Page 864 - Basic _ Clinical Pharmacology ( PDFDrive )

850 SECTION VIII Chemotherapeutic Drugs

TABLE 47–3 Clinical features and treatment options for infections with atypical mycobacteria.

Species Clinical Features Treatment Options
M kansasii Resembles tuberculosis Amikacin, clarithromycin, ethambutol, isoniazid, moxifloxacin, rifampin,
streptomycin, trimethoprim-sulfamethoxazole
M marinum Granulomatous cutaneous disease Amikacin, clarithromycin, ethambutol, doxycycline, levofloxacin, minocycline,
rifampin, trimethoprim-sulfamethoxazole
M scrofulaceum Cervical adenitis in children Amikacin, erythromycin (or other macrolide), rifampin, streptomycin
(Surgical excision is often curative and the treatment of choice.)
M avium complex Pulmonary disease in patients with chronic Amikacin, azithromycin, clarithromycin, ethambutol, moxifloxacin, rifabutin
(MAC) lung disease; disseminated infection in AIDS
M chelonae Abscess, sinus tract, ulcer; bone, joint, tendon Amikacin, doxycycline, imipenem, linezolid, macrolides, tobramycin
infection
M fortuitum Abscess, sinus tract, ulcer; bone, joint, tendon Amikacin, cefoxitin, ciprofloxacin, doxycycline, imipenem, minocycline,
infection moxifloxacin, ofloxacin, trimethoprim-sulfamethoxazole
M ulcerans Skin ulcers Clarithromycin, isoniazid, streptomycin, rifampin, minocycline, moxifloxacin
(Surgical excision may be effective.)

such as macrolides, sulfonamides, and tetracyclines, which are not DAPSONE & OTHER SULFONES
active against M tuberculosis, may be effective for infections caused
by NTM. Emergence of resistance during therapy is also a prob- Several drugs closely related to the sulfonamides have been used
lem with these mycobacterial species, and active infection should effectively in the long-term treatment of leprosy. The most widely
be treated with combinations of drugs. M kansasii is susceptible used is dapsone (diaminodiphenylsulfone). Like the sulfon-
to rifampin and ethambutol, partially susceptible to isoniazid, and amides, it inhibits folate synthesis. Resistance can emerge in large
completely resistant to pyrazinamide. A three-drug combination populations of M leprae, eg, in lepromatous leprosy, particularly
of isoniazid, rifampin, and ethambutol is the conventional treat- if low doses are given. Therefore, the combination of dapsone,
ment for M kansasii infection. A few representative pathogens, rifampin, and clofazimine is recommended for initial therapy of
with the clinical presentation and the drugs to which they are lepromatous leprosy. A combination of dapsone plus rifampin is
often susceptible, are given in Table 47–3. commonly used for leprosy with a lower organism burden. Dap-
M avium complex (MAC), which includes both M avium sone may also be used to prevent and treat Pneumocystis jiroveci
and M intracellulare, is an important and common cause of dis- pneumonia in AIDS patients.
seminated disease in late stages of AIDS (CD4 counts < 50/μL).
MAC is much less susceptible than M tuberculosis to most anti- O
tuberculous drugs. Combinations of agents are required to sup- NH 2 S NH 2
press the infection. Azithromycin, 500–600 mg once daily, or O
clarithromycin, 500 mg twice daily, plus ethambutol, 15 mg/kg/d, Dapsone
is an effective and well-tolerated regimen for treatment of dissemi-
nated disease. Some authorities recommend use of a third agent, Sulfones are well absorbed from the gut and widely distributed
especially rifabutin, 300 mg once daily. Other agents that may be throughout body fluids and tissues. Dapsone’s half-life is 1–2 days,
useful are listed in Table 47–3. Azithromycin and clarithromycin and drug tends to be retained in skin, muscle, liver, and kidney. Skin
are the prophylactic drugs of choice for preventing disseminated heavily infected with M leprae may contain several times more drug
MAC in AIDS patients with CD4 cell counts less than 50/μL. than normal skin. Sulfones are excreted into bile and reabsorbed
Rifabutin in a single daily dose of 300 mg has been shown to in the intestine. Excretion into urine is variable, and most excreted
reduce the incidence of MAC bacteremia but is less effective than drug is acetylated. In renal failure, the dose may have to be adjusted.
macrolides. The usual adult dosage in leprosy is 100 mg daily. For children, the
dose is proportionately less, depending on weight.
Dapsone is usually well tolerated. Many patients develop some
■ DRUGS USED IN LEPROSY hemolysis, particularly if they have glucose-6-phosphate dehydro-
genase deficiency. Methemoglobinemia is common but usually
Mycobacterium leprae has never been grown in vitro, but animal is not clinically significant. Gastrointestinal intolerance, fever,
models, such as growth in injected mouse footpads, have permit- pruritus, and rash occur. During dapsone therapy of lepromatous
ted laboratory evaluation of drugs. Only those drugs with the wid- leprosy, erythema nodosum leprosum often develops. It is some-
est clinical use are presented here. Because of increasing reports of times difficult to distinguish reactions to dapsone from manifesta-
dapsone resistance, treatment of leprosy with combinations of the tions of the underlying illness. Erythema nodosum leprosum may
drugs listed below is recommended. be suppressed by thalidomide (see Chapter 55).