1/3. Clinical use of levofloxacin in the long-term treatment of drug resistant tuberculosis.Multidrug-resistant (MDR) tuberculosis (TB) is a form of TB that is resistant to some of the first-line drugs used for the treatment of the disease. It is associated both with a higher incidence of treatment failures and of disease recurrence, as well as with higher mortality than forms of TB sensitive to first-line drugs. levofloxacin (LFX) represents one of the few second-line drugs recently introduced in the therapeutic regimens for MDR TB. We report our experience concerning in vitro activity and clinical safety of LFX in long term second-line regimens for MDR TB. in vitro ACTIVITY ON MYCOBACTERIA: The in vitro activity of ciprofloxacin, ofloxacin and LFX was studied on 28 strains belonging to different species of Mycobacteria. In Dubos medium, LFX inhibited the growth of both library and MDR clinical Mycobacteria strains in a range of 0.25-1 mcg/ml. In International Union Tuberculosis Medium (IUTM) the minimum inhibitory concentrations (MIC) were slightly higher, but LFX activity was not affected by the higher complexity of the medium. CLINICAL EXPERIENCE: Four patients with MDR TB were treated with a second-line regimen comprising oral LFX 500 mg twice daily, for at least 9 months. Two isolates obtained from the patients reported here showed multi resistance to isoniazid and rifampin, one to rifampin and streptomycin and one to isoniazid and ethambutol. During therapy, no significant alteration of either liver function tests, blood tests or any other described side effect of the fluoroquinolone class was observed. The 3 patients with pulmonary MDR TB showed radiologic and clinical improvement. CONCLUSION: We confirm the higher in vitro activity of LFX compared to older fluoroquinolones. Furthermore, in a limited number of MDR TB patients, second-line regimens comprising LFX 500 mg b.i.d. administered in a range of 9-24 months were well tolerated and safe.- - - - - - - - - - ranking = 1keywords = treatment failure (Clic here for more details about this article) |
2/3. Low serum antimycobacterial drug levels in non-hiv-infected tuberculosis patients.BACKGROUND: Despite the use of directly observed therapy (DOT) by tuberculosis control programs, patient treatment failure, relapse, and acquired drug resistance remain problematic in a small number. We investigated serum drug levels in non-hiv-infected tuberculosis patients who were receiving DOT by the health department and did not respond to treatment as expected. methods: The indications for checking levels were as follows: (1) slow clinical response or failure to convert the sputum culture within 12 weeks; (2) treatment failure, early disease relapse < 13 months since being declared cured; (3) relapse, late disease reactivation > or = 13 months since being declared cured; and (4) acquired drug resistance while receiving DOT. Baseline characteristics of control subjects who responded to therapy as expected were compared. Venous blood for analysis was obtained at 2 h after directly observed ingestion and measured by high-performance liquid chromatography. RESULTS: Twenty-four patients receiving daily or twice-weekly standard therapy with isoniazid (INH, 300 or 900 mg) and rifampin (RMP, 600 mg) were identified; 22 had drug levels evaluated at 2 h. For INH, 15 of 22 patients (68%) had levels less than the reported target range. For RMP, 14 of 22 patients (64%) had low levels. Among the 14 patients receiving INH, 900 mg, and RMP, 600 mg, 4 (29%) had very low levels of both. Use of a combination INH/RMP tablet was associated with lower INH levels (p=0.04); however, RMP levels were higher (p<0.02). Alcohol use was associated with significantly higher RMP (p<0.01) serum concentrations. CONCLUSIONS: Important questions remain concerning the utility and timing of serum drug measurements. However, if a patient is not responding to therapy as expected and one is assured that the mycobacterium tuberculosis organism is susceptible to the drugs given and that the patient is taking the medication as prescribed, drug level monitoring should be considered.- - - - - - - - - - ranking = 2keywords = treatment failure (Clic here for more details about this article) |
3/3. Fatal primary multidrug-resistant tuberculosis in a heart transplant recipient.The incidence of tuberculosis (TB) worldwide is currently on the rise, not only in the general population but also quite notably among immunosuppressed patients. Its incidence among patients undergoing antirejection therapy is considerably higher than in the general population, and heart transplant recipients have been found to carry the highest risk of TB. There are no reported data, however, on primary TB caused by multidrug-resistant (MDR) mycobacterium tuberculosis (M. tuberculosis) in heart transplant recipients. We describe the case of a patient who developed active primary MDR TB following the reactivation of a latent tuberculous infection 6 months after transplantation. The patient was most likely infected by M. tuberculosis during a period of time he spent in prison 10 years before undergoing transplantation, but he never developed active tuberculosis, nor did he ever receive antituberculous medication prior to transplantation. Because of the atypical clinical presentation, establishment of the diagnosis was postponed, and the resistance pattern of the isolate grown from bronchoalveolar lavage (BAL) specimens (resistant to isoniazid and rifampicin) led to treatment failure and a fatal outcome. The adoption of the most rapid diagnostic tools for the identification of M. tuberculosis and for a quick screening of drug-resistant isolates is urgently needed in those centers where organ transplantation is carried out.- - - - - - - - - - ranking = 1keywords = treatment failure (Clic here for more details about this article) |