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Abstract Details

Safety and tolerability of adjunctive linezolid with high or standard dose rifampin for the treatment of adults with HIV-associated tuberculous meningitis in Uganda: preliminary findings from the ALTER trial
Infectious Disease
S25 - Infectious Disease: Clinical Clues and Management (1:24 PM-1:36 PM)
003

Better treatments are needed for tuberculous meningitis (TBM), which leads to mortality in excess of 50%. Linezolid penetrates into cerebrospinal fluid and is effective against TB. Little is known about its use in often critically ill TBM patients.

To analyze preliminary safety data from the Adjunctive Linezolid for the Treatment of TubERculous Meningitis (ALTER) trial, a phase II trial of high or standard-dose rifampin with or without linezolid 1200 mg for the first 4 weeks of treatment on a backbone of isoniazid, pyrazinamide, and ethambutol.

 

Persons with HIV (PWH) with definite or suspected TBM were recruited from a rural hospital in southwestern Uganda. Participants were seen on day 2, weeks 1, 2, 4, 8, 12, 18, and 24 for symptom assessment, medication adherence, physical examination, visual testing, neuropathy screening, and/or safety labs.  

Of 23 participants enrolled (52% women, mean age 37 years, 78% with moderate to severe TBM grade), 12 were allocated to linezolid. Median CD4 count was 150 cells/mm3, (IQR 81-331) and 7 were on anti-retroviral therapy (ART). Twelve serious adverse events (SAEs) occurred, 6 among those on linezolid. The six included, sepsis (n=2), aspiration pneumonia (n=1), ART-related Stevens-Johnson syndrome (n=1), dehydration (n=1), and hyponatremia (n=1). Seven participants died, 2 on linezolid. No SAE was determined to be related to linezolid. No participants required linezolid discontinuation or dose reduction. Three participants developed >grade 3 hyponatremia. No >grade 3 anemia, thrombocytopenia, or neutropenia occurred. Mild grade 1 or 2 neuropathy symptoms were reported, more commonly among linezolid recipients (55% versus 0%, p=0.025), but resolved after treatment ended.

In this preliminary analysis, linezolid was generally safe and well tolerated in TBM patients. Data from the completed trial will increase the power to determine if linezolid is safe to use with high and standard dose rifampin in PWH and TBM.

Authors/Disclosures
Felicia Chow, MD (Zuckerberg San Francisco General Hospital)
PRESENTER
Dr. Chow has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Medicolegal consulting. The institution of Dr. Chow has received research support from NIH.
Freddie Mukasa Kibengo, MD (MRC/UVRI & LSHTM Uganda Research Unit) Dr. Kibengo has nothing to disclose.
Anita Kabarambi, MD (MRC/UVRI and LSHTM Uganda Research Unit) Dr. Kabarambi has nothing to disclose.
Paddy Kafeero, Other (MRC/UVRI & LSHTM Uganda Research Unit) Mr. Kafeero has nothing to disclose.
Muhumuza Patrick, MD Dr. Patrick has nothing to disclose.
Maria Assumpta Nakimbugwe, MBBS (MRC/UVRI and LSHTM Uganda Research Unit) Dr. NAKIMBUGWE has nothing to disclose.
Anthony Ssemaganda, Sr., RN (Medical Research Council) Mr. Ssemaganda has nothing to disclose.
Colman Tayebwa, RN (MRC/UVRI &LSHTM) Mr. Tayebwa has nothing to disclose.
Payam Nahid, MD,Other (UCSF) The institution of Dr. Nahid has received research support from NIH .
Fiona Cresswell The institution of Fiona Cresswell has received research support from Janssen.