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Maha Reda Farhat, M.D.,C.M., M.D.

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Mentoring
Available: 06/01/17, Expires: 06/01/19

Non-tuberculous Mycobacterial (NTM) infections are an increasing source of patient morbidity and health care cost. Recent estimates of Mycobacterium avium complex (MAC) disease burden report an annual prevalence increase by 36% in the last 10 years. NTM pulmonary disease is associated with high rates of morbidity and mortality, yet available treatment regimens are reported to result in no clinical or microbiological response in an estimated 8-41% of patients with MAC, and is much higher for patients with Mycobacterium abscessus where the rate is as high as 72%. Currently a limited number of patient and bacterial factors predict the poor response to therapy but include cavitary lung disease, high disease burden as indicated by positive AFB smears at baseline, isolates resistant or with inducible resistance to macrolides, a history of previous treatment among a few others. Due to the limited efficacy of medical therapy and the significant associated morbidity and mortality for some patients with pulmonary NTM disease, surgical resection of affected lung has been suggested as an adjunct to medical therapy. However data on the timing and the actual magnitude of benefit offered by surgery is limited. Most studies have been small case series that reported on outcomes of surgery without comparing these outcomes with outcomes of medical therapy alone. Macrolide resistant NTM carries a significantly worse prognosis than NTM that is sensitive to the drug as determined by in vitro drug susceptibility testing. To date it is not known how the rates of macrolide resistance for NTM are evolving over time. It is likely that with the more prevalent use of these antibiotics for treatment of other respiratory infections, and for the prophylaxis of chronic obstructive pulmonary disease and bronchiectasis exacerbations, that the rates will increase and this may pose an increasing public health threat. Here, the student will carry out a retrospective cohort study of MAC patients through the electronic review of medical records in the Partners HealthCare system. The mentor will apply for and secure IRB approval for the work before the student starts. The student will learn about NTM disease natural history, treatment and outcomes, retrospective study design and elements of how to think about and control for confounding. She will also learn how to search medical records, collect data using an abstraction form, develop an organize a database, and basics or more advanced training on biostatistical data analysis depending on the student's comfort level. The student will also gain experience in the scientific writing of the results.


Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. K01ES026835 (FARHAT, MAHA) Sep 30, 2015 - Jul 31, 2020
    NIH/NIEHS
    New Tools for the interpretation of Pathogen Genomic Data with a focus on Mycobacterium tuberculosis
    Role: Principal Investigator

Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  1. Farhat MR, Sixsmith J, Calderon R, Hicks ND, Fortune SM, Murray M. Rifampicin and rifabutin resistance in 1003 Mycobacterium tuberculosis clinical isolates. J Antimicrob Chemother. 2019 Jun 01; 74(6):1477-1483. PMID: 30793747.
    Citations:    
  2. Farhat MR, Freschi L, Calderon R, Ioerger T, Snyder M, Meehan CJ, de Jong B, Rigouts L, Sloutsky A, Kaur D, Sunyaev S, van Soolingen D, Shendure J, Sacchettini J, Murray M. GWAS for quantitative resistance phenotypes in Mycobacterium tuberculosis reveals resistance genes and regulatory regions. Nat Commun. 2019 05 13; 10(1):2128. PMID: 31086182.
    Citations:    
  3. Chen ML, Doddi A, Royer J, Freschi L, Schito M, Ezewudo M, Kohane IS, Beam A, Farhat M. Beyond multidrug resistance: Leveraging rare variants with machine and statistical learning models in Mycobacterium tuberculosis resistance prediction. EBioMedicine. 2019 Apr 29. PMID: 31047860.
    Citations:    
  4. Dixit A, Freschi L, Vargas R, Calderon R, Sacchettini J, Drobniewski F, Galea JT, Contreras C, Yataco R, Zhang Z, Lecca L, Kolokotronis SO, Mathema B, Farhat MR. Whole genome sequencing identifies bacterial factors affecting transmission of multidrug-resistant tuberculosis in a high-prevalence setting. Sci Rep. 2019 Apr 03; 9(1):5602. PMID: 30944370.
    Citations:    
  5. Schubert B, Maddamsetti R, Nyman J, Farhat MR, Marks DS. Genome-wide discovery of epistatic loci affecting antibiotic resistance in Neisseria gonorrhoeae using evolutionary couplings. Nat Microbiol. 2019 02; 4(2):328-338. PMID: 30510172.
