Key Issues in the Management of Multi-Drug Resistant Tuberculosis: A Case Report

  • Zorica Nanovic Institute of Lung Diseases and Tuberculosis, Skopje
  • Biserka Kaeva Jovkovska University Clinic of Pulmonology and Allergology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Gorica Breskovska University Clinic of Pulmonology and Allergology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Milena Petrovska Institute of Microbiology and Parasitology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
Keywords: MDR-TB, Molecular tests for TB, MDR-TB treatment

Abstract

BACKGROUND: Global tuberculosis (TB) epidemic is being driven to an increasing extent by the emergence and spread of drug-resistant strains of Mycobacterium tuberculosis complex (MTBC). We present a case of primary multidrug-resistant tuberculosis (MDR-TB), highlighting Macedonian MDR-TB management issues.

CASE REPORT: A 39-year old previously healthy Caucasian male, with no previous history of TB or close contact to TB, was admitted in referral TB-hospital due to respiratory bleeding. Chest X-ray revealed opacity with cavernous lesions in the right upper lobe. Sputum samples showed no presence of acid-fast bacilli (AFB) on fluorescence microscopy, but molecular tests (real-time PCR-based assay and multiplex PCR-based reverse hybridisation Line Probe Assay) confirmed the presence of MTBC, also revealing rifampicin and isoniazid resistance and absence of resistance to second-line anti-tubercular drugs. The strain was considered multidrug-resistant, lately confirmed by conventional methods in liquid and solid culture. Following the protocol of the World Health Organization, we started the longer treatment of MDR-TB comprised of at least five effective anti-tubercular drugs. Due to patient’s extreme non-adherence, we had to delay and modify the regimen (i.e. omitting parenteral aminoglycoside) and to discharge him from the hospital a month after directly observed therapy (DOT) in negative pressure room. As there is no legal remedy in our country regarding involuntary isolation, our patient continued the regimen under ambulatory control of referral TB-hospital. Ignoring the risk of additional acquisition of drug resistance and prolonged exposure of the community to MDR-TB strain - for which he was repeatedly advised - he decided to cease the therapy six months after beginning.

CONCLUSION: The benefit of molecular tests in the early diagnosis of TB and drug resistance is unequivocal for adequate treatment of resistant forms of TB. Whole genome sequencing ensures additional knowledge of circulating strains and their resistance patterns. These are essentials of effective TB control programs and can provide evidence to medical and legal authorities for more active policies of screening, involuntary confinement and compliance with therapy, and alternative modalities for successful treatment, as a part of infection control.

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References

Outhred AC, Jelfs P, Suliman B, Hill-Cawthorne GA, Crawford AB, Marais BJ, Sintchenko V. Added value of whole-genome sequencing for management of highly drug-resistant TB. Journal of Antimicrobial Chemotherapy. 2014; 70(4):1198-202. https://doi.org/10.1093/jac/dku508

Abubakar I, Zignol M, Falzon D, Raviglione M, Ditiu L, Masham S, Adetifa I, Ford N, Cox H, Lawn SD, Marais BJ. Drug-resistant tuberculosis: time for visionary political leadership. The Lancet infectious diseases. 2013; 13(6):529-39. https://doi.org/10.1016/S1473-3099(13)70030-6

Falzon D, Gandhi N, Migliori GB, et al. Resistance to fluoroquinolones and second-line injectable drugs: impact of multi-drug resistant TB outcomes. Eur Respir J. 2013; 42(1):156–168. https://doi.org/10.1183/09031936.00134712 PMid:23100499 PMCid:PMC4487776

Diel R, Vandeputte J, de Vries G, et al. Costs of tuberculosis disease in the European Union: a systematic analysis and cost calculation. Eur Respir J. 2014; 43(2):554–565. https://doi.org/10.1183/09031936.00079413 PMid:23949960

Garrido MS, Talhari AC, Antunes IA, Matsuda JD, Zaranza ED, Martinez-Espinosa FE, Bührer-Sékula S. Primary multidrug-resistant tuberculosis and its control implications in the State of Amazonas, Brazil: report of 3 cases. Revista da Sociedade Brasileira de Medicina Tropical. 2012; 45(4):530-2. https://doi.org/10.1590/S0037-86822012000400024 PMid:22930053

World Health Organization. Global tuberculosis report 2017. Geneva, Switzerland: World Health Organization, 2017.

