INTRODUCTION

In general, first-line treatment of tuberculosis consists of combination therapy with isoniazid, rifampin (rifapentine and rifabutin under specific situations), pyrazinamide, and ethambutol. In the setting of drug resistance or intolerance to first line agents, second-line agents may be used (table 1). These include fluoroquinolones, injectable agents and less effective agents or drugs for which clinical data are sparse.

The second-line antituberculous drugs are so classified because of relative lack of clinical data, unfavorable or poorly characterized pharmacokinetic profile, and/or increased incidence and severity of adverse events (table 2) [1,2]. Experience with some of these agents is increasing based upon the need for alternative therapies for treatment of drug resistant TB.

This topic will review pharmacologic issues related to use of second-line antituberculous drugs, with the exception of the fluoroquinolones and aminoglycosides (other than streptomycin); these are discussed separately. (See "Fluoroquinolones" and "Aminoglycosides".)

The clinical approaches to treatment of tuberculosis and drug-resistant tuberculosis are discussed separately. (See "Treatment of pulmonary tuberculosis in HIV-negative patients" and "Treatment of pulmonary tuberculosis in the HIV-infected patient" and "Diagnosis, treatment, and prevention of drug-resistant tuberculosis", section on 'Clinical approach'.)

INDICATIONS FOR USE

There are two major indications for the use of second-line therapy in the treatment of tuberculosis: resistance of the M. tuberculosis isolate to first-line agents, and/or patient intolerance (including hypersensitivity reactions) to first-line drugs.