Page 856 - Basic _ Clinical Pharmacology ( PDFDrive )

47 Antimycobacterial Drugs
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Camille E. Beauduy, PharmD, &
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Lisa G. Winston, MD

C ASE STUD Y

A 60-year-old man presents to the emergency department tuberculosis, the patient is placed in respiratory isolation.
with a 2-month history of fatigue, weight loss (10 kg), fevers, His first sputum smear shows many acid-fast bacilli, and an
night sweats, and a productive cough. He is currently living HIV test returns with a positive result. What drugs should
with friends and has been intermittently homeless, spending be started for treatment of presumptive pulmonary tubercu-
time in shelters. He reports drinking about 6 beers per day. losis? Does the patient have a heightened risk of developing
In the emergency department, a chest x-ray shows a right medication toxicity? If so, which medication(s) would be
apical infiltrate. Given the high suspicion for pulmonary likely to cause toxicity?

Mycobacteria are intrinsically resistant to most antibiotics. active drugs. An isoniazid-rifampin combination administered for
Because they grow more slowly than other bacteria, antibiotics 9 months will cure 95–98% of cases of tuberculosis caused by sus-
that are most active against rapidly growing cells are relatively ceptible strains. An initial intensive phase of treatment is recom-
ineffective. Mycobacterial cells can also be dormant and, thus, mended for the first 2 months due to the prevalence of resistant
resistant to many drugs or killed only very slowly. The lipid-rich strains. The addition of pyrazinamide during this intensive phase
mycobacterial cell wall is impermeable to many agents. Mycobac- allows the total duration of therapy to be reduced to 6 months
terial species are intracellular pathogens, and organisms residing without loss of efficacy. In practice, therapy is usually initiated
within macrophages are inaccessible to drugs that penetrate these with a four-drug regimen of isoniazid, rifampin, pyrazinamide,
cells poorly. Finally, mycobacteria are notorious for their ability and ethambutol until susceptibility of the clinical isolate has
to develop resistance. Combinations of two or more drugs are been determined. In susceptible isolates, the continuation phase
required to overcome these obstacles and to prevent emergence of consists of an additional 4 months with isoniazid and rifampin
resistance during the course of therapy. The response of mycobac- (Table 47–2). Neither ethambutol nor other drugs such as strep-
terial infections to chemotherapy is slow, and treatment must be tomycin adds substantially to the overall activity of the regimen
administered for months to years, depending on which drugs are (ie, the duration of treatment cannot be further reduced if another
used. The drugs used to treat tuberculosis, atypical mycobacterial drug is used), but the fourth drug provides additional cover-
infections, and leprosy are described in this chapter. age if the isolate proves to be resistant to isoniazid, rifampin,
or both. If therapy is initiated after the isolate is known to be
■ DRUGS USED IN TUBERCULOSIS susceptible to isoniazid and rifampin, ethambutol does not
need to be added. The prevalence of isoniazid resistance among
clinical isolates in the USA is approximately 10%. Prevalence
Isoniazid (INH), rifampin (or other rifamycin), pyrazinamide, of resistance to both isoniazid and rifampin (which is termed
and ethambutol are the traditional first-line agents for treatment multidrug resistance) ranged from 1 to 1.6% from the years
of tuberculosis (Table 47–1). Isoniazid and rifampin are the most
2000 to 2013 in the USA. Multidrug resistance is much more
prevalent in many other parts of the world. Resistance to
* The authors thank Henry F. Chambers, MD and Daniel H. Deck, rifampin alone is rare.
PharmD for their contributions to previous editions.
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