Penetration of isoniazid, rifampicin and pyrazinamide in tuberculous pleural effusion and psoas abscess.
METHODS
Tuberculosis Centre, University Medical Centre, Groningen, The Netherlands.


OBJECTIVE
To study intralesional concentrations of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) in tuberculous pleural effusions and psoas abscesses, and to compare these to reference serum values and minimal inhibitory concentration (MIC).


METHODS
Intralesional concentrations were measured 2 h after drug administration (six pleural effusions, 10 psoas abscesses).


RESULTS
A wide range of concentrations was found for pleural effusions and psoas abscesses. Concentrations were below MIC values in none of 15 patients for INH, in two of 13 for RMP, and in eight of nine for PZA. The Cmax:MIC ratio was always >4 for INH, in four of 13 for RMP, and in none of nine for PZA. In 5/8 patients receiving all three drugs, both RMP and PZA had Cmax:MIC ratios <4, indicating sub-therapeutic drug levels.


CONCLUSIONS
Penetration of INH was always sufficient, penetration of RMP mostly below the desired ratio, and for PZA on average 10 times too low. Five of eight patients on all three drugs had Cmax:MIC ratios <4. This indicates intralesional sub-therapeutic drug levels for RMP and PZA, and local monotherapy with INH. This could induce drug resistance. Drainage as additional therapy seems indicated.
Jutte
P C
PC
Department of Orthopedic Surgery, University Medical Center Groningen, Groningen, The Netherlands. p.c.jutte@orth.azg.nl
Rutgers
S R
SR
Van Altena
R
R
Uges
D R
DR
Van Horn
J R
JR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009426:Netherlands; D010996:Pleural Effusion / Q000150:complications / Q000378:metabolism*; D016659:Psoas Abscess / Q000150:complications / Q000378:metabolism*; D011718:Pyrazinamide / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012293:Rifampin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy; D055815:Young Adult
D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin