritis. None presented an associated rectitis. Three patients had a history of STI, and two had a discovery of related HIV disease. Urinary polymerase chain reaction (PCR) was positive for the symptomatic patient and negative for the others. Lymph node PCR was positive in all patients within a L2b serotype (searched in 4 out of 5 cases). CONCLUSION: LG should be evoked in any patient with inguinal adenomegaly, particularly in case of STI history or risk factors. Negativity of urinary PCR should lead to further investigations, essentially a lymph node cytopuncture to evidence C. trachomatis.