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. 2022 Jun 24;17(6):e0270201.
doi: 10.1371/journal.pone.0270201. eCollection 2022.

Long term outcomes of patients with tuberculous meningitis: The impact of drug resistance

Emily E Evans  1 , Teona Avaliani  2 , Mariam Gujabidze  2 , Tinatin Bakuradze  2 , Maia Kipiani  2 , Shorena Sabanadze  2 , Alison G C Smith  1 , Zaza Avaliani  2 , Jeffrey M Collins  3 , Russell R Kempker  1   3
Affiliations

Long term outcomes of patients with tuberculous meningitis: The impact of drug resistance

Emily E Evans et al. PLoS One. .

Abstract

Background: Little is known about the impact of drug-resistance on clinical outcomes among patients with tuberculosis meningitis (TBM).

Methods: A retrospective cohort study among patients treated for TBM in Tbilisi, Georgia. We performed medical chart abstraction to collect patient data. Long-term vital status was assessed using the Georgia National Death Registry. We utilized a Cox proportional-hazards model to evaluate the association of drug-resistance and mortality.

Results: Among 343 TBM suspects, 237 had a presentation consistent with TBM. Drug resistance was suspected (n = 5) or confirmed (n = 31) in 36 patients including 30 with multidrug- or rifampin-resistance and 6 with isoniazid-resistance. Thirty-four patients had HIV. The median follow-up time was 1331 days (IQR, 852-1767). Overall, 73 of 237 (30%) people died with 50 deaths occurring during and 23 after treatment. The proportion of death was higher among patients with drug-resistant vs. drug-susceptible disease (67% vs. 24%, p<0.001) and with HIV versus no HIV (59% vs 27%, p<0.001). Mortality was significantly higher in patients with drug-resistant TBM after 90 days of treatment (aHR = 7.2, CI95% [3.6-14.3], p < 0.001).

Conclusions: Mortality was high among patients with drug-resistant TBM with many deaths occurring post treatment. More effective treatment options are urgently needed for drug-resistant TBM.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flowchart of eligible and included patients treated for tuberculosis meningitis by drug-resistance pattern.
Fig 2
Fig 2
Kaplan Meier survival curves for (A) all patients treated for tuberculosis meningitis (TBM; n = 237) over the full period of observation and (B) over first 6 months. (C) Probable and definite TBM cases (n = 79) over the full period of observation and (D) over first 6 months of treatment. Mortality in persons treated for drug susceptible-TBM is depicted by the yellow line and for persons with drug resistant-TBM by the blue line. The shaded region surrounding the line depicts the 95% confidence interval of the mortality estimate.
See this image and copyright information in PMC

References

    1. Wilkinson RJ, Rohlwink U, Misra UK, van Crevel R, Mai NTH, Dooley KE, et al.. Tuberculous meningitis. Nat Rev Neurol. 2017;13(10):581–98. Epub 2017/09/09. doi: 10.1038/nrneurol.2017.120 . - DOI - PubMed
    1. Chandir S, Hussain H, Salahuddin N, Amir M, Ali F, Lotia I, et al.. Extrapulmonary tuberculosis: a retrospective review of 194 cases at a tertiary care hospital in Karachi, Pakistan. J Pak Med Assoc. 2010;60(2):105–9. Epub 2010/03/10. . - PubMed
    1. Qian X, Nguyen DT, Lyu J, Albers AE, Bi X, Graviss EA. Risk factors for extrapulmonary dissemination of tuberculosis and associated mortality during treatment for extrapulmonary tuberculosis. Emerg Microbes Infect. 2018;7(1):102. Epub 2018/06/07. doi: 10.1038/s41426-018-0106-1 ; PubMed Central PMCID: PMC5988830. - DOI - PMC - PubMed
    1. Torok ME, Nguyen DB, Tran TH, Nguyen TB, Thwaites GE, Hoang TQ, et al.. Dexamethasone and long-term outcome of tuberculous meningitis in Vietnamese adults and adolescents. PLoS One. 2011;6(12):e27821. doi: 10.1371/journal.pone.0027821 ; PubMed Central PMCID: PMC3234244. - DOI - PMC - PubMed
    1. Vinnard C, King L, Munsiff S, Crossa A, Iwata K, Pasipanodya J, et al.. Long-term Mortality of Patients With Tuberculous Meningitis in New York City: A Cohort Study. Clin Infect Dis. 2017;64(4):401–7. Epub 2016/12/09. doi: 10.1093/cid/ciw763 ; PubMed Central PMCID: PMC5850536. - DOI - PMC - PubMed

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