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Linezolid in the treatment of extensively drug-resistant tuberculosis

  • Clinical and Epidemiological Study
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Abstract

Purpose

To investigate the linezolid (LZD) treatment outcome and correlation between in vitro susceptibility to LZD and clinical outcome.

Methods

We retrospectively reviewed records of tuberculosis (TB) patients who received treatment with linezolid between March 2012 and February 2013.

Results

A total of 43 extensively drug-resistant (XDR) TB patients identified by drug susceptibility testing were enrolled in this study, including 15 (34.9 %) received LZD as part of individualized treatment regimens. Among the 43 XDR TB patients, 15 patients (34.9 %) obtained favorable clinical outcome, including 9 (60.0 %) from LZD group and 6 (21.4 %) from control group without LZD. Statistical analysis revealed that the percentage of favorable outcomes of LZD group was significantly higher than that of control group (P = 0.011). Furthermore, we analyzed the LZD minimum inhibitory concentrations of Mycobacterium tuberculosis (MTB) isolates from patients in LZD group and identified 4 (26.7 %) resistant to LZD. All of the patients with LZD resistance harbored adverse clinical outcome, while most of the patients infected with LZD sensitive MTB harbored favorable clinical outcome (81.8 %, 9/11). Statistical analysis revealed that the percentage of favorable outcome among the patients with LZD resistance was statistically lower than that among the LZD susceptible group (P = 0.011).

Conclusion

This study demonstrates that linezolid has efficacy against XDR pulmonary TB patients, even in shorter duration of administration. The XDR TB patients infected with LZD-resistant isolates were more likely to obtain the adverse clinical outcome under the treatment of regimen containing LZD.

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References

  1. Zhao Y, Xu S, Wang L, Chin DP, Wang S, Jiang G, et al. National survey of drug-resistant tuberculosis in China. N Engl J Med. 2012;366:2161–70.

    Article  CAS  PubMed  Google Scholar 

  2. Gandhi NR, Nunn P, Dheda K, Schaaf HS, Zignol M, van Soolingen D, et al. Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global control of tuberculosis. Lancet. 2010;375:1830–43.

    Article  PubMed  Google Scholar 

  3. World Health Organization. Anti-tuberculosis drug resistance in the world: fourth global report. WHO/HTM/TB/2008.394. Geneva: World Health Organization; 2008.

  4. Yew WW, Lange C, Leung CC. Treatment of tuberculosis: update 2010. Eur Respir J. 2011;37:441–62.

    Article  CAS  PubMed  Google Scholar 

  5. Migliori GB, Lange C, Centis R, Sotgiu G, Mütterlein R, Hoffmann H, et al. Resistance to second-line injectables and treatment outcomes in multidrug-resistant and extensively drug-resistant tuberculosis cases. Eur Respir J. 2008;31:1155–9.

    Article  CAS  PubMed  Google Scholar 

  6. Lee M, Lee J, Carroll MW, Choi H, Min S, Song T, et al. Linezolid for treatment of chronic extensively drug-resistant tuberculosis. N Engl J Med. 2012;367:1508–18.

    Article  CAS  Google Scholar 

  7. Ippolito JA, Kanyo ZF, Wang D, Morales G, Rahawi S, Kedar GC, et al. Crystal structure of the oxazolidinone antibiotic linezolid bound to the 50S ribosomal subunit. J Med Chem. 2008;51:3353–6.

    Article  CAS  PubMed  Google Scholar 

  8. Bozdogan B, Appelbaum PC. Oxazolidinones: activity, mode of action, and mechanism of resistance. Int J Antimicrob Agents. 2004;23:113–9.

    Article  CAS  PubMed  Google Scholar 

  9. Dietze R, Hadad DJ, McGee B, Molino LP, Maciel EL, Peloquin CA, et al. Early and extended early bactericidal activity of linezolid in pulmonary tuberculosis. Am J Respir Crit Care Med. 2008;178:1180–5.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Zurenko GE, Yagi BH, Schaadt RD, Allison JW, Kilburn JO, Glickman SE, et al. In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents. Antimicrob Agents Chemother. 1996;40:839–45.

