Why is disulfiram generally ineffective against most Gram-negative organisms, and which Gram-negative bacteria does it affect?
Label:chem
Topic
Disulfiram's activity against Gram-negative bacteria is limited.
Answer
Disulfiram does not inhibit the growth of most Gram-negative organisms, such as Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi, or Vibrio cholerae (MIC > 32 µg/mL). This is believed to be due to the antagonistic effects of glutathione, abundant in Gram-negative organisms, which reacts readily with disulfiram, cleaving it into diethyldithiocarbamate (DDTC). Unlike disulfiram, DDTC lacks the disulfide bond necessary for thiol-disulfide exchange to inhibit essential bacterial enzymes, resulting in no antibacterial activity against most Gram-positive organisms either. However, disulfiram has been shown to kill some Gram-negative organisms in vitro, including Borrelia burgdorferi (0.19–1.48 µg/mL), Francisella tularensis (0.50–9.50 µg/mL), and Bartonella henselae (2.5 µg/mL), and also shows activity against the atypical bacteria Mycoplasma spp. (0.19 µg/mL).
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