Pneumologie 2009; 63 - V159
DOI: 10.1055/s-0029-1214065

Safety, tolerability and efficacy of linezolid in the treatment of MDR- and XDR-TB. A TBNET survey

BM Giovanni 1, B Eker 2, M Richardson 3, G Sotgiu 4, J Zellweger 5, A Skrahina 6, J Ortmann 7, E Girardi 8, H Hoffmann 9, G Besozzi 10, R Centis 1
  • 1Fondazione S. Maugeri, Tradate, Italy
  • 2Research Center Borstel, Germany
  • 3PATH, Seattle, Washington, USA
  • 4University of Sassari, Sassari, Italy
  • 5University of Lausanne, Switzerland
  • 6Research Institute of Pulmonology and Tuberculosis, Minsk, Belarus
  • 7Hospital Gera
  • 8National Institute for Infectious Diseases, Rome, Italy
  • 9Asklepios Clinic Gauting
  • 10E. Morelli Hospital, Sondalo, Italy

Aims: Antibiotic resistance of Mycobacterium tuberculosis is an emerging problem in the fight against tuberculosis. Linezolid-containing multi-drug-regimen have been suggested for the treatment of complicated cases of MDR/XDR-TB, however, clinical data on the safety, tolerability and efficacy of linezolid in the treatment against tuberculosis are lacking.

Methods: We performed a retrospective, multi-center, observational cohort study with a nested case-control study at different centers in four European countries to evaluate the safety and tolerability of linezolid at 600mg once (OD) or twice daily (BD) in the treatment against MDR/XDR-TB. Efficacy was evaluated comparing endpoints of 45 linezolid-treated cases with a definitive treatment outcome against 110 controls.

Results: Eighty-five/195 patients with MDR/XDR-TB were treated with linezolid for a mean period of 221 days. Thirtee-five/85 (41.2%) patients experienced adverse drug-events attributed to linezolid, mainly anaemia, thrombocytopenia and polyneuropathy, requiring discontinuation of linezolid-treatment in 27 (77%) cases. Major adverse drug-events occurred more often with BD than with OD administration (p=0.0004) and in only 2/27 (4%) cases with BD administration in the first two months of treatment. Treatment outcome was similar in patients treated with linezolid and controls (p=0.8) although cases had a worse drug resistance profile and higher number of previous treatments than controls (p=0.002 for first-line and p=0.02 for second-line drugs).

Conclusion

The study results suggest the use of linezolid at the lower dosage of 600mg OD in the first two months of treatment in addition to an individualized multidrug-regimen only for the most difficult-to-treat MDR-/XDR-TB cases.