12 results on '"Bahr, Nathan C"'
Search Results
2. Implementation of single high-dose liposomal amphotericin B based induction therapy for treatment of HIV-associated cryptococcal meningitis in Uganda: a comparative prospective cohort study.
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Gakuru J, Kagimu E, Dai B, Okurut S, Nsangi L, Bahr NC, Okirwoth M, Namuju OC, Jarvis JN, Lawrence DS, Ahimbisibwe C, Ellis J, Tadeo KK, Boulware DR, Meya DB, and Tugume L
- Abstract
Background: In 2022, the World Health Organization (WHO) recommended a single 10mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of HIV-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda., Methods: We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022-2023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites., Results: During 2022-2023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018-2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95%CI 61.6%-76.3%) and AMBITION-cm trial participants in the intervention arm (71.7%; 95%CI 65.2%-78.8%; absolute risk difference = -3.1%; 95%CI -13.1% to 6.9%; p=.61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU/mL/day; p=.80) between groups. Among observational cohort participants discharged alive initially and for whom follow up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4/144)., Conclusion: The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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3. Comparison of early fungicidal activity and mortality between daily liposomal amphotericin B and daily amphotericin B deoxycholate among patients with HIV-associated cryptococcal meningitis.
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Kimuda S, Kwizera R, Dai B, Kigozi E, Kasozi D, Rutakingirwa MK, Tukundane A, Shifah N, Luggya T, Luswata A, Ndyetukira JF, Yueh S, Mulwana S, Wele A, Bahr NC, Meya DB, Boulware DR, and Skipper CP
- Abstract
Background: Limited data exist on the antifungal activity of daily liposomal amphotericin B with flucytosine induction regimens for cryptococcal meningitis, which are recommended in high-income countries. Liposomal amphotericin B monotherapy at 3 mg/kg previously failed to meet non-inferiority criteria compared to amphotericin B deoxycholate in its registrational clinical trial. We aimed to compare the quantitative antifungal activity and mortality between daily amphotericin B deoxycholate and daily liposomal amphotericin among persons with HIV-related cryptococcal meningitis receiving adjunctive flucytosine 100 mg/kg/day., Methods: We analyzed data from three clinical studies involving participants with HIV-associated cryptococcal meningitis receiving either daily liposomal amphotericin B at 3 mg/kg/day with flucytosine (N = 94) or amphotericin B deoxycholate at 0.7-1.0 mg/kg/day with flucytosine (N = 404) as induction therapy. We compared participant baseline characteristics, CSF early fungicidal activity (EFA), and 10-week mortality., Results: We included 498 participants in this analysis, of whom 201 had available EFA data (N = 46 liposomal amphotericin; N = 155 amphotericin deoxycholate). Overall, there is no statistical evidence that the antifungal activity of liposomal amphotericin B (mean EFA = 0.495 log10 CFU/mL/day; 95%CI, 0.355-0.634) differ from amphotericin B deoxycholate (mean EFA = 0.402 log10 CFU/mL; 95%CI, 0.360-0.445) (P = 0.13). Mortality at 10 weeks trended lower for liposomal amphotericin (28.2%) vs amphotericin B deoxycholate (34.6%) but was not statistically different when adjusting for baseline characteristics (adjusted Hazard Ratio = 0.74; 95%CI, 0.44-1.25; P = 0.26)., Conclusions: Daily liposomal amphotericin B induction demonstrated a similar rate of CSF fungal clearance and 10-week mortality as amphotericin B deoxycholate when combined with flucytosine for the treatment of HIV-associated cryptococcal meningitis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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4. Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.
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Pasqualotto AC, Lana DD, Godoy CSM, Leitão TDMJS, Bay MB, Damasceno LS, Soares RBA, Kist R, Silva LR, Wiltgen D, Melo M, Guimarães TF, Guimarães MR, Vechi HT, de Mesquita JRL, Monteiro GRG, Adenis A, Bahr NC, Spec A, Boulware DR, Israelski D, Chiller T, and Falci DR
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- Humans, Antifungal Agents adverse effects, HIV, Prospective Studies, Histoplasmosis drug therapy, Acquired Immunodeficiency Syndrome drug therapy, Drug-Related Side Effects and Adverse Reactions
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Background: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens., Methods: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14., Results: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82)., Conclusions: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access., Competing Interests: Potential conflicts of interest. A. C. P. has received research grants from Gilead, Pfizer, and IMMY (who also provided diagnostic tests for the study); he reports travel support from Pfizer, United Medical, and Merck; participation on a Data Safety Monitoring or Advisory Board for Gilead; and payment or honoraria for talks on behalf of Gilead, United Medical, Pfizer, Merck, Sharp & Dohme (MSD), IMMY, Astra-Zeneca, and Astellas Pharma. D. R. F. has received research grants and consulting fees from Pfizer, MSD, and Gilead Sciences. D. R. F. also reports travel support from Pfizer, United Medical, Janssen, and Merck; participation on Data Safety Monitoring or Advisory Boards for Gilead Sciences, Merck, and GlaxoSmithKline (GSK); has given paid lectures on behalf of United Medical, Pfizer, Janssen, GSK, Merck, Gilead Sciences, Knight Pharmaceuticals, and MSD, and received non-financial research support from IMMY. N. C. B. reports grants from National Institutes of Health (NIH) (grant numbers NINDS K23 NS110470 and NIAID R01 AI170158) and Karyopharm therapeutics (Site PI for 2020 clinical trial; funds paid to institution); and participation as chair of the Data and Safety Monitoring Board (DSMB) for NCT04335123. A. S. reports grants from Astellas and Mayne, and consulting fees from GSK and F2G. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2023
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5. Out of Bounds: A Critical Appraisal of the Changing Geography of the Endemic Mycoses.
