Drug Therapy: Tuberculosis Treatment

Study Notes

Requires prolonged therapy with multiple agents, due to the risk of decreased adherence and emergence of drug-resistant bacteria
Multidrug-resistant TB (MDR-TB): Resistance to both isoniazid and rifampin
Extensively drug-resistant TB (XDR-TB): Resistance to both isoniazid and rifampin, and to all fluoroquinolones, and at least one injectable second-line agent
Treatment regimens for active TB must always contain two or more drugs; isoniazid and rifampin are almost always included if the patient is not allergic, and the infecting organisms are not resistant
Nonadherence is the most common cause of treatment failure and drug-resistant TB
Directly Observed Therapy (DOT): Dosing in the presence of an observer, usually someone from the health department
Intermittent dosing schedules: Daily versus 2-3 times per week; DOT combined with intermittent dosing promotes adherence and decreases the risk of resistance

Induction phase: Two months in duration; Four agents: isoniazid, rifampin, pyrazinamide, ethambutol; Daily, twice weekly, or three times weekly dosing schedules; Goal is to eliminate actively dividing extracellular tubercle bacilli
Continuation phase: Four months in duration; Two agents: isoniazid and rifampin; Daily, twice weekly, or three times weekly dosing schedules; Goal is to eliminate intercellular persisters
Landmark TB Trial in October 2020: Results indicated that a four-month daily treatment regimen of high-dose, or “optimized", Rifapentine with Moxifloxacin is as safe and effective as the existing standard six-month daily regimen

Single-agent resistant infections: Resistance to either isoniazid or rifampin; Treatment is with the other three drugs; Duration of treatment is 18-24 months; Usually responds well to treatment
MDR and XDR TB: Much harder to manage; Treatment is prolonged, 24+ months; Initial therapy may require 5-7 agents; Uses second and third-line agents, more toxic/less effective; Prognosis is poorer

Incidence of TB is higher in the population of patients with HIV
Prolonged duration of TB treatment and more aggressive treatment is required in patients with HIV because patients with HIV are immunosuppressed
Rifampin is a cornerstone of TB treatment but should not be given with protease inhibitors and NNRTIs because the effectiveness of these HIV treatments are diminished with rifampin
No good answer exists for the dilemma of treating both TB and HIV in a patient when rifampin is needed but will impede the effectiveness of HIV treatments

Treatment for latent TB is lengthy and there is risk for drug toxicity
Testing and treatment limited to those who really need it; People suspected of having recently acquired the infection; Those at risk for progressing from latent to active TB due to immunocompromise
Two equally effective treatment options available in the U.S.: Isoniazid daily for nine months, total # of doses is 270; Isoniazid plus rifapentine taken weekly for three months, total # of doses is 12
Ruling out active TB before starting treatment for latent TB is critical to prevent undertreatment and emergence of resistant bacilli

Isoniazid
Rifampin
Rifampentine
Rifabutin
Pyrazinamide
Ethambutol
Usually a combination of 3-4 first-line agents are used to decrease the risk of resistance

Always used in combination with first-line agents
Generally less effective, more expensive, and more toxic than first-line drugs
Principle indication: Resistance to a first-line agent
Used in combination with first-line agents to treat severe pulmonary TB and disseminated TB