Interventions for Tuberculosis Control and Elimination 2002

Clarithromycin
Erythromycin, the prototype of the macrolide antibiotics, was first used to
treat infections in 1952. 1139
Clarithromycin is a macrolide that differs from erythromycin by the
methylation of the hydroxyl group at position 6 on the lactone ring. 1140
Clarithromycin has a wide anti-bacterial spectrum that includes
mycobacteria. 1132,1139,1141-1147 Most frequently it has been used as prophylactic
agent or against disease caused by M. avium complex. 1147-1154 While
it shows in vitro activity against M. tuberculosis complex in human
macrophages, 1145 the concentrations needed to inhibit growth appear to
exceed those achievable in the serum and lung tissue of humans. 1155 It has
therefore not been widely used in the treatment of tuberculosis.
Clarithromycin is usually rapidly absorbed and reaches C max after two
to three hours. 1140 Its serum elimination half life tβ 1/2 is 2.5 to 5 hours.
It undergoes extensive hepatic metabolism. Because of its predominant
renal excretion, dose adjustment might be necessary in patients with severe
renal impairment. 1140
Twice-daily 500 mg clarithromycin in AIDS patients was well tolerated,
prevented M. avium complex disease and reduced mortality. 1148 In
the treatment of M. avium complex disease, a dosage of twice daily 1,000 mg
has been given. 1149,1156
Fullerene derivatives
Fullerenes show an absolute lack of solubility in any polar solvent, and
covalent attachment of solubilizing chains was therefore developed, resulting
in the formation of water-soluble fulleropyrrolidines. 1157 Certain such
ionic fullerene derivatives have shown equally good activity against both
susceptible and multidrug-resistant isolates of M. tuberculosis.
Nitroimidazopyrans
A series of nitroimidazopyrans, originally investigated as radiosensitizers
for use in cancer chemotherapy, 1158 were shown to have in vitro and in
vivo activity against M. tuberculosis. 1141,1159 However, the original compounds
were shown to be mutagenic. 1160 Newer derivatives showed substantial
activity against M. tuberculosis and lacked the mutagenicity shown
previously with bicyclic nitroimidazoles. 1161 There is considerable in vivo
activity in the mouse model against M. tuberculosis, which is comparable
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