Munir MK, Rehman S, Iqbal R, Saeed MS. Development of MDR TB in short duration in a patient receiving treatment for simple TB: a case report. Annals of King Edward Medical University. 2015; 21(4):301. https://doi.org/10.21649/akemu.v21i4.779

Jonsson G, Furin J. Will molecular diagnosis of drug-resistant tuberculosis improve patient outcomes? [Perspectives]. The International Journal of Tuberculosis and Lung Disease. 2012; 16(1):4-5. https://doi.org/10.5588/ijtld.11.0419 PMid:22236840

Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, Allen J, Tahirli R, Blakemore R, Rustomjee R, Milovic A. Rapid molecular detection of tuberculosis and rifampin resistance. New England Journal of Medicine. 2010; 363(11):1005-15. https://doi.org/10.1056/NEJMoa0907847 PMid:20825313 PMCid:PMC2947799

World Health Organization. Policy Statement: Molecular line probe assays for rapid screening of patients at risk of multidrug-resistant tuberculosis (MDR-TB). Geneva, Switzerland: World Health Organization, 2008.

World Health Organization. Rapid Implementation of the Xpert MTB/RIF diagnostic test. Technical and Operational 'How-to' Practical considerations. Geneva, Switzerland: World Health Organization, 2011.

World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis, 2016 update. October 2016 revision. Geneva, Switzerland: World Health Organization, 2016.

European Centre for Disease Prevention and Control/WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2016. Stockholm, Sweden: European Centre for Disease Prevention and Control, 2016.

Siddiqi K, Lambert ML, Walley J. Clinical diagnosis of smear-negative pulmonary tuberculosis in low-income countries: the current evidence. The Lancet infectious diseases. 2003; 3(5):288-96. https://doi.org/10.1016/S1473-3099(03)00609-1

Ling D, Zwerling A, Pai M. Genotype MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis. Eur Respir J. 2008; 32:1165-74. https://doi.org/10.1183/09031936.00061808 PMid:18614561

Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. The Cochrane database of systematic reviews. 2014; 21(1):1. https://doi.org/10.1002/14651858.CD009593.pub3

World Health Organization. Xpert MTB/RIF implementation manual.Technical and operational 'how-to': practical considerations. Geneva, Switzerland: World Health Organization, 2014.

Atre S. An urgent need for building technical capacity for rapid diagnosis of multidrug-resistant tuberculosis (MDR-TB) among new cases: A case report from Maharashtra, India. J Infect Public Health. 2015; 8(5):502-5. https://doi.org/10.1016/j.jiph.2015.04.021 PMid:25956026

Ioannidis P, Papventsis D, Karabela S, Nikolaou S, et al. Cepheid GeneXpert MTB/RIF assay for Mycobacterium tuberculosis detection and rifampin resistanceidentification in patients with substantial clinical indication of tuberculosis and smear-negative microscopy results. J Clin Microbiol. 2011; 49:3068–70. https://doi.org/10.1128/JCM.00718-11 PMid:21677069 PMCid:PMC3147726

Yano S, Kobayashi K, Ikeda T. Reminder of important clinical lesson: Multidrug-resistant tuberculosis that required 2 years for diagnosis. BMJ case reports. 2012; 2012.

Zhang Y, Telenti A. Genetics of drug resistance in Mycobacterium tuberculosis. In: Hatfull G, Jacobs W R, eds. Molecular genetics of Mycobacteria. Washington DC, USA: ASM Press, 2000: 235–254.

Meacci F, Orrù G, Iona E, et al. Drug Resistance Evolution of a Mycobacterium tuberculosis Strain from a Noncompliant Patient. J Clin Microbiol. 2005; 43(7):3114-3120. https://doi.org/10.1128/JCM.43.7.3114-3120.2005 PMid:16000422 PMCid:PMC1169130

Van Rie A, Mellet K, John M-A, et al. False-positive rifampicin resistance on Xpert® MTB/RIF: case report and clinical implications. Int J Tuberc Lung Dis. 2012; 16(2): 206–8. https://doi.org/10.5588/ijtld.11.0395 PMid:22236921 PMCid:PMC3680645

