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Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 252 - 252
1 Sep 2005
Jutte P Rutgers S van Altena R van Horn J
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Introduction: Data on intralesional concentrations of modern anti-tuberculosis drugs isoniazid (H), rifampin (R) and pyrazinamid (Z) in tuberculous pleural effusions and psoas abscesses are scarce. Insight into drug penetration is important since subtherapeutic drug concentrations may result in the selection of a resistant bacterial population and lead to treatment failure.

Material and Methods: Intralesional concentrations were measured 2 hours after drug administration in 6 patients with pleural effusions, and 10 with psoas abscesses.

Results: Concentrations were variable. The same range was found for pleural effusions and psoas abscesses. Concentrations were below MIC values in none of 15 patients for H, in 2 of 13 for R, and in 8 of 9 for Z. Cmax:MIC ratio was always > 4 for H, in 4 of 13 for R, and in none of 9 for Z. In 5:8 patients receiving all 3 drugs both R and Z had Cmax:MIC ratios < 4, indicating subtherapeutic drug levels.

Conclusion: Intralesional drug concentrations of isoniazid (H), rifampin (R), and pyrazinamid (Z) were variable. The same range was found for pleural effusions and psoas abscesses. Cmax:MIC ratio for H was always sufficient, for R in most cases below the desired ratio, and for Z on average 10 times too low. In 5 of 8 patients receiving all 3 drugs, both R and Z had Cmax:MIC ratios below 4, indicating intralesional subtherapeutic drug levels for R and Z. This local monotherapy with H may result in the selection of a resistant bacterial population and lead to failure of treatment. Drainage as additional therapy seems indicated.