Evaluation of the Early Bactericidal Activity of Tedizolid and Linezolide Against Mycobacterium Tuberculosis (TEDITUB) (TEDITUB)
Tuberculosis, Multidrug Resistant Tuberculosis
About this trial
This is an interventional treatment trial for Tuberculosis focused on measuring Tuberculosis, Multidrug Resistant, Linezolid, Tedizolid, Pyrazinamide, Rifampicin, Isionazid, Ethambutol, Early Bactericidal Activity
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years old and <75 years old
- Patient with a first infection with Mycobacterium tuberculosis of pulmonary localization suspected by the presence of a clinical pulmonary symptomatology, a chest X-ray or an abnormal chest computed tomography, and the positive microscopic examination of a sputum (AFB +, presence of AFB) with confirmation of tuberculosis by a genotypic test demonstrating no resistance to rifampicin, without clinical signs of extra-thoracic involvement
- State medical assistance application being processed ( If patient does not benefit from social security),
- Signature of informed consent
Exclusion Criteria:
Exclusion Criteria :
- Resistance to one of the anti-tuberculosis drugs used detected by a genotypic test in accordance with the recommendations of the High Council of Public Health of 2015;
- History of anti-tuberculosis treatment;
- History of treatment in the previous two years with one of the antibiotics evaluated in this trial lasting more than one month;
- Absolute contraindication to the use of at least one of the test molecules (isoniazid, rifampicin, ethambutol, pyrazinamide, linezolid, tedizolid);
- Tuberculosis having, in the opinion of the investigator, severity criteria not allowing to wait 7 days before starting standard treatment (oxygenorequirement, severe immunosuppression, extra-pulmonary involvement, any sign of severity requiring treatment in intensive care unit);
- HIV-infected patient receiving protease inhibitors whose antiviral treatment cannot be changed and therefore cannot receive rifampicin;
- Neoplastic pathology during treatment with chemo and / or radiotherapy;
- Decompensated cirrhosis;
- Pregnancy, desire to become pregnant, breast-feeding (for women of childbearing potential, contraception should be used for the duration of the study; mechanical contraception will be strongly recommended);
- Significant laboratory abnormalities (hemoglobin <9g / dl, polynuclear neutrophils <500 / mm3, platelets <50,000 / mm3, creatinine clearance <30ml / min, ASAT or ALAT> 3N, and total bilirubin> 3N)
- Hyperuricaemia
- Porphyria
- Optic neuritis or peripheral neuropathy
- BMI≤ 16 kg/m2
- Participation in other interventional research
Sites / Locations
- Bacteriology department- Hôpital Saint-AntoineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
Tedizolid arm
Linezolid arm
Standard quadruple therapy arm
Patients will be taken 1 tablet per day of 200 mg film-coated of Tedizolid (SIVEXTRO®), in the morning for 7 days. Then, the early bactericidal activity will be measured and compared to the other arms.
Patients will be taken 2 tablets per day of 600 mg film-coated of Linezolid (ZYVOXID®) in the morning for 7 days. Then, the early bactericidal activity will be measured and compared to the other arms.
Patients will be taken : ISONIAZIDE : o A dosage of 3 to 5mg / kg / day for 7 days (to be taken in the morning on an empty stomach) of Isoniazid (RIMIFON®) RIFAMPICINE : o A dosage of 10mg / kg / day for 7 days (to be taken in the morning on an empty stomach) ETHAMBUTOL : o A dosage of 15-20mg / kg / day for 7 days (to be taken in the morning on an empty stomach) of Ethambutol PYRAZAMIDE : o A dosage of 20-25mg / kg / day for 7 days (to be taken in the morning on an empty stomach) of Pyrazinamide Then, the early bactericidal activity will be measured and compared to the other arms.