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Schwartz IS and Bahr NC
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- Humans, United States, Geography, Mycoses epidemiology
- Abstract
Competing Interests: Potential conflicts of interest. N. C. B. received grants from the National Institutes of Health: NINDS (K23 NS110470) and NIAID (R01AI170158) and served as the Data Safety Monitoring Board Chair for ClinicalTrials.gov (NCT04335123). N. C. B. also served as the Karyopharm site principal investigator for a study of Selinexor for COVID-19 (funds were paid to the author's institution in 2020). The author: No reported conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
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- 2023
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6. Recurrence of Symptoms Following Cryptococcal Meningitis: Characterizing a Diagnostic Conundrum With Multiple Etiologies.
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Bahr NC, Skipper CP, Huppler-Hullsiek K, Ssebambulidde K, Morawski BM, Engen NW, Nuwagira E, Quinn CM, Ramachandran PS, Evans EE, Lofgren SM, Abassi M, Muzoora C, Wilson MR, Meya DB, Rhein J, and Boulware DR
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- Humans, Antifungal Agents therapeutic use, Recurrence, Meningitis, Cryptococcal diagnosis, Meningitis, Cryptococcal drug therapy, AIDS-Related Opportunistic Infections drug therapy, HIV Infections complications, HIV Infections drug therapy
- Abstract
Background: Cryptococcal meningitis is a common cause of AIDS-related mortality. Although symptom recurrence after initial treatment is common, the etiology is often difficult to decipher. We sought to summarize characteristics, etiologies, and outcomes among persons with second-episode symptomatic recurrence., Methods: We prospectively enrolled Ugandans with cryptococcal meningitis and obtained patient characteristics, antiretroviral therapy (ART) and cryptococcosis histories, clinical outcomes, and cerebrospinal fluid (CSF) analysis results. We independently adjudicated cases of second-episode meningitis to categorize patients as (1) microbiological relapse, (2) paradoxical immune reconstitution inflammatory syndrome (IRIS), (3) persistent elevated intracranial pressure (ICP) only, or (4) persistent symptoms only, along with controls of primary cryptococcal meningitis. We compared groups with chi-square or Kruskal-Wallis tests as appropriate., Results: 724 participants were included (n = 607 primary episode, 81 relapse, 28 paradoxical IRIS, 2 persistently elevated ICP, 6 persistent symptoms). Participants with culture-positive relapse had lower CD4 (25 cells/μL; IQR: 9-76) and lower CSF white blood cell (WBC; 4 cells/μL; IQR: 4-85) counts than paradoxical IRIS (CD4: 78 cells/μL; IQR: 47-142; WBC: 45 cells/μL; IQR: 8-128). Among those with CSF WBC <5 cells/μL, 86% (43/50) had relapse. Among those with CD4 counts <50 cells/μL, 91% (39/43) had relapse. Eighteen-week mortality (from current symptom onset) was 47% among first episodes of cryptococcal meningitis, 31% in culture-positive relapses, and 14% in paradoxical IRIS., Conclusions: Poor immune reconstitution was noted more often in relapse than IRIS as evidenced by lower CSF WBC and blood CD4 counts. These easily obtained laboratory values should prompt initiation of antifungal treatment while awaiting culture results., Clinical Trials Registration: NCT01802385., Competing Interests: Potential conflicts of interest. N. C. B. reports Data and Safety Monitoring Board (DSMB) participation for an investigator-initiated trial of losartan safety in coronavirus disease 2019 (COVID-19) [Bengston CD, Montgomery RN, Nazir U et al. Front Med (Lausanne). 2021], doi: 10.3389/fmed.2021.630209 and grants or contracts from NIH NINDS (K23 NS110470). D. R. B. and C. P. S. report grants or contracts from NIH NIAID (T32 AI055433). C. P. S. also reports grants or contracts from NIH NIAID (T32AI055433). J. R. reports grants or contracts from NIH-FIC (K01TW010268). M. A. reports grants or contracts from NINDS/FIC (D43TW009345), NIH-NINDS (K23 NS122601), and NIH NIAID (T32 AI055433). S. M. L. reports grants or contracts from NINDS/FIC (D43TW009345) and NIH National Institute of Mental Health (NIMH) (K23 MH121220). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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7. Fujifilm SILVAMP TB LAM Assay on Cerebrospinal Fluid for the Detection of Tuberculous Meningitis in Adults With Human Immunodeficiency Virus.
