• Users Online: 511
  • Home
  • Print this page
  • Email this page


 
 Table of Contents  
CASE REPORT
Year : 2013  |  Volume : 2  |  Issue : 4  |  Page : 233-236

Multidrug-resistant tuberculosis treatment with linezolid-containing regimen


1 Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
2 Division of Pulmonary and Critical Care, University of Illinois at Chicago, IL, USA
3 Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine M/C 719, University of Illinois at Chicago, USA

Date of Web Publication28-Feb-2017

Correspondence Address:
Mehdi Mirsaeidi
Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine M/C 719, University of Illinois at Chicago, 840 S. Wood St., Chicago, IL 60612-7323
USA
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.1016/j.ijmyco.2013.09.002

Rights and Permissions
  Abstract 


The following is a case of multidrug-resistant pulmonary tuberculosis (MDR-TB) that was treated successfully with a linezolid-containing regimen. It was found that linezolid is an efficient medicine for MDR-TB treatment with an acceptable side effect profile. Treatment was maintained for 18 months, and closely monitoring toxicities did not reveal evidence of any neurologic adverse effects. However, despite our expectation, thrombocytopenia was seen after 2 years follow-up.

Keywords: Multidrug-resistant tuberculosis, Linezolid, Treatment, Thrombocytopenia


How to cite this article:
Farshidpour M, Ebrahimi G, Mirsaeidi M. Multidrug-resistant tuberculosis treatment with linezolid-containing regimen. Int J Mycobacteriol 2013;2:233-6

How to cite this URL:
Farshidpour M, Ebrahimi G, Mirsaeidi M. Multidrug-resistant tuberculosis treatment with linezolid-containing regimen. Int J Mycobacteriol [serial online] 2013 [cited 2021 Oct 28];2:233-6. Available from: https://www.ijmyco.org/text.asp?2013/2/4/233/201124




  Introduction Top


An estimated 9 million people are infected with tuberculosis (TB) worldwide [1]. In recent years, the epidemiology of TB has shown significant increases in developed countries because of immigration from countries with high prevalence as well as a rising incidence of TB and HIV infection [2]. As a result, an increase of multidrug-resistant (MDR)-TB is also anticipated over the next few years owing to population migration patterns [3]. MDR-TB signifies bacillary resistance to at least Isoniazid and Rifampicin [4]. Drug-resistant TB infection has presented since the beginning of the antibiotic era. Although genetic resistance to an anti-TB medication happens naturally, in consequence of chromosomal mutations that accompany mycobacterial replication, MDR-TB is a manmade phenomenon that has emerged owing to improper TB treatment [5],[6]. The management of MDR-TB is challenging, requiring prolonged administration of second-line drugs which are more expensive, often less effective, and more toxic than first-line agents [7],[8].

Linezolid, the first oxazolidinone approved for clinical use, has demonstrated excellent activity against drug-resistant strains of Mycobacterium tuberculosis (MTB) [7],[9],[10].

The following report describes a case of MDR-TB that was treated with a linezolid-containing regimen and discusses the challenges of long-term administration of linezolid in an adult with MDR-TB.


  Case report Top


A 29-year-old Bhutanese refugee man was referred to the clinic for TB evaluation with positive tuberculin skin (PPD>13 mm) and QuantiFERON-TB tests. He was living in a camp in Nepal for several years before moving to the United States. He complained of cough, fever, and weight loss for 9 months. His past medical history was not significant. The physical examination was remarkable for malnourishment (body mass index = 15.7), mildly tender bilateral cervical lymphadenopathies with maximum size of 2cm and decreased breath sounds in left lower zone of the chest. The rest of the examination was normal. Hematological and biochemical parameters were within normal limits except mild anemia.

Imaging studies were performed and showed a mild left pleural effusion in the chest radiograph. A chest computed tomography showed nodular opacities in the right upper lobe, minimal scarring in the ligula, hilum lymph nodes with maximum size of 19 mm, and mild left side pleural effusion.

The sputum specimens were sent for the Acid Fast Bacilli smear, mycological culture and drug susceptibility test (DST). The patient underwent excisional biopsy of the cervical lymph nodes, which the pathological examination reported as chronic necrotizing granulomatosis inflammation consistent with TB. Anti-TB therapy was started empirically with a regimen including: isoniazid, rifampin, pyrazinamide, and ethambutol on direct observe therapy. Eight weeks later, the sputum and lymph node cultures reported Mycobacterium tuberculosis complex, and DST confirmed the presence of a multiple drug-resistant strain, resistant to isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin and para aminosalicylic sodium. The susceptibility results and molecular study provided by the Center for Disease Control are shown in [Table 1] and [Table 2]. The previous anti-TB regimen was switched to amikacin 1500 mg/week, moxifloxacin 400 mg/day, cycloserine 500 mg/day, linezolid 600 mg/day and ethionamide 500 mg/day. The patient responded well to anti-TB medications, although he experienced multiple anti-TB medication side effects, including thrombocytopenia, hearing loss and upper gastrointestinal discomfort. Consequently, his treatment was modified to linezolid 300 mg/day, cycloserine 500 mg/day, levofloxacin 750 mg/day and capreomycin 1300 mg/week (it was stopped 6 months after sputum conversion due to hearing loss).
Table 1: Drug resistance results from sputum of MDR-TB patient.

