Antimycobacterial Drugs

Introduction to Antimycobacterial Drugs Tuberculosis, the disease caused by  Mycobacterium tuberculosis, is one of the world’s most formidable infections. Tuberculosis and other mycobacterial dis-eases are difficult to treat for several reasons.

Mycobacteria replicate more slowly than “typical”  bacteria such as  E. coli  or  Staphylococcus aureus.  This may seem to make the disease easier to control,  but it makes pharmacotherapy more difficult because rapidly dividing cells are most metabolically active and therefore susceptible to antibiotic chemotherapy.  Mycobacteria can also exist in a dormant state,  making them resistant to nearly  antibiotics. They are intracellular organisms, and therefore drugs that do not work within cells are ineffective. Mycobacteria also have cell walls that are structurally different from typical Gram-positive and Gram-negative bacteria. The outermost layer of mycobacteria consists of phospholipids and mycolic acids that make a waxy layer that resists penetration from antibiotics. Arabinogalactan and peptidoglycan are polysaccharide components of the cell wall, but the peptidoglycan is not accessible to beta-lactam antibiotics, and they are largely inactive. Figure 1  shows the basic structure of mycobacteria.

Figure 1: Mycobacterial Cell Wall

The pharmacotherapy of mycobacterial disease is complex. Combinations of drugs are always given for patients with active disease to minimize the development of resistance and shorten the duration of therapy. These combinations interact with each other and often with other medications that the patient is on, because immunocompromised patients are particularly vulnerable to mycobacterial dis-ease. Because mycobacteria grow slowly, susceptibility testing takes weeks instead of days to perform, so empiric regimens are often given for extended durations. For tuberculosis, the standard of care for patients with active infections is to start with a 4-drug regimen, so compliance and careful watching for drug interactions are important.

 First-line drugs for tuberculosis and MAC are discussed in this section. Many second-line drugs are available for tuberculosis; however, because the treatment of multidrug-resistant tuberculosis requires the management of an infectious diseases specialist, we omit them from this text. The following antimycobacterial drugs are listed in the anti-bacterial chapters: fluoroquinolones (moxifloxacin is particularly active), macrolides, and aminoglycosides. It is particularly important to know the toxicities of the first-line agents for tuberculosis, because they each have a characteristic one. You can expect questions about these characteristics to pop up on a lot of exams, both in school and for licensure.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.