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Quinn CM, Kagimu E, Okirworth M, Bangdiwala AS, Mugumya G, Ramachandran PS, Wilson MR, Meya DB, Cresswell FV, Bahr NC, and Boulware DR
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- Adult, Cerebrospinal Fluid, Diagnostic Tests, Routine, HIV, Humans, Lipopolysaccharides, Prospective Studies, Sensitivity and Specificity, Uganda, HIV Infections complications, Mycobacterium tuberculosis, Tuberculosis, Meningeal diagnosis
- Abstract
Background: Tuberculous meningitis (TBM) has a high fatality rate, with inadequate diagnostic tests being a major contributor. The rollout of Xpert MTB/Rif and Xpert MTB/RIF Ultra (Xpert Ultra) have improved time-to-diagnosis with sensitivities similar to culture, yet test availability and sensitivity are inadequate. The TB lipoarabinomannan lateral flow assay (AlereLAM) offers ease of use, but its low sensitivity in cerebrospinal fluid (CSF) limits clinical utility for TBM. The Fujifilm SILVAMP TB LAM (FujiLAM) assay has excellent sensitivity in urine, but performance on cerebrospinal fluid is uncertain., Methods: We conducted a prospective cohort study at Kiruddu National Referral Hospital in Kampala, Uganda, enrolling patients suspected to have TBM. CSF was tested using AlereLAM, Xpert Ultra, culture, and FujiLAM. Results were compared with 2 reference standards: probable and definite TBM or definite TBM alone by the uniform TBM case definition., Results: Of 101 patients enrolled (95/101 HIV-positive), 34 had definite TBM and 24 had probable TBM. FujiLAM sensitivity on CSF was 52% (30/58) for definite or probable TBM compared with 55% (32/58) for Xpert Ultra. AlereLAM had lower sensitivity than FujiLAM in the subgroup of patients tested with both assays (14% [4/28] vs 50% [14/28]; P < .01). FujiLAM specificity was 98% (42/43) for patients without probable or definite TBM., Conclusions: FujiLAM showed higher sensitivity than AlereLAM, with sensitivity potentially approaching that of Xpert Ultra. FujiLAM could improve time-to-treatment-initiation, especially in settings where the more technical Xpert Ultra system might not be feasible. Large confirmatory studies are needed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2021
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8. Cerebrospinal Fluid Bacillary Load by Xpert MTB/RIF Ultra Polymerase Chain Reaction Cycle Threshold Value Predicts 2-Week Mortality in Human Immunodeficiency Virus-Associated Tuberculous Meningitis.
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Martyn EM, Bangdiwala AS, Kagimu E, Rutakingirwa MK, Kasibante J, Okirwoth M, Stead G, Wadda V, Pullen MF, Bold TD, Meya DB, Boulware DR, Bahr NC, and Cresswell FV
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- Diagnostic Tests, Routine, HIV, Humans, Molecular Diagnostic Techniques, Polymerase Chain Reaction, Sensitivity and Specificity, HIV Infections complications, Mycobacterium tuberculosis genetics, Tuberculosis, Meningeal diagnosis
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Background: The World Health Organization recommends GeneXpert MTB/RIF Ultra (Xpert Ultra), a fully automated polymerase chain reaction (PCR) assay, as the initial tuberculous meningitis (TBM) diagnostic test. The assay's PCR cycle threshold (Ct) values represent the number of PCR cycles required for probe signal to be detected (low Ct value = high bacillary load) and may approximate tuberculosis (TB) bacillary load. We measured the relationship between cerebrospinal fluid (CSF) TB bacillary load with mortality., Methods: We prospectively enrolled 102 human immunodeficiency virus (HIV)-positive Ugandans with probable or definite TBM from April 2015 to August 2019. Xpert Ultra Ct tertiles and semi-quantitative categories were separately analyzed as predictors of 2-week mortality. We investigated associations between Ct and baseline clinical and CSF parameters., Results: Subjects with Ct values in the low tertile (ie, high bacillary load) had 57% 2-week mortality-worse than the intermediate (17%) and high (25%) Ct tertiles and Xpert Ultra-negative (30%) probable TBM cases (P = .01). In contrast, the reported semi-quantitative Xpert Ultra categorization was less precise; with the medium to low category trending toward worse 2-week survival (42%) compared with very low (28%), trace (26%), and negative (30%) categories (P = .48). Ct tertile was significantly associated with baseline CSF lactate (P = .03)., Conclusions: High CSF TB bacillary load, as measured by Xpert Ultra Ct tertile, is associated with an almost 2-fold higher 2-week mortality in HIV-associated TBM and is a better predictor than the reported Xpert Ultra semi-quantitative category. Xpert Ultra Ct values could identify TBM patients at increased risk of death who may benefit from enhanced supportive care., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)
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- 2021
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9. Xpert MTB/RIF Ultra for the Diagnosis of Tuberculous Meningitis: A Small Step Forward.