Boehme CC, Nicol MP, Nabeta P, Michael JS, Gotuzzo E, Tahirli R, Gler MT, Blakemore R, Worodria W, Gray C, Huang L. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. The Lancet. 2011; 377(9776):1495-505. https://doi.org/10.1016/S0140-6736(11)60438-8

Marlowe EM, Novak-Weekley SM, Cumpio J, et al. Evaluation of the Cepheid Xpert MTB/RIF assay for direct detection of Mycobacterium tuberculosis complex in respiratory specimens. J Clin Microbiol. 2011; 49(4):1621–3. https://doi.org/10.1128/JCM.02214-10 PMid:21289151 PMCid:PMC3122817

Hoek KG, Schaaf HS, Gey van Pittius NC, et al. Resistance to pyrazinamide and ethambutol compromises MDR/XDR-TB treatment. S Afr Med J. 2009; 99(11):785-7. PMid:20218473

Pfyffer GE, Strässle A, Brändli O, Shang H. Three Episodes of Tuberculosis—To Multidrug Resistance and Back to Susceptibility. Clinical infectious diseases. 1998; 26(1):219-20. https://doi.org/10.1086/517030 PMid:9455558

Turett GS, Fazal BA, Justman, JE, Alland D, Duncalf RM, and Telzak EE. Exogenous Reinfection with Multidrug-Resistant Mycobacterium tuberculosis. Clin Inf Dis. 1997; 24:513-4. https://doi.org/10.1093/clinids/24.3.513

Singh A, Gopinath K, Sharma P, et al. Comparative proteomic analysis of sequential isolates of Mycobacterium tuberculosis from a patient with pulmonary tuberculosis turning from drug sensitive to multidrug resistant . Indian J Med Res. 2015; 141(1): 27-45. https://doi.org/10.4103/0971-5916.154492 PMid:25857493 PMCid:PMC4405938

Mendez MP, Landon ME, McCloud MK, Davidson P, Christensen PJ. Co-infection with pansensitive and multidrug-resistant strains of Mycobacterium tuberculosis. Emerging infectious diseases. 2009; 15(4):578. https://doi.org/10.3201/eid1504.080592 PMid:19331736 PMCid:PMC2671451

Williams OM, Abeel T, Casali N, Cohen K, Pym AS, Mungall SB, Desjardins CA, Banerjee A, Drobniewski F, Earl AM, Cooke GS. Fatal nosocomial MDR TB identified through routine genetic analysis and whole-genome sequencing. Emerging Infectious Diseases. 2015; 21(6):1082. https://doi.org/10.3201/eid2106.141903 PMid:25988581 PMCid:PMC4451893

Diarra B, Siddiqui S, Sogoba D, Traore B, Maiga M, Washington J, Tounkara A, Polis MA. Mycobacterium tuberculosis Beijing Strain, Bamako, Mali. Emerging infectious diseases. 2010; 16(2):362. https://doi.org/10.3201/eid1602.090501 PMid:20113590

Ahmad S. Molecular fingerprinting reveals familial transmission of rifampin-resistant tuberculosis in Kuwait. Ann Saudi Med. 2005; 25(2):150-3. PMid:15977695

Umubyeyi A, Shamputa IC, Rigouts L, Dediste A, Struelens M, Portaels F. Evidence of 'amplifier effect'in pulmonary multidrug-resistant tuberculosis: report of three cases. International journal of infectious diseases. 2007; 11(6):508-12. https://doi.org/10.1016/j.ijid.2007.01.009 PMid:17376726

Tostmann A, Kik SV, Kalisvaart NA, Sebek MM, Verver S, Boeree MJ, van Soolingen D. Tuberculosis transmission by patients with smear-negative pulmonary tuberculosis in a large cohort in the Netherlands. Clinical Infectious Diseases. 2008; 47(9):1135-42. https://doi.org/10.1086/591974 PMid:18823268

Hingley-Wilson SM, Casey R, Connell D, Bremang S, Evans JT, Hawkey PM, Smith GE, Jepson A, Philip S, Kon OM, Lalvani A. Undetected multidrug-resistant tuberculosis amplified by first-line therapy in mixed infection. Emerging infectious diseases. 2013; 19(7):1138. https://doi.org/10.3201/eid1907.130313 PMid:23764343 PMCid:PMC3713993

