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Brooks, Meredith

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Brooks

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Meredith

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Brooks, Meredith
Author's Publications: search.filters.isAuthorOfPublication.192a7871-d1f4-4e6c-a318-20927ffc7928

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    Treatment Outcomes for Adolescents With Multidrug-Resistant Tuberculosis in Lima, Peru
    (SAGE Publications, 2016) Tierney, Dylan; Brooks, Meredith; Manjourides, Justin; Furin, Jennifer J.; Mitnick, Carole
    Treatment outcomes for adolescents with multidrug-resistant tuberculosis are rarely reported and, to date, have been poor. Among 90 adolescents from Lima, Peru, 68 (75.6%) achieved cure or completion of treatment. Unsuccessful treatment was less common in the Peru cohort than previously described in the literature.
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    Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method
    (European Respiratory Society, 2016) Mitnick, Carole; White, Richard A.; Lu, Chunling; Rodriguez, Carly; Bayona, Jaime; Becerra, Mercedes; Burgos, Marcos; Centis, Rosella; Cohen, Theodore; Cox, Helen; D'Ambrosio, Lia; Danilovitz, Manfred; Falzon, Dennis; Gelmanova, Irina Y.; Gler, Maria T.; Grinsdale, Jennifer A.; Holtz, Timothy H.; Keshavjee, Salmaan; Leimane, Vaira; Menzies, Dick; Migliori, Giovanni Battista; Brooks, Meredith; Mishustin, Sergey P.; Pagano, Marcello; Quelapio, Maria I.; Shean, Karen; Shin, Sonya; Tolman, Arielle W.; van der Walt, Martha L.; Van Deun, Armand; Viiklepp, Piret
    Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection. We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference. Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34–0.42) for all patients and 0.33 (0.25–0.42) for HIV-co-infected patients. Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.
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    Evaluation of high-dose rifampin in patients with new, smear-positive tuberculosis (HIRIF): study protocol for a randomized controlled trial
    (BioMed Central, 2016) Brooks, Meredith; Lecca, Leonid; Peloquin, Charles; Mitchison, Denis; Seung, Kwonjune; Pagano, Marcello; Coleman, David; Osso, Elna; Coit, Julia; Vargas Vasquez, Dante Elmo; Sanchez Garavito, Epifanio; Calderon, Roger; Contreras, Carmen; Davies, Geraint; Mitnick, Carole
    Background: Evidence has existed for decades that higher doses of rifampin may be more effective, but potentially more toxic, than standard doses used in tuberculosis treatment. Whether increased doses of rifampin could safely shorten treatment remains an open question. Methods/Design The HIRIF study is a phase II randomized trial comparing rifampin doses of 20 and 15 mg/kg/day to the standard 10 mg/kg/day for the first 2 months of tuberculosis treatment. All participants receive standard doses of companion drugs and a standard continuation-phase treatment (4 months, 2 drugs). They are followed for 6 months post treatment. Study participants are adults with newly diagnosed, previously untreated, smear positive (≥2+) pulmonary tuberculosis. The primary outcome is rifampin area under the plasma concentration-time curve (AUC0–24) after at least 14 days of study treatment/minimum inhibitory concentration. 180 randomized participants affords 90 % statistical power to detect a difference of at least 14 mcg/mL*hr between the 20 mg/kg group and the 10 mg/kg group, assuming a loss to follow-up of up to 17 %. Discussion Extant evidence suggests the potential for increased doses of rifampin to shorten tuberculosis treatment duration. Early studies that explored this potential using intermittent, higher dosing were derailed by toxicity. Given the continued large, global burden of tuberculosis with nearly 10 million new cases annually, shortened regimens with existing drugs would offer an important advantage to patients and health systems. Trial registration This trial was registered with clinicaltrials.gov (registration number: NCT01408914) on 2 August 2011.