multidrug-resistant tuberculosis Dutch experience Tjip van der Werf University of Groningen University Medical Center Groningen The Netherlands

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1 multidrug-resistant tuberculosis Dutch experience Tjip van der Werf University of Groningen University Medical Center Groningen The Netherlands

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3 Murray CJ, et al. Lancet 2014

4 Pietersen E, et al. Lancet 2014; 383:

5 Am J Trop Med Hyg 2014;91(4):

6 NETHERLANDS KNCV Tuberculosis Foundation, The Hague, 2014

7 NETHERLANDS KNCV Tuberculosis Foundation, The Hague, 2014

8 KNCV Tuberculosis Foundation, The Hague, 2014

9 Dutch Polder Model: collaboration between Hospital-based Service and Public Health-based TB Service TB: notifiable disease; GGD (Municipal Health Authority) with TB Department perform contactand source investigations CPT: KNCV Tuberculosis Foundation provides platform for ongoing training and guideline development & revisions Mtb strains from >40 labs all submitted for DST in the National Mycobacteriological Reference Lab MDRTB: all cases referred to dedicated TB centers

10 LEDEN VAN DE WERKGROEP (IN ALFABETISCHE VOLGORDE): Drs. O. (Onno) Akkerman, longarts Tuberculosecentrum Beatrixoord, Universitair Medisch Centrum Groningen, Groningen (vanaf ) Drs. R. (Richard) van Altena, longarts Tuberculosecentrum Beatrixoord, Universitair Medisch Centrum Groningen, Groningen (tot ) Drs. M.J. (Martin) Boeree, longarts Tuberculosecentrum Dekkerswald, Universitair Centrum voor Chronische Longziekten, Radboud Universitair Medisch Centrum, Nijmegen Dr. N.A.H. (Rob) van Hest, arts maatschappij en gezondheid/epidemioloog, GGD Rotterdam- Rijnmond, Rotterdam en GGD Groningen, Groningen Drs. W. (Wouter) Hoefsloot, longarts Tuberculosecentrum Dekkerswald, Universitair Centrum voor Chronische Longziekten, Radboud Universitair Medisch Centrum, Nijmegen (vanaf ) Drs. W.C.M. (Wiel) de Lange, longarts Tuberculosecentrum Beatrixoord, Universitair Medisch Centrum Groningen, Groningen Drs. C. (Cécile) Magis-Escurra, longarts Tuberculosecentrum Dekkerswald, Universitair Centrum voor Chronische Longziekten, Radboud Universitair Medisch Centrum, Nijmegen Drs. M.E. (Marlies) Mensen, longarts, GGD Amsterdam, Amsterdam Prof. D. (Dick) van Soolingen, hoofd Nationaal Tuberculose Referentie Laboratorium, Centrum voor Infectieziektebestrijding, RIVM, Bilthoven Dr. G. (Gerard) de Vries (secretaris), arts maatschappij en gezondheid/epidemioloog, KNCV Tuberculosefonds, Den Haag en tuberculosecoördinator bij het Centrum voor Infectieziektebestrijding, RIVM, Bilthoven 6 december 2013 Commissie voor Praktische Tuberculosebestrijding. Revisie december KNCV Tuberculosefonds Den Haag, december 2013 KNCV

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13 Beatrixoord: Rehabilitation Centre TB Unit, >25 (30) beds > 140 admissions annually >80% of patients are foreign born All Multi-Drug Resistant TB is referred 17M population

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19 MDR-TB - role of surgery Beatrixoord NL y 6 M (0) Total of all reported patients 499 Mean, 36.4 yrs 291 M (64%) 287 (57.5%) 10 (2%) 15 (3%) 85 (17%) BPF: 17 (3%) 8 all survivors did well 251 / 287 = 87.5%

20 41-yr old Chinese man, XDR-TB

21 Haar et al, submitted

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23 PK studies in MDR-TB

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25 B o

26 B o

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31 Dekkerswald, Rehabilitation Centre, Radboud University Nijmegen 8-bed Unit with isolation facilities focus on NTM disease; PK studies scientific programs in Africa and Indonesia

32 Geerligs WA, et al. IJTLD 2000; Thorax 2002; NEJM 1998

33 41/44 (92%) favourable outcome Geerligs WA, et al. IJTLD 2000; Thorax 2002; NEJM 1998

34 MDRTB Netherlands, DST results were obtained from the RIVM absolute concentration method was used for most second-line TB drugs for moxifloxacin and linezolid, three different concentrations were tested to assess the minimal inhibitory concentration (MIC) during the last few years of the study period All Mycobacterium tuberculosis complex isolates were submitted to the RIVM for identification, DST and genotyping during the study period

35 linezolid 0/54 clofazimine 0/96 PAS 0/31 cycloserine 1/95 protionamide 9/111 * fluoroquinolones 7/110 moxifloxacin 9/111 ciprofloxacin 6/97 * aminoglycosides 10/112 capreomycin 3/19 amikacin 8/112 kanamycin 5/23 pyrazinamide 22/105 ethambutol 36/112 clarithromycin 61/93 streptomycin 76/112 rifabutin 81/103 rifampin 112/112 isoniazid 111/111 TB drug resistance (% tested) 0 0,2 0,4 0,6 0,8 1

36 No of drugs to which isolates tested drug-resistant; n=112

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38 Results 113 patients with MDR-TB M/F ratio % foreign born age (median) 29 yr 95 (84%) had pulmonary TB, 55 (49%) had smearpositive sputum 14 (12%) were HIV co-infected

39 Results (2)

40 Results (3) Of 104 (92%) started on MDR-TB treatment, 86% had favourable outcome using median 6 drugs; 8 had pulmonary surgery Multivariable regression: HIV negative status associated with favourable outcome (OR 10.1; p<0.01)

41 pretomanid

42 acknowledgements UMCG TB PK Research team: Jan Willem Alffenaar, Jos Kosterink, Donald Uges PhD students: Mathieu Bolhuis, Arianna Pranger UMCG clinical TB team: Wiel de Lange, Onno Akkerman, Richard van Altena nursing staff, physiotherapists, dieticians TB Team Radboud UMC: Martin Boeree, Cecile Magis- Escurra, Wouter Hoefsloot GGD; CPT; LcI, RIVM; KNCV Tuberculosis Foundation Gerard de Vries, Rob van Hest, Susan van den Hof UMCG ID team: Ymkje Stienstra,Wouter Bierman UMCG MMB team: Bhanu Sinha, Jerome Lo Ten Foe, Alex Friedrich TB National Reference Lab: Dick van Soolingen, Mycobacteriology Lab

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