Interventions for Tuberculosis Control and Elimination 2002

Numerous drugs other than the first-line anti-tuberculosis drugs discussed
in Chapter 1, and often called “second-line drugs”, have shown activity
against M. tuberculosis. Generally, these medications are less efficacious,
associated with a higher frequency of adverse drug events, and are more
expensive. In most low-income countries, these drugs are not routinely
available in national programs. Where they are, their use is best limited
to specialists with experience in dealing with adverse drug events.
Nevertheless, the global emergence of multidrug resistance (resistance
to at least isoniazid and rifampicin) has brought up the discussion about
their use on a wider scale. 605,607-609,611,981-983 For this reason, brief summaries
of these drugs are presented here.
Aminoglycosides (other than streptomycin)
Amikacin
Appendix 2
Active agents other
than essential drugs and drug classes
(second-line drugs)
Amikacin is a semi-synthetic aminoglycoside, synthesized by Kawaguchi
and collaborators through acetylation of the 1-aminogroup of the 2-desoxistreptamine
moiety of kanamycin A at the Bristol-Banyu research laboratories
in Japan, 984 and reported in 1972. 985
Amikacin has broad activity, particularly against gram-negative bacteria
986 and is active against M. tuberculosis. 987 Some researchers have found
it to be usually more active against M. tuberculosis than other aminoglycosides.
224,283 Cross-resistance with other aminoglycosides may occur, 283
and is particularly frequent with kanamycin, and incomplete with the
polypeptide capreomycin. 988 Amikacin is frequently active against streptomycin-resistant
strains of M. tuberculosis. 989 However, it appears to have
little early bactericidal activity. 990 Like other aminoglycosides, amikacin
is not absorbed orally and the usual route of administration is intramuscular
or intravenous, at a dose of 7.5 mg/kg to 15 mg/kg (depending on the
dosage interval).
153