Maia KRO, de Castro Viana GM, Custódio Neto da Silva MA, do Desterro Soares Brandão Nascimento M, de Souza VL, Monteiro SG. Resistant tuberculosis in Maranhão, Brazil: a case series. BMC Res Notes. 2016; 9:260. https://doi.org/10.1186/s13104-016-2063-x PMid:27145827 PMCid:PMC4857409

Sharma SK, Mohan A. Multidrug-resistant tuberculosis: a menace that threatens to destabilize tuberculosis control. Chest. 2006; 130(1):261-72. https://doi.org/10.1016/S0012-3692(15)50981-1

Toyota E, Sekiguchi JI, Shimizu H, et al. Further acquisition ofdrug-resistance in multidrug-resistant tuberculosis during chemotherapy. Jpn J. Infect. Dis. 2004; 57: 292-294. PMid:15623961

Tiberi S, D'Ambrosio L, De Lorenzo S, Viggiani P, Centis R, Migliori GB. Tuberculosis elimination, patients' lives and rational use of new drugs: revisited. European Respiratory Journal. 2016; 47(2): 664-7. https://doi.org/10.1183/13993003.01297-2015 PMid:26541536

Jeyakumar D. A case of primary drug resistant tuberculosis. Med J Malaysia. 2000; 55 (1): 129-31. PMid:11072497

Elkomy H, Awad M, El-Shora A, Elsherbeni B. Assessment of the efficacy of Directly Observed Treatment with short course (DOTS) for pulmonary tuberculosis in Sharkia governorate. Egyptian Journal of Chest Diseases and Tuberculosis. 2013; 62(2):257-61. https://doi.org/10.1016/j.ejcdt.2013.04.003

Igbudu TJ, Egwuda L, Mbaave TP. Family-Member Variant of Directory Observed Therapy Short Course (DOTS) in Current Pulmonary Tuberculosis (PTB) Management: A Way Out in Resource-Constrained Settings – A Case Report. Int J Med Res. 2015; 3(3): 13-15. https://doi.org/10.5455/ijmr.20160724051241

Luyirika E, Nsobya H, Batamwita R, Busingye P, Musoke W, Nabiddo L, Karamagi Y, Mukasa B. A home-based approach to managing multi-drug resistant tuberculosis in Uganda: a case report. AIDS research and therapy. 2012; 9(1):12. https://doi.org/10.1186/1742-6405-9-12 PMid:22524486 PMCid:PMC3349607

Centers for Disease Control and Prevention. Patient adherence to tuberculosis treatment, 1999. Available at: http://www.heartlandntbc.org/assets/training/mini-fellowship/PediatricToolBox/CDC/ ed_training/publications/ssmodules/pdfs/9.pdf (Accessed January 8, 2018).

Worild Health Organization. Ethics guidance for the implementation of the End TB strategy. Geneva, Switzerland: World Health Organization, 2017.

Muigano MN. Involuntary detention and compulsory treatment of non-adherent tuberculosis patients in Kenya: an ethical discourse. Int J Community Med Public Health. 2016; 3(9):2677-2682. https://doi.org/10.18203/2394-6040.ijcmph20163095

Weiler-Ravell D, Leventhal A, Coker RJ, Chemtob D. Compulsory detention of recalcitrant tuberculosis patients in the context of a new tuberculosis control programme in Israel. Public health. 2004; 118(5):323-8. https://doi.org/10.1016/j.puhe.2003.10.005 PMid:15178138

Becerra MC, Appleton SC, Franke MF, Chalco K, Arteaga F, Bayona J, Murray M, Atwood SS, Mitnick CD. Tuberculosis burden in households of patients with multidrug-resistant and extensively drug-resistant tuberculosis: a retrospective cohort study. The Lancet. 2011; 377(9760):147-52. https://doi.org/10.1016/S0140-6736(10)61972-1

WHO, World Health Organization. Guidelines on the management of latent tuberculosis infection. World Health Organization, 2015.

Published
2018-07-14
How to Cite
1.
Nanovic Z, Kaeva Jovkovska B, Breskovska G, Petrovska M. Key Issues in the Management of Multi-Drug Resistant Tuberculosis: A Case Report. Open Access Maced J Med Sci [Internet]. 2018Jul.14 [cited 2020Nov.29];6(7):1282-8. Available from: https://www.id-press.eu/mjms/article/view/oamjms.2018.290
Section
C- Case Reports