Ryan_ch27_p489-506.indd

manage their side eff ects. Second-line agents are less preferred and reserved for use when
there is resistance to the fi rst-line agents. Th
e approach with new cases is to start the patient on multiple (usually four) fi rst-line drugs while waiting for the results of susceptibility tests. When these results are available, the regimen is dropped back to two or three agents known to be active against the patient's isolate.
Isoniazid and rifampin are active against both intra- and extracellular organisms, and pyrazinamide acts at the acidic pH found within cells. Streptomycin does not penetrate into cells and is thus active only against extracellular organisms. MTB is also susceptible to other drugs that may be used to replace those of the primary group if they are inappropri- ate because of resistance or drug toxicity. Th e fl uoroquinolones, such as ciprofl oxacin and ofl oxacin, are active against MTB and penetrate well into infected cells. Th treatment of tuberculosis is under evaluation. Isoniazid and ethambutol act on the mycolic acid (isoniazid) and LAM (ethambutol) elements of mycobacterial cell wall synthesis. Th molecular targets of the other agents have yet to be defi ned except for the general antibacte-rial agents (rifampin, streptomycin, fl uoroquinolones) discussed in Chapter 23.
Because of the high bacterial load and long duration of anti-MTB therapy, the emergence of resistance during treatment is of greater concern than with more acute infections. For this reason, the use of multiple drugs each with a diff erent mode of action is the norm. Expres-sion of resistance would then theoretically require a double mutant, a very low probability when the frequency of single mutants is 10-7 to 10-10. Th strains resistant to fi rst-line drugs varies between 5% and 15%, but it appears to be increas-ing, particularly among those who have been treated previously. Of particular concern is the emergence in the last two decades of multidrug-resistant tuberculosis (MDR-TB) strains, which are resistant to isoniazid and rifampin, the mainstays of primary treatment. MDR-TBs now represent almost 5% of the worldwide cases, and over half of these are con-centrated in three countries, China, India, and the Russian Federation. Although still rare, strains that add resistance to one or more second-line drugs (called extensively drug resis-tant [XDR-TB]) are now being seen.
Eff ective treatment renders the patient noninfectious within 1 or 2 weeks, which has shift ed the care of tuberculous patients from isolation hospitals and sanatoriums to the e duration of therapy varies, based on some clinical factors but is usually 6 to 9 months. In patients whose organisms display resistance to one or more of these drugs, and in those with HIV infection, a more prolonged treatment course is used. Th e eff ectiveness of chemotherapy on most forms of tuberculosis has been dramatic and has greatly reduced the need for surgical procedures such as pulmonary lobectomy. Failure of chemotherapy is oft en associated with lack of adherence to the regimen by the patient, the presence of resistant organisms, or both.
PREVENTION
ere are a number of situations in which persons are felt to be at increased risk for tuber- culosis even though they have no clinical evidence of disease (healthy, negative chest x-ray, etc.). Th e most common of these situations are close exposure to an open case (particu- larly a child) and conversion of the tuberculin skin test from negative to positive. In these instances, prophylactic chemotherapy with isoniazid (alone) is administered for 6 to 9 months. In the exposed person, the goal is to prevent a primary infection. Th tive person has already had a primary infection; therefore, the goal is to reduce the chance of reactivation tuberculosis by eradicating any dormant MTB in the body. Th phylaxis has clear value for the exposed person and recent skin test converters. It is less certain for those whose time of conversion is uncertain and could have been many years ago. Isoniazid may cause a form of hepatitis in adults so its administration carries some risk. ::: Chemoprophylaxis, p. 426 BCG is a live vaccine derived originally from a strain of M bovis that was attenuated by repeated subculture. It is administered intradermally to tuberculin-negative subjects and leads to self-limiting local multiplication of the organism with development of tuber- e latter negates the PPD as a diagnostic and epidemiologic tool. BCG has been used for prevention of tuberculosis in various countries since 1923, with results rang-ing from ineff ective to 80% protection. In most studies, however, BCG has substantially

Source: http://langetextbooks.com/0071604022/quizzes/references/Ryan_CH27_p500.pdf