    Citations:    Fields:    
  6. Allix-Béguec C, Arandjelovic I, Bi L, Beckert P, Bonnet M, Bradley P, Cabibbe AM, Cancino-Muñoz I, Caulfield MJ, Chaiprasert A, Cirillo DM, Clifton DA, Comas I, Crook DW, De Filippo MR, de Neeling H, Diel R, Drobniewski FA, Faksri K, Farhat MR, Fleming J, Fowler P, Fowler TA, Gao Q, Gardy J, Gascoyne-Binzi D, Gibertoni-Cruz AL, Gil-Brusola A, Golubchik T, Gonzalo X, Grandjean L, He G, Guthrie JL, Hoosdally S, Hunt M, Iqbal Z, Ismail N, Johnston J, Khanzada FM, Khor CC, Kohl TA, Kong C, Lipworth S, Liu Q, Maphalala G, Martinez E, Mathys V, Merker M, Miotto P, Mistry N, Moore DAJ, Murray M, Niemann S, Omar SV, Ong RT, Peto TEA, Posey JE, Prammananan T, Pym A, Rodrigues C, Rodrigues M, Rodwell T, Rossolini GM, Sánchez Padilla E, Schito M, Shen X, Shendure J, Sintchenko V, Sloutsky A, Smith EG, Snyder M, Soetaert K, Starks AM, Supply P, Suriyapol P, Tahseen S, Tang P, Teo YY, Thuong TNT, Thwaites G, Tortoli E, van Soolingen D, Walker AS, Walker TM, Wilcox M, Wilson DJ, Wyllie D, Yang Y, Zhang H, Zhao Y, Zhu B. Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing. N Engl J Med. 2018 10 11; 379(15):1403-1415. PMID: 30280646.
    Citations:    Fields:    Translation:HumansCells
  7. Pollock N, Dhiman R, Daifalla N, Farhat M, Campos-Neto A. Discovery of a unique Mycobacterium tuberculosis protein through proteomic analysis of urine from patients with active tuberculosis. Microbes Infect. 2018 04; 20(4):228-235. PMID: 29306028.
    Citations:    Fields:    
  8. Farhat MR, Jacobson KR, Franke MF, Kaur D, Murray M, Mitnick CD. Fluoroquinolone Resistance Mutation Detection Is Equivalent to Culture-Based Drug Sensitivity Testing for Predicting Multidrug-Resistant Tuberculosis Treatment Outcome: A Retrospective Cohort Study. Clin Infect Dis. 2017 Oct 15; 65(8):1364-1370. PMID: 29017248.
    Citations:    Fields:    Translation:HumansCells
  9. Nebenzahl-Guimaraes H, van Laarhoven A, Farhat MR, Koeken VACM, Mandemakers JJ, Zomer A, van Hijum SAFT, Netea MG, Murray M, van Crevel R, van Soolingen D. Transmissible Mycobacterium tuberculosis Strains Share Genetic Markers and Immune Phenotypes. Am J Respir Crit Care Med. 2017 06 01; 195(11):1519-1527. PMID: 27997216.
    Citations: 3     Fields:    Translation:Cells
  10. Farhat MR, Sultana R, Iartchouk O, Bozeman S, Galagan J, Sisk P, Stolte C, Nebenzahl-Guimaraes H, Jacobson K, Sloutsky A, Kaur D, Posey J, Kreiswirth BN, Kurepina N, Rigouts L, Streicher EM, Victor TC, Warren RM, van Soolingen D, Murray M. Genetic Determinants of Drug Resistance in Mycobacterium tuberculosis and Their Diagnostic Value. Am J Respir Crit Care Med. 2016 09 01; 194(5):621-30. PMID: 26910495.
    Citations: 14     Fields:    Translation:HumansCells
  11. Andre E, Isaacs C, Affolabi D, Alagna R, Brockmann D, de Jong BC, Cambau E, Churchyard G, Cohen T, Delmee M, Delvenne JC, Farhat M, Habib A, Holme P, Keshavjee S, Khan A, Lightfoot P, Moore D, Moreno Y, Mundade Y, Pai M, Patel S, Nyaruhirira AU, Rocha LE, Takle J, Trébucq A, Creswell J, Boehme C. Connectivity of diagnostic technologies: improving surveillance and accelerating tuberculosis elimination. Int J Tuberc Lung Dis. 2016 08; 20(8):999-1003. PMID: 27393530.
    Citations: 7     Fields:    Translation:HumansPHPublic Health
  12. Farhat MR, Jacobson KR, Franke MF, Kaur D, Sloutsky A, Mitnick CD, Murray M. Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis. J Clin Microbiol. 2016 Mar; 54(3):727-33. PMID: 26763957.