Click here to view
Table 2: Results for molecular detection of drug resistance in MDR-TB patient.

Click here to view


The anti-TB medicines were continued for 12 months after sputum conversion to negative (total duration of treatment was 18 months). The patient was free of symptoms and his cervical lymphadenitis subsided. He was closely followed up and no signs of relapse were observed up to 24 months after completion of treatment. Thrombocytopenia (platelet counts: 86 × 1000 per microliter) was seen even 24 months after stopping linezolid.


  Discussion Top


Multidrug-resistant Mycobacterium tuberculosis is a rising and alarming medical problem. The actual management and treatment regimens for MDR-TB are difficult, expensive, long-term, and linked with high rates of adverse effects and high morbidity and mortality [11],[12]. Incomplete and inadequate treatment is the most significant factor leading to the development of MDR-TB [13].

Linezolid is a synthetic antibacterial agent that inhibits bacterial protein synthesis at an early stage of translation [14]. The oral bioavailability of linezolid is nearly 100%, with a high volume of distribution and high concentrations in alveolar macrophages [15]. Alternatively, various adverse drug reactions have been described with long-term use of linezolid, primarily bone marrow suppression and peripheral and/or optic neuropathy. Hematologic adverse reactions ensuing from the prolonged use of linezolid are dose dependent and reversible secondary to inhibition of mitochondrial protein synthesis, while peripheral neuropathy might be irreversible depending on the prolonged duration of the therapy rather than dosage; however, optic neuropathy appears to resolve after stopping linezolid [10],[16]. In this case, treatment was maintained for 18 months and closely monitoring toxicities did not reveal evidence of any neurologic adverse effects. However, despite previous reports, thrombocytopenia was seen after 2 years of follow-up [17].

The optimal dose of linezolid for MDR-TB is not apparent. In this case, linezolid was given at a dose of 300 mg/day. This decision was directed by preliminary data regarding linezolid in the treatment of MDR-TB in adults being treated with 600 mg/day instead of 1200 mg/day, which is the Food and Drug Administration-approved dose for Gram-positive organisms [18]. In these studies, a daily 300 mg dose of linezolid was seen to be effective with less toxicity [19].


  Conclusion Top


Specific strategies and measures should be engaged to prevent the propagation and dissemination of MDR-TB. Concerning MDR-TB treatment, risks and benefits of each medication should be deemed when tailoring a therapy. In this case, linezolid was found to be an effective drug available to treat MDR-TB. Although linezolid was efficacious in this study, randomized clinical trials are necessary to measure outcomes and permanent side effects of linezolid-containing regimens before the clinical role of linezolid as a treatment for MDR-TB can be recommended.


  Conflict of interest Top


None.


  Acknowledgment Top


The authors appreciate Mary Beth Allen PhD(c) for editorial assistance.



 
  References Top

1.
Guidance for National Tuberculosis Programmes on the management of tuberculosis in children. Chapter 1: Introduction and diagnosis of tuberculosis in children. Int. J. Tuberc. Lung. Dis. 10 (10) (2006) 1091–1097.  Back to cited text no. 1
    
2.
T. Lillebaek, A.B. Andersen, J. Bauer, et al, Risk of Mycobacterium tuberculosis transmission in a low-incidence country due to immigration from high-incidence areas, J. Clin. Microbiol. 39 (3) (2001) 855–861.  Back to cited text no. 2
    
3.
D. Falzon, E. Jaramillo, H.J. Schunemann, et al, WHO guidelines for the programmatic management of drugresistant tuberculosis: 2011 update, Eur. Respir. J. 38 (3) (2011) 516–528.  Back to cited text no. 3
    
4.
E.D. Chan, V. Laurel, M.J. Strand, et al, Treatment and outcome analysis of 205 patients with multidrug-resistant tuberculosis, Am. J. Respir. Crit Care Med. 169 (10) (2004) 1103– 1109.  Back to cited text no. 4
    
5.
K.C. Chang, W.W. Yew, Management of difficult multidrugresistant tuberculosis and extensively drug-resistant tuberculosis: update 2012, Respirology 18 (1) (2013) 8–21.  Back to cited text no. 5
    
6.
Y. Zhang, W.W. Yew, Mechanisms of drug resistance in Mycobacterium tuberculosis, Int. J. Tuberc. Lung Dis. 13 (11) (2009) 1320–1330.  Back to cited text no. 6
    
7.
M. Pinon, C. Scolfaro, E. Bignamini, et al, Two pediatric cases of multidrug-resistant tuberculosis treated with linezolid and moxifloxacin, Pediatrics 126 (5) (2010) e1253–e1256.  Back to cited text no. 7
    
8.
S.M. Mirsaeidi, P. Tabarsi, K. Khoshnood, et al, Treatment of multiple drug-resistant tuberculosis (MDR-TB) in Iran, Int. J. Infect. Dis. 9 (6) (2005) 317–322.  Back to cited text no. 8
    