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Donovan J, Cresswell FV, Thuong NTT, Boulware DR, Thwaites GE, and Bahr NC
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- Diagnostic Tests, Routine, Humans, Molecular Diagnostic Techniques, Sensitivity and Specificity, Mycobacterium tuberculosis genetics, Tuberculosis, Meningeal diagnosis
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The delayed diagnosis of tuberculous meningitis (TBM) leads to poor outcomes, yet the current diagnostic methods for identifying Mycobacterium tuberculosis in cerebrospinal fluid (CSF) are inadequate. The first comparative study of the new GeneXpert MTB/RIF Ultra (Xpert Ultra) for TBM diagnosis suggested increased sensitivity of Xpert Ultra. Two subsequent studies have shown Xpert Ultra has improved sensitivity, but has insufficient negative predictive value to exclude TBM. Collecting and processing large volumes of CSF for mycobacterial testing are important for optimal diagnostic test performance. But clinical, radiological, and laboratory parameters remain essential for TBM diagnosis and empiric therapy is often needed. We therefore caution against the use of Xpert Ultra as a single diagnostic test for TBM; it cannot be used to "rule out" TBM., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)
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- 2020
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10. Eosinophilic Meningitis Due to Infection With Paragonimus kellicotti.
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Bahr NC, Trotman RL, Samman H, Jung RS, Rosterman LR, Weil GJ, and Hinthorn DR
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- Adolescent, Adult, Animals, Eosinophilia etiology, Humans, Male, Meningitis etiology, United States, Eosinophilia parasitology, Eosinophilia pathology, Meningitis parasitology, Meningitis pathology, Paragonimiasis diagnosis, Paragonimiasis pathology, Paragonimus isolation & purification
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Paragonimus kellicotti is an emerging pathogen in the United States with 19 previously reported cases, most in Missouri. Pulmonary symptoms with eosinophilia are most common, though 1 case did involve the central nervous system with few symptoms. We describe the first 2 cases of eosinophilic meningitis due to Paragonimus kellicotti., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2017
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11. GeneXpert MTB/Rif to Diagnose Tuberculous Meningitis: Perhaps the First Test but not the Last.
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Bahr NC, Marais S, Caws M, van Crevel R, Wilkinson RJ, Tyagi JS, Thwaites GE, and Boulware DR
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- DNA, Bacterial, Humans, Mycobacterium tuberculosis genetics, Nucleic Acid Amplification Techniques methods, Tuberculosis, Meningeal diagnosis
- Abstract
Tuberculous meningitis (TBM) is the most severe form of tuberculous with substantial mortality. In May 2015, 54 researchers from 10 countries met in Da Lat, Vietnam, to discuss advances in TBM. Among the attendees were researchers involved in pivotal studies on the use of Xpert MTB/Rif for TBM diagnosis. Attendees discussed the 2014 World Health Organization strong recommendation favoring the use of Xpert "in preference to conventional microscopy and culture as the initial diagnostic test for cerebrospinal fluid (CSF) if the sample volume is low or if additional specimens cannot be obtained to make a quick diagnosis." Attendees were concerned that the limitations of Xpert testing for TBM are not emphasized. Clear guidance is needed for the investigational pathway for TBM, including recommendations on the diagnostic package of investigations, which does not stop with Xpert testing. Second, emphasis on the large CSF volumes (ideally 8-10 mL) needed for Xpert testing is required. Guidelines should also emphasize that TBM is a medical emergency and early treatment reduces mortality., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)
- Published
- 2016
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12. Rapid access to comprehensive care may explain better outcomes in persons with sepsis with solid organ transplant versus those without solid organ transplant.
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Bahr NC, Beaudoin A, and Drekonja D
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- Female, Humans, Male, Bacteremia mortality, Transplant Recipients
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- 2015
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