Interventions for Tuberculosis Control and Elimination 2002

Similar to aminoglycosides, capreomycin causes auditory, vestibular,
and renal toxicity. 1004 Also like aminoglycosides, it is not orally absorbed
and the usual administration is intramuscular. Rare adverse drug events
include hypokalemia. 1004
Cross-resistance between kanamycin and capreomycin is incomplete. 1005
Cycloserine
Cycloserine (originally called orientomycin) was first isolated in 1952 from
a Streptomyces strain, designated strain K-300 by Kurosawa. 1006 The identity
with the compound discovered two years later in the United States was
elucidated by Shoji, 1007 and Mitui and Imaizumi in 1957, 1008 but not before
Lederle Laboratories also isolated the compound and recognized its identity
with oxamycin, isolated by the Merck Laboratories, 1009-1011 and the Pfizer
Laboratories which also isolated the compound. 1012 Cycloserine can be isolated
from Streptomyces orchidaceus, S. garyphalus, or S. lavendulae.
Cycloserine is active against M. tuberculosis and several species of
gram-positive bacteria. 1006
Cycloserine inhibits cell wall synthesis 1013,1014 by inhibiting the synthesis
of peptidoglycan by blocking action of D-alanine racemase and Dalanine:alanine
synthase. 46
Cycloserine is rapidly absorbed after oral administration, with a peak
serum level of 10 to 50 mg/L following administration of 0.75 g to 1 g
after 0.5 to 4 hours.
The usual dosage is two to three times daily (250 mg/day), 1015 but it
is often given as a single dose.
The main adverse drug events due to cycloserine are neurologic and
psychiatric, 159,1016-1022 although it has also been used in the treatment of mentally
ill tuberculosis patients without observation of major mental toxicity.
1023 In a summary of several reports, cycloserine toxic adverse drug
events were reported in over 20%. 1006 Most frequently reported or observed
were vertigo and disorientation. Neuropsychiatric changes including drowsiness,
slurred speech, psychoses, epileptiform reactions, 1016 as well as electroencephalographic
changes and coma, were frequently noted. These effects
of cycloserine are probably due to an interaction with the action of some
monoamine oxidase inhibitors, as shown in experimental animals. 1024
Cardiac depression, pareses, paresthesias and headache, pruritic rashes,
drug fever, liver enzyme elevations, and gastrointestinal disturbances were less
frequently reported adverse drug events. Smaller doses, and administration
155