9.
F. Ntziora, M.E. Falagas, Linezolid for the treatment of patients with [corrected] mycobacterial infections [corrected] a systematic review, Int. J. Tuberc. Lung Dis. 11 (6) (2007) 606– 611.  Back to cited text no. 9
    
10.
I.N. Park, S.B. Hong, Y.M. Oh, et al, Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis, J. Antimicrob. Chemother. 58 (3) (2006) 701–704.  Back to cited text no. 10
    
11.
U.G. Lalloo, R. Naidoo, A. Ambaram, Recent advances in the medical and surgical treatment of multi-drug resistant tuberculosis, Curr. Opin. Pulm. Med. 12 (3) (2006) 179–185.  Back to cited text no. 11
    
12.
M. Mirsaeidi, After 40 years, new medicine for combating TB, Int. J. Mycobacteriol. 2 (1) (2013) 1–2.  Back to cited text no. 12
    
13.
S.K. Sharma, A. Mohan, Multidrug-resistant tuberculosis: a menace that threatens to destabilize tuberculosis control, Chest 130 (1) (2006 Jul) 261–272.  Back to cited text no. 13
    
14.
D.L. Shinabarger, K.R. Marotti, R.W. Murray, et al, Mechanism of action of oxazolidinones: effects of linezolid and eperezolid on translation reactions, Antimicrob. Agents Chemother. 41 (10) (1997) 2132–2136.  Back to cited text no. 14
    
15.
D. Honeybourne, C. Tobin, G. Jevons, J. Andrews, R. Wise, Intrapulmonary penetration of linezolid, J. Antimicrob. Chemother. 51 (6) (2003) 1431–1434.  Back to cited text no. 15
    
16.
G.B. Migliori, B. Eker, M.D. Richardson, et al, A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis, Eur. Respir. J. 34 (2) (2009) 387–393.  Back to cited text no. 16
    
17.
S.L. Gerson, S.L. Kaplan, J.B. Bruss, et al, Hematologic effects of linezolid: summary of clinical experience, Antimicrob. Agents Chemother. 46 (8) (2002) 2723–2726.  Back to cited text no. 17
    
18.
G.F. Schecter, C. Scott, L. True, A. Raftery, J. Flood, S. Mase, Linezolid in the treatment of multidrug-resistant tuberculosis, Clin. Infect. Dis. 50 (1) (2010) 49–55.  Back to cited text no. 18
    
19.
W.J. Koh, Y.R. Kang, K. Jeon, et al, Daily 300 mg dose of linezolid for multidrug-resistant and extensively drugresistant tuberculosis: updated analysis of 51 patients, J. Antimicrob. Chemother. 67 (6) (2012) 1503–1507.  Back to cited text no. 19
    



 
 
    Tables

  [Table 1], [Table 2]


This article has been cited by
1 Medicinal plants used in the treatment of tuberculosis - Ethnobotanical and ethnopharmacological approaches
Javad Sharifi-Rad,Bahare Salehi,Zorica Z. Stojanovic-Radic,Patrick Valere Tsouh Fokou,Marzieh Sharifi-Rad,Gail B. Mahady,Majid Sharifi-Rad,Mohammad-Reza Masjedi,Temitope O. Lawal,Seyed Abdulmajid Ayatollahi,Javid Masjedi,Razieh Sharifi-Rad,William N. Setzer,Mehdi Sharifi-Rad,Farzad Kobarfard,Atta-ur Rahman,Muhammad Iqbal Choudhary,Athar Ata,Marcello Iriti
Biotechnology Advances. 2020; 44: 107629
[Pubmed] | [DOI]
2 Linezolid for drug-resistant pulmonary tuberculosis
Bhagteshwar Singh,Derek Cocker,Hannah Ryan,Derek J Sloan
Cochrane Database of Systematic Reviews. 2019;
[Pubmed] | [DOI]
3 Medicinal plants used in the treatment of tuberculosis - Ethnobotanical and ethnopharmacological approaches
Javad Sharifi-Rad,Bahare Salehi,Zorica Z. Stojanovic-Radic,Patrick Valere Tsouh Fokou,Marzieh Sharifi-Rad,Gail B. Mahady,Majid Sharifi-Rad,Mohammad-Reza Masjedi,Temitope O. Lawal,Seyed Abdulmajid Ayatollahi,Javid Masjedi,Razieh Sharifi-Rad,William N. Setzer,Mehdi Sharifi-Rad,Farzad Kobarfard,Atta-ur Rahman,Muhammad Iqbal Choudhary,Athar Ata,Marcello Iriti
Biotechnology Advances. 2017;
[Pubmed] | [DOI]
4 Antibacterials/antituberculars
Reactions Weekly. 2014; 1484(1): 7
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Case report
Discussion
Conclusion
Conflict of interest
Acknowledgment
References
Article Tables

 Article Access Statistics
    Viewed1204    
    Printed34    
    Emailed0    
    PDF Downloaded71    
    Comments [Add]    
    Cited by others 4    

Recommend this journal