Implementation of Bedaquiline, Pretomanid, and Linezolid in the United States: Experience Using a Novel All-Oral Treatment Regimen for Treatment of Rifampin-Resistant or Rifampin-Intolerant Tuberculosis Disease.

BACKGROUND: Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring. METHODS: Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring. RESULTS: Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. CONCLUSIONS: BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible.

Paraplegia complicating percutaneous vertebroplasty for osteoporotic vertebral fracture: case report.

We report a case of spinal cord and root compression during percutaneous transpedicular polymethylmethacrylate vertebroplasty (PTPV) for a compression fracture due to osteoporosis. Sudden onset of excruciating pain in the distribution of the right sixth intercostal nerve with hyperemia along its path, prompted the interruption of the procedure. Under narcotic sedation the patient was taken to the ICU and 10mg of dexamethasone was administered intravenously. Few hours later she developed paraplegia with preservation of light touch and a CT scan and MRI showed epidural extravasation of polymethylmethacrylate with spinal cord and root compression. Surgical decompression was followed by neurological recovery. The cement could be removed after been thinned out by high speed drill, with microsurgical technique, through a wide three level laminectomy of D5 to D7. Extravasation of cement is commonly encountered in PTPV and most of the time it is asymptomatic. Root compression may require surgical intervention if nonresponsive to steroid treatment. Cord compression is less often seen and requires emergency surgery. The cement does not adhere to the duramater and it can be removed easily.

Paraplegia complicating percutaneous vertebroplasty for osteoporotic vertebral fracture: case report

Relatamos um caso de compressão medular e radicular durante vertebroplastia percutanea transpedicular com polimetilmetacrilato (VPTP) para tratamento de fratura com compressão por osteoporose. O início súbito de dor lancinante na distribuição do 6º nervo intercostal direito, com hiperemia ao longo de seu trajeto, determinou a interrupção do procedimento. Sob sedação com narcóticos, a paciente foi levada ao CTI, sendo administrados 10mg de dexametazona por via endovenosa. Após algumas horas, ela desenvolveu paraplegia com preservação do tato, e a TC e a RM mostraram extravazamento epidural de polimetilmetacrilato com compressão medular e radicular. Descompressão cirúrgica resultou em recuperação neurológica. O cimento foi removido após ter sua espessura diminuída com o uso de broca de alta rotação, usando técnica microcirúrgica através de laminectomia ampla de tres níveis de T5 a T7. Extravazamento de cimento é comumente encontrado em VPTP, sendo assintomático na maioria das vezes. Compressão radicular pode requerer intervenção cirúrgica se não responsiva ao tratamento com corticosteróides. Compressão medular é vista com menos frequência e requer cirurgia de emergência. O cimento não adere à dura-máter e pode ser removido facilmente.