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Sood R, Bhadauriya T, Rao M, Gautam R, Malhotra S, Barman TK, et al. Antimycobacterial activities of oxazolidinones: a review. Infect Disord Drug Targets. 2006;6:343–54.

    Article  CAS  PubMed  Google Scholar 

  12. Rodriguez JC, Ruiz M, Lopez M, Lopez M, Royo G. In vitro activity of moxifloxacin, levofloxacin, gatifloxacin and linezolid against Mycobacterium tuberculosis. Int J Antimicrob Agents. 2002;20:464–7.

    Article  CAS  PubMed  Google Scholar 

  13. Cynamon MH, Klemens SP, Sharpe CA, Sharpe CA, Chase S. Activities of several novel oxazolidinones against Mycobacterium tuberculosis in a murine model. Antimicrob Agents Chemother. 1999;43:1189–91.

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Ntziora F, Falagas ME. Linezolid for the treatment of patients with mycobacterial infections: a systematic review. Int J Tuberc Lung Dis. 2007;11:606–11.

    CAS  PubMed  Google Scholar 

  15. Richter E, Rusch-Gerdes S, Hillemann D. First linezolid-resistant clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2007;51:1534–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Anger HA, Dworkin F, Sharma S, Munsiff SS, Nilsen DM, Ahuja SD, et al. Linezolid use for treatment of multidrug-resistant and extensively drug-resistant tuberculosis, New York City, 2000–06. J Antimicrob Chemother. 2010;65:775–83.

    Article  CAS  PubMed  Google Scholar 

  17. Sotgiu G, Centis R, D'Ambrosio L, Alffenaar JW, Anger HA, Caminero JA, et al. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis. Eur Respir J. 2012;40:1430–42.

    Article  CAS  PubMed  Google Scholar 

  18. Xu HB, Jiang RH, Li L, Xiao HP. Linezolid in the treatment of MDR-TB: a retrospective clinical study. Int J Tuberc Lung Dis. 2012;16:358–63.

    Article  PubMed  Google Scholar 

  19. Schecter GF, Scott C, True L, Raftery A, Flood J, Mase S. Linezolid in the treatment of multidrug-resistant tuberculosis. Clin Infect Dis. 2010;50:49–55.

    Article  CAS  PubMed  Google Scholar 

  20. World Health Organization. Guidelines for surveillance of drug resistance in tuberculosis, 4th ed. WHO/HTM/TB/2009.422. Geneva: World Health Organization; 2009.

  21. Pang Y, Lu J, Wang Y, Song Y, Wang S, Zhao Y. Study of the rifampin monoresistance mechanism in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2013;57:893–900.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Pang Y, Zhou Y, Zhao B, Liu G, Jiang G, Xia H, et al. Spoligotyping and drug resistance analysis of Mycobacterium tuberculosis strains from national survey in China. PLoS ONE. 2012;7:e32976.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Condos R, Hadgiangelis N, Leibert E, Jacquette G, Harkin T, Rom WN. Case series report of a linezolid-containing regimen for extensively drug-resistant tuberculosis. Chest. 2008;134:187–92.

    Article  CAS  PubMed  Google Scholar 

  24. Yew WW, Chau CH, Wen KH. Linezolid in the treatment of ‘difficult’ multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2008;12:345–6.

    CAS  PubMed  Google Scholar 

  25. Hillemann D, Rusch-Gerdes S, Richter E. In vitro-selected linezolid-resistant Mycobacterium tuberculosis mutants. Antimicrob Agents Chemother. 2008;52:800–1.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The study was supported by National Key Project (2013003ZX003).

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Authors

Corresponding authors

Correspondence to M. Gao, H. Huang or Y. Zhao.

Additional information

Liqun Zhang, Yu Pang and Xia Yu have contributed equally to this study.

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Zhang, L., Pang, Y., Yu, X. et al. Linezolid in the treatment of extensively drug-resistant tuberculosis. Infection 42, 705–711 (2014). https://doi.org/10.1007/s15010-014-0632-2

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  • DOI: https://doi.org/10.1007/s15010-014-0632-2

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