ANTIMYCOBACTERIAL AGENTS: INTRODUCTION
The physician is greatly challenged to provide optimal therapy for mycobacterial illnesses because of the increase in both drug-susceptible and multidrug-resistant tuberculosis; the increasing number of pathogenic nontuberculous mycobacteria (NTM); drug-related toxicities and drug-drug interactions (especially in patients who have AIDS, with their complex antiretroviral drug regimens); and the plethora of new antibiotics with antimycobacterial potential. This chapter reviews the therapeutic agents used for treatment of tuberculosis, leprosy (Hansen’s disease), and diseases caused by NTM, including the Mycobacterium avium complex (MAC), M. kansasii, the rapidly growing mycobacteria, and M. marinum. The use of first-line antimycobacterial agents in patients with renal or hepatic disease and in pregnant women is summarized in Table 161-1. The effects of antimycobacterial agents on the levels, activity, and toxicity of other commonly used drugs are summarized in Table 161-2. The reader is referred to the other chapters in this section for a more complete discussion of therapy for specific mycobacterial diseases.
Table 161-1 Use of First-Line Antimycobacterial Agents in Patients with Renal or Hepatic Disease and in Pregnant Women
|
Use in Indicated Circumstances |
|
|
Renal Disease: Creatinine Clearance Rate |
|
| Agent |
Severe Hepatic Disease |
<60 but >30 mL/min |
£30 mL/min |
Pregnancy
a
|
| Azithromycin |
No change |
No change |
?Decrease dose |
No evidence of risk (B) |
| Clarithromycin |
No change |
No change |
Decrease dose |
Risk cannot be ruled out (C) |
| Ethambutol |
No change |
No change |
No change |
Risk cannot be ruled out (C) |
| Isoniazid |
Avoid use or monitor carefully |
No change |
No change |
Risk cannot be ruled out (C) |
| Pyrazinamide |
Avoid use or monitor carefully |
No change |
Decrease dose
b
|
Risk cannot be ruled out (C)
c
|
| Rifabutin |
No change |
No change |
No change |
No evidence of risk (B) |
| Rifampin |
Avoid use or monitor carefully |
No change |
No change |
Risk cannot be ruled out (C) |
| Rifapentine |
Avoid use or monitor carefully |
No change |
No change |
Risk cannot be ruled out (C) |
| Streptomycin |
No change |
Decrease dose |
Decrease dose and frequency |
Definite evidence of risk (D) |
a
Based on Food and Drug Administration pregnancy categories of A–D, X.
bPrudent but not absolutely necessary.
c
Use in pregnancy is recommended by international organizations outside the United States.
Table 161-2 Effects of Major Antimycobacterial Agents on Levels/Activity/Toxicity of Other Commonly Used Drugs
a
Rifampin/rifabutin
b
Acetaminophen (↓)
Antiarrhythmics (↓)
Anticonvulsants (↓)
Azole antifungals (↓)
Barbiturates (↓)
β Blockers (↓)
Calcium channel blockers (↓)
Chloramphenicol (↓)
Clarithromycin (↓)
Cyclosporine (↓)
Dapsone (↓)
Delavirdine (↓)
Diazepam (↓)
Digoxin (↓)
Doxycycline (↓)
Fluoroquinolones (↓)
Glucocorticoids (↓)
Halothane (↓)
Hormonal contraceptives (↓)
Narcotics (↓)
NNRTIs
c
(↓)
Oral hypoglycemics (↓)
Probenecid (↓)
Protease inhibitors (↓)
Quinidine (↓)
Theophylline (↓)
Tricyclic antidepressants (↓)
Warfarin (↓)
Zidovudine (↓)
|
Isoniazid
Alcohol (↑ in risk of hepatitis)
Carbamazepine (↑)
Diphenylhydantoin (↑)
Enflurane (↑ in risk of renal failure)
Warfarin (↑)
Clarithromycin
Astemizole (↑)
Carbamazepine (↑)
Digoxin (↑)
Rifabutin (↑)
Ritonavir (↓)
Terfenadine (↑)
Zidovudine (↓)
|
a
The following antimycobacterial agents have no or minimal effects on other drugs: amikacin, azithromycin, capreomycin, ethambutol, streptomycin, pyrazinamide.
b
Rifabutin, which induces the cytochrome P450 system, has the same effects (↓) as rifampin but to a lesser degree. All drugs whose half-life is decreased by rifampin induction of hepatic microsomal enzymes may be subject to the same effect when coadministered with rifabutin; however, this point has not yet been studied.
c
NNRTIs, nonnucleoside reverse transcriptase inhibitors.
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