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TUBERCULOSIS•Diagnosis•Indications for testing•Definitive diagnosis•Chest x-ray•Sputum culture•Evaluating drug sensitivity•Treatment regimens•Duration of treatment•Promoting adherence•Evaluating treatment
CAUSES OF DRUG RESISTANCE•Some infecting bacilli inherently resistant•Some develop resistance over course of treatment•Resistance to one drug vs. many drugs•Infection with resistant TB acquired through:•Contact with someone who harbors resistant bacteria•Repeated ineffectual courses of therapy
MULTIDRUG RESISTANCE WITH TUBERCULOSIS•Multidrug-resistant TB (MDR TB)•Resistant to both isoniazid and rifampin•Extensively drug-resistant TB (XDR TB)•Resistant to:•Isoniazid (INH) and rifampin•All fluoroquinolones•At least one of the injectable second-line drugs
TREATMENT REGIMENS FOR TUBERCULOSIS•The prime directive of treatment:ALWAYS treat tuberculosis with two or moredrugs!
TREATMENT REGIMENS FOR TUBERCULOSIS•Determine drug sensitivity•Treatment regimens: two phases•Induction phase•Eliminate actively dividing tubercle bacilli•Continuation phase•Eliminate intracellular “persisters”
TREATMENT REGIMENS FOR TUBERCULOSIS•Drug-sensitive tuberculosis•Isoniazid or rifampin-resistant tuberculosis•MDR TB and XDR TB•Patients with TB and HIV infection•Duration of treatment•Minimum 6 months for drug-sensitive TB•Up to 24 months for MDR or HIV/AIDS
PROMOTING TREATMENT ADHERENCE•Direct observation therapy (DOT)•Patient nonadherence•Allows for ongoing assessment of clinical signs•Intermittent dosing•2–3 times a week
EVALUATION OF TREATMENT•Three modes to evaluate therapy•Bacteriologic evaluation of sputum•Clinical evaluation•Chest radiographs
DIAGNOSIS AND TREATMENT OF LATENT TUBERCULOSIS•9–14 million people in United States have latent TB (LTB)•5%–10% will develop active TB without treatment•Targeted TB testing•Who should be tested?•Testing for latent TB•TB skin test (TST)•QuantiFERON-TB Gold (QFT-G) blood test
DIAGNOSIS AND TREATMENT OF LATENT TUBERCULOSIS•INH •Treatment of choice•Drawbacks of INH•Short-course therapy: rifampin alone•Short-course therapy: rifampin plus pyrazinamide•Vaccination against tuberculosis
ANTITUBERCULOSIS DRUGS •First-line drugs•Isoniazid, rifampin•Rifapentine, rifabutin, pyrazinamide, and ethambutol•Second-line drugs•Levofloxacin, moxifloxacin, kanamycin, amikacin, capreomycin, para-aminosalicylic acid, ethionamide, and cycloserine
RIFAMPIN (RIFADIN)•Adverse effects•Hepatotoxic/hepatitis•Discoloration of body fluids•GI disturbances•Drug interactions•Induces P450; can hasten drug metabolism •Oral contraceptives•Warfarin•Drugs for HIV infection
PYRAZINAMIDE•Bactericidal to M. tuberculosis•Use•Tuberculosis•Adverse effects•Hepatotoxicity•Hyperuricemia•GI disturbances