    Citations: 8     Fields:    Translation:HumansCells
  13. Ramly EP, Bohnen JD, Farhat MR, Razmdjou S, Mavros MN, Yeh DD, Lee J, Butler K, De Moya M, Velmahos GC, Kaafarani HM. The nature, patterns, clinical outcomes, and financial impact of intraoperative adverse events in emergency surgery. Am J Surg. 2016 Jul; 212(1):16-23. PMID: 26601649.
    Citations: 1     Fields:    Translation:Humans
  14. Farhat MR, Mitnick CD, Franke MF, Kaur D, Sloutsky A, Murray M, Jacobson KR. Concordance of Mycobacterium tuberculosis fluoroquinolone resistance testing: implications for treatment. Int J Tuberc Lung Dis. 2015 Mar; 19(3):339-41. PMID: 25686144.
    Citations: 4     Fields:    Translation:HumansCells
  15. Farhat MR, Shapiro BJ, Sheppard SK, Colijn C, Murray M. A phylogeny-based sampling strategy and power calculator informs genome-wide associations study design for microbial pathogens. Genome Med. 2014; 6(11):101. PMID: 25484920.
    Citations: 7     Fields:    
  16. Nebenzahl-Guimaraes H, Jacobson KR, Farhat MR, Murray MB. Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis. J Antimicrob Chemother. 2014 Feb; 69(2):331-42. PMID: 24055765.
    Citations: 26     Fields:    Translation:HumansAnimalsCells
  17. Farhat MR, Shapiro BJ, Kieser KJ, Sultana R, Jacobson KR, Victor TC, Warren RM, Streicher EM, Calver A, Sloutsky A, Kaur D, Posey JE, Plikaytis B, Oggioni MR, Gardy JL, Johnston JC, Rodrigues M, Tang PK, Kato-Maeda M, Borowsky ML, Muddukrishna B, Kreiswirth BN, Kurepina N, Galagan J, Gagneux S, Birren B, Rubin EJ, Lander ES, Sabeti PC, Murray M. Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis. Nat Genet. 2013 Oct; 45(10):1183-9. PMID: 23995135.
    Citations: 91     Fields:    Translation:Cells
  18. Farhat MR, Loring SH, Riskind P, Weinhouse G. Disturbance of respiratory muscle control in a patient with early-stage multiple sclerosis. Eur Respir J. 2013 Jun; 41(6):1454-6. PMID: 23728406.
    Citations: 2     Fields:    Translation:Humans
  19. Karvellas CJ, Farhat MR, Sajjad I, Mogensen SS, Leung AA, Wald R, Bagshaw SM. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis. Crit Care. 2011; 15(1):R72. PMID: 21352532.
    Citations: 87     Fields:    Translation:Humans
  20. Colijn C, Brandes A, Zucker J, Lun DS, Weiner B, Farhat MR, Cheng TY, Moody DB, Murray M, Galagan JE. Interpreting expression data with metabolic flux models: predicting Mycobacterium tuberculosis mycolic acid production. PLoS Comput Biol. 2009 Aug; 5(8):e1000489. PMID: 19714220.
    Citations: 115     Fields:    Translation:Cells
  21. Menzies D, Gardiner G, Farhat M, Greenaway C, Pai M. Thinking in three dimensions: a web-based algorithm to aid the interpretation of tuberculin skin test results. Int J Tuberc Lung Dis. 2008 May; 12(5):498-505. PMID: 18419884.
    Citations: 19     Fields:    Translation:Humans
  22. Cobelens FG, Menzies D, Farhat M. False-positive tuberculin reactions due to non-tuberculous mycobacterial infections. Int J Tuberc Lung Dis. 2007 Aug; 11(8):934-5;author reply 935. PMID: 17705966.
    Citations: 3     Fields:    Translation:HumansCells
  23. Farhat M, Greenaway C, Pai M, Menzies D. False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria? Int J Tuberc Lung Dis. 2006 Nov; 10(11):1192-204. PMID: 17131776.
    Citations: 146     Fields:    Translation:HumansCells
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Funded by the NIH/NCATS Clinical and Translational Science Award (CTSA) program, grant number UL1TR001102, and through institutional support from Harvard University, Harvard Medical School, Harvard T.H. Chan School of Public Health, Beth Israel Deaconess Medical Center, Boston Children's Hospital, Brigham and Women's Hospital, Massachusetts General Hospital and the Dana Farber Cancer Institute.