Interventions for Tuberculosis Control and Elimination 2002
Interventions for Tuberculosis Control and Elimination 2002
Interventions for Tuberculosis Control and Elimination 2002
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published a scientific blueprint <strong>for</strong> drug development that should assist in<br />
overcoming some of the barriers that impede the development, testing, <strong>and</strong><br />
marketing of new compounds. 1069<br />
Among the currently most promising c<strong>and</strong>idates are long-acting<br />
rifamycins <strong>and</strong> fluoroquinolones (discussed above), oxazolidinone compounds,<br />
<strong>and</strong> nitroimidazopyrans. These <strong>and</strong> some other compounds under<br />
investigation are briefly summarized here.<br />
Acetamides<br />
Acetamides belong to a new class of compounds designed to inhibit the βketoacyl<br />
synthase reaction of fatty acid synthesis in mycobacteria. 1122<br />
Because of their specific target, they exhibit virtually no activity against<br />
microorganisms other than mycobacteria. The MICs of the most potent<br />
compounds compare to those obtained with the most efficacious first-line<br />
drugs. 1122<br />
Amoxicillin plus clavulanic acid<br />
M. tuberculosis possesses a beta-lactamase that might be responsible <strong>for</strong> its<br />
natural resistance to beta-lactam antibiotics. 1123-1125 Thus, beta-lactam antibiotics<br />
are essentially inactive against tubercle bacilli. Clavulanic acid is a<br />
beta-lactamase blocker <strong>and</strong>, if given simultaneously with amoxicillin, makes<br />
the latter active against beta-lactam producing microorganisms. This combination<br />
has also been proposed <strong>and</strong> used in the treatment of drug-resistant<br />
tuberculosis. 1126,1127<br />
Amoxicillin was synthesized in the Beecham Research Laboratories,<br />
patented in 1964, <strong>and</strong> described <strong>for</strong> the first time in 1970/71. 1128,1129<br />
The addition of clavulanic acid to amoxicillin has shown in vitro activity<br />
against M. tuberculosis. 1130-1133 Since then, several reports have appeared<br />
demonstrating successes in the treatment of patients with multidrug-resistant<br />
tuberculosis who also received amoxicillin plus clavulanic acid. 1134-1137<br />
The daily dosage might be 2 g of the combination. 402<br />
The most important adverse drug event seen with beta-lactam antibiotics<br />
are hypersensitivity reactions, which might be immediate (urticaria,<br />
laryngeal edema, bronchospasm, hypotension, or local swelling), late (morbilli<strong>for</strong>m<br />
rashes, serum sickness, or urticaria), or other than late reactions<br />
(toxic epidermal necrolysis, interstitial nephritis, pulmonary infiltration, vasculitis,<br />
hemolytic anemia, neutropenia, or thrombocytopenia). 1138<br />
162
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