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In vitro antimicrobial activity of diethyldithiocarbamate and dimethyldithiocarbamate against methicillin-resistant
Abstract:
Staphylococcus aureus has appeared which is highly resistant to both methicillin and aminoglycosides. Current therapy involves long-term intravenous therapy of vancomycin. Since vancomycin is currently the only drug used to treat these patients, there is a need to develop additional antimicrobial therapy. The in vitro antimicrobial effect of the metal chelator, diethyldithiocarbamate (DDTC) and its structural analog dimethyldithiocarbamate (DMTC) were investigated. Both DDTC and DMTC were effective against S. aureus including methicillin-resistant S. aureus (MRSA). By agar diffusion, DDTC at 10 micrograms per disk produced zone sizes of 12 to 21 mm and at 100 micrograms per disk produced zone sizes of 26 to 34 mm against MRSA. The DMTC produced slightly greater zone sizes against MRSA of 16 to 24 mm and 24 to 37 mm for 10 micrograms per disk and 100 micrograms per disk, respectively. The minimum inhibitory concentration (MIC) for DMTC against MRSA was 6 micrograms per ml. Both DDTC and DMTC were also effective against enterococci, Proteus mirabilis, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Salmonella species, Serratia marcescens and Citrobacter freundii at 100 micrograms per disk. The MICs of DMTC for Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Salmonella and Citrobacter freundii were approximately 128 micrograms per ml while the MICs for Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa and Serratia marcescens was greater than or equal to 256 micrograms per ml. In addition, DMTC was synergistic with gentamicin against MRSA and coagulase-negative staphylococcus species, Enterobacter cloacae, Klebsiella pneumoniae and Pseudomonas aeruginosa. Additive and synergistic effects of DMTC were displayed with gentamicin against S. aureus including methicillin-resistant S. aureus.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Metal chelators diethyldithiocarbamate (DDTC) and dimethyldithiocarbamate (DMTC) show effectiveness against resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA). These compounds, particularly DMTC, demonstrate potential as novel antimicrobial agents, even showing synergy with gentamicin.
Area of Science:
- Microbiology and Infectious Diseases
- Pharmacology and Drug Discovery
- Antimicrobial Resistance
Background:
- Emergence of multidrug-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), poses a significant clinical challenge.
- Current treatment options for MRSA infections, primarily vancomycin, are limited, necessitating the development of alternative antimicrobial therapies.
- Metal chelators are being explored for their potential antimicrobial properties.
Purpose of the Study:
- To investigate the in vitro antimicrobial activity of diethyldithiocarbamate (DDTC) and dimethyldithiocarbamate (DMTC) against resistant bacterial strains.
- To evaluate the potential of DDTC and DMTC as standalone or synergistic antimicrobial agents.
Main Methods:
- Agar diffusion assays were performed to assess the zone of inhibition for DDTC and DMTC against MRSA.
- Minimum inhibitory concentrations (MICs) were determined for DMTC against various bacterial species.
- Synergistic effects of DMTC in combination with gentamicin were evaluated against MRSA and other Gram-negative bacteria.
Main Results:
- Both DDTC and DMTC exhibited significant in vitro activity against MRSA, with DMTC showing slightly larger inhibition zones.
- DMTC demonstrated effective MICs against MRSA and a range of other Gram-negative pathogens, including Klebsiella pneumoniae and Escherichia coli.
- DMTC displayed synergistic effects when combined with gentamicin against MRSA and several Gram-negative bacterial species.
Conclusions:
- Diethyldithiocarbamate (DDTC) and dimethyldithiocarbamate (DMTC) are promising candidates for novel antimicrobial therapies against resistant bacteria.
- Dimethyldithiocarbamate (DMTC) shows broad-spectrum activity and synergistic potential with existing antibiotics like gentamicin.
- Further research into DMTC and DDTC could lead to new treatment strategies for challenging bacterial infections.