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Published in: Infection 4/2014

01-08-2014 | Clinical and Epidemiological Study

Linezolid in the treatment of extensively drug-resistant tuberculosis

Authors: L. Zhang, Y. Pang, X. Yu, Y. Wang, M. Gao, H. Huang, Y. Zhao

Published in: Infection | Issue 4/2014

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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.
Literature
1.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
2.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
3.
go back to reference World Health Organization. Anti-tuberculosis drug resistance in the world: fourth global report. WHO/HTM/TB/2008.394. Geneva: World Health Organization; 2008. World Health Organization. Anti-tuberculosis drug resistance in the world: fourth global report. WHO/HTM/TB/2008.394. Geneva: World Health Organization; 2008.
4.
5.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
6.
go back to reference 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.CrossRef 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.CrossRef
7.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
8.
go back to reference Bozdogan B, Appelbaum PC. Oxazolidinones: activity, mode of action, and mechanism of resistance. Int J Antimicrob Agents. 2004;23:113–9.PubMedCrossRef Bozdogan B, Appelbaum PC. Oxazolidinones: activity, mode of action, and mechanism of resistance. Int J Antimicrob Agents. 2004;23:113–9.PubMedCrossRef
9.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
10.
go back to reference 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.PubMedCentralPubMed 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.PubMedCentralPubMed
11.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
12.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
13.
go back to reference 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.PubMedCentralPubMed 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.PubMedCentralPubMed
14.
go back to reference 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.PubMed 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.PubMed
15.
go back to reference Richter E, Rusch-Gerdes S, Hillemann D. First linezolid-resistant clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2007;51:1534–6.PubMedCentralPubMedCrossRef Richter E, Rusch-Gerdes S, Hillemann D. First linezolid-resistant clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2007;51:1534–6.PubMedCentralPubMedCrossRef
16.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
17.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference World Health Organization. Guidelines for surveillance of drug resistance in tuberculosis, 4th ed. WHO/HTM/TB/2009.422. Geneva: World Health Organization; 2009. World Health Organization. Guidelines for surveillance of drug resistance in tuberculosis, 4th ed. WHO/HTM/TB/2009.422. Geneva: World Health Organization; 2009.
21.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
22.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference Yew WW, Chau CH, Wen KH. Linezolid in the treatment of ‘difficult’ multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2008;12:345–6.PubMed Yew WW, Chau CH, Wen KH. Linezolid in the treatment of ‘difficult’ multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2008;12:345–6.PubMed
25.
go back to reference Hillemann D, Rusch-Gerdes S, Richter E. In vitro-selected linezolid-resistant Mycobacterium tuberculosis mutants. Antimicrob Agents Chemother. 2008;52:800–1.PubMedCentralPubMedCrossRef Hillemann D, Rusch-Gerdes S, Richter E. In vitro-selected linezolid-resistant Mycobacterium tuberculosis mutants. Antimicrob Agents Chemother. 2008;52:800–1.PubMedCentralPubMedCrossRef
Metadata
Title
Linezolid in the treatment of extensively drug-resistant tuberculosis
Authors
L. Zhang
Y. Pang
X. Yu
Y. Wang
M. Gao
H. Huang
Y. Zhao
Publication date
01-08-2014
Publisher
Springer Berlin Heidelberg
Published in
Infection / Issue 4/2014
Print ISSN: 0300-8126
Electronic ISSN: 1439-0973
DOI
https://doi.org/10.1007/s15010-014-0632-2

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