Skip to Main Content

++

INTRODUCTION

++

Mycobacteria cause tuberculosis (TB) and leprosy. Although the burden of leprosy has decreased, TB is still the most important infectious killer of humans. Mycobacterium avium-intracellulare (or Mycobacterium avium complex [MAC]) infection continues to be difficult to treat, mainly due to 3 natural barriers:

++

  • Cell wallMore than 60% of the cell wall is lipid, mainly mycolic acids composed of 2-branched, 73-hydroxy fatty acids with chains made of 76-90 carbon atoms. This shield prevents many pharmacological compounds from getting to the bacterial cell membrane or inside the cytosol.

  • Efflux pumps—These transport proteins export potentially harmful chemicals from the bacterial cytoplasm into the extracellular space, preventing accumulation of effective drug concentrations in the cell. These exporters are responsible for the native resistance of mycobacteria to many standard antibiotics. As an example, ATP-binding cassette (ABC) permeases comprise a full 2.5% of the genome of Mycobacterium tuberculosis.

  • Location in host—Some of the bacilli hide inside the patient's cells, adding an extra physicochemical barrier that antimicrobial agents must cross to be effective.

++

Mycobacteria are defined by their rate of growth on agar as rapid and slow growers (Table 56-1). Slow growers tend to be susceptible to antibiotics developed specifically for Mycobacteria; rapid growers tend to be also susceptible to antibiotics used against many other bacteria.

++
Table Graphic Jump Location
Table 56–1Pathogenic Mycobacterial Rapid and Slow Growers (Runyon Classification)
++

The mechanisms of action of the anti-mycobacterial drugs are summarized in Figure 56-1. Figure 56-2 depicts the mechanisms of resistance to these drugs. Tables 56–2 and 56–3 summarize the pharmacokinetic parameters of the antimycobacterial agents.

++
Table Graphic Jump Location
Table 56–2Population Pharmacokinetic Parameter Estimates for Antimycobacterial Drugs in Adult Patients

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.