Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Spontaneous Spinal Epidural Hematoma in a Patient on Apixaban for Nonvalvular Atrial Fibrillation

Background. With the rise in the use of direct oral anticoagulants (DOACs), more hemorrhagic complications are being encountered. Since the first description of a case of spontaneous spinal epidural hematoma (SSEH) related to the utilization of DOACs in 2012, there have been few reports describing a similar association. However, no cases so far have reported an association between SSEHs and apixaban. Case Description: A 76-year-old lady, with a history of nonvalvular atrial fibrillation, presented with a new onset of progressive left lower and upper extremity weakness. She reported back pain and numbness in the left leg up to the knee along with numbness in the left arm up to the shoulder. A CT scan of the neck was suggestive of an epidural hematoma extending from C2-C3 level to C6-C7. As the patient was on apixaban at the time, surgical treatment was delayed for two days to decrease the risk of intraoperative bleeding. Nine days later, she was discharged. Her physical exam was almost unchanged from that on presentation, except for resolution of pain and minimal improvement in motor power in her left lower extremity from 1/5 to 2/5 distally. Conclusions. Spinal hematomas represent surgical emergencies with earlier intervention portending better outcome. Based on the few case reports that point to DOACs as a potential culprit, it appears that a high suspicion index resulting in earlier SSEH diagnosis and intervention is crucial for improved neurological outcome and recovery. Prompt diagnosis remains a challenge, especially that SSEH can mimic cerebrovascular accidents