Disulfiram inhibits the in vitro growth of methicillin-resistant staphylococcus aureus

Abstract

Several antibiotics have disulfiram-like effects; we evaluated disulfiram for its antibiotic-like effects. Disulfiram inhibited the in vitro growth of methicillin-resistant Staphylococcus aureus, with an MIC of 1.33 ,ig/ml, but was not effective against members of the family Enterobacteriaceae or Pseudomonas species.The medical management of chronic alcohol abuse frequently includes treatment with disulfiram (DSF) as an aid to maintaining long-term sobriety. A patient who consumes an alcoholic beverage during treatment with DSF will promptly experience the subjectively unpleasant disulfiram-ethanol reaction, which includes palpitations, malaise, flushing, nausea, and vomiting. The molecular basis of this interaction has been ascribed to the noncompetitive inhibition of aldehyde dehydrogenase by DSF, so that the ingestion of ethanol is followed by the accumulation of its first metabolite, acetaldehyde, in toxic quantities (8,10,13,16). However, the disulfiram-ethanol reaction might also be mediated by other enzymes, including dopamine P-hydroxylase (19) and alcohol dehydrogenase (2), which are also inhibited by DSF.It is now well known that patients treated with a number of antimicrobial agents are also at risk for a clinically similar reaction should they consume any alcohol. Disulfiram-like interactions with ethanol have been observed during treatments with cephalosporins, metronidazole, quinacrine, chloramphenicol, and moxalactam (6,12,25).While it is apparent that these antibiotics can simulate the clinical effects of DSF, there is now evidence to suggest that the converse might also be true, i.e., that DSF may in some cases act as an antibiotic. Scheibel et al. (24) found that DSF inhibited the growth of the human malaria parasite Plasmodium falciparum in vitro. The major breakdown product of DSF in vivo is diethyldithiocarbamate (7) (DDC), which has activity against Pityrosporum canis and inhibits the growth of ear mites (Otodectes cynotis) in cats and dogs (17). DDC may also act as an immunomodulator and viricide and may clinically benefit patients suffering from infection with human immunodeficiency virus (14,23 were included in each test run.Preparation of bacterial cultures. Organisms were obtained from stock cultures maintained on cystine-tryptic agar by the Clinical Microbiology Laboratory of St. Vincent's Medical Center of Richmond. S. aureus isolates were identified by colonial morphology, catalase production, and latex particle agglutination (Staphaurex; Wellcome Diagnostics, Research Triangle Park, N.C.). A microtiter identification system was used to identify members of the family Enterobacteriaceae and Pseudomonas species to the species level and to determine antibiotic susceptibility (MicroScan; Baxter Healthcare Corp., West Sacramento, Calif.). Each organism was subcultured from cystine-tryptic agar onto tryptic soy agar containing 5% sheep blood and incubated aerobically at 35°C for 18 h. MRSA was defined as an organism for which the oxacillin MIC was greater than or equal to 4.0 mg/ml and...

Disulfiram and Copper Ions Kill Mycobacterium tuberculosis in a Synergistic Manner

“…Faiman et al reported for humans that with a daily dose of 250 mg of disulfiram, the blood concentration of its metabolite, DETC, is 0.77 g/ml (ϳ5 M), which is equivalent to ϳ2.5 M disulfiram (48). However, according to other reports, concentrations of 50 M, 4.4 M, or 27 M, would be necessary to inhibit the growth of Pseudomonas aeruginosa (23), S. aureus (20), or M. tuberculosis (28) in vitro, respectively. Our reassessment of the antibacterial properties of disulfiram and its major metabolite, DETC, revealed that these compounds may be far more potent against at least M. tuberculosis than previously thought.…”

“…1A). Though copper ions have been found to play a role in disulfiram's anticancer activity (26), whether or not they are also essential for the previously reported antibacterial properties of disulfiram against M. tuberculosis (21,28) and other microbes (20,23) has not been sufficiently addressed.…”

“…Studies to evaluate the potency of disulfiram against certain types of cancer (12)(13)(14), Menkes disease (15), and HIV-1 infections are ongoing or have just been completed (16,17). Of additional interest to the medical community are its antinematode (18), antifungal (19), and, importantly, its antibacterial properties (11,(20)(21)(22)(23)(24).…”

Copper Complexation Screen Reveals Compounds with Potent Antibiotic Properties against Methicillin-Resistant Staphylococcus aureus

“…1A) inhibits the growth of MRSA (29,30). Disulfiram and its metabolites form copper complexes in the stomach, the small intestine, and the blood (31).…”

Antitubercular Activity of Disulfiram, an Antialcoholism Drug, against Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Isolates

“…Disulfiram (DSF; tetraethyl thiuram disulfide) has been used orally in the clinical treatment of alcoholism since 1949 and has been proven to exert an inhibitory effect on aldehyde dehydrogenase in vivo with 80% bioavailability and established safety profiles (13,33). Both DSF and its first metabolite, diethyldithiocarbamate (DDC), were reported to exhibit growth-inhibitory activity against bacteria, fungi, protozoa, and viruses (2,18,23,26,27). In the mid-1950s, the tuberculostatic effects of DSF and DDC were demonstrated in vivo using guinea pigs (17).…”